Author: "Muller, David C." / Publication Type: Electronic Resources - Searchworks@Jio Institute Digital Library Search Results

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253 results on '"Muller, David C."'

1. Headache in the international cohort study of mobile phone use and health (COSMOS) in the Netherlands and the United Kingdom

Author: IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Traini, Eugenio, Smith, Rachel B, Vermeulen, Roel, Kromhout, Hans, Schüz, Joachim, Feychting, Maria, Auvinen, Anssi, Poulsen, Aslak Harbo, Deltour, Isabelle, Muller, David C, Heller, Joël, Tettamanti, Giorgio, Elliott, Paul, Huss, Anke, Toledano, Mireille B, IRAS OH Epidemiology Chemical Agents, IRAS – One Health Chemical, Traini, Eugenio, Smith, Rachel B, Vermeulen, Roel, Kromhout, Hans, Schüz, Joachim, Feychting, Maria, Auvinen, Anssi, Poulsen, Aslak Harbo, Deltour, Isabelle, Muller, David C, Heller, Joël, Tettamanti, Giorgio, Elliott, Paul, Huss, Anke, and Toledano, Mireille B
Published: 2024

2. Reproductive and hormonal factors and risk of renal cell carcinoma among women in the European Prospective Investigation into Cancer and Nutrition

Author: Clasen, Joanna L., Mabunda, Rita, Heath, Alicia K., Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B., Birukov, Anna, Tagliabue, Giovanna, Chiodini, Paolo, Tumino, Rosario, Milani, Lorenzo, Braaten, Tonje, Gram, Inger, Lukic, Marko, Luján-Barroso, Leila, Rodriguez-Barranco, Miguel, Chirlaque, María-Dolores, Ardanaz, Eva, Amiano, Pilar, Manjer, Jonas, Huss, Linnea, Ljungberg, Börje, Travis, Ruth, Smith-Byrne, Karl, Gunter, Marc, Johansson, Matthias, Rinaldi, Sabina, Weiderpass, Elisabete, Riboli, Elio, Cross, Amanda J., Muller, David C., Clasen, Joanna L., Mabunda, Rita, Heath, Alicia K., Kaaks, Rudolf, Katzke, Verena, Schulze, Matthias B., Birukov, Anna, Tagliabue, Giovanna, Chiodini, Paolo, Tumino, Rosario, Milani, Lorenzo, Braaten, Tonje, Gram, Inger, Lukic, Marko, Luján-Barroso, Leila, Rodriguez-Barranco, Miguel, Chirlaque, María-Dolores, Ardanaz, Eva, Amiano, Pilar, Manjer, Jonas, Huss, Linnea, Ljungberg, Börje, Travis, Ruth, Smith-Byrne, Karl, Gunter, Marc, Johansson, Matthias, Rinaldi, Sabina, Weiderpass, Elisabete, Riboli, Elio, Cross, Amanda J., and Muller, David C.
Abstract: Background: Renal cell carcinoma (RCC) is twice as common among men compared with women, and hormonal factors have been suggested to partially explain this difference. There is currently little evidence on the roles of reproductive and hormonal risk factors in RCC aetiology. Materials & Methods: We investigated associations of age at menarche and age at menopause, pregnancy-related factors, hysterectomy and ovariectomy and exogenous hormone use with RCC risk among 298,042 women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Results: During 15 years of follow-up, 438 RCC cases were identified. Parous women had higher rates of RCC compared with nulliparous women (HR = 1.71, 95% CI 1.18, 2.46), and women who were older at age of first pregnancy had lower rates of RCC (30 years + vs. <20 years HR = 0.53, 95% CI 0.34, 0.82). Additionally, we identified a positive association for hysterectomy (HR = 1.43 95% CI 1.09, 1.86) and bilateral ovariectomy (HR = 1.67, 95% CI 1.13, 2.47), but not unilateral ovariectomy (HR = 0.99, 95% CI 0.61, 1.62) with RCC risk. No clear associations were found for age at menarche, age at menopause or exogenous hormone use. Conclusion: Our results suggest that parity and reproductive organ surgeries may play a role in RCC aetiology.
Published: 2023
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3. Evaluation of pre-diagnostic blood protein measurements for predicting survival after lung cancer diagnosis

Author: Feng, Xiaoshuang, Muller, David C., Zahed, Hana, Alcala, Karine, Guida, Florence, Smith-Byrne, Karl, Yuan, Jian-Min, Koh, Woon-Puay, Wang, Renwei, Milne, Roger L., Bassett, Julie K., Langhammer, Arnulf, Hveem, Kristian, Stevens, Victoria L., Wang, Ying, Johansson, Mikael, Tjønneland, Anne, Tumino, Rosario, Sheikh, Mahdi, Johansson, Mattias, Robbins, Hilary A., Feng, Xiaoshuang, Muller, David C., Zahed, Hana, Alcala, Karine, Guida, Florence, Smith-Byrne, Karl, Yuan, Jian-Min, Koh, Woon-Puay, Wang, Renwei, Milne, Roger L., Bassett, Julie K., Langhammer, Arnulf, Hveem, Kristian, Stevens, Victoria L., Wang, Ying, Johansson, Mikael, Tjønneland, Anne, Tumino, Rosario, Sheikh, Mahdi, Johansson, Mattias, and Robbins, Hilary A.
Abstract: Background: To evaluate whether circulating proteins are associated with survival after lung cancer diagnosis, and whether they can improve prediction of prognosis. Methods: We measured up to 1159 proteins in blood samples from 708 participants in 6 cohorts. Samples were collected within 3 years prior to lung cancer diagnosis. We used Cox proportional hazards models to identify proteins associated with overall mortality after lung cancer diagnosis. To evaluate model performance, we used a round-robin approach in which models were fit in 5 cohorts and evaluated in the 6th cohort. Specifically, we fit a model including 5 proteins and clinical parameters and compared its performance with clinical parameters only. Findings: There were 86 proteins nominally associated with mortality (p < 0.05), but only CDCP1 remained statistically significant after accounting for multiple testing (hazard ratio per standard deviation: 1.19, 95% CI: 1.10–1.30, unadjusted p = 0.00004). The external C-index for the protein-based model was 0.63 (95% CI: 0.61–0.66), compared with 0.62 (95% CI: 0.59–0.64) for the model with clinical parameters only. Inclusion of proteins did not provide a statistically significant improvement in discrimination (C-index difference: 0.015, 95% CI: −0.003 to 0.035). Interpretation: Blood proteins measured within 3 years prior to lung cancer diagnosis were not strongly associated with lung cancer survival, nor did they importantly improve prediction of prognosis beyond clinical information.
Published: 2023
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4. Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Author: Heath, Alicia K., Muller, David C., van den Brandt, Piet A., Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Ferrari, Pietro, Merritt, Melissa A., Rostgaard-Hansen, Agnetha L., Tjønneland, Anne, Overvad, Kim, Katzke, Verena, Srour, Bernard, Masala, Giovanna, Sacerdote, Carlotta, Ricceri, Fulvio, Pasanisi, Fabrizio, Bueno-de-Mesquita, Bas, Downward, George S., Skeie, Guri, Sandanger, Torkjel M., Crous-Bou, Marta, Rodríguez-Barranco, Miguel, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Drake, Isabel, Johansson, Mikael, Johansson, Ingegerd, Key, Tim, Papadimitriou, Nikos, Riboli, Elio, Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Heath, Alicia K., Muller, David C., van den Brandt, Piet A., Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Ferrari, Pietro, Merritt, Melissa A., Rostgaard-Hansen, Agnetha L., Tjønneland, Anne, Overvad, Kim, Katzke, Verena, Srour, Bernard, Masala, Giovanna, Sacerdote, Carlotta, Ricceri, Fulvio, Pasanisi, Fabrizio, Bueno-de-Mesquita, Bas, Downward, George S., Skeie, Guri, Sandanger, Torkjel M., Crous-Bou, Marta, Rodríguez-Barranco, Miguel, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Drake, Isabel, Johansson, Mikael, Johansson, Ingegerd, Key, Tim, Papadimitriou, Nikos, Riboli, Elio, Tzoulaki, Ioanna, and Tsilidis, Konstantinos K.
Abstract: It is unclear whether diet, and in particular certain foods or nutrients, are associated with lung cancer risk. We assessed associations of 92 dietary factors with lung cancer risk in 327 790 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC). Cox regression yielded adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) per SD higher intake/day of each food/nutrient. Correction for multiple comparisons was performed using the false discovery rate and identified associations were evaluated in the Netherlands Cohort Study (NLCS). In EPIC, 2420 incident lung cancer cases were identified during a median of 15 years of follow-up. Higher intakes of fibre (HR per 1 SD higher intake/day = 0.91, 95% CI 0.87-0.96), fruit (HR = 0.91, 95% CI 0.86-0.96) and vitamin C (HR = 0.91, 95% CI 0.86-0.96) were associated with a lower risk of lung cancer, whereas offal (HR = 1.08, 95% CI 1.03-1.14), retinol (HR = 1.06, 95% CI 1.03-1.10) and beer/cider (HR = 1.04, 95% CI 1.02-1.07) intakes were positively associated with lung cancer risk. Associations did not differ by sex and there was less evidence for associations among never smokers. None of the six associations with overall lung cancer risk identified in EPIC were replicated in the NLCS (2861 cases), however in analyses of histological subtypes, inverse associations of fruit and vitamin C with squamous cell carcinoma were replicated in the NLCS. Overall, there is little evidence that intakes of specific foods and nutrients play a major role in primary lung cancer risk, but fruit and vitamin C intakes seem to be inversely associated with squamous cell lung cancer.
Published: 2022
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5. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author: Papadimitriou, Nikos, Bouras, Emmanouil, van den Brandt, Piet A., Muller, David C., Papadopoulou, Areti, Heath, Alicia K., Critselis, Elena, Gunter, Marc J., Vineis, Paolo, Ferrari, Pietro, Weiderpass, Elisabete, Boeing, Heiner, Bastide, Nadia, Merritt, Melissa A., Lopez, David S., Bergmann, Manuela M., Perez-Cornago, Aurora, Schulze, Matthias, Skeie, Guri, Srour, Bernard, Eriksen, Anne Kirstine, Bodén, Stina, Johansson, Ingegerd, Nøst, Therese Haugdahl, Lukic, Marco, Ricceri, Fulvio, Ericson, Ulrika, Huerta, José María, Dahm, Christina C., Agnoli, Claudia, Amiano, Pilar Exezarreta, Tjønneland, Anne, Gurrea, Aurelio Barricarte, Bueno-de-Mesquita, Bas, Ardanaz, Eva, Berntsson, Jonna, Sánchez, Maria-Jose, Tumino, Rosario, Panico, Salvatore, Katzke, Verena, Jakszyn, Paula, Masala, Giovanna, Derksen, Jeroen W.G., Quirós, J. Ramón, Severi, Gianluca, Cross, Amanda J., Riboli, Ellio, Tzoulaki, Ioanna, Tsilidis, Konstantinos K., Papadimitriou, Nikos, Bouras, Emmanouil, van den Brandt, Piet A., Muller, David C., Papadopoulou, Areti, Heath, Alicia K., Critselis, Elena, Gunter, Marc J., Vineis, Paolo, Ferrari, Pietro, Weiderpass, Elisabete, Boeing, Heiner, Bastide, Nadia, Merritt, Melissa A., Lopez, David S., Bergmann, Manuela M., Perez-Cornago, Aurora, Schulze, Matthias, Skeie, Guri, Srour, Bernard, Eriksen, Anne Kirstine, Bodén, Stina, Johansson, Ingegerd, Nøst, Therese Haugdahl, Lukic, Marco, Ricceri, Fulvio, Ericson, Ulrika, Huerta, José María, Dahm, Christina C., Agnoli, Claudia, Amiano, Pilar Exezarreta, Tjønneland, Anne, Gurrea, Aurelio Barricarte, Bueno-de-Mesquita, Bas, Ardanaz, Eva, Berntsson, Jonna, Sánchez, Maria-Jose, Tumino, Rosario, Panico, Salvatore, Katzke, Verena, Jakszyn, Paula, Masala, Giovanna, Derksen, Jeroen W.G., Quirós, J. Ramón, Severi, Gianluca, Cross, Amanda J., Riboli, Ellio, Tzoulaki, Ioanna, and Tsilidis, Konstantinos K.
Abstract: Background & Aims: Evidence regarding the association of dietary exposures with colorectal cancer (CRC) risk is not consistent with a few exceptions. Therefore, we conducted a diet-wide association study (DWAS) in the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the associations between several dietary exposures with CRC risk. Methods: The association of 92 food and nutrient intakes with CRC risk was assessed in 386,792 participants, 5069 of whom developed incident CRC. Correction for multiple comparisons was performed using the false discovery rate, and emerging associations were examined in the Netherlands Cohort Study (NLCS). Multiplicative gene-nutrient interactions were also tested in EPIC based on known CRC-associated loci. Results: In EPIC, alcohol, liquor/spirits, wine, beer/cider, soft drinks, and pork were positively associated with CRC, whereas milk, cheese, calcium, phosphorus, magnesium, potassium, riboflavin, vitamin B6, beta carotene, fruit, fiber, nonwhite bread, banana, and total protein intakes were inversely associated. Of these 20 associations, 13 were replicated in the NLCS, for which a meta-analysis was performed, namely alcohol (summary hazard ratio [HR] per 1-SD increment in intake: 1.07; 95% confidence interval [CI], 1.04–1.09), liquor/spirits (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.06), wine (HR per 1-SD increment in intake, 1.04; 95% CI, 1.02–1.07), beer/cider (HR per 1-SD increment in intake, 1.06; 95% CI, 1.04–1.08), milk (HR per 1-SD increment in intake, 0.95; 95% CI, 0.93–0.98), cheese (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), calcium (HR per 1-SD increment in intake, 0.93; 95% CI, 0.90–0.95), phosphorus (HR per 1-SD increment in intake, 0.92; 95% CI, 0.90–0.95), magnesium (HR per 1-SD increment in intake, 0.95; 95% CI, 0.92–0.98), potassium (HR per 1-SD increment in intake, 0.96; 95% CI, 0.94–0.99), riboflavin (HR per 1-SD increment in intake, 0.94; 95% CI, 0.92–0
Published: 2022
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6. Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Author: IRAS OH Epidemiology Chemical Agents, Heath, Alicia K, Muller, David C, van den Brandt, Piet A, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Ferrari, Pietro, Merritt, Melissa A, Rostgaard-Hansen, Agnetha L, Tjønneland, Anne, Overvad, Kim, Katzke, Verena, Srour, Bernard, Masala, Giovanna, Sacerdote, Carlotta, Ricceri, Fulvio, Pasanisi, Fabrizio, Bueno-de-Mesquita, Bas, Downward, George S, Skeie, Guri, Sandanger, Torkjel M, Crous-Bou, Marta, Rodríguez-Barranco, Miguel, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Drake, Isabel, Johansson, Mikael, Johansson, Ingegerd, Key, Tim, Papadimitriou, Nikos, Riboli, Elio, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, IRAS OH Epidemiology Chemical Agents, Heath, Alicia K, Muller, David C, van den Brandt, Piet A, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Ferrari, Pietro, Merritt, Melissa A, Rostgaard-Hansen, Agnetha L, Tjønneland, Anne, Overvad, Kim, Katzke, Verena, Srour, Bernard, Masala, Giovanna, Sacerdote, Carlotta, Ricceri, Fulvio, Pasanisi, Fabrizio, Bueno-de-Mesquita, Bas, Downward, George S, Skeie, Guri, Sandanger, Torkjel M, Crous-Bou, Marta, Rodríguez-Barranco, Miguel, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Drake, Isabel, Johansson, Mikael, Johansson, Ingegerd, Key, Tim, Papadimitriou, Nikos, Riboli, Elio, Tzoulaki, Ioanna, and Tsilidis, Konstantinos K
Published: 2022

7. Diet-wide association study of 92 foods and nutrients and lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study and the Netherlands Cohort Study

Author: MS MDL 1, Planetary Health & Exposoom, Heath, Alicia K, Muller, David C, van den Brandt, Piet A, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Ferrari, Pietro, Merritt, Melissa A, Rostgaard-Hansen, Agnetha L, Tjønneland, Anne, Overvad, Kim, Katzke, Verena, Srour, Bernard, Masala, Giovanna, Sacerdote, Carlotta, Ricceri, Fulvio, Pasanisi, Fabrizio, Bueno-de-Mesquita, Bas, Downward, George S, Skeie, Guri, Sandanger, Torkjel M, Crous-Bou, Marta, Rodríguez-Barranco, Miguel, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Drake, Isabel, Johansson, Mikael, Johansson, Ingegerd, Key, Tim, Papadimitriou, Nikos, Riboli, Elio, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, MS MDL 1, Planetary Health & Exposoom, Heath, Alicia K, Muller, David C, van den Brandt, Piet A, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Boeing, Heiner, Ferrari, Pietro, Merritt, Melissa A, Rostgaard-Hansen, Agnetha L, Tjønneland, Anne, Overvad, Kim, Katzke, Verena, Srour, Bernard, Masala, Giovanna, Sacerdote, Carlotta, Ricceri, Fulvio, Pasanisi, Fabrizio, Bueno-de-Mesquita, Bas, Downward, George S, Skeie, Guri, Sandanger, Torkjel M, Crous-Bou, Marta, Rodríguez-Barranco, Miguel, Amiano, Pilar, Huerta, José María, Ardanaz, Eva, Drake, Isabel, Johansson, Mikael, Johansson, Ingegerd, Key, Tim, Papadimitriou, Nikos, Riboli, Elio, Tzoulaki, Ioanna, and Tsilidis, Konstantinos K
Published: 2022

8. A Prospective Diet-Wide Association Study for Risk of Colorectal Cancer in EPIC

Author: MS MDL 1, Epi Kanker Team B, Cancer, Papadimitriou, Nikos, Bouras, Emmanouil, van den Brandt, Piet A, Muller, David C, Papadopoulou, Areti, Heath, Alicia K, Critselis, Elena, Gunter, Marc J, Vineis, Paolo, Ferrari, Pietro, Weiderpass, Elisabete, Boeing, Heiner, Bastide, Nadia, Merritt, Melissa A, Lopez, David S, Bergmann, Manuela M, Perez-Cornago, Aurora, Schulze, Matthias, Skeie, Guri, Srour, Bernard, Eriksen, Anne Kirstine, Boden, Stina, Johansson, Ingegerd, Nøst, Therese Haugdahl, Lukic, Marco, Ricceri, Fulvio, Ericson, Ulrika, Huerta, José María, Dahm, Christina C, Agnoli, Claudia, Amiano, Pilar Exezarreta, Tjønneland, Anne, Gurrea, Aurelio Barricarte, Bueno-de-Mesquita, Bas, Ardanaz, Eva, Berntsson, Jonna, Sánchez, Maria-Jose, Tumino, Rosario, Panico, Salvatore, Katzke, Verena, Jakszyn, Paula, Masala, Giovanna, Derksen, Jeroen W G, Quirós, J Ramón, Severi, Gianluca, Cross, Amanda J, Riboli, Ellio, Tzoulaki, Ioanna, Tsilidis, Konstantinos K, MS MDL 1, Epi Kanker Team B, Cancer, Papadimitriou, Nikos, Bouras, Emmanouil, van den Brandt, Piet A, Muller, David C, Papadopoulou, Areti, Heath, Alicia K, Critselis, Elena, Gunter, Marc J, Vineis, Paolo, Ferrari, Pietro, Weiderpass, Elisabete, Boeing, Heiner, Bastide, Nadia, Merritt, Melissa A, Lopez, David S, Bergmann, Manuela M, Perez-Cornago, Aurora, Schulze, Matthias, Skeie, Guri, Srour, Bernard, Eriksen, Anne Kirstine, Boden, Stina, Johansson, Ingegerd, Nøst, Therese Haugdahl, Lukic, Marco, Ricceri, Fulvio, Ericson, Ulrika, Huerta, José María, Dahm, Christina C, Agnoli, Claudia, Amiano, Pilar Exezarreta, Tjønneland, Anne, Gurrea, Aurelio Barricarte, Bueno-de-Mesquita, Bas, Ardanaz, Eva, Berntsson, Jonna, Sánchez, Maria-Jose, Tumino, Rosario, Panico, Salvatore, Katzke, Verena, Jakszyn, Paula, Masala, Giovanna, Derksen, Jeroen W G, Quirós, J Ramón, Severi, Gianluca, Cross, Amanda J, Riboli, Ellio, Tzoulaki, Ioanna, and Tsilidis, Konstantinos K
Published: 2022

9. Weight change in middle adulthood and risk of cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Christakoudi, Sofia, Pagoni, Panagiota, Ferrari, Pietro, Cross, Amanda J., Tzoulaki, Ioanna, Muller, David C., Weiderpass, Elisabete, Freisling, Heinz, Murphy, Neil, Dossus, Laure, Turzanski Fortner, Renee, Agudo, Antonio, Overvad, Kim, Perez-Cornago, Aurora, Key, Timothy J., Brennan, Paul, Johansson, Mattias, Tjønneland, Anne, Halkjær, Jytte, Boutron-Ruault, Marie-Christine, Artaud, Fanny, Severi, Gianluca, Kaaks, Rudolf, Schulze, Matthias B., Bergmann, Manuela M., Masala, Giovanna, Grioni, Sara, Simeon, Vittorio, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Rylander, Charlotta, Borch, Kristin Benjaminsen, Quirós, J. Ramón, Rodriguez-Barranco, Miguel, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Drake, Isabel, Stocks, Tanja, Häggström, Christel, Harlid, Sophia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K., Christakoudi, Sofia, Pagoni, Panagiota, Ferrari, Pietro, Cross, Amanda J., Tzoulaki, Ioanna, Muller, David C., Weiderpass, Elisabete, Freisling, Heinz, Murphy, Neil, Dossus, Laure, Turzanski Fortner, Renee, Agudo, Antonio, Overvad, Kim, Perez-Cornago, Aurora, Key, Timothy J., Brennan, Paul, Johansson, Mattias, Tjønneland, Anne, Halkjær, Jytte, Boutron-Ruault, Marie-Christine, Artaud, Fanny, Severi, Gianluca, Kaaks, Rudolf, Schulze, Matthias B., Bergmann, Manuela M., Masala, Giovanna, Grioni, Sara, Simeon, Vittorio, Tumino, Rosario, Sacerdote, Carlotta, Skeie, Guri, Rylander, Charlotta, Borch, Kristin Benjaminsen, Quirós, J. Ramón, Rodriguez-Barranco, Miguel, Chirlaque, Maria-Dolores, Ardanaz, Eva, Amiano, Pilar, Drake, Isabel, Stocks, Tanja, Häggström, Christel, Harlid, Sophia, Ellingjord-Dale, Merete, Riboli, Elio, and Tsilidis, Konstantinos K.
Abstract: Obesity is a risk factor for several major cancers. Associations of weight change in middle adulthood with cancer risk, however, are less clear. We examined the association of change in weight and body mass index (BMI) category during middle adulthood with 42 cancers, using multivariable Cox proportional hazards models in the European Prospective Investigation into Cancer and Nutrition cohort. Of 241 323 participants (31% men), 20% lost and 32% gained weight (>0.4 to 5.0 kg/year) during 6.9 years (average). During 8.0 years of follow-up after the second weight assessment, 20 960 incident cancers were ascertained. Independent of baseline BMI, weight gain (per one kg/year increment) was positively associated with cancer of the corpus uteri (hazard ratio [HR] = 1.14; 95% confidence interval: 1.05-1.23). Compared to stable weight (+/- 0.4 kg/year), weight gain (>0.4 to 5.0 kg/year) was positively associated with cancers of the gallbladder and bile ducts (HR = 1.41; 1.01-1.96), postmenopausal breast (HR = 1.08; 1.00-1.16) and thyroid (HR = 1.40; 1.04-1.90). Compared to maintaining normal weight, maintaining overweight or obese BMI (World Health Organisation categories) was positively associated with most obesity-related cancers. Compared to maintaining the baseline BMI category, weight gain to a higher BMI category was positively associated with cancers of the postmenopausal breast (HR = 1.19; 1.06-1.33), ovary (HR = 1.40; 1.04-1.91), corpus uteri (HR = 1.42; 1.06-1.91), kidney (HR = 1.80; 1.20-2.68) and pancreas in men (HR = 1.81; 1.11-2.95). Losing weight to a lower BMI category, however, was inversely associated with cancers of the corpus uteri (HR = 0.40; 0.23-0.69) and colon (HR = 0.69; 0.52-0.92). Our findings support avoiding weight gain and encouraging weight loss in middle adulthood.
Published: 2021
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10. The blood metabolome of incident kidney cancer: A case-control study nested within the MetKid consortium

Author: Guida, Florence, Tan, Vanessa Y., Corbin, Laura J., Smith-Byrne, Karl, Alcala, Karine, Langenberg, Claudia, Stewart, Isobel D., Butterworth, Adam S., Surendran, Praveen, Achaintre, David, Adamski, Jerzy, Exezarreta, Pilar Amiano, Bergmann, Manuela M., Bull, Caroline J., Dahm, Christina C., Gicquiau, Audrey, Giles, Graham G., Gunter, Marc J., Haller, Toomas, Langhammer, Arnulf, Larose, Tricia L., Ljungberg, Börje, Metspalu, Andres, Milne, Roger L., Muller, David C., Nøst, Therese H., Sørgjerd, Elin Pettersen, Prehn, Cornelia, Riboli, Elio, Rinaldi, Sabina, Rothwell, Joseph A., Scalbert, Augustin, Schmidt, Julie A., Severi, Gianluca, Sieri, Sabina, Vermeulen, Roel, Vincent, Emma E., Waldenberger, Melanie, Timpson, Nicholas J., Johansson, Mattias, Guida, Florence, Tan, Vanessa Y., Corbin, Laura J., Smith-Byrne, Karl, Alcala, Karine, Langenberg, Claudia, Stewart, Isobel D., Butterworth, Adam S., Surendran, Praveen, Achaintre, David, Adamski, Jerzy, Exezarreta, Pilar Amiano, Bergmann, Manuela M., Bull, Caroline J., Dahm, Christina C., Gicquiau, Audrey, Giles, Graham G., Gunter, Marc J., Haller, Toomas, Langhammer, Arnulf, Larose, Tricia L., Ljungberg, Börje, Metspalu, Andres, Milne, Roger L., Muller, David C., Nøst, Therese H., Sørgjerd, Elin Pettersen, Prehn, Cornelia, Riboli, Elio, Rinaldi, Sabina, Rothwell, Joseph A., Scalbert, Augustin, Schmidt, Julie A., Severi, Gianluca, Sieri, Sabina, Vermeulen, Roel, Vincent, Emma E., Waldenberger, Melanie, Timpson, Nicholas J., and Johansson, Mattias
Abstract: Background: Excess bodyweight and related metabolic perturbations have been implicated in kidney cancer aetiology, but the specific molecular mechanisms underlying these relationships are poorly understood. In this study, we sought to identify circulating metabolites that predispose kidney cancer and to evaluate the extent to which they are influenced by body mass index (BMI). Methods and findings: We assessed the association between circulating levels of 1,416 metabolites and incident kidney cancer using pre-diagnostic blood samples from up to 1,305 kidney cancer case–control pairs from 5 prospective cohort studies. Cases were diagnosed on average 8 years after blood collection. We found 25 metabolites robustly associated with kidney cancer risk. In particular, 14 glycerophospholipids (GPLs) were inversely associated with risk, including 8 phosphatidylcholines (PCs) and 2 plasmalogens. The PC with the strongest association was PC ae C34:3 with an odds ratio (OR) for 1 standard deviation (SD) increment of 0.75 (95% confidence interval [CI]: 0.68 to 0.83, p = 2.6 × 10−8). In contrast, 4 amino acids, including glutamate (OR for 1 SD = 1.39, 95% CI: 1.20 to 1.60, p = 1.6 × 10−5), were positively associated with risk. Adjusting for BMI partly attenuated the risk association for some—but not all—metabolites, whereas other known risk factors of kidney cancer, such as smoking and alcohol consumption, had minimal impact on the observed associations. A mendelian randomisation (MR) analysis of the influence of BMI on the blood metabolome highlighted that some metabolites associated with kidney cancer risk are influenced by BMI. Specifically, elevated BMI appeared to decrease levels of several GPLs that were also found inversely associated with kidney cancer risk (e.g., −0.17 SD change [ßBMI] in 1-(1-enyl-palmitoyl)-2-linoleoyl-GPC (P-16:0/18:2) levels per SD change in BMI, p = 3.4 × 10−5). BMI was also associated with increased levels of glutamate (ßBMI: 0.12, p = 1.5 × 10−3)
Published: 2021
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11. A comparison of complementary measures of vitamin B6 status, function, and metabolism in the European Prospective Investigation into Cancer and Nutrition (EPIC) study

Author: Clasen, Joanna L., Heath, Alicia K., Van Puyvelde, Heleen, Huybrechts, Inge, Park, Jin Young, Ferrari, Pietro, Johansson, Mattias, Scelo, Ghislaine, Ulvik, Arve, Midttun, Øivind, Ueland, Per Magne, Dahm, Christina C., Halkjær, Jytte, Olsen, Anja, Johnson, Theron, Katzke, Verena, Schulze, Matthias B., Masala, Giovanna, Segrado, Francesco, de Magistris, Maria Santucci, Sacerdote, Carlotta, Ocké, Marga C., Luján-Barroso, Leila, Ching-López, Ana, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Manjer, Jonas, Gylling, Björn, Johansson, Ingegerd, Schmidt, Julie, Weiderpass, Elisabete, Riboli, Elio, Cross, Amanda J., Muller, David C., Clasen, Joanna L., Heath, Alicia K., Van Puyvelde, Heleen, Huybrechts, Inge, Park, Jin Young, Ferrari, Pietro, Johansson, Mattias, Scelo, Ghislaine, Ulvik, Arve, Midttun, Øivind, Ueland, Per Magne, Dahm, Christina C., Halkjær, Jytte, Olsen, Anja, Johnson, Theron, Katzke, Verena, Schulze, Matthias B., Masala, Giovanna, Segrado, Francesco, de Magistris, Maria Santucci, Sacerdote, Carlotta, Ocké, Marga C., Luján-Barroso, Leila, Ching-López, Ana, Huerta, José María, Ardanaz, Eva, Amiano, Pilar, Ericson, Ulrika, Manjer, Jonas, Gylling, Björn, Johansson, Ingegerd, Schmidt, Julie, Weiderpass, Elisabete, Riboli, Elio, Cross, Amanda J., and Muller, David C.
Abstract: BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.
Published: 2021
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12. Soft drink and juice consumption and renal cell carcinoma incidence and mortality in the european prospective investigation into cancer and nutrition

Author: Heath, Alicia K., Clasen, Joanna L., Jayanth, Nick P., Jenab, Mazda, Tjønneland, Anne, Petersen, Kristina Elin Nielsen, Overvad, Kim, Srour, Bernard, Katzke, Verena, Bergmann, Manuela M., Schulze, Matthias B., Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Catalano, Alberto, Pasanisi, Fabrizio, Brustad, Magritt, Standahl Olsen, Karina, Skeie, Guri, Lujan-Barroso, Leila, Rodríguez-Barranco, Miguel, Amiano, Pilar, Santiuste, Carmen, Barricarte Gurrea, Aurelio, Axelson, Hakan, Ramne, Stina, Ljungberg, Börje, Watts, Eleanor L., Huybrechts, Inge, Weiderpass, Elisabete, Riboli, Elio, Muller, David C., Heath, Alicia K., Clasen, Joanna L., Jayanth, Nick P., Jenab, Mazda, Tjønneland, Anne, Petersen, Kristina Elin Nielsen, Overvad, Kim, Srour, Bernard, Katzke, Verena, Bergmann, Manuela M., Schulze, Matthias B., Masala, Giovanna, Krogh, Vittorio, Tumino, Rosario, Catalano, Alberto, Pasanisi, Fabrizio, Brustad, Magritt, Standahl Olsen, Karina, Skeie, Guri, Lujan-Barroso, Leila, Rodríguez-Barranco, Miguel, Amiano, Pilar, Santiuste, Carmen, Barricarte Gurrea, Aurelio, Axelson, Hakan, Ramne, Stina, Ljungberg, Börje, Watts, Eleanor L., Huybrechts, Inge, Weiderpass, Elisabete, Riboli, Elio, and Muller, David C.
Abstract: Background: Renal cell carcinoma (RCC) accounts for more than 80% of kidney cancers in adults, and obesity is a known risk factor. Regular consumption of sweetened beverages has been linked to obesity and several chronic diseases, including some types of cancer. It is uncertain whether soft drink and juice consumption is associated with risk of RCC. We investigated the associations of soft drink and juice consumption with RCC incidence and mortality in the European Prospective Investigation into Cancer and Nutrition (EPIC). Methods: A total of 389,220 EPIC participants with median age of 52 years at recruitment (1991-2000) were included. Cox regression yielded adjusted HRs and 95% confidence intervals (CI) for RCC incidence and mortality in relation to intakes of juices and total, sugar-sweetened, and artificially sweetened soft drinks. Results: A total of 888 incident RCCs and 356 RCC deaths were identified. In models including adjustment for body mass index and energy intake, there was no higher risk of incident RCC associated with consumption of juices (HR per 100 g/day increment ¼ 1.03; 95% CI, 0.97-1.09), total soft drinks (HR ¼ 1.01; 95% CI, 0.98-1.05), sugar-sweetened soft drinks (HR ¼ 0.99; 95% CI, 0.94-1.05), or artificially sweetened soft drinks (HR ¼ 1.02; 95% CI, 0.96-1.08). In these fully adjusted models, none of the beverages was associated with RCC mortality (HR, 95% CI per 100 g/day increment 1.06, 0.97-1.16; 1.03, 0.98-1.09; 0.97, 0.89-1.07; and 1.06, 0.99-1.14, respectively). Conclusions: Consumption of juices or soft drinks was not associated with RCC incidence or mortality after adjusting for obesity. Impact: Soft drink and juice intakes are unlikely to play an independent role in RCC development or mortality.
Published: 2021
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13. Risk prediction for renal cell Carcinoma: Results from the European Prospective Investigation into Cancer and nutrition (EPIC) prospective cohort study

Author: Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Börje, Harbs, Justin, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, Muller, David C., Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Börje, Harbs, Justin, Olsen, Anja, Tjønneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, and Muller, David C.
Abstract: Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives. Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure. Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679–0.721]). Our model had slightly improved discrimination (0.714 [0.694–0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025. Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population. Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
Published: 2021
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14. Response to Li and Hopper

Author: Thomas, Minta, Sakoda, Lori C., Hoffmeister, Michael, Rosenthal, Elisabeth A., Lee, Jeffrey K., van Duijnhoven, Franzel J.B., Platz, Elizabeth A., Wu, Anna H., Dampier, Christopher H., de la Chapelle, Albert, Wolk, Alicja, Joshi, Amit D., Burnett-Hartman, Andrea, Gsur, Andrea, Lindblom, Annika, Castells, Antoni, Win, Aung Ko, Namjou, Bahram, van Guelpen, Bethany, Tangen, Catherine M., He, Qianchuan, Li, Christopher I., Schafmayer, Clemens, Joshu, Corinne E., Ulrich, Cornelia M., Bishop, D. Timothy, Buchanan, Daniel D., Schaid, Daniel, Drew, David A., Muller, David C., Duggan, David, Crosslin, David R., Albanes, Demetrius, Giovannucci, Edward L., Larson, Eric, Qu, Flora, Mentch, Frank, Giles, Graham G., Hakonarson, Hakon, Hampel, Heather, Stanaway, Ian B., Figueiredo, Jane C., Huyghe, Jeroen R., Minnier, Jessica, Chang-Claude, Jenny, Hampe, Jochen, Harley, John B., Visvanathan, Kala, Curtis, Keith R., Offit, Kenneth, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Gunter, Marc J., Jenkins, Mark A., Slattery, Martha L., Lemire, Mathieu, Woods, Michael O., Song, Mingyang, Murphy, Neil, Lindor, Noralane M., Dikilitas, Ozan, Pharoah, Paul D.P., Campbell, Peter T., Newcomb, Polly A., Milne, Roger L., MacInnis, Robert J., Castellví-Bel, Sergi, Ogino, Shuji, Berndt, Sonja I., Bézieau, Stéphane, Thibodeau, Stephen N., Gallinger, Steven J., Zaidi, Syed H., Harrison, Tabitha A., Keku, Temitope O., Hudson, Thomas J., Vymetalkova, Veronika, Moreno, Victor, Martín, Vicente, Arndt, Volker, Wei, Wei-Qi, Chung, Wendy, Su, Yu-Ru, Hayes, Richard B., White, Emily, Vodicka, Pavel, Casey, Graham, Gruber, Stephen B., Schoen, Robert E., Chan, Andrew T., Potter, John D., Brenner, Hermann, Jarvik, Gail P., Corley, Douglas A., Peters, Ulrike, Hsu, Li, Thomas, Minta, Sakoda, Lori C., Hoffmeister, Michael, Rosenthal, Elisabeth A., Lee, Jeffrey K., van Duijnhoven, Franzel J.B., Platz, Elizabeth A., Wu, Anna H., Dampier, Christopher H., de la Chapelle, Albert, Wolk, Alicja, Joshi, Amit D., Burnett-Hartman, Andrea, Gsur, Andrea, Lindblom, Annika, Castells, Antoni, Win, Aung Ko, Namjou, Bahram, van Guelpen, Bethany, Tangen, Catherine M., He, Qianchuan, Li, Christopher I., Schafmayer, Clemens, Joshu, Corinne E., Ulrich, Cornelia M., Bishop, D. Timothy, Buchanan, Daniel D., Schaid, Daniel, Drew, David A., Muller, David C., Duggan, David, Crosslin, David R., Albanes, Demetrius, Giovannucci, Edward L., Larson, Eric, Qu, Flora, Mentch, Frank, Giles, Graham G., Hakonarson, Hakon, Hampel, Heather, Stanaway, Ian B., Figueiredo, Jane C., Huyghe, Jeroen R., Minnier, Jessica, Chang-Claude, Jenny, Hampe, Jochen, Harley, John B., Visvanathan, Kala, Curtis, Keith R., Offit, Kenneth, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Gunter, Marc J., Jenkins, Mark A., Slattery, Martha L., Lemire, Mathieu, Woods, Michael O., Song, Mingyang, Murphy, Neil, Lindor, Noralane M., Dikilitas, Ozan, Pharoah, Paul D.P., Campbell, Peter T., Newcomb, Polly A., Milne, Roger L., MacInnis, Robert J., Castellví-Bel, Sergi, Ogino, Shuji, Berndt, Sonja I., Bézieau, Stéphane, Thibodeau, Stephen N., Gallinger, Steven J., Zaidi, Syed H., Harrison, Tabitha A., Keku, Temitope O., Hudson, Thomas J., Vymetalkova, Veronika, Moreno, Victor, Martín, Vicente, Arndt, Volker, Wei, Wei-Qi, Chung, Wendy, Su, Yu-Ru, Hayes, Richard B., White, Emily, Vodicka, Pavel, Casey, Graham, Gruber, Stephen B., Schoen, Robert E., Chan, Andrew T., Potter, John D., Brenner, Hermann, Jarvik, Gail P., Corley, Douglas A., Peters, Ulrike, and Hsu, Li
Published: 2021
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15. Risk Prediction for Renal Cell Carcinoma:Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) Prospective Cohort Study

Author: Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Borje, Harbs, Justin, Olsen, Anja, Tjonneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, Muller, David C., Singleton, Rosie K., Heath, Alicia K., Clasen, Joanna L., Scelo, Ghislaine, Johansson, Mattias, Le Calvez-Kelm, Florence, Weiderpass, Elisabete, Liedberg, Fredrik, Ljungberg, Borje, Harbs, Justin, Olsen, Anja, Tjonneland, Anne, Dahm, Christina C., Kaaks, Rudolf, Fortner, Renee T., Panico, Salvatore, Tagliabue, Giovanna, Masala, Giovanna, Tumino, Rosario, Ricceri, Fulvio, Gram, Inger T., Santiuste, Carmen, Bonet, Catalina, Rodriguez-Barranco, Miguel, Schulze, Mattias B., Bergmann, Manuela M., Travis, Ruth C., Tzoulaki, Ioanna, Riboli, Elio, and Muller, David C.
Abstract: Background: Early detection of renal cell carcinoma (RCC) has the potential to improve disease outcomes. No screening program for sporadic RCC is in place. Given relatively low incidence, screening would need to focus on people at high risk of clinically meaningful disease so as to limit overdiagnosis and screen-detected false positives.Methods: Among 192,172 participants from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (including 588 incident RCC cases), we evaluated a published RCC risk prediction model (including age, sex, BMI, and smoking status) in terms of discrimination (C-statistic) and calibration (observed probability as a function of predicted probability). We used a flexible parametric survival model to develop an expanded model including age, sex, BMI, and smoking status, with the addition of self-reported history of hypertension and measured blood pressure.Results: The previously published model yielded well-calibrated probabilities and good discrimination (C-statistic [95% CI]: 0.699 [0.679-0.721]). Our model had slightly improved discrimination (0.714 [0.694-0.735], bootstrap optimism-corrected C-statistic: 0.709). Despite this good performance, predicted risk was low for the vast majority of participants, with 70% of participants having 10-year risk less than 0.0025.Conclusions: Although the models performed well for the prediction of incident RCC, they are currently insufficiently powerful to identify individuals at substantial risk of RCC in a general population.Impact: Despite the promising performance of the EPIC RCC risk prediction model, further development of the model, possibly including biomarkers of risk, is required to enable risk stratification of RCC.
Published: 2021

16. Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk.

Author: Thomas, Minta, Sakoda, Lori C, Hoffmeister, Michael, Rosenthal, Elisabeth A, Lee, Jeffrey K, van Duijnhoven, Franzel J B, Platz, Elizabeth A, Wu, Anna H, Dampier, Christopher H, de la Chapelle, Albert, Wolk, Alicja, Joshi, Amit D, Burnett-Hartman, Andrea, Gsur, Andrea, Lindblom, Annika, Castells, Antoni, Win, Aung Ko, Namjou, Bahram, Van Guelpen, Bethany, Tangen, Catherine M, He, Qianchuan, Li, Christopher I, Schafmayer, Clemens, Joshu, Corinne E, Ulrich, Cornelia M, Bishop, D Timothy, Buchanan, Daniel D, Schaid, Daniel, Drew, David A, Muller, David C, Duggan, David, Crosslin, David R, Albanes, Demetrius, Giovannucci, Edward L, Larson, Eric, Qu, Flora, Mentch, Frank, Giles, Graham G, Hakonarson, Hakon, Hampel, Heather, Stanaway, Ian B, Figueiredo, Jane C, Huyghe, Jeroen R, Minnier, Jessica, Chang-Claude, Jenny, Hampe, Jochen, Harley, John B, Visvanathan, Kala, Curtis, Keith R, Offit, Kenneth, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Gunter, Marc J, Jenkins, Mark A, Slattery, Martha L, Lemire, Mathieu, Woods, Michael O, Song, Mingyang, Murphy, Neil, Lindor, Noralane M, Dikilitas, Ozan, Pharoah, Paul D P, Campbell, Peter T, Newcomb, Polly A, Milne, Roger L, MacInnis, Robert J, Castellví-Bel, Sergi, Ogino, Shuji, Berndt, Sonja I, Bézieau, Stéphane, Thibodeau, Stephen N, Gallinger, Steven J, Zaidi, Syed H, Harrison, Tabitha A, Keku, Temitope O, Hudson, Thomas J, Vymetalkova, Veronika, Moreno, Victor, Martín, Vicente, Arndt, Volker, Wei, Wei-Qi, Chung, Wendy, Su, Yu-Ru, Hayes, Richard B, White, Emily, Vodicka, Pavel, Casey, Graham, Gruber, Stephen B, Schoen, Robert E, Chan, Andrew T, Potter, John D, Brenner, Hermann, Jarvik, Gail P, Corley, Douglas A, Peters, Ulrike, Hsu, Li, Thomas, Minta, Sakoda, Lori C, Hoffmeister, Michael, Rosenthal, Elisabeth A, Lee, Jeffrey K, van Duijnhoven, Franzel J B, Platz, Elizabeth A, Wu, Anna H, Dampier, Christopher H, de la Chapelle, Albert, Wolk, Alicja, Joshi, Amit D, Burnett-Hartman, Andrea, Gsur, Andrea, Lindblom, Annika, Castells, Antoni, Win, Aung Ko, Namjou, Bahram, Van Guelpen, Bethany, Tangen, Catherine M, He, Qianchuan, Li, Christopher I, Schafmayer, Clemens, Joshu, Corinne E, Ulrich, Cornelia M, Bishop, D Timothy, Buchanan, Daniel D, Schaid, Daniel, Drew, David A, Muller, David C, Duggan, David, Crosslin, David R, Albanes, Demetrius, Giovannucci, Edward L, Larson, Eric, Qu, Flora, Mentch, Frank, Giles, Graham G, Hakonarson, Hakon, Hampel, Heather, Stanaway, Ian B, Figueiredo, Jane C, Huyghe, Jeroen R, Minnier, Jessica, Chang-Claude, Jenny, Hampe, Jochen, Harley, John B, Visvanathan, Kala, Curtis, Keith R, Offit, Kenneth, Li, Li, Le Marchand, Loic, Vodickova, Ludmila, Gunter, Marc J, Jenkins, Mark A, Slattery, Martha L, Lemire, Mathieu, Woods, Michael O, Song, Mingyang, Murphy, Neil, Lindor, Noralane M, Dikilitas, Ozan, Pharoah, Paul D P, Campbell, Peter T, Newcomb, Polly A, Milne, Roger L, MacInnis, Robert J, Castellví-Bel, Sergi, Ogino, Shuji, Berndt, Sonja I, Bézieau, Stéphane, Thibodeau, Stephen N, Gallinger, Steven J, Zaidi, Syed H, Harrison, Tabitha A, Keku, Temitope O, Hudson, Thomas J, Vymetalkova, Veronika, Moreno, Victor, Martín, Vicente, Arndt, Volker, Wei, Wei-Qi, Chung, Wendy, Su, Yu-Ru, Hayes, Richard B, White, Emily, Vodicka, Pavel, Casey, Graham, Gruber, Stephen B, Schoen, Robert E, Chan, Andrew T, Potter, John D, Brenner, Hermann, Jarvik, Gail P, Corley, Douglas A, Peters, Ulrike, and Hsu, Li
Abstract: Accurate colorectal cancer (CRC) risk prediction models are critical for identifying individuals at low and high risk of developing CRC, as they can then be offered targeted screening and interventions to address their risks of developing disease (if they are in a high-risk group) and avoid unnecessary screening and interventions (if they are in a low-risk group). As it is likely that thousands of genetic variants contribute to CRC risk, it is clinically important to investigate whether these genetic variants can be used jointly for CRC risk prediction. In this paper, we derived and compared different approaches to generating predictive polygenic risk scores (PRS) from genome-wide association studies (GWASs) including 55,105 CRC-affected case subjects and 65,079 control subjects of European ancestry. We built the PRS in three ways, using (1) 140 previously identified and validated CRC loci; (2) SNP selection based on linkage disequilibrium (LD) clumping followed by machine-learning approaches; and (3) LDpred, a Bayesian approach for genome-wide risk prediction. We tested the PRS in an independent cohort of 101,987 individuals with 1,699 CRC-affected case subjects. The discriminatory accuracy, calculated by the age- and sex-adjusted area under the receiver operating characteristics curve (AUC), was highest for the LDpred-derived PRS (AUC = 0.654) including nearly 1.2 M genetic variants (the proportion of causal genetic variants for CRC assumed to be 0.003), whereas the PRS of the 140 known variants identified from GWASs had the lowest AUC (AUC = 0.629). Based on the LDpred-derived PRS, we are able to identify 30% of individuals without a family history as having risk for CRC similar to those with a family history of CRC, whereas the PRS based on known GWAS variants identified only top 10% as having a similar relative risk. About 90% of these individuals have no family history and would have been considered average risk under current screening guidelines, but might be
Published: 2020
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17. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity : results from a large European cohort

Author: Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Soederberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjonneland, Anne, Halkjaer, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kuehn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quiros, J. Ramon, Agudo, Antonio, Sanchez, Maria-Jose, Cirera, Lluis, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay-Tee, Wareham, Nicholas J., Tong, Tammy Y. N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, Riboli, Elio, Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Soederberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjonneland, Anne, Halkjaer, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kuehn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quiros, J. Ramon, Agudo, Antonio, Sanchez, Maria-Jose, Cirera, Lluis, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay-Tee, Wareham, Nicholas J., Tong, Tammy Y. N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, and Riboli, Elio
Abstract: Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI<18.5 kg/m(2)) or obese (BMI30 kg/m(2)) categories, while the highest quartile of ABSI separated 18-39% of the individuals within each BMI category, which had 22-55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
Published: 2020
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18. Protein-altering germline mutations implicate novel genes related to lung cancer development

Author: Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., Amos, Christopher, I, Ji, Xuemei, Mukherjee, Semanti, Landi, Maria Teresa, Bosse, Yohan, Joubert, Philippe, Zhu, Dakai, Gorlov, Ivan, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Brhane, Yonathan, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Byun, Jinyoung, Dragnev, Konstantin H., Field, John K., Kiemeney, Lambertus F. A., Lazarus, Philip, Zienolddiny, Shan, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier A., Pesatori, Angela C., Diao, Nancy, Su, Li, Song, Lei, Zhang, Ruyang, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, Erich, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Tsao, Ming-Sound, Shepherd, Frances, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Butler, Lesley M., Offit, Kenneth, Srinivasan, Preethi, Bandlamudi, Chaitanya, Hellmann, Matthew D., Solit, David B., Robson, Mark E., Rudin, Charles M., Stadler, Zsofia K., Taylor, Barry S., Berger, Michael F., Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, 'en, Timens, Wim, Artigas, Maria Soler, Shete, Sanjay, Brenner, Hermann, Chanock, Stephen, Brennan, Paul, McKay, James D., and Amos, Christopher, I
Abstract: Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Published: 2020
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19. Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Author: Heath, Alicia K, Muller, David C., van den Brandt, Piet A., Papadimitriou, Nikos, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Fagherazzi, Guy, Boeing, Heiner, Ferrari, Pietro, Olsen, Anja, Tjønneland, Anne, Arveux, Patrick, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Turzanski-Fortner, Renée, Schulze, Matthias B., Karakatsani, Anna, Thriskos, Paschalis, Trichopoulou, Antonia, Masala, Giovanna, Contiero, Paolo, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, Bas, Bakker, Marije F., van Gils, Carla H., Standahl Olsen, Karina Standahl, Skeie, Guri, Lasheras, Cristina, Agudo, Antonio, Rodríguez-Barranco, Miguel, Sánchez, Maria-José, Amiano, Pilar, Chirlaque, María-Dolores, Barricarte, Aurelio, Drake, Isabel, Ericson, Ulrika, Johansson, Ingegerd, Winkvist, Anna, Key, Tim, Freisling, Heinz, His, Mathilde, Huybrechts, Inge, Christakoudi, Sofia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K., Tzoulaki, Ioanna, Heath, Alicia K, Muller, David C., van den Brandt, Piet A., Papadimitriou, Nikos, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Fagherazzi, Guy, Boeing, Heiner, Ferrari, Pietro, Olsen, Anja, Tjønneland, Anne, Arveux, Patrick, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Turzanski-Fortner, Renée, Schulze, Matthias B., Karakatsani, Anna, Thriskos, Paschalis, Trichopoulou, Antonia, Masala, Giovanna, Contiero, Paolo, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, Bas, Bakker, Marije F., van Gils, Carla H., Standahl Olsen, Karina Standahl, Skeie, Guri, Lasheras, Cristina, Agudo, Antonio, Rodríguez-Barranco, Miguel, Sánchez, Maria-José, Amiano, Pilar, Chirlaque, María-Dolores, Barricarte, Aurelio, Drake, Isabel, Ericson, Ulrika, Johansson, Ingegerd, Winkvist, Anna, Key, Tim, Freisling, Heinz, His, Mathilde, Huybrechts, Inge, Christakoudi, Sofia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K., and Tzoulaki, Ioanna
Abstract: BACKGROUND: Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. METHODS: Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). RESULTS: Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. CONCLUSIONS: Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
Published: 2020
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20. Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Author: MS MDL 1, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Heath, Alicia K, Muller, David C, van den Brandt, Piet A, Papadimitriou, Nikos, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Fagherazzi, Guy, Boeing, Heiner, Ferrari, Pietro, Olsen, Anja, Tjønneland, Anne, Arveux, Patrick, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Turzanski-Fortner, Renée, Schulze, Matthias B, Karakatsani, Anna, Thriskos, Paschalis, Trichopoulou, Antonia, Masala, Giovanna, Contiero, Paolo, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, Bas, Bakker, Marije F, van Gils, Carla H, Olsen, Karina Standahl, Skeie, Guri, Lasheras, Cristina, Agudo, Antonio, Rodríguez-Barranco, Miguel, Sánchez, Maria-José, Amiano, Pilar, Chirlaque, María-Dolores, Barricarte, Aurelio, Drake, Isabel, Ericson, Ulrika, Johansson, Ingegerd, Winkvist, Anna, Key, Tim, Freisling, Heinz, His, Mathilde, Huybrechts, Inge, Christakoudi, Sofia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K, Tzoulaki, Ioanna, MS MDL 1, Epi Kanker Team A, Cancer, JC onderzoeksprogramma Kanker, Heath, Alicia K, Muller, David C, van den Brandt, Piet A, Papadimitriou, Nikos, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Fagherazzi, Guy, Boeing, Heiner, Ferrari, Pietro, Olsen, Anja, Tjønneland, Anne, Arveux, Patrick, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Turzanski-Fortner, Renée, Schulze, Matthias B, Karakatsani, Anna, Thriskos, Paschalis, Trichopoulou, Antonia, Masala, Giovanna, Contiero, Paolo, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, Bas, Bakker, Marije F, van Gils, Carla H, Olsen, Karina Standahl, Skeie, Guri, Lasheras, Cristina, Agudo, Antonio, Rodríguez-Barranco, Miguel, Sánchez, Maria-José, Amiano, Pilar, Chirlaque, María-Dolores, Barricarte, Aurelio, Drake, Isabel, Ericson, Ulrika, Johansson, Ingegerd, Winkvist, Anna, Key, Tim, Freisling, Heinz, His, Mathilde, Huybrechts, Inge, Christakoudi, Sofia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K, and Tzoulaki, Ioanna
Published: 2020

21. Nutrient-wide association study of 92 foods and nutrients and breast cancer risk

Author: Heath, Alicia K., Muller, David C., van den Brandt, Piet A., Papadimitriou, Nikos, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Fagherazzi, Guy, Boeing, Heiner, Ferrari, Pietro, Olsen, Anja, Tjonneland, Anne, Arveux, Patrick, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kuehn, Tilman, Turzanski-Fortner, Renee, Schulze, Matthias B., Karakatsani, Anna, Thriskos, Paschalis, Trichopoulou, Antonia, Masala, Giovanna, Contiero, Paolo, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, Bas, Bakker, Marije F., van Gils, Carla H., Olsen, Karina Standahl, Skeie, Guri, Lasheras, Cristina, Agudo, Antonio, Rodriguez-Barranco, Miguel, Sanchez, Maria-Jose, Amiano, Pilar, Chirlaque, Maria-Dolores, Barricarte, Aurelio., Drake, Isabel, Ericson, Ulrika, Johansson, Ingegerd, Winkvist, Anna, Key, Tim, Freisling, Heinz, His, Mathilde, Huybrechts, Inge, Christakoudi, Sofia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K., Tzoulaki, Ioanna, Heath, Alicia K., Muller, David C., van den Brandt, Piet A., Papadimitriou, Nikos, Critselis, Elena, Gunter, Marc, Vineis, Paolo, Weiderpass, Elisabete, Fagherazzi, Guy, Boeing, Heiner, Ferrari, Pietro, Olsen, Anja, Tjonneland, Anne, Arveux, Patrick, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kuehn, Tilman, Turzanski-Fortner, Renee, Schulze, Matthias B., Karakatsani, Anna, Thriskos, Paschalis, Trichopoulou, Antonia, Masala, Giovanna, Contiero, Paolo, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, Bas, Bakker, Marije F., van Gils, Carla H., Olsen, Karina Standahl, Skeie, Guri, Lasheras, Cristina, Agudo, Antonio, Rodriguez-Barranco, Miguel, Sanchez, Maria-Jose, Amiano, Pilar, Chirlaque, Maria-Dolores, Barricarte, Aurelio., Drake, Isabel, Ericson, Ulrika, Johansson, Ingegerd, Winkvist, Anna, Key, Tim, Freisling, Heinz, His, Mathilde, Huybrechts, Inge, Christakoudi, Sofia, Ellingjord-Dale, Merete, Riboli, Elio, Tsilidis, Konstantinos K., and Tzoulaki, Ioanna
Abstract: Background Several dietary factors have been reported to be associated with risk of breast cancer, but to date, unequivocal evidence only exists for alcohol consumption. We sought to systematically assess the association between intake of 92 foods and nutrients and breast cancer risk using a nutrient-wide association study. Methods Using data from 272,098 women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, we assessed dietary intake of 92 foods and nutrients estimated by dietary questionnaires. Cox regression was used to quantify the association between each food/nutrient and risk of breast cancer. A false discovery rate (FDR) of 0.05 was used to select the set of foods and nutrients to be replicated in the independent Netherlands Cohort Study (NLCS). Results Six foods and nutrients were identified as associated with risk of breast cancer in the EPIC study (10,979 cases). Higher intake of alcohol overall was associated with a higher risk of breast cancer (hazard ratio (HR) for a 1 SD increment in intake = 1.05, 95% CI 1.03-1.07), as was beer/cider intake and wine intake (HRs per 1 SD increment = 1.05, 95% CI 1.03-1.06 and 1.04, 95% CI 1.02-1.06, respectively), whereas higher intakes of fibre, apple/pear, and carbohydrates were associated with a lower risk of breast cancer (HRs per 1 SD increment = 0.96, 95% CI 0.94-0.98; 0.96, 95% CI 0.94-0.99; and 0.96, 95% CI 0.95-0.98, respectively). When evaluated in the NLCS (2368 cases), estimates for each of these foods and nutrients were similar in magnitude and direction, with the exception of beer/cider intake, which was not associated with risk in the NLCS. Conclusions Our findings confirm a positive association of alcohol consumption and suggest an inverse association of dietary fibre and possibly fruit intake with breast cancer risk.
Published: 2020

22. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity:results from a large European cohort

Author: Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay Tee, Wareham, Nicholas J., Tong, Tammy Y.N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, Riboli, Elio, Christakoudi, Sofia, Tsilidis, Konstantinos K., Muller, David C., Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C., Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B., Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J. Ramón, Agudo, Antonio, Sánchez, Maria Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M., Khaw, Kay Tee, Wareham, Nicholas J., Tong, Tammy Y.N., Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K., Ellingjord-Dale, Merete, Ward, Heather A., Aune, Dagfinn, and Riboli, Elio
Abstract: Abdominal and general adiposity are independently associated with mortality, but there is no consensus on how best to assess abdominal adiposity. We compared the ability of alternative waist indices to complement body mass index (BMI) when assessing all-cause mortality. We used data from 352,985 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) and Cox proportional hazards models adjusted for other risk factors. During a mean follow-up of 16.1 years, 38,178 participants died. Combining in one model BMI and a strongly correlated waist index altered the association patterns with mortality, to a predominantly negative association for BMI and a stronger positive association for the waist index, while combining BMI with the uncorrelated A Body Shape Index (ABSI) preserved the association patterns. Sex-specific cohort-wide quartiles of waist indices correlated with BMI could not separate high-risk from low-risk individuals within underweight (BMI < 18.5 kg/m2) or obese (BMI ≥ 30 kg/m2) categories, while the highest quartile of ABSI separated 18–39% of the individuals within each BMI category, which had 22–55% higher risk of death. In conclusion, only a waist index independent of BMI by design, such as ABSI, complements BMI and enables efficient risk stratification, which could facilitate personalisation of screening, treatment and monitoring.
Published: 2020

23. A Body Shape Index (ABSI) achieves better mortality risk stratification than alternative indices of abdominal obesity: results from a large European cohort

Author: Utrecht Palliatie Centrum, MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Christakoudi, Sofia, Tsilidis, Konstantinos K, Muller, David C, Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C, Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B, Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M, Khaw, Kay-Tee, Wareham, Nicholas J, Tong, Tammy Y N, Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K, Ellingjord-Dale, Merete, Ward, Heather A, Aune, Dagfinn, Riboli, Elio, Utrecht Palliatie Centrum, MS MDL 1, Epidemiology & Health Economics, Cancer, JC onderzoeksprogramma Kanker, Christakoudi, Sofia, Tsilidis, Konstantinos K, Muller, David C, Freisling, Heinz, Weiderpass, Elisabete, Overvad, Kim, Söderberg, Stefan, Häggström, Christel, Pischon, Tobias, Dahm, Christina C, Zhang, Jie, Tjønneland, Anne, Halkjær, Jytte, MacDonald, Conor, Boutron-Ruault, Marie-Christine, Mancini, Francesca Romana, Kühn, Tilman, Kaaks, Rudolf, Schulze, Matthias B, Trichopoulou, Antonia, Karakatsani, Anna, Peppa, Eleni, Masala, Giovanna, Pala, Valeria, Panico, Salvatore, Tumino, Rosario, Sacerdote, Carlotta, Quirós, J Ramón, Agudo, Antonio, Sánchez, Maria-Jose, Cirera, Lluís, Barricarte-Gurrea, Aurelio, Amiano, Pilar, Memarian, Ensieh, Sonestedt, Emily, Bueno-de-Mesquita, Bas, May, Anne M, Khaw, Kay-Tee, Wareham, Nicholas J, Tong, Tammy Y N, Huybrechts, Inge, Noh, Hwayoung, Aglago, Elom K, Ellingjord-Dale, Merete, Ward, Heather A, Aune, Dagfinn, and Riboli, Elio
Published: 2020

24. The influence of obesity-related factors in the etiology of renal cell carcinoma—A mendelian randomization study

Author: Johansson, Mattias, Carreras-Torres, Robert, Scelo, Ghislaine, Purdue, Mark P., Mariosa, Daniela, Muller, David C., Timpson, Nicolas J., Haycock, Philip C., Brown, Kevin M., Wang, Zhaoming, Ye, Yuanqing, Hofmann, Jonathan N., Foll, Matthieu, Gaborieau, Valerie, Machiela, Mitchell J., Colli, Leandro M., Li, Peng, Garnier, Jean-Guillaume, Blanche, Helene, Boland, Anne, Burdette, Laurie, Prokhortchouk, Egor, Skryabin, Konstantin G., Yeager, Meredith, Radojevic-Skodric, Sanja, Ognjanovic, Simona, Foretova, Lenka, Holcatova, Ivana, Janout, Vladimir, Mates, Dana, Mukeriya, Anush, Rascu, Stefan, Zaridze, David, Bencko, Vladimir, Cybulski, Cezary, Fabianova, Eleonora, Jinga, Viorel, Lissowska, Jolanta, Lubinski, Jan, Navratilova, Marie, Rudnai, Peter, Benhamou, Simone, Cancel-Tassin, Geraldine, Cussenot, Olivier, Weiderpass, Elisabete, Ljungberg, Borje, Sitaram, Raviprakash Tumkur, Häggström, Christel, Bruinsma, Fiona, Jordan, Susan J., Severi, Gianluca, Winship, Ingrid, Hveem, Kristian, Vatten, Lars J., Fletcher, Tony, Larsson, Susanna C., Wolk, Alicja, Banks, Rosamonde E., Selby, Peter J., Easton, Douglas F., Andreotti, Gabriella, Freeman, Laura E. Beane, Koutros, Stella, Mannisto, Satu, Weinstein, Stephanie, Clark, Peter E., Edwards, Todd L., Lipworth, Loren, Gapstur, Susan M., Stevens, Victoria L., Carol, Hallie, Freedman, Matthew L., Pomerantz, Mark M., Cho, Eunyoung, Wilson, Kathryn M., Gaziano, J. Michael, Sesso, Howard D., Freedman, Neal D., Parker, Alexander S., Eckel-Passow, Jeanette E., Huang, Wen-Yi, Kahnoski, Richard J., Lane, Brian R., Noyes, Sabrina L., Petillo, David, Teh, Bin Tean, Peters, Ulrike, White, Emily, Anderson, Garnet L., Johnson, Lisa, Luo, Juhua, Buring, Julie, Lee, I-Min, Chow, Wong-Ho, Moore, Lee E., Eisen, Timothy, Henrion, Marc, Larkin, James, Barman, Poulami, Leibovich, Bradley C., Choueiri, Toni K., Lathrop, G. Mark, Deleuze, Jean-Francois, Gunter, Marc, McKay, James D., Wu, Xifeng, Houlston, Richard S., Chanock, Stephen J., Relton, Caroline, Richards, J. Brent, Martin, Richard M., Smith, George Davey, Brennan, Paul, Johansson, Mattias, Carreras-Torres, Robert, Scelo, Ghislaine, Purdue, Mark P., Mariosa, Daniela, Muller, David C., Timpson, Nicolas J., Haycock, Philip C., Brown, Kevin M., Wang, Zhaoming, Ye, Yuanqing, Hofmann, Jonathan N., Foll, Matthieu, Gaborieau, Valerie, Machiela, Mitchell J., Colli, Leandro M., Li, Peng, Garnier, Jean-Guillaume, Blanche, Helene, Boland, Anne, Burdette, Laurie, Prokhortchouk, Egor, Skryabin, Konstantin G., Yeager, Meredith, Radojevic-Skodric, Sanja, Ognjanovic, Simona, Foretova, Lenka, Holcatova, Ivana, Janout, Vladimir, Mates, Dana, Mukeriya, Anush, Rascu, Stefan, Zaridze, David, Bencko, Vladimir, Cybulski, Cezary, Fabianova, Eleonora, Jinga, Viorel, Lissowska, Jolanta, Lubinski, Jan, Navratilova, Marie, Rudnai, Peter, Benhamou, Simone, Cancel-Tassin, Geraldine, Cussenot, Olivier, Weiderpass, Elisabete, Ljungberg, Borje, Sitaram, Raviprakash Tumkur, Häggström, Christel, Bruinsma, Fiona, Jordan, Susan J., Severi, Gianluca, Winship, Ingrid, Hveem, Kristian, Vatten, Lars J., Fletcher, Tony, Larsson, Susanna C., Wolk, Alicja, Banks, Rosamonde E., Selby, Peter J., Easton, Douglas F., Andreotti, Gabriella, Freeman, Laura E. Beane, Koutros, Stella, Mannisto, Satu, Weinstein, Stephanie, Clark, Peter E., Edwards, Todd L., Lipworth, Loren, Gapstur, Susan M., Stevens, Victoria L., Carol, Hallie, Freedman, Matthew L., Pomerantz, Mark M., Cho, Eunyoung, Wilson, Kathryn M., Gaziano, J. Michael, Sesso, Howard D., Freedman, Neal D., Parker, Alexander S., Eckel-Passow, Jeanette E., Huang, Wen-Yi, Kahnoski, Richard J., Lane, Brian R., Noyes, Sabrina L., Petillo, David, Teh, Bin Tean, Peters, Ulrike, White, Emily, Anderson, Garnet L., Johnson, Lisa, Luo, Juhua, Buring, Julie, Lee, I-Min, Chow, Wong-Ho, Moore, Lee E., Eisen, Timothy, Henrion, Marc, Larkin, James, Barman, Poulami, Leibovich, Bradley C., Choueiri, Toni K., Lathrop, G. Mark, Deleuze, Jean-Francois, Gunter, Marc, McKay, James D., Wu, Xifeng, Houlston, Richard S., Chanock, Stephen J., Relton, Caroline, Richards, J. Brent, Martin, Richard M., Smith, George Davey, and Brennan, Paul
Abstract: Background: Several obesity-related factors have been associated with renal cell carcinoma (RCC), but it is unclear which individual factors directly influence risk. We addressed this question using genetic markers as proxies for putative risk factors and evaluated their relation to RCC risk in a mendelian randomization (MR) framework. This methodology limits bias due to confounding and is not affected by reverse causation. Methods and findings: Genetic markers associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose were initially identified as instrumental variables, and their association with RCC risk was subsequently evaluated in a genome-wide association study (GWAS) of 10,784 RCC patients and 20,406 control participants in a 2-sample MR framework. The effect on RCC risk was estimated by calculating odds ratios (ORSD) for a standard deviation (SD) increment in each risk factor. The MR analysis indicated that higher body mass index increases the risk of RCC (ORSD: 1.56, 95% confidence interval [CI] 1.44–1.70), with comparable results for waist-to-hip ratio (ORSD: 1.63, 95% CI 1.40–1.90) and body fat percentage (ORSD: 1.66, 95% CI 1.44–1.90). This analysis further indicated that higher fasting insulin (ORSD: 1.82, 95% CI 1.30–2.55) and diastolic blood pressure (DBP; ORSD: 1.28, 95% CI 1.11–1.47), but not systolic blood pressure (ORSD: 0.98, 95% CI 0.84–1.14), increase the risk for RCC. No association with RCC risk was seen for lipids, overall type 2 diabetes, or fasting glucose. Conclusions: This study provides novel evidence for an etiological role of insulin in RCC, as well as confirmatory evidence that obesity and DBP influence RCC risk.
Published: 2019
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25. Genetic interaction analysis among oncogenesis-related genes revealed novel genes and networks in lung cancer development

Author: Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Bossé, Yohan, Gorlova, Olga, Gorlov, Ivan, Han, Younghun, Byun, Jinyoung, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H. Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Han, Jiali, Siminovitch, Katherine, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: The development of cancer is driven by the accumulation of many oncogenesis-related genetic alterations and tumorigenesis is triggered by complex networks of involved genes rather than independent actions. To explore the epistasis existing among oncogenesis-related genes in lung cancer development, we conducted pairwise genetic interaction analyses among 35,031 SNPs from 2027 oncogenesis-related genes. The genotypes from three independent genome-wide association studies including a total of 24,037 lung cancer patients and 20,401 healthy controls with Caucasian ancestry were analyzed in the study. Using a two-stage study design including discovery and replication studies, and stringent Bonferroni correction for multiple statistical analysis, we identified significant genetic interactions between SNPs in RGL1:RAD51B (OR=0.44, p value=3.27x10-11 in overall lung cancer and OR=0.41, p value=9.71x10-11 in non-small cell lung cancer), SYNE1:RNF43 (OR=0.73, p value=1.01x10-12 in adenocarcinoma) and FHIT:TSPAN8 (OR=1.82, p value=7.62x10-11 in squamous cell carcinoma) in our analysis. None of these genes have been identified from previous main effect association studies in lung cancer. Further eQTL gene expression analysis in lung tissues provided information supporting the functional role of the identified epistasis in lung tumorigenesis. Gene set enrichment analysis revealed potential pathways and gene networks underlying molecular mechanisms in overall lung cancer as well as histology subtypes development. Our results provide evidence that genetic interactions between oncogenesis-related genes play an important role in lung tumorigenesis and epistasis analysis, combined with functional annotation, provides a valuable tool for uncovering functional novel susceptibility genes that contribute to lung cancer development by interacting with other modifier genes.
Published: 2019
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26. Circulating high sensitivity C reactive protein concentrations and risk of lung cancer : nested case-control study within Lung Cancer Cohort Consortium

Author: Muller, David C., Larose, Tricia L., Hodge, Allison, Guida, Florence, Langhammer, Arnulf, Grankvist, Kjell, Meyer, Klaus, Cai, Qiuyin, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Albanes, Demetrius, Giles, Graham G., Sesso, Howard D., Lee, I-Min, Gaziano, J. Michael, Yuan, Jian-Min, Bolton, Judith Hoffman, Buring, Julie E., Visvanathan, Kala, Le Marchand, Loic, Purdue, Mark P., Caporaso, Neil E., Midttun, Oivind, Ueland, Per M., Prentice, Ross L., Weinstein, Stephanie J., Stevens, Victoria L., Zheng, Wei, Blot, William J., Shu, Xiao-Ou, Zhang, Xuehong, Xiang, Yong-Bing, Koh, Woon-Puay, Hveem, Kristian, Thomson, Cynthia A., Pettinger, Mary, Engstrom, Gunnar, Brunnstrom, Hans, Milne, Roger L., Stampfer, Meir J., Han, Jiali, Johansson, Mikael, Brennan, Paul, Severi, Gianluca, Johansson, Mattias, Muller, David C., Larose, Tricia L., Hodge, Allison, Guida, Florence, Langhammer, Arnulf, Grankvist, Kjell, Meyer, Klaus, Cai, Qiuyin, Arslan, Alan A., Zeleniuch-Jacquotte, Anne, Albanes, Demetrius, Giles, Graham G., Sesso, Howard D., Lee, I-Min, Gaziano, J. Michael, Yuan, Jian-Min, Bolton, Judith Hoffman, Buring, Julie E., Visvanathan, Kala, Le Marchand, Loic, Purdue, Mark P., Caporaso, Neil E., Midttun, Oivind, Ueland, Per M., Prentice, Ross L., Weinstein, Stephanie J., Stevens, Victoria L., Zheng, Wei, Blot, William J., Shu, Xiao-Ou, Zhang, Xuehong, Xiang, Yong-Bing, Koh, Woon-Puay, Hveem, Kristian, Thomson, Cynthia A., Pettinger, Mary, Engstrom, Gunnar, Brunnstrom, Hans, Milne, Roger L., Stampfer, Meir J., Han, Jiali, Johansson, Mikael, Brennan, Paul, Severi, Gianluca, and Johansson, Mattias
Abstract: Objectives To conduct a comprehensive analysis of prospectively measured circulating high sensitivity C reactive protein (hsCRP) concentration and risk of lung cancer overall, by smoking status (never, former, and current smokers), and histological sub-type. Design Nested case-control study. Setting 20 population based cohort studies in Asia, Europe, Australia, and the United States. Participants 5299 patients with incident lung cancer, with individually incidence density matched controls. Exposure Circulating hsCRP concentrations in prediagnostic serum or plasma samples. Main outcome measure Incident lung cancer diagnosis. Results A positive association between circulating hsCRP concentration and the risk of lung cancer for current (odds ratio associated with a doubling in hsCRP concentration 1.09, 95% confidence interval 1.05 to 1.13) and former smokers (1.09, 1.04 to 1.14) was observed, but not for never smokers (P<0.01 for interaction). This association was strong and consistent across all histological subtypes, except for adenocarcinoma, which was not strongly associated with hsCRP concentration regardless of smoking status (odds ratio for adenocarcinoma overall 0.97, 95% confidence interval 0.94 to 1.01). The association between circulating hsCRP concentration and the risk of lung cancer was strongest in the first two years of follow-up for former and current smokers. Including hsCRP concentration in a risk model, in addition to smoking based variables, did not improve risk discrimination overall, but slightly improved discrimination for cancers diagnosed in the first two years of follow-up. Conclusions Former and current smokers with higher circulating hsCRP concentrations had a higher risk of lung cancer overall. Circulating hsCRP concentration was not associated with the risk of lung adenocarcinoma. Circulating hsCRP concentration could be a prediagnostic marker of lung cancer rather than a causal risk factor.
Published: 2019
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27. Sex specific associations in genome wide association analysis of renal cell carcinoma

Author: Laskar, Ruhina S, Muller, David C, Li, Peng, Machiela, Mitchell J, Ye, Yuanqing, Gaborieau, Valerie, Foll, Matthieu, Hofmann, Jonathan N, Colli, Leandro, Sampson, Joshua N, Wang, Zhaoming, Bacq-Daian, Delphine, Boland, Anne, Abedi-Ardekani, Behnoush, Durand, Geoffroy, Le Calvez-Kelm, Florence, Robinot, Nivonirina, Blanche, Helene, Prokhortchouk, Egor, Skryabin, Konstantin G, Burdett, Laurie, Yeager, Meredith, Radojevic-Skodric, Sanja, Savic, Slavisa, Foretova, Lenka, Holcatova, Ivana, Janout, Vladimir, Mates, Dana, Rascu, Stefan, Mukeria, Anush, Zaridze, David, Bencko, Vladimir, Cybulski, Cezary, Fabianova, Eleonora, Jinga, Viorel, Lissowska, Jolanta, Lubinski, Jan, Navratilova, Marie, Rudnai, Peter, Świątkowska, Beata, Benhamou, Simone, Cancel-Tassin, Geraldine, Cussenot, Olivier, Trichopoulou, Antonia, Riboli, Elio, Overvad, Kim, Panico, Salvatore, Ljungberg, Börje, Tumkur Sitaram, Raviprakash, Giles, Graham G, Milne, Roger L, Severi, Gianluca, Bruinsma, Fiona, Fletcher, Tony, Koppova, Kvetoslava, Larsson, Susanna C, Wolk, Alicja, Banks, Rosamonde E, Selby, Peter J, Easton, Douglas F, Pharoah, Paul, Andreotti, Gabriella, Beane Freeman, Laura E, Koutros, Stella, Albanes, Demetrius, Männistö, Satu, Weinstein, Stephanie, Clark, Peter E, Edwards, Todd L, Lipworth, Loren, Carol, Hallie, Freedman, Matthew L, Pomerantz, Mark M, Cho, Eunyoung, Kraft, Peter, Preston, Mark A, Wilson, Kathryn M, Michael Gaziano, J, Sesso, Howard D, Black, Amanda, Freedman, Neal D, Huang, Wen-Yi, Anema, John G, Kahnoski, Richard J, Lane, Brian R, Noyes, Sabrina L, Petillo, David, Teh, Bin Tean, Peters, Ulrike, White, Emily, Anderson, Garnet L, Johnson, Lisa, Luo, Juhua, Chow, Wong-Ho, Moore, Lee E, Choueiri, Toni K, Wood, Christopher, Johansson, Mattias, McKay, James D, Brown, Kevin M, Rothman, Nathaniel, Lathrop, Mark G, Deleuze, Jean-Francois, Wu, Xifeng, Brennan, Paul, Chanock, Stephen J, Purdue, Mark P, Scelo, Ghislaine, Laskar, Ruhina S, Muller, David C, Li, Peng, Machiela, Mitchell J, Ye, Yuanqing, Gaborieau, Valerie, Foll, Matthieu, Hofmann, Jonathan N, Colli, Leandro, Sampson, Joshua N, Wang, Zhaoming, Bacq-Daian, Delphine, Boland, Anne, Abedi-Ardekani, Behnoush, Durand, Geoffroy, Le Calvez-Kelm, Florence, Robinot, Nivonirina, Blanche, Helene, Prokhortchouk, Egor, Skryabin, Konstantin G, Burdett, Laurie, Yeager, Meredith, Radojevic-Skodric, Sanja, Savic, Slavisa, Foretova, Lenka, Holcatova, Ivana, Janout, Vladimir, Mates, Dana, Rascu, Stefan, Mukeria, Anush, Zaridze, David, Bencko, Vladimir, Cybulski, Cezary, Fabianova, Eleonora, Jinga, Viorel, Lissowska, Jolanta, Lubinski, Jan, Navratilova, Marie, Rudnai, Peter, Świątkowska, Beata, Benhamou, Simone, Cancel-Tassin, Geraldine, Cussenot, Olivier, Trichopoulou, Antonia, Riboli, Elio, Overvad, Kim, Panico, Salvatore, Ljungberg, Börje, Tumkur Sitaram, Raviprakash, Giles, Graham G, Milne, Roger L, Severi, Gianluca, Bruinsma, Fiona, Fletcher, Tony, Koppova, Kvetoslava, Larsson, Susanna C, Wolk, Alicja, Banks, Rosamonde E, Selby, Peter J, Easton, Douglas F, Pharoah, Paul, Andreotti, Gabriella, Beane Freeman, Laura E, Koutros, Stella, Albanes, Demetrius, Männistö, Satu, Weinstein, Stephanie, Clark, Peter E, Edwards, Todd L, Lipworth, Loren, Carol, Hallie, Freedman, Matthew L, Pomerantz, Mark M, Cho, Eunyoung, Kraft, Peter, Preston, Mark A, Wilson, Kathryn M, Michael Gaziano, J, Sesso, Howard D, Black, Amanda, Freedman, Neal D, Huang, Wen-Yi, Anema, John G, Kahnoski, Richard J, Lane, Brian R, Noyes, Sabrina L, Petillo, David, Teh, Bin Tean, Peters, Ulrike, White, Emily, Anderson, Garnet L, Johnson, Lisa, Luo, Juhua, Chow, Wong-Ho, Moore, Lee E, Choueiri, Toni K, Wood, Christopher, Johansson, Mattias, McKay, James D, Brown, Kevin M, Rothman, Nathaniel, Lathrop, Mark G, Deleuze, Jean-Francois, Wu, Xifeng, Brennan, Paul, Chanock, Stephen J, Purdue, Mark P, and Scelo, Ghislaine
Abstract: Renal cell carcinoma (RCC) has an undisputed genetic component and a stable 2:1 male to female sex ratio in its incidence across populations, suggesting possible sexual dimorphism in its genetic susceptibility. We conducted the first sex-specific genome-wide association analysis of RCC for men (3227 cases, 4916 controls) and women (1992 cases, 3095 controls) of European ancestry from two RCC genome-wide scans and replicated the top findings using an additional series of men (2261 cases, 5852 controls) and women (1399 cases, 1575 controls) from two independent cohorts of European origin. Our study confirmed sex-specific associations for two known RCC risk loci at 14q24.2 (DPF3) and 2p21(EPAS1). We also identified two additional suggestive male-specific loci at 6q24.3 (SAMD5, male odds ratio (ORmale) = 0.83 [95% CI = 0.78-0.89], Pmale = 1.71 × 10-8 compared with female odds ratio (ORfemale) = 0.98 [95% CI = 0.90-1.07], Pfemale = 0.68) and 12q23.3 (intergenic, ORmale = 0.75 [95% CI = 0.68-0.83], Pmale = 1.59 × 10-8 compared with ORfemale = 0.93 [95% CI = 0.82-1.06], Pfemale = 0.21) that attained genome-wide significance in the joint meta-analysis. Herein, we provide evidence of sex-specific associations in RCC genetic susceptibility and advocate the necessity of larger genetic and genomic studies to unravel the endogenous causes of sex bias in sexually dimorphic traits and diseases like RCC.
Published: 2019
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28. Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Ward, Heather A., Whitman, Julia, Muller, David C., Johansson, Mattias, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjonneland, Anne, Hansen, Louise, Dahm, Christina C., Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Affret, Aurelie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Nost, Therese Haugdahl, Sandanger, Torkjel M., Ramon Quiros, Jose, Agudo, Antonio, Rodriguez-Barranco, Miguel, Larranaga, Nerea, Maria Huerta, Jose, Ardanaz, Eva, Drake, Isabel, Brunnstrom, Hans, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C., Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A., Riboli, Elio, Cross, Amanda J., Ward, Heather A., Whitman, Julia, Muller, David C., Johansson, Mattias, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjonneland, Anne, Hansen, Louise, Dahm, Christina C., Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Affret, Aurelie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Nost, Therese Haugdahl, Sandanger, Torkjel M., Ramon Quiros, Jose, Agudo, Antonio, Rodriguez-Barranco, Miguel, Larranaga, Nerea, Maria Huerta, Jose, Ardanaz, Eva, Drake, Isabel, Brunnstrom, Hans, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C., Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A., Riboli, Elio, and Cross, Amanda J.
Abstract: Background: Epidemiological studies suggest that haem iron, which is found predominantly in red meat and increases endogenous formation of carcinogenic N-nitroso compounds, may be positively associated with lung cancer. The objective was to examine the relationship between haem iron intake and lung cancer risk using detailed smoking history data and serum cotinine to control for potential confounding. Methods: In the European Prospective Investigation into Cancer and Nutrition (EPIC), 416,746 individuals from 10 countries completed demographic and dietary questionnaires at recruitment. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for incident lung cancer (n = 3731) risk relative to haem iron, non-haem iron, and total dietary iron intake. A corresponding analysis was conducted among a nested subset of 800 lung cancer cases and 1489 matched controls for whom serum cotinine was available. Results: Haem iron was associated with lung cancer risk, including after adjustment for details of smoking history (time since quitting, number of cigarettes per day): as a continuous variable (HR per 0.3 mg/1000 kcal 1.03, 95% CI 1.00-1.07), and in the highest versus lowest quintile (HR 1.16, 95% CI 1.02-1.32; trend across quintiles: P = 0.035). In contrast, non-haem iron intake was related inversely with lung cancer risk; however, this association attenuated after adjustment for smoking history. Additional adjustment for serum cotinine did not considerably alter the associations detected in the nested case-control subset. Conclusions: Greater haem iron intake may be modestly associated with lung cancer risk.
Published: 2019
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29. Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals : a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

Author: Smith, Todd, Muller, David C., Moons, Karel G. M., Cross, Amanda J., Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H. M., Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E., Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J., Aleksandrova, Krasimira Jekova, Tzoulaki, Ioanna, Smith, Todd, Muller, David C., Moons, Karel G. M., Cross, Amanda J., Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H. M., Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E., Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J., Aleksandrova, Krasimira Jekova, and Tzoulaki, Ioanna
Abstract: OBJECTIVE: To systematically identify and validate published colorectal cancer risk prediction models that do not require invasive testing in two large population-based prospective cohorts. DESIGN: Models were identified through an update of a published systematic review and validated in the European Prospective Investigation into Cancer and Nutrition (EPIC) and the UK Biobank. The performance of the models to predict the occurrence of colorectal cancer within 5 or 10 years after study enrolment was assessed by discrimination (C-statistic) and calibration (plots of observed vs predicted probability). RESULTS: The systematic review and its update identified 16 models from 8 publications (8 colorectal, 5 colon and 3 rectal). The number of participants included in each model validation ranged from 41 587 to 396 515, and the number of cases ranged from 115 to 1781. Eligible and ineligible participants across the models were largely comparable. Calibration of the models, where assessable, was very good and further improved by recalibration. The C-statistics of the models were largely similar between validation cohorts with the highest values achieved being 0.70 (95% CI 0.68 to 0.72) in the UK Biobank and 0.71 (95% CI 0.67 to 0.74) in EPIC. CONCLUSION: Several of these non-invasive models exhibited good calibration and discrimination within both external validation populations and are therefore potentially suitable candidates for the facilitation of risk stratification in population-based colorectal screening programmes. Future work should both evaluate this potential, through modelling and impact studies, and ascertain if further enhancement in their performance can be obtained.
Published: 2019
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30. Coffee and tea consumption and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition

Author: Sen, Abhijit, Papadimitriou, Nikos, Lagiou, Pagona, Perez-Cornago, Aurora, Travis, Ruth C., Key, Timothy J., Murphy, Neil, Gunter, Marc, Freisling, Heinz, Tzoulaki, Ioanna, Muller, David C., Cross, Amanda J., Lopez, David S., Bergmann, Manuela, Boeing, Heiner, Bamia, Christina, Kotanidou, Anastasia, Karakatsani, Anna, Tjonneland, Anne, Kyrø, Cecilie, Outzen, Malene, Redondo, Maria-Luisa, Cayssials, Valerie, Chirlaque, Maria-Dolores, Barricarte, Aurelio, Sanchez, Maria-Jose, Larranaga, Nerea, Tumino, Rosario, Grioni, Sara, Palli, Domenico, Caini, Saverio, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Kuehn, Tilman, Kaaks, Rudolf, Nilsson, Lena Maria, Landberg, Rikard, Wallström, Peter, Drake, Isabel, Bech, Bodil Hammer, Overvad, Kim, Aune, Dagfinn, Khaw, Kay-Tee, Riboli, Elio, Trichopoulos, Dimitrios, Trichopoulou, Antonia, Tsilidis, Konstantinos K., Sen, Abhijit, Papadimitriou, Nikos, Lagiou, Pagona, Perez-Cornago, Aurora, Travis, Ruth C., Key, Timothy J., Murphy, Neil, Gunter, Marc, Freisling, Heinz, Tzoulaki, Ioanna, Muller, David C., Cross, Amanda J., Lopez, David S., Bergmann, Manuela, Boeing, Heiner, Bamia, Christina, Kotanidou, Anastasia, Karakatsani, Anna, Tjonneland, Anne, Kyrø, Cecilie, Outzen, Malene, Redondo, Maria-Luisa, Cayssials, Valerie, Chirlaque, Maria-Dolores, Barricarte, Aurelio, Sanchez, Maria-Jose, Larranaga, Nerea, Tumino, Rosario, Grioni, Sara, Palli, Domenico, Caini, Saverio, Sacerdote, Carlotta, Bueno-de-Mesquita, Bas, Kuehn, Tilman, Kaaks, Rudolf, Nilsson, Lena Maria, Landberg, Rikard, Wallström, Peter, Drake, Isabel, Bech, Bodil Hammer, Overvad, Kim, Aune, Dagfinn, Khaw, Kay-Tee, Riboli, Elio, Trichopoulos, Dimitrios, Trichopoulou, Antonia, and Tsilidis, Konstantinos K.
Abstract: The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94-1.09) and 0.98 (95% CI, 0.90-1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79-1.21) and 0.89 (95% CI, 0.70-1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.
Published: 2019
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31. Comparison of prognostic models to predict the occurrence of colorectal cancer in asymptomatic individuals: a systematic literature review and external validation in the EPIC and UK Biobank prospective cohort studies

Author: Epi Methoden, Child Health, Cancer, Circulatory Health, JC onderzoeksprogramma Methodologie, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, MS MDL 1, Smith, Todd, Muller, David C, Moons, Karel G M, Cross, Amanda J, Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H M, Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E, Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, Van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J, Aleksandrova, Krasimira Jekova, Tzoulaki, Ioanna, Epi Methoden, Child Health, Cancer, Circulatory Health, JC onderzoeksprogramma Methodologie, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, MS MDL 1, Smith, Todd, Muller, David C, Moons, Karel G M, Cross, Amanda J, Johansson, Mattias, Ferrari, Pietro, Fagherazzi, Guy, Peeters, Petra H M, Severi, Gianluca, Hüsing, Anika, Kaaks, Rudolf, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Bonet, Catalina, Rodriguez-Barranco, Miguel, Huerta, Jose Maria, Barricarte Gurrea, Aurelio, Bradbury, Kathryn E, Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Palli, Domenico, Pala, Valeria, Vineis, Paolo, Bueno-de-Mesquita, Bas, Ohlsson, Bodil, Harlid, Sophia, Van Guelpen, Bethany, Skeie, Guri, Weiderpass, Elisabete, Jenab, Mazda, Murphy, Neil, Riboli, Elio, Gunter, Marc J, Aleksandrova, Krasimira Jekova, and Tzoulaki, Ioanna
Published: 2019

32. Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: Public Health Practice, MS MDL 1, Epi Methoden Team 3, Cancer, JC onderzoeksprogramma Kanker, Ward, Heather A., Whitman, Julia, Muller, David C., Johansson, Mattias, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjønneland, Anne, Hansen, Louise, Dahm, Christina C., Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie Christine, Affret, Aurélie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Nøst, Therese Haugdahl, Sandanger, Torkjel M., Quirós, Jose Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Larrañaga, Nerea, Huerta, Jose Maria, Ardanaz, Eva, Drake, Isabel, Brunnström, Hans, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C., Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A., Riboli, Elio, Cross, Amanda J., Public Health Practice, MS MDL 1, Epi Methoden Team 3, Cancer, JC onderzoeksprogramma Kanker, Ward, Heather A., Whitman, Julia, Muller, David C., Johansson, Mattias, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjønneland, Anne, Hansen, Louise, Dahm, Christina C., Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie Christine, Affret, Aurélie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Nøst, Therese Haugdahl, Sandanger, Torkjel M., Quirós, Jose Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Larrañaga, Nerea, Huerta, Jose Maria, Ardanaz, Eva, Drake, Isabel, Brunnström, Hans, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C., Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A., Riboli, Elio, and Cross, Amanda J.
Published: 2019

33. Genome-wide interaction study of smoking behavior and non-small cell lung cancer risk in Caucasian population

Author: Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B, Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., Amos, Christopher I., Li, Yafang, Xiao, Xiangjun, Han, Younghun, Gorlova, Olga, Qian, David, Leighl, Natasha, Johansen, Jakob S., Barnett, Matt, Chen, Chu, Goodman, Gary, Cox, Angela, Taylor, Fiona, Woll, Penella, Wichmann, H-Erich, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Houlston, Richard, Artigas, María Soler, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Liu, Geoffrey, Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B, Andrew, Angeline S., Bertazzi, Pier Alberto, Pesatori, Angela C., Christiani, David C., Caporaso, Neil, Johansson, Mattias, McKay, James D., Brennan, Paul, Hung, Rayjean J., and Amos, Christopher I.
Abstract: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Both environmental and genetic risk factors contribute to lung carcinogenesis. We conducted a genome-wide interaction analysis between SNPs and smoking status (never vs ever smokers) in a European-descent population. We adopted a two-step analysis strategy in the discovery stage: we first conducted a case-only interaction analysis to assess the relationship between SNPs and smoking behavior using 13,336 NSCLC cases. Candidate SNPs with p-value less than 0.001 were further analyzed using a standard case-control interaction analysis including 13970 controls. The significant SNPs with p-value less than 3.5x10-5 (correcting for multiple tests) from the case-control analysis in the discovery stage were further validated using an independent replication dataset comprising 5377 controls and 3054 NSCLC cases. We further stratified the analysis by histological subtypes. Two novel SNPs, rs6441286 and rs17723637, were identified for overall lung cancer risk. The interaction odds ratio and meta-analysis p-value for these two SNPs were 1.24 with 6.96x10-7 and 1.37 with 3.49x10-7, respectively. Additionally, interaction of smoking with rs4751674 was identified in squamous cell lung carcinoma with an odds ratio of 0.58 and p-value of 8.12x10-7. This study is by far the largest genome-wide SNP-smoking interaction analysis reported for lung cancer. The three identified novel SNPs provide potential candidate biomarkers for lung cancer risk screening and intervention. The results from our study reinforce that gene-smoking interactions play important roles in the etiology of lung cancer and account for part of the missing heritability of this disease.
Published: 2018
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34. Risk prediction for estrogen receptor-specific breast cancers in two large prospective cohorts

Author: Li, Kuanrong, Anderson, Garnet, Viallon, Vivian, Arveux, Patrick, Kvaskoff, Marina, Fournier, Agnès, Krogh, Vittorio, Tumino, Rosario, Sánchez, Maria-Jose, Ardanaz, Eva, Chirlaque, María-Dolores, Agudo, Antonio, Muller, David C, Smith, Todd, Tzoulaki, Ioanna, Key, Timothy J, Bueno-de-Mesquita, Bas, Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Kaaks, Rudolf, Hüsing, Anika, Fortner, Renée T, Zeleniuch-Jacquotte, Anne, Sund, Malin, Dahm, Christina C, Overvad, Kim, Aune, Dagfinn, Weiderpass, Elisabete, Romieu, Isabelle, Riboli, Elio, Gunter, Marc J, Dossus, Laure, Prentice, Ross, Ferrari, Pietro, Li, Kuanrong, Anderson, Garnet, Viallon, Vivian, Arveux, Patrick, Kvaskoff, Marina, Fournier, Agnès, Krogh, Vittorio, Tumino, Rosario, Sánchez, Maria-Jose, Ardanaz, Eva, Chirlaque, María-Dolores, Agudo, Antonio, Muller, David C, Smith, Todd, Tzoulaki, Ioanna, Key, Timothy J, Bueno-de-Mesquita, Bas, Trichopoulou, Antonia, Bamia, Christina, Orfanos, Philippos, Kaaks, Rudolf, Hüsing, Anika, Fortner, Renée T, Zeleniuch-Jacquotte, Anne, Sund, Malin, Dahm, Christina C, Overvad, Kim, Aune, Dagfinn, Weiderpass, Elisabete, Romieu, Isabelle, Riboli, Elio, Gunter, Marc J, Dossus, Laure, Prentice, Ross, and Ferrari, Pietro
Abstract: BACKGROUND: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction. METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention. RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+
Published: 2018
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35. Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Author: Guida, Florence, Sun, Nan, Bantis, Leonidas E., Muller, David C., Li, Peng, Taguchi, Ayumu, Dhillon, Dilsher, Kundnani, Deepali L., Patel, Nikul J., Yan, Qingxiang, Byrnes, Graham, Moons, Karel G. M., Tjonneland, Anne, Panico, Salvatore, Agnoli, Claudia, Vineis, Paolo, Palli, Domenico, Bueno-de-Mesquita, Bas, Peeters, Petra H., Agudo, Antonio, Huerta, Jose M., Dorronsoro, Miren, Rodriguez Barranco, Miguel, Ardanaz, Eva, Travis, Ruth C., Byme, Karl Smith, Boeing, Heiner, Steffen, Annika, Kaaks, Rudolf, Huesing, Anika, Trichopoulou, Antonia, Lagiou, Pagona, La Vecchia, Carlo, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M., Weiderpass, Elisabete, Nost, Therese H., Tsilidis, Kostas, Riboli, Elio, Grankvist, Kjell, Johansson, Mikael, Goodman, Gary E., Feng, Ziding, Brennan, Paul, Johansson, Mattias, Hanash, Samir M., Guida, Florence, Sun, Nan, Bantis, Leonidas E., Muller, David C., Li, Peng, Taguchi, Ayumu, Dhillon, Dilsher, Kundnani, Deepali L., Patel, Nikul J., Yan, Qingxiang, Byrnes, Graham, Moons, Karel G. M., Tjonneland, Anne, Panico, Salvatore, Agnoli, Claudia, Vineis, Paolo, Palli, Domenico, Bueno-de-Mesquita, Bas, Peeters, Petra H., Agudo, Antonio, Huerta, Jose M., Dorronsoro, Miren, Rodriguez Barranco, Miguel, Ardanaz, Eva, Travis, Ruth C., Byme, Karl Smith, Boeing, Heiner, Steffen, Annika, Kaaks, Rudolf, Huesing, Anika, Trichopoulou, Antonia, Lagiou, Pagona, La Vecchia, Carlo, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M., Weiderpass, Elisabete, Nost, Therese H., Tsilidis, Kostas, Riboli, Elio, Grankvist, Kjell, Johansson, Mikael, Goodman, Gary E., Feng, Ziding, Brennan, Paul, Johansson, Mattias, and Hanash, Samir M.
Abstract: Importance There is an urgent need to improve lung cancer risk assessment because current screening criteria miss a large proportion of cases. Objective To investigate whether a lung cancer risk prediction model based on a panel of selected circulating protein biomarkers can outperform a traditional risk prediction model and current US screening criteria. Design, Setting, and Participants Prediagnostic samples from 108 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and samples from 216 smoking-matched controls from the Carotene and Retinol Efficacy Trial (CARET) cohort were used to develop a biomarker risk score based on 4 proteins (cancer antigen 125 [CA125], carcinoembryonic antigen [CEA], cytokeratin-19 fragment [CYFRA 21-1], and the precursor form of surfactant protein B [Pro-SFTPB]). The biomarker score was subsequently validated blindly using absolute risk estimates among 63 ever-smoking patients with lung cancer diagnosed within 1 year after blood collection and 90 matched controls from 2 large European population-based cohorts, the European Prospective Investigation into Cancer and Nutrition (EPIC) and the Northern Sweden Health and Disease Study (NSHDS). Main Outcomes and Measures Model validity in discriminating between future lung cancer cases and controls. Discrimination estimates were weighted to reflect the background populations of EPIC and NSHDS validation studies (area under the receiver-operating characteristics curve [AUC], sensitivity, and specificity). Results In the validation study of 63 ever-smoking patients with lung cancer and 90 matched controls (mean [SD] age, 57.7 [8.7] years; 68.6% men) from EPIC and NSHDS, an integrated risk prediction model that combined smoking exposure with the biomarker score yielded an AUC of 0.83 (95% CI, 0.76-0.90) compared with 0.73 (95% CI, 0.64-0.82) for a model based on smoking exposure alone (P = .003 for difference in AUC). At an overall specificity of 0.83, base, En rättelse har publicerats. DOI: 10.1001/jamaoncol.2018.4576.A correction has been published. DOI: 10.1001/jamaoncol.2018.4576.
Published: 2018
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36. Identification of susceptibility pathways for the role of chromosome 15q25.1 in modifying lung cancer risk

Author: Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, Amos, Christopher I., Ji, Xuemei, Bosse, Yohan, Landi, Maria Teresa, Gui, Jiang, Xiao, Xiangjun, Qian, David, Joubert, Philippe, Lamontagne, Maxime, Li, Yafang, Gorlov, Ivan, de Biasi, Mariella, Han, Younghun, Gorlova, Olga, Hung, Rayjean J., Wu, Xifeng, Mckay, James, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil, Johansson, Mattias, Liu, Geoffrey, Bojesen, Stig E., Le Marchand, Loic, Albanes, Demetrios, Bickeboeller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Chen, Chu, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier A., Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher, Wilkens, Lynne, Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Erik H. F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnstrom, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brueske, Irene, Manz, Judith, Muley, Thomas, Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances, Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard, McLaughlin, John, Stevens, Victoria, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Gu, Fangyi, Byun, Jinyoung, Kamal, Ahsan, Zhu, Dakai, Tyndale, Rachel F., Wei, Wei-Qi, Chanock, Stephen, Brennan, Paul, and Amos, Christopher I.
Abstract: Genome-wide association studies (GWAS) identified the chromosome 15q25.1 locus as a leading susceptibility region for lung cancer. However, the pathogenic pathways, through which susceptibility SNPs within chromosome 15q25.1 affects lung cancer risk, have not been explored. We analyzed three cohorts with GWAS data consisting 42,901 individuals and lung expression quantitative trait loci (eQTL) data on 409 individuals to identify and validate the underlying pathways and to investigate the combined effect of genes from the identified susceptibility pathways. The KEGG neuroactive ligand receptor interaction pathway, two Reactome pathways, and 22 Gene Ontology terms were identified and replicated to be significantly associated with lung cancer risk, with P values less than 0.05 and FDR less than 0.1. Functional annotation of eQTL analysis results showed that the neuroactive ligand receptor interaction pathway and gated channel activity were involved in lung cancer risk. These pathways provide important insights for the etiology of lung cancer.
Published: 2018
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37. Circulating Folate, Vitamin B6, and Methionine in Relation to Lung Cancer Risk in the Lung Cancer Cohort Consortium (LC3)

Author: Fanidi, Anouar, Muller, David C, Yuan, Jian-Min, Stevens, Victoria L, Weinstein, Stephanie J, Albanes, Demetrius, Prentice, Ross, Thomsen, Cynthia A, Pettinger, Mary, Cai, Qiuyin, Blot, William J, Wu, Jie, Arslan, Alan A, Zeleniuch-Jacquotte, Anne, McCullough, Marjorie L, Le Marchand, Loic, Wilkens, Lynne R, Haiman, Christopher A, Zhang, Xuehong, Han, Jiali, Stampfer, Meir J, Smith-Warner, Stephanie A, Giovannucci, Edward, Giles, Graham G, Hodge, Allison M, Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Krokstad, Steinar, Næss, Marit, Wang, Renwei, Gao, Yu-Tang, Butler, Lesley M, Koh, Woon-Puay, Shu, Xiao-Ou, Xiang, Yong-Bing, Li, Honglan, Zheng, Wei, Lan, Qing, Visvanathan, Kala, Bolton, Judith Hoffman, Ueland, Per Magne, Midttun, Øivind, Ulvik, Arve, Caporaso, Neil E, Purdue, Mark, Ziegler, Regina G, Freedman, Neal D, Buring, Julie E, Lee, I-Min, Sesso, Howard D, Gaziano, J Michael, Manjer, Jonas, Ericson, Ulrika, Relton, Caroline, Brennan, Paul, Johansson, Mattias, Fanidi, Anouar, Muller, David C, Yuan, Jian-Min, Stevens, Victoria L, Weinstein, Stephanie J, Albanes, Demetrius, Prentice, Ross, Thomsen, Cynthia A, Pettinger, Mary, Cai, Qiuyin, Blot, William J, Wu, Jie, Arslan, Alan A, Zeleniuch-Jacquotte, Anne, McCullough, Marjorie L, Le Marchand, Loic, Wilkens, Lynne R, Haiman, Christopher A, Zhang, Xuehong, Han, Jiali, Stampfer, Meir J, Smith-Warner, Stephanie A, Giovannucci, Edward, Giles, Graham G, Hodge, Allison M, Severi, Gianluca, Johansson, Mikael, Grankvist, Kjell, Langhammer, Arnulf, Krokstad, Steinar, Næss, Marit, Wang, Renwei, Gao, Yu-Tang, Butler, Lesley M, Koh, Woon-Puay, Shu, Xiao-Ou, Xiang, Yong-Bing, Li, Honglan, Zheng, Wei, Lan, Qing, Visvanathan, Kala, Bolton, Judith Hoffman, Ueland, Per Magne, Midttun, Øivind, Ulvik, Arve, Caporaso, Neil E, Purdue, Mark, Ziegler, Regina G, Freedman, Neal D, Buring, Julie E, Lee, I-Min, Sesso, Howard D, Gaziano, J Michael, Manjer, Jonas, Ericson, Ulrika, Relton, Caroline, Brennan, Paul, and Johansson, Mattias
Abstract: Background: Circulating concentrations of B vitamins and factors related to one-carbon metabolism have been found to be strongly inversely associated with lung cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. The extent to which these associations are present in other study populations is unknown. Methods: Within 20 prospective cohorts from the National Cancer Institute Cohort Consortium, a nested case-control study was designed including 5364 incident lung cancer case patients and 5364 control subjects who were individually matched to case patients by age, sex, cohort, and smoking status. Centralized biochemical analyses were performed to measure circulating concentrations of vitamin B6, folate, and methionine, as well as cotinine as an indicator of recent tobacco exposure. The association between these biomarkers and lung cancer risk was evaluated using conditional logistic regression models. Results: Participants with higher circulating concentrations of vitamin B6 and folate had a modestly decreased risk of lung cancer risk overall, the odds ratios when comparing the top and bottom fourths (OR 4vs1 ) being 0.88 (95% confidence interval [CI] = 0.78 to 1.00) and 0.86 (95% CI = 0.74 to 0.99), respectively. We found stronger associations among men (vitamin B6: OR 4vs1 = 0.74, 95% CI = 0.62 to 0.89; folate: OR 4vs1 = 0.75, 95% CI = 0.61 to 0.93) and ever smokers (vitamin B6: OR 4vs1 = 0.78, 95% CI = 0.67 to 0.91; folate: OR 4vs1 = 0.87, 95% CI = 0.73 to 1.03). We further noted that the association of folate was restricted to Europe/Australia and Asia, whereas no clear association was observed for the United States. Circulating concentrations of methionine were not associated with lung cancer risk overall or in important subgroups. Conclusions: Although confounding by tobacco exposure or reverse causation cannot be ruled out, these study results are compatible with a small decrease in lung cancer risk in ever smokers who av
Published: 2018
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38. KIM-1 as a blood-based marker for early detection of kidney cancer : A prospective nested case–control study

Author: Scelo, Ghislaine, Muller, David C., Riboli, Elio, Johansson, Mattias, Cross, Amanda J., Vineis, Paolo, Tsilidis, Konstantinos K., Brennan, Paul, Boeing, Heiner, Peeters, Petra H.M., Vermeulen, Roel C.H., Overvad, Kim, Bas Bueno-de-Mesquita, H., Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, Vecchia, Carlo La, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M., Nøst, Therese H., Agudo, Antonio, Ramon Quiros, J., Rodríguez-Barranco, Miguel, Chirlaque, Maria Dolores, Key, Timothy J., Khanna, Prateek, Bonventre, Joseph V., Sabbisetti, Venkata S., Bhatt, Rupal S., Scelo, Ghislaine, Muller, David C., Riboli, Elio, Johansson, Mattias, Cross, Amanda J., Vineis, Paolo, Tsilidis, Konstantinos K., Brennan, Paul, Boeing, Heiner, Peeters, Petra H.M., Vermeulen, Roel C.H., Overvad, Kim, Bas Bueno-de-Mesquita, H., Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, Vecchia, Carlo La, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M., Nøst, Therese H., Agudo, Antonio, Ramon Quiros, J., Rodríguez-Barranco, Miguel, Chirlaque, Maria Dolores, Key, Timothy J., Khanna, Prateek, Bonventre, Joseph V., Sabbisetti, Venkata S., and Bhatt, Rupal S.
Published: 2018

39. Haem iron intake and risk of lung cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Author: One Health Chemisch, dIRAS RA-2, Ward, Heather A., Whitman, Julia, Muller, David C., Johansson, Mattias, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjønneland, Anne, Hansen, Louise, Dahm, Christina C., Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie Christine, Affret, Aurélie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Nøst, Therese Haugdahl, Sandanger, Torkjel M., Quirós, Jose Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Larrañaga, Nerea, Huerta, Jose Maria, Ardanaz, Eva, Drake, Isabel, Brunnström, Hans, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C., Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A., Riboli, Elio, Cross, Amanda J., One Health Chemisch, dIRAS RA-2, Ward, Heather A., Whitman, Julia, Muller, David C., Johansson, Mattias, Jakszyn, Paula, Weiderpass, Elisabete, Palli, Domenico, Fanidi, Anouar, Vermeulen, Roel, Tjønneland, Anne, Hansen, Louise, Dahm, Christina C., Overvad, Kim, Severi, Gianluca, Boutron-Ruault, Marie Christine, Affret, Aurélie, Kaaks, Rudolf, Fortner, Renee, Boeing, Heiner, Trichopoulou, Antonia, La Vecchia, Carlo, Kotanidou, Anastasia, Berrino, Franco, Krogh, Vittorio, Tumino, Rosario, Ricceri, Fulvio, Panico, Salvatore, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Nøst, Therese Haugdahl, Sandanger, Torkjel M., Quirós, Jose Ramón, Agudo, Antonio, Rodríguez-Barranco, Miguel, Larrañaga, Nerea, Huerta, Jose Maria, Ardanaz, Eva, Drake, Isabel, Brunnström, Hans, Johansson, Mikael, Grankvist, Kjell, Travis, Ruth C., Freisling, Heinz, Stepien, Magdalena, Merritt, Melissa A., Riboli, Elio, and Cross, Amanda J.
Published: 2018

40. KIM-1 as a Blood-Based Marker for Early Detection of Kidney Cancer: A Prospective Nested Case-Control Study

Author: One Health Chemisch, dIRAS RA-2, Scelo, Ghislaine, Muller, David C, Riboli, Elio, Johansson, Mattias, Cross, Amanda J, Vineis, Paolo, Tsilidis, Konstantinos K, Brennan, Paul, Boeing, Heiner, Peeters, Petra H M, Vermeulen, Roel C H, Overvad, Kim, Bueno-de-Mesquita, H Bas, Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M, Nøst, Therese H, Agudo, Antonio, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Chirlaque, Maria-Dolores, Key, Timothy J, Khanna, Prateek, Bonventre, Joseph V, Sabbisetti, Venkata S, Bhatt, Rupal S, One Health Chemisch, dIRAS RA-2, Scelo, Ghislaine, Muller, David C, Riboli, Elio, Johansson, Mattias, Cross, Amanda J, Vineis, Paolo, Tsilidis, Konstantinos K, Brennan, Paul, Boeing, Heiner, Peeters, Petra H M, Vermeulen, Roel C H, Overvad, Kim, Bueno-de-Mesquita, H Bas, Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, La Vecchia, Carlo, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M, Nøst, Therese H, Agudo, Antonio, Quirós, J Ramón, Rodríguez-Barranco, Miguel, Chirlaque, Maria-Dolores, Key, Timothy J, Khanna, Prateek, Bonventre, Joseph V, Sabbisetti, Venkata S, and Bhatt, Rupal S
Published: 2018

41. DNA methylation and associated gene expression in blood prior to lung cancer diagnosis in the Norwegian Women and Cancer cohort

Author: One Health Chemisch, dIRAS RA-2, Sandanger, Torkjel Manning, Nøst, Therese Haugdahl, Guida, Florence, Rylander, Charlotta, Campanella, Gianluca, Muller, David C, van Dongen, Jenny, Boomsma, Dorret I, Johansson, Mattias, Vineis, Paolo, Vermeulen, Roel, Lund, Eiliv, Chadeau-Hyam, Marc, One Health Chemisch, dIRAS RA-2, Sandanger, Torkjel Manning, Nøst, Therese Haugdahl, Guida, Florence, Rylander, Charlotta, Campanella, Gianluca, Muller, David C, van Dongen, Jenny, Boomsma, Dorret I, Johansson, Mattias, Vineis, Paolo, Vermeulen, Roel, Lund, Eiliv, and Chadeau-Hyam, Marc
Published: 2018

42. KIM-1 as a blood-based marker for early detection of kidney cancer: A prospective nested case–control study

Author: Epi Kanker Team 1, Cancer, JC onderzoeksprogramma Kanker, Public Health Practice, Scelo, Ghislaine, Muller, David C., Riboli, Elio, Johansson, Mattias, Cross, Amanda J., Vineis, Paolo, Tsilidis, Konstantinos K., Brennan, Paul, Boeing, Heiner, Peeters, Petra H.M., Vermeulen, Roel C.H., Overvad, Kim, Bas Bueno-de-Mesquita, H., Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, Vecchia, Carlo La, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M., Nøst, Therese H., Agudo, Antonio, Ramon Quiros, J., Rodríguez-Barranco, Miguel, Chirlaque, Maria Dolores, Key, Timothy J., Khanna, Prateek, Bonventre, Joseph V., Sabbisetti, Venkata S., Bhatt, Rupal S., Epi Kanker Team 1, Cancer, JC onderzoeksprogramma Kanker, Public Health Practice, Scelo, Ghislaine, Muller, David C., Riboli, Elio, Johansson, Mattias, Cross, Amanda J., Vineis, Paolo, Tsilidis, Konstantinos K., Brennan, Paul, Boeing, Heiner, Peeters, Petra H.M., Vermeulen, Roel C.H., Overvad, Kim, Bas Bueno-de-Mesquita, H., Severi, Gianluca, Perduca, Vittorio, Kvaskoff, Marina, Trichopoulou, Antonia, Vecchia, Carlo La, Karakatsani, Anna, Palli, Domenico, Sieri, Sabina, Panico, Salvatore, Weiderpass, Elisabete, Sandanger, Torkjel M., Nøst, Therese H., Agudo, Antonio, Ramon Quiros, J., Rodríguez-Barranco, Miguel, Chirlaque, Maria Dolores, Key, Timothy J., Khanna, Prateek, Bonventre, Joseph V., Sabbisetti, Venkata S., and Bhatt, Rupal S.
Published: 2018

43. Assessment of Lung Cancer Risk on the Basis of a Biomarker Panel of Circulating Proteins

Author: Epi Methoden, Child Health, Cancer, Circulatory Health, JC onderzoeksprogramma Methodologie, MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Guida, Florence, Sun, Nan, Bantis, Leonidas E, Muller, David C, Li, Peng, Taguchi, Ayumu, Dhillon, Dilsher, Kundnani, Deepali L, Patel, Nikul J, Yan, Qingxiang, Byrnes, Graham, Moons, Karel G M, Tjønneland, Anne, Panico, Salvatore, Agnoli, Claudia, Vineis, Paolo, Palli, Domenico, Bueno-de-Mesquita, Bas, Peeters, Petra H, Agudo, Antonio, Huerta, Jose M, Dorronsoro, Miren, Barranco, Miguel Rodriguez, Ardanaz, Eva, Travis, Ruth C, Byrne, Karl Smith, Boeing, Heiner, Steffen, Annika, Kaaks, Rudolf, Hüsing, Anika, Trichopoulou, Antonia, Lagiou, Pagona, La Vecchia, Carlo, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M, Weiderpass, Elisabete, Nøst, Therese H, Tsilidis, Kostas, Riboli, Elio, Grankvist, Kjell, Johansson, Mikael, Goodman, Gary E, Feng, Ziding, Brennan, Paul, Johansson, Mattias, Hanash, Samir M, Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer, Epi Methoden, Child Health, Cancer, Circulatory Health, JC onderzoeksprogramma Methodologie, MS MDL 1, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Guida, Florence, Sun, Nan, Bantis, Leonidas E, Muller, David C, Li, Peng, Taguchi, Ayumu, Dhillon, Dilsher, Kundnani, Deepali L, Patel, Nikul J, Yan, Qingxiang, Byrnes, Graham, Moons, Karel G M, Tjønneland, Anne, Panico, Salvatore, Agnoli, Claudia, Vineis, Paolo, Palli, Domenico, Bueno-de-Mesquita, Bas, Peeters, Petra H, Agudo, Antonio, Huerta, Jose M, Dorronsoro, Miren, Barranco, Miguel Rodriguez, Ardanaz, Eva, Travis, Ruth C, Byrne, Karl Smith, Boeing, Heiner, Steffen, Annika, Kaaks, Rudolf, Hüsing, Anika, Trichopoulou, Antonia, Lagiou, Pagona, La Vecchia, Carlo, Severi, Gianluca, Boutron-Ruault, Marie-Christine, Sandanger, Torkjel M, Weiderpass, Elisabete, Nøst, Therese H, Tsilidis, Kostas, Riboli, Elio, Grankvist, Kjell, Johansson, Mikael, Goodman, Gary E, Feng, Ziding, Brennan, Paul, Johansson, Mattias, Hanash, Samir M, and Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Consortium for Early Detection of Lung Cancer
Published: 2018

44. Inflammatory Cytokines and Lung Cancer Risk in 3 Prospective Studies

Author: Brenner, Darren R., Fanidi, Anouar, Grankvist, Kjell, Muller, David C., Brennan, Paul, Manjer, Jonas, Byrnes, Graham, Hodge, Allison, Severi, Gianluca, Giles, Graham G., Johansson, Mikael, Johansson, Mattias, Brenner, Darren R., Fanidi, Anouar, Grankvist, Kjell, Muller, David C., Brennan, Paul, Manjer, Jonas, Byrnes, Graham, Hodge, Allison, Severi, Gianluca, Giles, Graham G., Johansson, Mikael, and Johansson, Mattias
Abstract: To further investigate the role of inflammation in lung carcinogenesis, we evaluated associations between proinflammatory cytokines and lung cancer risk. We conducted a case-control study nested within 3 prospective cohort studies-the Melbourne Collaborative Cohort Study (1990-1994), the Malm Diet and Cancer Study (1991-1996), and the Northern Sweden Health and Disease Study (initiated in 1985)-involving 807 incident lung cancer cases and 807 smoking-matched controls. Conditional logistic regression models adjusting for serum cotinine concentrations were used to estimate odds ratios for lung cancer risk associated with concentrations of interleukin (IL)-1 beta, IL-2, IL-6, IL-8, IL-10, IL-12, interferon., tumor necrosis factor a, and granulocyte-macrophage colony-stimulating factor. We observed a higher lung cancer risk for participants with elevated concentrations of IL-6 and IL-8. These associations seemed to be stronger among former smokers (for fourth quartile vs. first quartile, odds ratio (OR) = 2.70, 95% confidence interval (CI): 1.55, 4.70) and current smokers (OR = 1.99, 95% CI: 1.15, 3.44) for IL-6 and among former smokers (OR = 2.83, 95% CI: 1.18, 6.75) and current smokers (OR = 1.30, 95% CI: 0.69, 2.44) for IL-8. No notable associations were observed among never smokers. Risk associations with IL-6 and IL-8 were observed for blood samples taken close to diagnosis (< 5 years) as well as more than 15 years postdiagnosis.
Published: 2017
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45. Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes

Author: McKay, James D., Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil E., Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Byun, Jinyoung, Dunning, Alison, Pooley, Karen A., Qian, David C., Ji, Xuemei, Liu, Geoffrey, Timofeeva, Maria N., Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier Alberto, Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher A., Wilkens, Lynne R., Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Henricus F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer A., Barnett, Matt P., Chen, Chu, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brüske, Irene, Wichmann, H-Erich, Manz, Judith, Muley, Thomas R., Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard S., McLaughlin, John, Stevens, Victoria L., Joubert, Philippe, Lamontagne, Maxime, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Kachuri, Linda, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Rafnar, Thorunn, Thorgeirsson, Thorgeir E., Reginsson, Gunnar W., Stefansson, Kari, Hancock, Dana B., Bierut, Laura J., Spitz, Margaret R., Gaddis, Nathan C., Lutz, Sharon M., Gu, Fangyi, Johnson, Eric O., Kamal, Ahsan, Pikielny, Claudio, Zhu, Dakai, Lindström, Sara, Jiang, Xia, Tyndale, Rachel F., Chenevix-Trench, Georgia, Beesley, Jonathan, Bossé, Yohan, Chanock, Stephen, Brennan, Paul, Landi, Maria Teresa, Amos, Christopher I., McKay, James D., Hung, Rayjean J., Han, Younghun, Zong, Xuchen, Carreras-Torres, Robert, Christiani, David C., Caporaso, Neil E., Johansson, Mattias, Xiao, Xiangjun, Li, Yafang, Byun, Jinyoung, Dunning, Alison, Pooley, Karen A., Qian, David C., Ji, Xuemei, Liu, Geoffrey, Timofeeva, Maria N., Bojesen, Stig E., Wu, Xifeng, Le Marchand, Loic, Albanes, Demetrios, Bickeböller, Heike, Aldrich, Melinda C., Bush, William S., Tardon, Adonina, Rennert, Gad, Teare, M. Dawn, Field, John K., Kiemeney, Lambertus A., Lazarus, Philip, Haugen, Aage, Lam, Stephen, Schabath, Matthew B., Andrew, Angeline S., Shen, Hongbing, Hong, Yun-Chul, Yuan, Jian-Min, Bertazzi, Pier Alberto, Pesatori, Angela C., Ye, Yuanqing, Diao, Nancy, Su, Li, Zhang, Ruyang, Brhane, Yonathan, Leighl, Natasha, Johansen, Jakob S., Mellemgaard, Anders, Saliba, Walid, Haiman, Christopher A., Wilkens, Lynne R., Fernandez-Somoano, Ana, Fernandez-Tardon, Guillermo, van der Heijden, Henricus F. M., Kim, Jin Hee, Dai, Juncheng, Hu, Zhibin, Davies, Michael P. A., Marcus, Michael W., Brunnström, Hans, Manjer, Jonas, Melander, Olle, Muller, David C., Overvad, Kim, Trichopoulou, Antonia, Tumino, Rosario, Doherty, Jennifer A., Barnett, Matt P., Chen, Chu, Goodman, Gary E., Cox, Angela, Taylor, Fiona, Woll, Penella, Brüske, Irene, Wichmann, H-Erich, Manz, Judith, Muley, Thomas R., Risch, Angela, Rosenberger, Albert, Grankvist, Kjell, Johansson, Mikael, Shepherd, Frances A., Tsao, Ming-Sound, Arnold, Susanne M., Haura, Eric B., Bolca, Ciprian, Holcatova, Ivana, Janout, Vladimir, Kontic, Milica, Lissowska, Jolanta, Mukeria, Anush, Ognjanovic, Simona, Orlowski, Tadeusz M., Scelo, Ghislaine, Swiatkowska, Beata, Zaridze, David, Bakke, Per, Skaug, Vidar, Zienolddiny, Shanbeh, Duell, Eric J., Butler, Lesley M., Koh, Woon-Puay, Gao, Yu-Tang, Houlston, Richard S., McLaughlin, John, Stevens, Victoria L., Joubert, Philippe, Lamontagne, Maxime, Nickle, David C., Obeidat, Ma'en, Timens, Wim, Zhu, Bin, Song, Lei, Kachuri, Linda, Artigas, Maria Soler, Tobin, Martin D., Wain, Louise V., Rafnar, Thorunn, Thorgeirsson, Thorgeir E., Reginsson, Gunnar W., Stefansson, Kari, Hancock, Dana B., Bierut, Laura J., Spitz, Margaret R., Gaddis, Nathan C., Lutz, Sharon M., Gu, Fangyi, Johnson, Eric O., Kamal, Ahsan, Pikielny, Claudio, Zhu, Dakai, Lindström, Sara, Jiang, Xia, Tyndale, Rachel F., Chenevix-Trench, Georgia, Beesley, Jonathan, Bossé, Yohan, Chanock, Stephen, Brennan, Paul, Landi, Maria Teresa, and Amos, Christopher I.
Abstract: Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genomewide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer.
Published: 2017
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46. Measured Adiposity in Relation to Head and Neck Cancer Risk in the European Prospective Investigation into Cancer and Nutrition

Author: Ward, Heather A., Wark, Petra A., Muller, David C., Steffen, Annika, Johansson, Mattias, Norat, Teresa, Gunter, Marc J., Overvad, Kim, Dahm, Christina C., Halkjaer, Jytte, Tojonneland, Anne, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Mesrine, Sylvie, Brennan, Paul, Freisling, Heinz, Li, Kuanrong, Kaaks, Rudolf, Trichopoulou, Antonia, Lagiou, Pagona, Panico, Salavatore, Grioni, Sara, Tumino, Rosario, Vineis, Paolo, Palli, Domenico, Peeters, Petra H. M., Bueno-de-Mesquita, H. Bas., Weiderpass, Elisabete, Agudo, Antonio, Ramon Quiros, Jose, Larranaga, Nerea, Ardanaz, Eva, Maria Huerta, Jose, Sanchez, Maria-Jose, Laurell, Goran, Johansson, Ingegerd, Westin, Ulla, Wallstrom, Peter, Bradbury, Kathryn E., Wareham, Nicholas J., Khaw, Kay-Tee, Pearson, Clare, Boeing, Heiner, Riboli, Elio, Ward, Heather A., Wark, Petra A., Muller, David C., Steffen, Annika, Johansson, Mattias, Norat, Teresa, Gunter, Marc J., Overvad, Kim, Dahm, Christina C., Halkjaer, Jytte, Tojonneland, Anne, Boutron-Ruault, Marie-Christine, Fagherazzi, Guy, Mesrine, Sylvie, Brennan, Paul, Freisling, Heinz, Li, Kuanrong, Kaaks, Rudolf, Trichopoulou, Antonia, Lagiou, Pagona, Panico, Salavatore, Grioni, Sara, Tumino, Rosario, Vineis, Paolo, Palli, Domenico, Peeters, Petra H. M., Bueno-de-Mesquita, H. Bas., Weiderpass, Elisabete, Agudo, Antonio, Ramon Quiros, Jose, Larranaga, Nerea, Ardanaz, Eva, Maria Huerta, Jose, Sanchez, Maria-Jose, Laurell, Goran, Johansson, Ingegerd, Westin, Ulla, Wallstrom, Peter, Bradbury, Kathryn E., Wareham, Nicholas J., Khaw, Kay-Tee, Pearson, Clare, Boeing, Heiner, and Riboli, Elio
Abstract: Background: Emerging evidence from cohort studies indicates that adiposity is associated with greater incidence of head and neck cancer. However, most studies have used self-reported anthropometry which is prone to error. Methods: Among 363,094 participants in the European Prospective Investigation into Cancer and Nutrition study (EPIC) with measured anthropometry, there were 837 incident cases of head and neck cancer. Head and neck cancer risk was examined in relation to body mass index (BMI) [lean: <22.5 kg/m(2), normal weight (reference): 22.5-24.9 kg/m(2), overweight 25-29.9 kg/m(2), obese: >= 30 kg/m(2)], waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) using Cox proportional hazards models. Results: Among men, a BMI <22.5 kg/m(2) was associated with higher head and neck cancer risk [HR 1.62; 95% confidence interval (CI), 1.23-2.12)]; BMI was not associated with head and neck cancer among women. WC and WHR were associated with greater risk of head and neck cancer among women (WC per 5 cm: HR, 1.08; 95% CI, 1.02-1.15; WHR per 0.1 unit: HR, 1.64; 95% CI, 1.38-1.93). After stratification by smoking status, the association for WHR was present only among smokers (P-interaction = 0.004). Among men, WC and WHR were associated with head and neck cancer only upon additional adjustment for BMI (WC per 5 cm: HR 1.16; 95% CI, 1.07-1.26; WHR per 0.1 unit: HR, 1.42; 95% CI, 1.21-1.65). Conclusions: Central adiposity, particularly among women, may have a stronger association with head and neck cancer risk than previously estimated.
Published: 2017
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47. Circulating concentrations of biomarkers and metabolites related to vitamin status, one-carbon and the kynurenine pathways in US, Nordic, Asian, and Australian populations

Author: Midttun, Oivind, Theofylaktopoulou, Despoina, McCann, Adrian, Fanidi, Anouar, Muller, David C., Meyer, Klaus, Ulvik, Arve, Zheng, Wei, Shu, Xiao-Ou, Xiang, Yong-Bing, Prentice, Ross, Thomson, Cynthia A., Pettinger, Mary, Giles, Graham G., Hodge, Allison, Cai, Qiuyin, Blot, William J., Wu, Jie, Johansson, Mikael, Hultdin, Johan, Grankvist, Kjell, Stevens, Victoria L., McCullough, Marjorie L., Weinstein, Stephanie J., Albanes, Demetrius, Langhammer, Arnulf, Hveem, Kristian, Naess, Marit, Sesso, Howard D., Gaziano, J. Michael, Buring, Julie E., Lee, I-Min, Severi, Gianluca, Zhang, Xuehong, Han, Jiali, Stampfer, Meir J., Smith-Warner, Stephanie A., Zeleniuch-Jacquotte, Anne, le Marchand, Loic, Yuan, Jian-Min, Butler, Lesley M., Koh, Woon-Puay, Wang, Renwei, Gao, Yu-Tang, Ericson, Ulrika, Sonestedt, Emily, Ziegler, Regina G., Freedman, Neal D., Visvanathan, Kala, Jones, Miranda R., Relton, Caroline, Brennan, Paul, Johansson, Mattias, Ueland, Per M., Midttun, Oivind, Theofylaktopoulou, Despoina, McCann, Adrian, Fanidi, Anouar, Muller, David C., Meyer, Klaus, Ulvik, Arve, Zheng, Wei, Shu, Xiao-Ou, Xiang, Yong-Bing, Prentice, Ross, Thomson, Cynthia A., Pettinger, Mary, Giles, Graham G., Hodge, Allison, Cai, Qiuyin, Blot, William J., Wu, Jie, Johansson, Mikael, Hultdin, Johan, Grankvist, Kjell, Stevens, Victoria L., McCullough, Marjorie L., Weinstein, Stephanie J., Albanes, Demetrius, Langhammer, Arnulf, Hveem, Kristian, Naess, Marit, Sesso, Howard D., Gaziano, J. Michael, Buring, Julie E., Lee, I-Min, Severi, Gianluca, Zhang, Xuehong, Han, Jiali, Stampfer, Meir J., Smith-Warner, Stephanie A., Zeleniuch-Jacquotte, Anne, le Marchand, Loic, Yuan, Jian-Min, Butler, Lesley M., Koh, Woon-Puay, Wang, Renwei, Gao, Yu-Tang, Ericson, Ulrika, Sonestedt, Emily, Ziegler, Regina G., Freedman, Neal D., Visvanathan, Kala, Jones, Miranda R., Relton, Caroline, Brennan, Paul, Johansson, Mattias, and Ueland, Per M.
Abstract: Background: Circulating concentrations of biomarkers that are related to vitamin status vary by factors such as diet, fortification, and supplement use. Published biomarker concentrations have also been influenced by the variation across laboratories, which complicates a comparison of results from different studies. Objective: We robustly and comprehensively assessed differences in biomarkers that are related to vitamin status across geographic regions. Design: The trial was a cross-sectional study in which we investigated 38 biomarkers that are related to vitamin status and one-carbon and tryptophan metabolism in serum and plasma from 5314 healthy control subjects representing 20 cohorts recruited from the United States, Nordic countries, Asia, and Australia, participating in the Lung Cancer Cohort Consortium. All samples were analyzed in a centralized laboratory. Results: Circulating concentrations of riboflavin, pyridoxal 5'-phosphate, folate, vitamin B-12, all-trans retinol, 25-hydroxyvitamin D, and a-tocopherol as well as combined vitamin scores that were based on these nutrients showed that the general B-vitamin concentration was highest in the United States and that the B vitamins and lipid soluble vitamins were low in Asians. Conversely, circulating concentrations of metabolites that are inversely related to B vitamins involved in the one-carbon and kynurenine pathways were high in Asians. The high B-vitamin concentration in the United States appears to be driven mainly by multivitamin-supplement users. Conclusions: The observed differences likely reflect the variation in intake of vitamins and, in particular, the widespread multivitamin-supplement use in the United States. The results provide valuable information about the differences in biomarker concentrations in populations across continents.
Published: 2017
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48. Coffee drinking and mortality in 10 European countries : A multinational cohort study

Author: Gunter, Marc J., Murphy, Neil, Cross, Amanda J., Dossus, Laure, Dartois, Laureen, Fagherazzi, Guy, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Larsen, Sofus Christian, Cornejo, Maria Luisa Redondo, Agudo, Antonio, Pérez, María José Sánchez, Altzibar, Jone M., Navarro, Carmen, Ardanaz, Eva, Khaw, Kay Tee, Butterworth, Adam, Bradbury, Kathryn E., Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Grioni, Sara, Vineis, Paolo, Panico, Salvatore, Tumino, Rosario, Bueno-De-Mesquita, Bas, Siersema, Peter, Leenders, Max, Beulens, Joline W.J., Uiterwaal, Cuno U., Wallström, Peter, Nilsson, Lena Maria, Landberg, Rikard, Weiderpass, Elisabete, Skeie, Guri, Braaten, Tonje, Brennan, Paul, Licaj, Idlir, Muller, David C., Sinha, Rashmi, Wareham, Nick, Riboli, Elio, Gunter, Marc J., Murphy, Neil, Cross, Amanda J., Dossus, Laure, Dartois, Laureen, Fagherazzi, Guy, Kaaks, Rudolf, Kühn, Tilman, Boeing, Heiner, Aleksandrova, Krasimira, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Larsen, Sofus Christian, Cornejo, Maria Luisa Redondo, Agudo, Antonio, Pérez, María José Sánchez, Altzibar, Jone M., Navarro, Carmen, Ardanaz, Eva, Khaw, Kay Tee, Butterworth, Adam, Bradbury, Kathryn E., Trichopoulou, Antonia, Lagiou, Pagona, Trichopoulos, Dimitrios, Palli, Domenico, Grioni, Sara, Vineis, Paolo, Panico, Salvatore, Tumino, Rosario, Bueno-De-Mesquita, Bas, Siersema, Peter, Leenders, Max, Beulens, Joline W.J., Uiterwaal, Cuno U., Wallström, Peter, Nilsson, Lena Maria, Landberg, Rikard, Weiderpass, Elisabete, Skeie, Guri, Braaten, Tonje, Brennan, Paul, Licaj, Idlir, Muller, David C., Sinha, Rashmi, Wareham, Nick, and Riboli, Elio
Published: 2017

49. Plasma microRNAs as biomarkers of pancreatic cancer risk in a prospective cohort study

Author: Duell, Eric J., Lujan-Barroso, Leila, Sala, Núria, Deitz McElyea, Samantha, Overvad, Kim, Tjonneland, Anne, Olsen, Anja, Weiderpass, Elisabete, Busund, Lill Tove, Moi, Line, Muller, David C., Vineis, Paolo, Aune, Dagfinn, Matullo, Giuseppe, Naccarati, Alessio, Panico, Salvatore, Tagliabue, Giovanna, Tumino, Rosario, Palli, Domenico, Kaaks, Rudolf, Katzke, Verena A., Boeing, Heiner, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Trichopoulou, Antonia, Lagiou, Pagona, Kotanidou, Anastasia, Travis, Ruth C., Wareham, Nick, Khaw, Kay Tee, Ramon Quiros, Jose, Rodríguez-Barranco, Miguel, Dorronsoro, Miren, Chirlaque, María Dolores, Ardanaz, Eva, Severi, Gianluca, Boutron-Ruault, Marie Christine, Rebours, Vinciane, Brennan, Paul, Gunter, Marc J., Scelo, Ghislaine, Cote, Greg, Sherman, Stuart, Korc, Murray, Duell, Eric J., Lujan-Barroso, Leila, Sala, Núria, Deitz McElyea, Samantha, Overvad, Kim, Tjonneland, Anne, Olsen, Anja, Weiderpass, Elisabete, Busund, Lill Tove, Moi, Line, Muller, David C., Vineis, Paolo, Aune, Dagfinn, Matullo, Giuseppe, Naccarati, Alessio, Panico, Salvatore, Tagliabue, Giovanna, Tumino, Rosario, Palli, Domenico, Kaaks, Rudolf, Katzke, Verena A., Boeing, Heiner, Bueno-de-Mesquita, H. Bas, Peeters, Petra H., Trichopoulou, Antonia, Lagiou, Pagona, Kotanidou, Anastasia, Travis, Ruth C., Wareham, Nick, Khaw, Kay Tee, Ramon Quiros, Jose, Rodríguez-Barranco, Miguel, Dorronsoro, Miren, Chirlaque, María Dolores, Ardanaz, Eva, Severi, Gianluca, Boutron-Ruault, Marie Christine, Rebours, Vinciane, Brennan, Paul, Gunter, Marc J., Scelo, Ghislaine, Cote, Greg, Sherman, Stuart, and Korc, Murray
Published: 2017

50. DNA methylome analysis identifies accelerated epigenetic ageing associated with postmenopausal breast cancer susceptibility

Author: Ambatipudi, Srikant, Horvath, Steve, Perrier, Flavie, Cuenin, Cyrille, Hernandez-Vargas, Hector, Le Calvez-Kelm, Florence, Durand, Geoffroy, Byrnes, Graham, Ferrari, Pietro, Bouaoun, Liacine, Sklias, Athena, Chajes, Véronique, Overvad, Kim, Severi, Gianluca, Baglietto, Laura, Clavel-Chapelon, Françoise, Kaaks, Rudolf, Barrdahl, Myrto, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Naska, Androniki, Masala, Giovanna, Agnoli, Claudia, Polidoro, Silvia, Tumino, Rosario, Panico, Salvatore, Dollé, Martijn, Peeters, Petra H M, Onland-Moret, N. Charlotte, Sandanger, Torkjel M., Nøst, Therese H., Weiderpass Vainio, Elisabete, Quirós, J. Ramón, Agudo, Antonio, Rodriguez-Barranco, Miguel, Huerta Castaño, José María, Barricarte, Aurelio, Fernández, Ander Matheu, Travis, Ruth C., Vineis, Paolo, Muller, David C., Riboli, Elio, Gunter, Marc, Romieu, Isabelle, Herceg, Zdenko, Ambatipudi, Srikant, Horvath, Steve, Perrier, Flavie, Cuenin, Cyrille, Hernandez-Vargas, Hector, Le Calvez-Kelm, Florence, Durand, Geoffroy, Byrnes, Graham, Ferrari, Pietro, Bouaoun, Liacine, Sklias, Athena, Chajes, Véronique, Overvad, Kim, Severi, Gianluca, Baglietto, Laura, Clavel-Chapelon, Françoise, Kaaks, Rudolf, Barrdahl, Myrto, Boeing, Heiner, Trichopoulou, Antonia, Lagiou, Pagona, Naska, Androniki, Masala, Giovanna, Agnoli, Claudia, Polidoro, Silvia, Tumino, Rosario, Panico, Salvatore, Dollé, Martijn, Peeters, Petra H M, Onland-Moret, N. Charlotte, Sandanger, Torkjel M., Nøst, Therese H., Weiderpass Vainio, Elisabete, Quirós, J. Ramón, Agudo, Antonio, Rodriguez-Barranco, Miguel, Huerta Castaño, José María, Barricarte, Aurelio, Fernández, Ander Matheu, Travis, Ruth C., Vineis, Paolo, Muller, David C., Riboli, Elio, Gunter, Marc, Romieu, Isabelle, and Herceg, Zdenko
Published: 2017

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