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1. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

Author

Yarmolinsky, J, Robinson, JW, Mariosa, D, Karhunen, V, Huang, J, Dimou, N, Murphy, N, Burrows, K, Bouras, E, Smith-Byrne, K, Lewis, SJ, Galesloot, TE, Kiemeney, LA, Vermeulen, S, Martin, P, Albanes, D, Hou, L, Newcomb, PA, White, E, Wolk, A, Wu, AH, Le Marchand, L, Phipps, AI, Buchanan, DD, International Lung Cancer Consortium, PRACTICAL Consortium, Zhao, SS, Gill, D, Chanock, SJ, Purdue, MP, Davey Smith, G, Brennan, P, Herzig, K-H, Järvelin, M-R, Amos, CI, Hung, RJ, Dehghan, A, Johansson, M, Gunter, MJ, Tsilidis, KK, Martin, RM, Yarmolinsky, J, Robinson, JW, Mariosa, D, Karhunen, V, Huang, J, Dimou, N, Murphy, N, Burrows, K, Bouras, E, Smith-Byrne, K, Lewis, SJ, Galesloot, TE, Kiemeney, LA, Vermeulen, S, Martin, P, Albanes, D, Hou, L, Newcomb, PA, White, E, Wolk, A, Wu, AH, Le Marchand, L, Phipps, AI, Buchanan, DD, International Lung Cancer Consortium, PRACTICAL Consortium, Zhao, SS, Gill, D, Chanock, SJ, Purdue, MP, Davey Smith, G, Brennan, P, Herzig, K-H, Järvelin, M-R, Amos, CI, Hung, RJ, Dehghan, A, Johansson, M, Gunter, MJ, Tsilidis, KK, and Martin, RM

Abstract

BACKGROUND: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear. METHODS: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10-8) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r2 < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") <0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH4) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis. FINDINGS: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH4 = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0.055, PP

Published
2024

2. Body size at different ages and risk of six cancers: a Mendelian randomization and prospective cohort study

Author

Mariosa, D, Smith-Byrne, K, Richardson, TG, Ferrari, P, Gunter, MJ, Papadimitriou, N, Murphy, N, Christakoudi, S, Tsilidis, KK, Riboli, E, Muller, D, Purdue, MP, Chanock, SJ, Hung, RJ, Amos, CI, O'Mara, TA, Amiano, P, Pasanisi, F, Rodriguez-Barranco, M, Krogh, V, Tjønneland, A, Halkjær, J, Perez-Cornago, A, Chirlaque, M-D, Skeie, G, Rylander, C, Borch, KB, Aune, D, Heath, AK, Ward, HA, Schulze, M, Bonet, C, Weiderpass, E, Smith, GD, Brennan, P, Johansson, M, Mariosa, Daniela, Smith-Byrne, Karl, Richardson, Tom G, Ferrari, Pietro, Gunter, Marc J, Papadimitriou, Niko, Murphy, Neil, Christakoudi, Sofia, Tsilidis, Konstantinos K, Riboli, Elio, Muller, David, Purdue, Mark P, Chanock, Stephen J, Hung, Rayjean J, Amos, Christopher I, O'Mara, Tracy A, Amiano, Pilar, Pasanisi, Fabrizio, Rodriguez-Barranco, Miguel, Krogh, Vittorio, Tjønneland, Anne, Halkjær, Jytte, Perez-Cornago, Aurora, Chirlaque, María-Dolore, Skeie, Guri, Rylander, Charlotta, Borch, Kristin Benjaminsen, Aune, Dagfinn, Heath, Alicia K, Ward, Heather A, Schulze, Matthia, Bonet, Catalina, Weiderpass, Elisabete, Smith, George Davey, Brennan, Paul, and Johansson, Mattias

Subjects
Adult, SUSCEPTIBILITY LOCI, Epidemiology, OVARIAN-CANCER, Body Mass Index, 1117 Public Health and Health Services, POOLED ANALYSIS, Cohort Studies, MASS INDEX, Neoplasms, Body Size, Humans, Obesity, Prospective Studies, Genetics & Heredity, LIFE-COURSE, 0604 Genetics, Science & Technology, IDENTIFICATION, ENDOMETRIAL CANCER, Mendelian Randomization Analysis, Oncology, ADIPOSITY, Mathematical & Computational Biology, Life Sciences & Biomedicine, ANTHROPOMETRIC FACTORS, Genome-Wide Association Study
Abstract

It is unclear if body weight in early life affects cancer risk independently of adult body weight. To investigate this question for six obesity-related cancers, we performed univariable and multivariable analyses using i) Mendelian randomization (MR) analysis and ii) longitudinal analyses in prospective cohorts. Both the MR and longitudinal analyses indicated that larger body size at age 10 was associated with higher risk of endometrial (ORMR=1.61, 95%CI = 1.23-2.11) and kidney cancer (ORMR=1.40, 95%CI = 1.09-1.80). These associations were attenuated after accounting for adult body size in both the MR and cohort analyses. Early life BMI was not consistently associated with the other investigated cancers. The lack of clear independent risk associations suggests that early life BMI influences endometrial and kidney cancer risk mainly through pathways that are common with adult BMI.

Published
2022

3. Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals

Author

Chen, H, Majumdar, A, Wang, L, Kar, S, Brown, KM, Feng, H, Turman, C, Dennis, J, Easton, D, Michailidou, K, Simard, J, Breast Cancer Association Consortium (BCAC), Bishop, T, Cheng, IC, Huyghe, JR, Schmit, SL, Colorectal Transdisciplinary Study (CORECT), Colon Cancer Family Registry Study (CCFR), Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO, O'Mara, TA, Spurdle, AB, Endometrial Cancer Association Consortium (ECAC), Gharahkhani, P, Schumacher, J, Jankowski, J, Gockel, I, Esophageal Cancer GWAS Consortium, Bondy, ML, Houlston, RS, Jenkins, RB, Melin, B, Glioma International Case Control Consortium (GICC), Lesseur, C, Ness, AR, Diergaarde, B, Olshan, AF, Head-Neck Cancer GWAS Consortium, Amos, CI, Christiani, DC, Landi, MT, McKay, JD, International Lung Cancer Consortium (ILCCO), Brossard, M, Iles, MM, Law, MH, MacGregor, S, Melanoma GWAS Consortium, Beesley, J, Jones, MR, Tyrer, J, Winham, SJ, Ovarian Cancer Association Consortium (OCAC), Klein, AP, Petersen, G, Li, D, Wolpin, BM, Pancreatic Cancer Case-Control Consortium (PANC4), Pancreatic Cancer Cohort Consortium (PanScan), Eeles, RA, Haiman, CA, Kote-Jarai, Z, Schumacher, FR, PRACTICAL consortium, CRUK, BPC3, CAPS, PEGASUS, Brennan, P, Chanock, SJ, Gaborieau, V, Purdue, MP, Renal Cancer GWAS Consortium, Pharoah, P, Hung, RJ, Amundadottir, LT, Kraft, P, Pasaniuc, B, and Lindström, S

Abstract

Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.

Published
2021

4. Genetically Determined Height and Risk of Non-hodgkin Lymphoma

Author

Moore, A, Kane, E, Wang, Z, Panagiotou, OA, Teras, LR, Monnereau, A, Wong Doo, N, Machiela, MJ, Skibola, CF, Slager, SL, Salles, G, Camp, NJ, Bracci, PM, Nieters, A, Vermeulen, RCH, Vijai, J, Smedby, KE, Zhang, Y, Vajdic, CM, Cozen, W, Spinelli, JJ, Hjalgrim, H, Giles, GG, Link, BK, Clavel, J, Arslan, AA, Purdue, MP, Tinker, LF, Albanes, D, Ferri, GM, Habermann, TM, Adami, H-O, Becker, N, Benavente, Y, Bisanzi, S, Boffetta, P, Brennan, P, Brooks-Wilson, AR, Canzian, F, Conde, L, Cox, DG, Curtin, K, Foretova, L, Gapstur, SM, Ghesquieres, H, Glenn, M, Glimelius, B, Jackson, RD, Lan, Q, Liebow, M, Maynadie, M, McKay, J, Melbye, M, Miligi, L, Milne, RL, Molina, TJ, Morton, LM, North, KE, Offit, K, Padoan, M, Patel, AV, Piro, S, Ravichandran, V, Riboli, E, de Sanjose, S, Severson, RK, Southey, MC, Staines, A, Stewart, C, Travis, RC, Weiderpass, E, Weinstein, S, Zheng, T, Chanock, SJ, Chatterjee, N, Rothman, N, Birmann, BM, Cerhan, JR, Berndt, SI, Moore, A, Kane, E, Wang, Z, Panagiotou, OA, Teras, LR, Monnereau, A, Wong Doo, N, Machiela, MJ, Skibola, CF, Slager, SL, Salles, G, Camp, NJ, Bracci, PM, Nieters, A, Vermeulen, RCH, Vijai, J, Smedby, KE, Zhang, Y, Vajdic, CM, Cozen, W, Spinelli, JJ, Hjalgrim, H, Giles, GG, Link, BK, Clavel, J, Arslan, AA, Purdue, MP, Tinker, LF, Albanes, D, Ferri, GM, Habermann, TM, Adami, H-O, Becker, N, Benavente, Y, Bisanzi, S, Boffetta, P, Brennan, P, Brooks-Wilson, AR, Canzian, F, Conde, L, Cox, DG, Curtin, K, Foretova, L, Gapstur, SM, Ghesquieres, H, Glenn, M, Glimelius, B, Jackson, RD, Lan, Q, Liebow, M, Maynadie, M, McKay, J, Melbye, M, Miligi, L, Milne, RL, Molina, TJ, Morton, LM, North, KE, Offit, K, Padoan, M, Patel, AV, Piro, S, Ravichandran, V, Riboli, E, de Sanjose, S, Severson, RK, Southey, MC, Staines, A, Stewart, C, Travis, RC, Weiderpass, E, Weinstein, S, Zheng, T, Chanock, SJ, Chatterjee, N, Rothman, N, Birmann, BM, Cerhan, JR, and Berndt, SI

Abstract

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.

Published
2020

5. Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

Author

Zhang, YD, Hurson, AN, Zhang, H, Choudhury, PP, Easton, DF, Milne, RL, Simard, J, Hall, P, Michailidou, K, Dennis, J, Schmidt, MK, Chang-Claude, J, Gharahkhani, P, Whiteman, D, Campbell, PT, Hoffmeister, M, Jenkins, M, Peters, U, Hsu, L, Gruber, SB, Casey, G, Schmit, SL, O'Mara, TA, Spurdle, AB, Thompson, DJ, Tomlinson, I, De Vivo, I, Landi, MT, Law, MH, Iles, MM, Demenais, F, Kumar, R, MacGregor, S, Bishop, DT, Ward, SV, Bondy, ML, Houlston, R, Wiencke, JK, Melin, B, Barnholtz-Sloan, J, Kinnersley, B, Wrensch, MR, Amos, CI, Hung, RJ, Brennan, P, McKay, J, Caporaso, NE, Berndt, SI, Birmann, BM, Camp, NJ, Kraft, P, Rothman, N, Slager, SL, Berchuck, A, Pharoah, PDP, Sellers, TA, Gayther, SA, Pearce, CL, Goode, EL, Schildkraut, JM, Moysich, KB, Amundadottir, LT, Jacobs, EJ, Klein, AP, Petersen, GM, Risch, HA, Stolzenberg-Solomon, RZ, Wolpin, BM, Li, D, Eeles, RA, Haiman, CA, Kote-Jarai, Z, Schumacher, FR, Al Olama, AA, Purdue, MP, Scelo, G, Dalgaard, MD, Greene, MH, Grotmol, T, Kanetsky, PA, McGlynn, KA, Nathanson, KL, Turnbull, C, Wiklund, F, Chanock, SJ, Chatterjee, N, Garcia-Closas, M, Zhang, YD, Hurson, AN, Zhang, H, Choudhury, PP, Easton, DF, Milne, RL, Simard, J, Hall, P, Michailidou, K, Dennis, J, Schmidt, MK, Chang-Claude, J, Gharahkhani, P, Whiteman, D, Campbell, PT, Hoffmeister, M, Jenkins, M, Peters, U, Hsu, L, Gruber, SB, Casey, G, Schmit, SL, O'Mara, TA, Spurdle, AB, Thompson, DJ, Tomlinson, I, De Vivo, I, Landi, MT, Law, MH, Iles, MM, Demenais, F, Kumar, R, MacGregor, S, Bishop, DT, Ward, SV, Bondy, ML, Houlston, R, Wiencke, JK, Melin, B, Barnholtz-Sloan, J, Kinnersley, B, Wrensch, MR, Amos, CI, Hung, RJ, Brennan, P, McKay, J, Caporaso, NE, Berndt, SI, Birmann, BM, Camp, NJ, Kraft, P, Rothman, N, Slager, SL, Berchuck, A, Pharoah, PDP, Sellers, TA, Gayther, SA, Pearce, CL, Goode, EL, Schildkraut, JM, Moysich, KB, Amundadottir, LT, Jacobs, EJ, Klein, AP, Petersen, GM, Risch, HA, Stolzenberg-Solomon, RZ, Wolpin, BM, Li, D, Eeles, RA, Haiman, CA, Kote-Jarai, Z, Schumacher, FR, Al Olama, AA, Purdue, MP, Scelo, G, Dalgaard, MD, Greene, MH, Grotmol, T, Kanetsky, PA, McGlynn, KA, Nathanson, KL, Turnbull, C, Wiklund, F, Chanock, SJ, Chatterjee, N, and Garcia-Closas, M

Abstract

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.

Published
2020

6. Circulating markers of cellular immune activation in prediagnostic blood sample and lung cancer risk in the Lung Cancer Cohort Consortium (LC3)

Author

Huang, JY, Larose, TL, Luu, HN, Wang, R, Fanidi, A, Alcala, K, Stevens, VL, Weinstein, SJ, Albanes, D, Caporaso, NE, Purdue, MP, Ziegler, RG, Freedman, ND, Lan, Q, Prentice, RL, Pettinger, M, Thomson, CA, Cai, Q, Wu, J, Blot, WJ, Shu, X-O, Zheng, W, Arslan, AA, Zeleniuch-Jacquotte, A, Le Marchand, L, Wilkens, LR, Haiman, CA, Zhang, X, Stampfer, MJ, Giles, GG, Hodge, AM, Severi, G, Johansson, M, Grankvist, K, Langhammer, A, Hveem, K, Xiang, Y-B, Li, H-L, Gao, Y-T, Visvanathan, K, Ueland, PM, Midttun, O, Ulvi, A, Buring, JE, Lee, I-M, SeSS, HD, Gaziano, JM, Manjer, J, Relton, C, Koh, W-P, Brennan, P, Yuan, J-M, Han, J, Huang, JY, Larose, TL, Luu, HN, Wang, R, Fanidi, A, Alcala, K, Stevens, VL, Weinstein, SJ, Albanes, D, Caporaso, NE, Purdue, MP, Ziegler, RG, Freedman, ND, Lan, Q, Prentice, RL, Pettinger, M, Thomson, CA, Cai, Q, Wu, J, Blot, WJ, Shu, X-O, Zheng, W, Arslan, AA, Zeleniuch-Jacquotte, A, Le Marchand, L, Wilkens, LR, Haiman, CA, Zhang, X, Stampfer, MJ, Giles, GG, Hodge, AM, Severi, G, Johansson, M, Grankvist, K, Langhammer, A, Hveem, K, Xiang, Y-B, Li, H-L, Gao, Y-T, Visvanathan, K, Ueland, PM, Midttun, O, Ulvi, A, Buring, JE, Lee, I-M, SeSS, HD, Gaziano, JM, Manjer, J, Relton, C, Koh, W-P, Brennan, P, Yuan, J-M, and Han, J

Abstract

Cell-mediated immune suppression may play an important role in lung carcinogenesis. We investigated the associations for circulating levels of tryptophan, kynurenine, kynurenine:tryptophan ratio (KTR), quinolinic acid (QA) and neopterin as markers of immune regulation and inflammation with lung cancer risk in 5,364 smoking-matched case-control pairs from 20 prospective cohorts included in the international Lung Cancer Cohort Consortium. All biomarkers were quantified by mass spectrometry-based methods in serum/plasma samples collected on average 6 years before lung cancer diagnosis. Odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with individual biomarkers were calculated using conditional logistic regression with adjustment for circulating cotinine. Compared to the lowest quintile, the highest quintiles of kynurenine, KTR, QA and neopterin were associated with a 20-30% higher risk, and tryptophan with a 15% lower risk of lung cancer (all ptrend < 0.05). The strongest associations were seen for current smokers, where the adjusted ORs (95% CIs) of lung cancer for the highest quintile of KTR, QA and neopterin were 1.42 (1.15-1.75), 1.42 (1.14-1.76) and 1.45 (1.13-1.86), respectively. A stronger association was also seen for KTR and QA with risk of lung squamous cell carcinoma followed by adenocarcinoma, and for lung cancer diagnosed within the first 2 years after blood draw. This study demonstrated that components of the tryptophan-kynurenine pathway with immunomodulatory effects are associated with risk of lung cancer overall, especially for current smokers. Further research is needed to evaluate the role of these biomarkers in lung carcinogenesis and progression.

Published
2019

7. Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes

Author

Din, L, Sheikh, M, Kosaraju, N, Smedby, KE, Bernatsky, S, Berndt, S, Skibola, CF, Nieters, A, Wang, S, McKay, JD, Cocco, P, Maynadie, M, Foretova, L, Staines, A, Mack, TM, de Sanjose, S, Vyse, TJ, Padyukov, L, Monnereau, A, Arslan, AA, Moore, A, Brooks-Wilson, AR, Novak, AJ, Glimelius, B, Birmann, BM, Link, BK, Stewart, C, Vajdic, CM, Haioun, C, Magnani, C, Conti, D, Cox, DG, Casabonne, D, Albanes, D, Kane, E, Roman, E, Muzi, G, Salles, G, Giles, GG, Adami, H-O, Ghesquieres, H, De Vivo, I, Clavel, J, Cerhan, JR, Spinelli, JJ, Hofmann, J, Vijai, J, Curtin, K, Costenbader, KH, Onel, K, Offit, K, Teras, LR, Morton, L, Conde, L, Miligi, L, Melbye, M, Ennas, MG, Liebow, M, Purdue, MP, Glenn, M, Southey, MC, Din, M, Rothman, N, Camp, NJ, Doo, NW, Becker, N, Pradhan, N, Bracci, PM, Boffetta, P, Vineis, P, Brennan, P, Kraft, P, Lan, Q, Severson, RK, Vermeulen, RCH, Milne, RL, Kaaks, R, Travis, RC, Weinstein, SJ, Chanock, SJ, Ansell, SM, Slager, SL, Zheng, T, Zhang, Y, Benavente, Y, Taub, Z, Madireddy, L, Gourraud, P-A, Oksenberg, JR, Cozen, W, Hjalgrim, H, Khankhanian, P, Din, L, Sheikh, M, Kosaraju, N, Smedby, KE, Bernatsky, S, Berndt, S, Skibola, CF, Nieters, A, Wang, S, McKay, JD, Cocco, P, Maynadie, M, Foretova, L, Staines, A, Mack, TM, de Sanjose, S, Vyse, TJ, Padyukov, L, Monnereau, A, Arslan, AA, Moore, A, Brooks-Wilson, AR, Novak, AJ, Glimelius, B, Birmann, BM, Link, BK, Stewart, C, Vajdic, CM, Haioun, C, Magnani, C, Conti, D, Cox, DG, Casabonne, D, Albanes, D, Kane, E, Roman, E, Muzi, G, Salles, G, Giles, GG, Adami, H-O, Ghesquieres, H, De Vivo, I, Clavel, J, Cerhan, JR, Spinelli, JJ, Hofmann, J, Vijai, J, Curtin, K, Costenbader, KH, Onel, K, Offit, K, Teras, LR, Morton, L, Conde, L, Miligi, L, Melbye, M, Ennas, MG, Liebow, M, Purdue, MP, Glenn, M, Southey, MC, Din, M, Rothman, N, Camp, NJ, Doo, NW, Becker, N, Pradhan, N, Bracci, PM, Boffetta, P, Vineis, P, Brennan, P, Kraft, P, Lan, Q, Severson, RK, Vermeulen, RCH, Milne, RL, Kaaks, R, Travis, RC, Weinstein, SJ, Chanock, SJ, Ansell, SM, Slager, SL, Zheng, T, Zhang, Y, Benavente, Y, Taub, Z, Madireddy, L, Gourraud, P-A, Oksenberg, JR, Cozen, W, Hjalgrim, H, and Khankhanian, P

Abstract

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.

Published
2019

8. Circulating high sensitivity C reactive protein concentrations and lung cancer risk: a nested case-control study within the Lung Cancer Cohort Consortium

Author

Muller, D, Laros, TL, Hodge, A, Guida, F, Langhammer, A, Grankvist, K, Meyer, K, Cai, Q, Arslan, AA, Zeleniuch-Jacquotte, A, Albanes, D, Giles, GG, Sesso, HD, Lee, I-M, Gaziano, JM, Yuan, J-M, Hoffman Bolton, J, Buring, JE, Visvanathan, K, Le Marchand, L, Purdue, MP, Caporaso, NE, Midttun, Ø, Ueland, PM, Prentice, RL, Weinstein, SJ, Stevens, VL, Zheng, W, Blot, WJ, Shu, X-O, Zhang, X, Xiang, Y-B, Koh, W-P, Hveem, K, Thompson, CA, Pettinger, M, Engstrom, G, Brunnstrom, H, Milne, RL, Stampfer, M, Han, J, Johansson, M, Brennan, P, Severi, G, and Cancer Research UK

Subjects
Science & Technology, Medicine, General & Internal, VITAMIN STATUS, General & Internal Medicine, PRIMARY-CARE, cardiovascular diseases, METABOLISM, CRP, Life Sciences & Biomedicine, INFLAMMATION MARKERS, POINT
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

Published
2018

9. Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Author

Scelo, G, Purdue, MP, Brown, KM, Johansson, M, Wang, Z, Eckel-Passow, JE, Ye, Y, Hoffman, JN, Choi, J, Foll, M, Gaborieau, V, Machiela, MJ, Colli, LM, Li, P, Sampson, JN, Abedi-Ardekani, B, Besse, C, Blanche, H, Boland, A, Burdette, L, Charbrier, A, Durand, G, Le Calvez-Kelm, F, Prokhortchouk, E, Robinot, N, Skyrabin, KG, Wozniak, MB, Yeager, M, Basta-Jovanovich, G, Dzamic, Z, Foretova, L, Holcatova, I, Janout, V, Mates, D, Mukeriya, A, Rascu, S, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Szeszenia-Dabrowska, N, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Baglietto, L, Boeing, H, Khaw, K-T, Weiderpass, E, Ljungberg, B, Sitaram, RT, Bruinsma, F, Jordan, SJ, Severi, G, Winship, I, Hveem, K, Vatten, LJ, Fletcher, T, Koppova, K, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Pharoah, P, Andreotti, G, Beane Freeman, LE, Koutros, S, Albanes, D, Mannisto, S, Weinstein, S, Clark, PE, Edwards, TL, Lipworth, L, Gapstur, SM, Stevens, VL, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Kraft, P, Preston, MA, Wilson, KM, Gaziano, JM, Sesso, HD, Black, A, Freedman, ND, Huang, WY, Anema, JG, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Teh, BT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Buring, J, Lee, I-M, Chow, W-H, Moore, LE, Wood, C, Eisen, T, Henrion, M, Larkin, J, Barman, P, Leibovich, BC, Choueiri, TK, Lathrop, GM, Rothman, N, Deleuze, J-F, McKay, JD, Parker, AS, Wu, X, Houlston, RS, Brennan, P, and Chanock, SJ

Abstract

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

Published
2017

10. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukemia

Author

Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, JJ, Kraft, P, Grazia Ennas, M, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, De Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, R, and Slager, S

Subjects
RISK, CHROMATIN, Science & Technology, LOCI, VARIANTS, DISEASE, Multidisciplinary Sciences, TRANSCRIPTION FACTORS, MD Multidisciplinary, IMPUTATION, Science & Technology - Other Topics, BREAST-CANCER, COMMON VARIATION, METAANALYSIS
Abstract

Several chronic lymphocytic leukemia (CLL) susceptibility loci have been reported, however much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1000 Genomes and UK10K data, totaling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P = 5.04x10-13), 1q42.13 (rs41271473, P = 1.06x10-10), 4q24 (rs71597109, P = 1.37x10-10), 4q35.1 (rs57214277, P = 3.69x10-8), 6p21.31 (rs3800461, P = 1.97x10-8), 11q23.2 (rs61904987, P = 2.64x10-11), 18q21.1 (rs1036935, P = 3.27x10-8), 19p13.3 (rs7254272, P = 4.67x10-8) and 22q13.33 (rs140522, P = 2.70x10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for key determinants of B-cell development and immune response.

Published
2016

11. Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

Author

Santo, L, Teras, LR, Giles, GG, Weinstein, SJ, Albanes, D, Wang, Y, Pfeiffer, RM, Lan, Q, Rothman, N, Birmann, BM, Colditz, GA, Pollak, MN, Purdue, MP, Hofmann, JN, Santo, L, Teras, LR, Giles, GG, Weinstein, SJ, Albanes, D, Wang, Y, Pfeiffer, RM, Lan, Q, Rothman, N, Birmann, BM, Colditz, GA, Pollak, MN, Purdue, MP, and Hofmann, JN

Abstract

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men.

Published
2017

12. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Author

Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Lan, Q, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, JJ, Kraft, P, Ennas, MG, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, de Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, R, Slager, SL, Law, PJ, Berndt, SI, Speedy, HE, Camp, NJ, Sava, GP, Skibola, CF, Holroyd, A, Joseph, V, Sunter, NJ, Nieters, A, Bea, S, Monnereau, A, Martin-Garcia, D, Goldin, LR, Clot, G, Teras, LR, Quintela, I, Birmann, BM, Jayne, S, Cozen, W, Majid, A, Smedby, KE, Lan, Q, Dearden, C, Brooks-Wilson, AR, Hall, AG, Purdue, MP, Mainou-Fowler, T, Vajdic, CM, Jackson, GH, Cocco, P, Marr, H, Zhang, Y, Zheng, T, Giles, GG, Lawrence, C, Call, TG, Liebow, M, Melbye, M, Glimelius, B, Mansouri, L, Glenn, M, Curtin, K, Diver, WR, Link, BK, Conde, L, Bracci, PM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Boffetta, P, Brennan, P, Maynadie, M, McKay, J, Albanes, D, Weinstein, S, Wang, Z, Caporaso, NE, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Vermeulen, RCH, Southey, MC, Milne, RL, Clavel, J, Topka, S, Spinelli, JJ, Kraft, P, Ennas, MG, Summerfield, G, Ferri, GM, Harris, RJ, Miligi, L, Pettitt, AR, North, KE, Allsup, DJ, Fraumeni, JF, Bailey, JR, Offit, K, Pratt, G, Hjalgrim, H, Pepper, C, Chanock, SJ, Fegan, C, Rosenquist, R, de Sanjose, S, Carracedo, A, Dyer, MJS, Catovsky, D, Campo, E, Cerhan, JR, Allan, JM, Rothman, N, Houlston, R, and Slager, SL

Abstract

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10-13), 1q42.13 (rs41271473, P=1.06 × 10-10), 4q24 (rs71597109, P=1.37 × 10-10), 4q35.1 (rs57214277, P=3.69 × 10-8), 6p21.31 (rs3800461, P=1.97 × 10-8), 11q23.2 (rs61904987, P=2.64 × 10-11), 18q21.1 (rs1036935, P=3.27 × 10-8), 19p13.3 (rs7254272, P=4.67 × 10-8) and 22q13.33 (rs140522, P=2.70 × 10-9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response.

Published
2017

13. Lupus-related single nucleotide polymorphisms and risk of diffuse large B-cell lymphoma

Author

Bernatsky, S, Garcia, HAV, Spinelli, JJ, Gaffney, P, Smedby, KE, Ramsey-Goldman, R, Wang, SS, Adami, H-O, Albanes, D, Angelucci, E, Ansell, SM, Asmann, YW, Becker, N, Benavente, Y, Berndt, SI, Bertrand, KA, Birmann, BM, Boeing, H, Boffetta, P, Bracci, PM, Brennan, P, Brooks-Wilson, AR, Cerhan, JR, Chanock, SJ, Clavel, J, Conde, L, Cotenbader, KH, Cox, DG, Cozen, W, Crouch, S, De Roos, AJ, de Sanjose, S, Di Lollo, S, Diver, WR, Dogan, A, Foretova, L, Ghesquieres, H, Giles, GG, Glimelius, B, Habermann, TM, Haioun, C, Hartge, P, Hjalgrim, H, Holford, TR, Holly, EA, Jackson, RD, Kaaks, R, Kane, E, Kelly, RS, Klein, RJ, Kraft, P, Kricker, A, Lan, Q, Lawrence, C, Liebow, M, Lightfoot, T, Link, BK, Maynadie, M, Mckay, J, Melbye, M, Molina, TJ, Monnereau, A, Morton, LM, Nieters, A, North, KE, Novak, AJ, Offit, K, Purdue, MP, Rais, M, Riby, J, Roman, E, Rothman, N, Salles, G, Severi, G, Severson, RK, Skibola, CF, Slager, SL, Smith, A, Smith, MT, Southey, MC, Staines, A, Teras, LR, Thompson, CA, Tilly, H, Tinker, LF, Tjonneland, A, Turner, J, Vajdic, CM, Vermeulen, RCH, Vijai, J, Vineis, P, Virtamo, J, Wang, Z, Weinstein, S, Witzig, TE, Zelenetz, A, Zeleniuch-Jacquotte, A, Zhang, Y, Zheng, T, Zucca, M, Clarke, AE, Bernatsky, S, Garcia, HAV, Spinelli, JJ, Gaffney, P, Smedby, KE, Ramsey-Goldman, R, Wang, SS, Adami, H-O, Albanes, D, Angelucci, E, Ansell, SM, Asmann, YW, Becker, N, Benavente, Y, Berndt, SI, Bertrand, KA, Birmann, BM, Boeing, H, Boffetta, P, Bracci, PM, Brennan, P, Brooks-Wilson, AR, Cerhan, JR, Chanock, SJ, Clavel, J, Conde, L, Cotenbader, KH, Cox, DG, Cozen, W, Crouch, S, De Roos, AJ, de Sanjose, S, Di Lollo, S, Diver, WR, Dogan, A, Foretova, L, Ghesquieres, H, Giles, GG, Glimelius, B, Habermann, TM, Haioun, C, Hartge, P, Hjalgrim, H, Holford, TR, Holly, EA, Jackson, RD, Kaaks, R, Kane, E, Kelly, RS, Klein, RJ, Kraft, P, Kricker, A, Lan, Q, Lawrence, C, Liebow, M, Lightfoot, T, Link, BK, Maynadie, M, Mckay, J, Melbye, M, Molina, TJ, Monnereau, A, Morton, LM, Nieters, A, North, KE, Novak, AJ, Offit, K, Purdue, MP, Rais, M, Riby, J, Roman, E, Rothman, N, Salles, G, Severi, G, Severson, RK, Skibola, CF, Slager, SL, Smith, A, Smith, MT, Southey, MC, Staines, A, Teras, LR, Thompson, CA, Tilly, H, Tinker, LF, Tjonneland, A, Turner, J, Vajdic, CM, Vermeulen, RCH, Vijai, J, Vineis, P, Virtamo, J, Wang, Z, Weinstein, S, Witzig, TE, Zelenetz, A, Zeleniuch-Jacquotte, A, Zhang, Y, Zheng, T, Zucca, M, and Clarke, AE

Abstract

OBJECTIVE: Determinants of the increased risk of diffuse large B-cell lymphoma (DLBCL) in SLE are unclear. Using data from a recent lymphoma genome-wide association study (GWAS), we assessed whether certain lupus-related single nucleotide polymorphisms (SNPs) were also associated with DLBCL. METHODS: GWAS data on European Caucasians from the International Lymphoma Epidemiology Consortium (InterLymph) provided a total of 3857 DLBCL cases and 7666 general-population controls. Data were pooled in a random-effects meta-analysis. RESULTS: Among the 28 SLE-related SNPs investigated, the two most convincingly associated with risk of DLBCL included the CD40 SLE risk allele rs4810485 on chromosome 20q13 (OR per risk allele=1.09, 95% CI 1.02 to 1.16, p=0.0134), and the HLA SLE risk allele rs1270942 on chromosome 6p21.33 (OR per risk allele=1.17, 95% CI 1.01 to 1.36, p=0.0362). Of additional possible interest were rs2205960 and rs12537284. The rs2205960 SNP, related to a cytokine of the tumour necrosis factor superfamily TNFSF4, was associated with an OR per risk allele of 1.07, 95% CI 1.00 to 1.16, p=0.0549. The OR for the rs12537284 (chromosome 7q32, IRF5 gene) risk allele was 1.08, 95% CI 0.99 to 1.18, p=0.0765. CONCLUSIONS: These data suggest several plausible genetic links between DLBCL and SLE.

Published
2017

14. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome

Author

Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-de-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreon, T, Chaffee, KG, Chang, I-S, Chatterjee, N, Chen, C, Chen, K, Chung, CC, Cook, LS, Bou, MC, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, J-H, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, Y-T, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, Y-C, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, A, Lan, Q, Landi, MT, Le Marchand, L, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patino-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, Y-L, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Setiawan, VW, Severi, G, Shen, H, Sheng, X, Shin, M-H, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, Z-Z, Taylor, PR, Teras, LR, Tobias, GS, Van den Berg, D, Visvanathan, K, Wacholder, S, Wang, J-C, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, Y-L, Wunder, JS, Xia, L, Yang, HP, Yang, P-C, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M, Chanock, SJ, Machiela, MJ, Zhou, W, Karlins, E, Sampson, JN, Freedman, ND, Yang, Q, Hicks, B, Dagnall, C, Hautman, C, Jacobs, KB, Abnet, CC, Aldrich, MC, Amos, C, Amundadottir, LT, Arslan, AA, Beane-Freeman, LE, Berndt, SI, Black, A, Blot, WJ, Bock, CH, Bracci, PM, Brinton, LA, Bueno-de-Mesquita, HB, Burdett, L, Buring, JE, Butler, MA, Canzian, F, Carreon, T, Chaffee, KG, Chang, I-S, Chatterjee, N, Chen, C, Chen, K, Chung, CC, Cook, LS, Bou, MC, Cullen, M, Davis, FG, De Vivo, I, Ding, T, Doherty, J, Duell, EJ, Epstein, CG, Fan, J-H, Figueroa, JD, Fraumeni, JF, Friedenreich, CM, Fuchs, CS, Gallinger, S, Gao, Y-T, Gapstur, SM, Garcia-Closas, M, Gaudet, MM, Gaziano, JM, Giles, GG, Gillanders, EM, Giovannucci, EL, Goldin, L, Goldstein, AM, Haiman, CA, Hallmans, G, Hankinson, SE, Harris, CC, Henriksson, R, Holly, EA, Hong, Y-C, Hoover, RN, Hsiung, CA, Hu, N, Hu, W, Hunter, DJ, Hutchinson, A, Jenab, M, Johansen, C, Khaw, K-T, Kim, HN, Kim, YH, Kim, YT, Klein, AP, Klein, R, Koh, W-P, Kolonel, LN, Kooperberg, C, Kraft, P, Krogh, V, Kurtz, RC, LaCroix, A, Lan, Q, Landi, MT, Le Marchand, L, Li, D, Liang, X, Liao, LM, Lin, D, Liu, J, Lissowska, J, Lu, L, Magliocco, AM, Malats, N, Matsuo, K, McNeill, LH, McWilliams, RR, Melin, BS, Mirabello, L, Moore, L, Olson, SH, Orlow, I, Park, JY, Patino-Garcia, A, Peplonska, B, Peters, U, Petersen, GM, Pooler, L, Prescott, J, Prokunina-Olsson, L, Purdue, MP, Qiao, Y-L, Rajaraman, P, Real, FX, Riboli, E, Risch, HA, Rodriguez-Santiago, B, Ruder, AM, Savage, SA, Schumacher, F, Schwartz, AG, Schwartz, KL, Seow, A, Setiawan, VW, Severi, G, Shen, H, Sheng, X, Shin, M-H, Shu, X-O, Silverman, DT, Spitz, MR, Stevens, VL, Stolzenberg-Solomon, R, Stram, D, Tang, Z-Z, Taylor, PR, Teras, LR, Tobias, GS, Van den Berg, D, Visvanathan, K, Wacholder, S, Wang, J-C, Wang, Z, Wentzensen, N, Wheeler, W, White, E, Wiencke, JK, Wolpin, BM, Wong, MP, Wu, C, Wu, T, Wu, X, Wu, Y-L, Wunder, JS, Xia, L, Yang, HP, Yang, P-C, Yu, K, Zanetti, KA, Zeleniuch-Jacquotte, A, Zheng, W, Zhou, B, Ziegler, RG, Perez-Jurado, LA, Caporaso, NE, Rothman, N, Tucker, M, Dean, MC, Yeager, M, and Chanock, SJ

Abstract

To investigate large structural clonal mosaicism of chromosome X, we analysed the SNP microarray intensity data of 38,303 women from cancer genome-wide association studies (20,878 cases and 17,425 controls) and detected 124 mosaic X events >2 Mb in 97 (0.25%) women. Here we show rates for X-chromosome mosaicism are four times higher than mean autosomal rates; X mosaic events more often include the entire chromosome and participants with X events more likely harbour autosomal mosaic events. X mosaicism frequency increases with age (0.11% in 50-year olds; 0.45% in 75-year olds), as reported for Y and autosomes. Methylation array analyses of 33 women with X mosaicism indicate events preferentially involve the inactive X chromosome. Our results provide further evidence that the sex chromosomes undergo mosaic events more frequently than autosomes, which could have implications for understanding the underlying mechanisms of mosaic events and their possible contribution to risk for chronic diseases.

Published
2016

15. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

Author

Berndt, SI, Camp, NJ, Skibola, CF, Vijai, J, Wang, Z, Gu, J, Nieters, A, Kelly, RS, Smedby, KE, Monnereau, A, Cozen, W, Cox, A, Wang, SS, Lan, Q, Teras, LR, Machado, M, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Vajdic, CM, Cocco, P, Zhang, Y, Giles, GG, Zeleniuch-Jacquotte, A, Lawrence, C, Montalvan, R, Burdett, L, Hutchinson, A, Ye, Y, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Cunningham, JM, Allmer, C, Hjalgrim, H, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Arnett, DK, Zhi, D, Leach, JM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Sala, N, Casabonne, D, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Chaffee, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Leis, JF, Weinberg, JB, Caporaso, NE, Norman, AD, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Southey, MC, Milne, RL, Albanese, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Villano, DJ, Maria, A, Spinelli, JJ, Gascoyne, RD, Connors, JM, Bertrand, KA, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Ma, B, Huang, J, Crouch, S, Park, J-H, Chatterjee, N, North, KE, Snowden, JA, Wright, J, Fraumeni, JF, Offit, K, Wu, X, de Sanjose, S, Cerhan, JR, Chanock, SJ, Rothman, N, Slager, SL, Berndt, SI, Camp, NJ, Skibola, CF, Vijai, J, Wang, Z, Gu, J, Nieters, A, Kelly, RS, Smedby, KE, Monnereau, A, Cozen, W, Cox, A, Wang, SS, Lan, Q, Teras, LR, Machado, M, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Vajdic, CM, Cocco, P, Zhang, Y, Giles, GG, Zeleniuch-Jacquotte, A, Lawrence, C, Montalvan, R, Burdett, L, Hutchinson, A, Ye, Y, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Cunningham, JM, Allmer, C, Hjalgrim, H, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Arnett, DK, Zhi, D, Leach, JM, Holly, EA, Jackson, RD, Tinker, LF, Benavente, Y, Sala, N, Casabonne, D, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Chaffee, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Leis, JF, Weinberg, JB, Caporaso, NE, Norman, AD, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Southey, MC, Milne, RL, Albanese, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Villano, DJ, Maria, A, Spinelli, JJ, Gascoyne, RD, Connors, JM, Bertrand, KA, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Ma, B, Huang, J, Crouch, S, Park, J-H, Chatterjee, N, North, KE, Snowden, JA, Wright, J, Fraumeni, JF, Offit, K, Wu, X, de Sanjose, S, Cerhan, JR, Chanock, SJ, Rothman, N, and Slager, SL

Abstract

Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10(-11)), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10(-8)) and 3q28 (rs9815073, LPP, P=3.62 × 10(-8)), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10(-11)) in the combined analysis. We find suggestive evidence (P<5 × 10(-7)) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10(-8)) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10(-7)). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility.

Published
2016

16. Genome-wide association study of renal cell carcinoma identifiestwo susceptibility loci on 2p21 and 11q13.3

Author

Purdue MP, Johansson M, Zelenika D, Toro JR, Scelo G, Moore LE, Prokhortchouk E, Wu X, Kiemeney LA, Gaborieau V, Jacobs KB, Chow WH, Zaridze D, Matveev V, Lubinski J, Trubicka J, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Bucur A, Bencko V, Foretova L, Janout V, Boffetta P, Colt JS, Davis FG, Schwartz KL, Banks RE, Selby PJ, Harnden P, Berg CD, Hsing AW, Grubb RL 3rd, Boeing H, Vineis P, Clavel Chapelon F, Palli D, Tumino R, Krogh V, Duell EJ, Quirós JR, Sanchez MJ, Navarro C, Ardanaz E, Dorronsoro M, Khaw KT, Allen NE, Bueno de Mesquita HB, Peeters PH, Trichopoulos D, Linseisen J, Ljungberg B, Overvad K, Tjønneland A, Romieu I, Riboli E, Mukeria A, Shangina O, Stevens VL, Thun MJ, Diver WR, Gapstur SM, Pharoah PD, Easton DF, Albanes D, Weinstein SJ, Virtamo J, Vatten L, Hveem K, Njølstad I, Tell GS, Stoltenberg C, Kumar R, Koppova K, Cussenot O, Benhamou S, Oosterwijk E, Vermeulen SH, Aben KK, van der Marel SL, Ye Y, Wood CG, Pu X, Mazur AM, Boulygina ES, Chekanov NN, Foglio M, Lechner D, Gut I, Heath S, Blanche H, Hutchinson A, Thomas G, Wang Z, Yeager M, Fraumeni JF Jr, Skryabin KG, McKay JD, Rothman N, Chanock SJ, Lathrop M, Brennan P., PANICO, SALVATORE, Purdue, Mp, Johansson, M, Zelenika, D, Toro, Jr, Scelo, G, Moore, Le, Prokhortchouk, E, Wu, X, Kiemeney, La, Gaborieau, V, Jacobs, Kb, Chow, Wh, Zaridze, D, Matveev, V, Lubinski, J, Trubicka, J, Szeszenia Dabrowska, N, Lissowska, J, Rudnai, P, Fabianova, E, Bucur, A, Bencko, V, Foretova, L, Janout, V, Boffetta, P, Colt, J, Davis, Fg, Schwartz, Kl, Banks, Re, Selby, Pj, Harnden, P, Berg, Cd, Hsing, Aw, Grubb RL, 3rd, Boeing, H, Vineis, P, Clavel Chapelon, F, Palli, D, Tumino, R, Krogh, V, Panico, Salvatore, Duell, Ej, Quirós, Jr, Sanchez, Mj, Navarro, C, Ardanaz, E, Dorronsoro, M, Khaw, Kt, Allen, Ne, Bueno de Mesquita, Hb, Peeters, Ph, Trichopoulos, D, Linseisen, J, Ljungberg, B, Overvad, K, Tjønneland, A, Romieu, I, Riboli, E, Mukeria, A, Shangina, O, Stevens, Vl, Thun, Mj, Diver, Wr, Gapstur, Sm, Pharoah, Pd, Easton, Df, Albanes, D, Weinstein, Sj, Virtamo, J, Vatten, L, Hveem, K, Njølstad, I, Tell, G, Stoltenberg, C, Kumar, R, Koppova, K, Cussenot, O, Benhamou, S, Oosterwijk, E, Vermeulen, Sh, Aben, Kk, van der Marel, Sl, Ye, Y, Wood, Cg, Pu, X, Mazur, Am, Boulygina, E, Chekanov, Nn, Foglio, M, Lechner, D, Gut, I, Heath, S, Blanche, H, Hutchinson, A, Thomas, G, Wang, Z, Yeager, M, Fraumeni JF, Jr, Skryabin, Kg, Mckay, Jd, Rothman, N, Chanock, Sj, Lathrop, M, and Brennan, P.

Published
2011

17. Association between Class III Obesity (BMI of 40-59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies

Author

Kitahara, CM, Flint, AJ, Berrington de Gonzalez, A, Bernstein, L, Brotzman, M, MacInnis, RJ, Moore, SC, Robien, K, Rosenberg, PS, Singh, PN, Weiderpass, E, Adami, HO, Anton-Culver, H, Ballard-Barbash, R, Buring, JE, Freedman, DM, Fraser, GE, Beane Freeman, LE, Gapstur, SM, Gaziano, JM, Giles, GG, Håkansson, N, Hoppin, JA, Hu, FB, Koenig, K, Linet, MS, Park, Y, Patel, AV, Purdue, MP, Schairer, C, Sesso, HD, Visvanathan, K, White, E, Wolk, A, Zeleniuch-Jacquotte, A, and Hartge, P

Abstract

Background:The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity.Methods and Findings:In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7.3), 8.9 (95% CI: 7.4-10.4), 9.8 (95% CI: 7.4-12.2), and 13.7 (95% CI: 10.5-16.9) y of life lost. A limitation was that BMI was mainly ascertained by self-report.Conclusions:Class III obesity is associated with substantially elevated rates of total mortality, with most of the excess deaths due to heart disease, cancer, and diabetes, and major reductions in life expectancy compared with normal weight.Please see later in the article for the Editors' Summary.

Published
2014

18. A genome-wide association study of marginal zone lymphoma shows association to the HLA region

Author

Vijai, J, Wang, Z, Berndt, SI, Skibola, CF, Slager, SL, de Sanjose, S, Melbye, M, Glimelius, B, Bracci, PM, Conde, L, Birmann, BM, Wang, SS, Brooks-Wilson, AR, Lan, Q, de Bakker, PIW, Vermeulen, RCH, Portlock, C, Ansell, SM, Link, BK, Riby, J, North, KE, Gu, J, Hjalgrim, H, Cozen, W, Becker, N, Teras, LR, Spinelli, JJ, Turner, J, Zhang, Y, Purdue, MP, Giles, GG, Kelly, RS, Zeleniuch-Jacquotte, A, Ennas, MG, Monnereau, A, Bertrand, KA, Albanes, D, Lightfoot, T, Yeager, M, Chung, CC, Burdett, L, Hutchinson, A, Lawrence, C, Montalvan, R, Liang, L, Huang, J, Ma, B, Villano, DJ, Maria, A, Corines, M, Thomas, T, Novak, AJ, Dogan, A, Liebow, M, Thompson, CA, Witzig, TE, Habermann, TM, Weiner, GJ, Smith, MT, Holly, EA, Jackson, RD, Tinker, LF, Ye, Y, Adami, H-O, Smedby, KE, De Roos, AJ, Hartge, P, Morton, LM, Severson, RK, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Mckay, J, Staines, A, Diver, WR, Vajdic, CM, Armstrong, BK, Kricker, A, Zheng, T, Holford, TR, Severi, G, Vineis, P, Ferri, GM, Ricco, R, Miligi, L, Clavel, J, Giovannucci, E, Kraft, P, Virtamo, J, Smith, A, Kane, E, Roman, E, Chiu, BCH, Fraumeni, JF, Wu, X, Cerhan, JR, Offit, K, Chanock, SJ, Rothman, N, Nieters, A, Vijai, J, Wang, Z, Berndt, SI, Skibola, CF, Slager, SL, de Sanjose, S, Melbye, M, Glimelius, B, Bracci, PM, Conde, L, Birmann, BM, Wang, SS, Brooks-Wilson, AR, Lan, Q, de Bakker, PIW, Vermeulen, RCH, Portlock, C, Ansell, SM, Link, BK, Riby, J, North, KE, Gu, J, Hjalgrim, H, Cozen, W, Becker, N, Teras, LR, Spinelli, JJ, Turner, J, Zhang, Y, Purdue, MP, Giles, GG, Kelly, RS, Zeleniuch-Jacquotte, A, Ennas, MG, Monnereau, A, Bertrand, KA, Albanes, D, Lightfoot, T, Yeager, M, Chung, CC, Burdett, L, Hutchinson, A, Lawrence, C, Montalvan, R, Liang, L, Huang, J, Ma, B, Villano, DJ, Maria, A, Corines, M, Thomas, T, Novak, AJ, Dogan, A, Liebow, M, Thompson, CA, Witzig, TE, Habermann, TM, Weiner, GJ, Smith, MT, Holly, EA, Jackson, RD, Tinker, LF, Ye, Y, Adami, H-O, Smedby, KE, De Roos, AJ, Hartge, P, Morton, LM, Severson, RK, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Mckay, J, Staines, A, Diver, WR, Vajdic, CM, Armstrong, BK, Kricker, A, Zheng, T, Holford, TR, Severi, G, Vineis, P, Ferri, GM, Ricco, R, Miligi, L, Clavel, J, Giovannucci, E, Kraft, P, Virtamo, J, Smith, A, Kane, E, Roman, E, Chiu, BCH, Fraumeni, JF, Wu, X, Cerhan, JR, Offit, K, Chanock, SJ, Rothman, N, and Nieters, A

Abstract

Marginal zone lymphoma (MZL) is the third most common subtype of B-cell non-Hodgkin lymphoma. Here we perform a two-stage GWAS of 1,281 MZL cases and 7,127 controls of European ancestry and identify two independent loci near BTNL2 (rs9461741, P=3.95 × 10(-15)) and HLA-B (rs2922994, P=2.43 × 10(-9)) in the HLA region significantly associated with MZL risk. This is the first evidence that genetic variation in the major histocompatibility complex influences MZL susceptibility.

Published
2015

19. Genome-wide association study identifies multiple susceptibility loci for diffuse large B cell lymphoma

Author

Cerhan, JR, Berndt, SI, Vijai, J, Ghesquieres, H, McKay, J, Wang, SS, Wang, Z, Yeager, M, Conde, L, de Bakker, PIW, Nieters, A, Cox, D, Burdett, L, Monnereau, A, Flowers, CR, De Roos, AJ, Brooks-Wilson, AR, Lan, Q, Severi, G, Melbye, M, Gu, J, Jackson, RD, Kane, E, Teras, LR, Purdue, MP, Vajdic, CM, Spinelli, JJ, Giles, GG, Albanes, D, Kelly, RS, Zucca, M, Bertrand, KA, Zeleniuch-Jacquotte, A, Lawrence, C, Hutchinson, A, Zhi, D, Habermann, TM, Link, BK, Novak, AJ, Dogan, A, Asmann, YW, Liebow, M, Thompson, CA, Ansell, SM, Witzig, TE, Weiner, GJ, Veron, AS, Zelenika, D, Tilly, H, Haioun, C, Molina, TJ, Hjalgrim, H, Glimelius, B, Adami, H-O, Bracci, PM, Riby, J, Smith, MT, Holly, EA, Cozen, W, Hartge, P, Morton, LM, Severson, RK, Tinker, LF, North, KE, Becker, N, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, Lightfoot, T, Crouch, S, Smith, A, Roman, E, Diver, WR, Offit, K, Zelenetz, A, Klein, RJ, Villano, DJ, Zheng, T, Zhang, Y, Holford, TR, Kricker, A, Turner, J, Southey, MC, Clavel, J, Virtamo, J, Weinstein, S, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Vermeulen, RCH, Boeing, H, Tjonneland, A, Angelucci, E, Di Lollo, S, Rais, M, Birmann, BM, Laden, F, Giovannucci, E, Kraft, P, Huang, J, Ma, B, Ye, Y, Chiu, BCH, Sampson, J, Liang, L, Park, J-H, Chung, CC, Weisenburger, DD, Chatterjee, N, Fraumeni, JF, Slager, SL, Wu, X, de Sanjose, S, Smedby, KE, Salles, G, Skibola, CF, Rothman, N, Chanock, SJ, Cerhan, JR, Berndt, SI, Vijai, J, Ghesquieres, H, McKay, J, Wang, SS, Wang, Z, Yeager, M, Conde, L, de Bakker, PIW, Nieters, A, Cox, D, Burdett, L, Monnereau, A, Flowers, CR, De Roos, AJ, Brooks-Wilson, AR, Lan, Q, Severi, G, Melbye, M, Gu, J, Jackson, RD, Kane, E, Teras, LR, Purdue, MP, Vajdic, CM, Spinelli, JJ, Giles, GG, Albanes, D, Kelly, RS, Zucca, M, Bertrand, KA, Zeleniuch-Jacquotte, A, Lawrence, C, Hutchinson, A, Zhi, D, Habermann, TM, Link, BK, Novak, AJ, Dogan, A, Asmann, YW, Liebow, M, Thompson, CA, Ansell, SM, Witzig, TE, Weiner, GJ, Veron, AS, Zelenika, D, Tilly, H, Haioun, C, Molina, TJ, Hjalgrim, H, Glimelius, B, Adami, H-O, Bracci, PM, Riby, J, Smith, MT, Holly, EA, Cozen, W, Hartge, P, Morton, LM, Severson, RK, Tinker, LF, North, KE, Becker, N, Benavente, Y, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, Staines, A, Lightfoot, T, Crouch, S, Smith, A, Roman, E, Diver, WR, Offit, K, Zelenetz, A, Klein, RJ, Villano, DJ, Zheng, T, Zhang, Y, Holford, TR, Kricker, A, Turner, J, Southey, MC, Clavel, J, Virtamo, J, Weinstein, S, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Vermeulen, RCH, Boeing, H, Tjonneland, A, Angelucci, E, Di Lollo, S, Rais, M, Birmann, BM, Laden, F, Giovannucci, E, Kraft, P, Huang, J, Ma, B, Ye, Y, Chiu, BCH, Sampson, J, Liang, L, Park, J-H, Chung, CC, Weisenburger, DD, Chatterjee, N, Fraumeni, JF, Slager, SL, Wu, X, de Sanjose, S, Smedby, KE, Salles, G, Skibola, CF, Rothman, N, and Chanock, SJ

Abstract

Diffuse large B cell lymphoma (DLBCL) is the most common lymphoma subtype and is clinically aggressive. To identify genetic susceptibility loci for DLBCL, we conducted a meta-analysis of 3 new genome-wide association studies (GWAS) and 1 previous scan, totaling 3,857 cases and 7,666 controls of European ancestry, with additional genotyping of 9 promising SNPs in 1,359 cases and 4,557 controls. In our multi-stage analysis, five independent SNPs in four loci achieved genome-wide significance marked by rs116446171 at 6p25.3 (EXOC2; P = 2.33 × 10(-21)), rs2523607 at 6p21.33 (HLA-B; P = 2.40 × 10(-10)), rs79480871 at 2p23.3 (NCOA1; P = 4.23 × 10(-8)) and two independent SNPs, rs13255292 and rs4733601, at 8q24.21 (PVT1; P = 9.98 × 10(-13) and 3.63 × 10(-11), respectively). These data provide substantial new evidence for genetic susceptibility to this B cell malignancy and point to pathways involved in immune recognition and immune function in the pathogenesis of DLBCL.

Published
2014

20. Association between Class III Obesity (BMI of 40-59 kg/m(2)) and Mortality: A Pooled Analysis of 20 Prospective Studies

Author

Khaw, K-T, Kitahara, CM, Flint, AJ, de Gonzalez, AB, Bernstein, L, Brotzman, M, MacInnis, RJ, Moore, SC, Robien, K, Rosenberg, PS, Singh, PN, Weiderpass, E, Adami, HO, Anton-Culver, H, Ballard-Barbash, R, Buring, JE, Freedman, DM, Fraser, GE, Freeman, LEB, Gapstur, SM, Gaziano, JM, Giles, GG, Hakansson, N, Hoppin, JA, Hu, FB, Koenig, K, Linet, MS, Park, Y, Patel, AV, Purdue, MP, Schairer, C, Sesso, HD, Visvanathan, K, White, E, Wolk, A, Zeleniuch-Jacquotte, A, Hartge, P, Khaw, K-T, Kitahara, CM, Flint, AJ, de Gonzalez, AB, Bernstein, L, Brotzman, M, MacInnis, RJ, Moore, SC, Robien, K, Rosenberg, PS, Singh, PN, Weiderpass, E, Adami, HO, Anton-Culver, H, Ballard-Barbash, R, Buring, JE, Freedman, DM, Fraser, GE, Freeman, LEB, Gapstur, SM, Gaziano, JM, Giles, GG, Hakansson, N, Hoppin, JA, Hu, FB, Koenig, K, Linet, MS, Park, Y, Patel, AV, Purdue, MP, Schairer, C, Sesso, HD, Visvanathan, K, White, E, Wolk, A, Zeleniuch-Jacquotte, A, and Hartge, P

Abstract

BACKGROUND: The prevalence of class III obesity (body mass index [BMI]≥40 kg/m2) has increased dramatically in several countries and currently affects 6% of adults in the US, with uncertain impact on the risks of illness and death. Using data from a large pooled study, we evaluated the risk of death, overall and due to a wide range of causes, and years of life expectancy lost associated with class III obesity. METHODS AND FINDINGS: In a pooled analysis of 20 prospective studies from the United States, Sweden, and Australia, we estimated sex- and age-adjusted total and cause-specific mortality rates (deaths per 100,000 persons per year) and multivariable-adjusted hazard ratios for adults, aged 19-83 y at baseline, classified as obese class III (BMI 40.0-59.9 kg/m2) compared with those classified as normal weight (BMI 18.5-24.9 kg/m2). Participants reporting ever smoking cigarettes or a history of chronic disease (heart disease, cancer, stroke, or emphysema) on baseline questionnaires were excluded. Among 9,564 class III obesity participants, mortality rates were 856.0 in men and 663.0 in women during the study period (1976-2009). Among 304,011 normal-weight participants, rates were 346.7 and 280.5 in men and women, respectively. Deaths from heart disease contributed largely to the excess rates in the class III obesity group (rate differences = 238.9 and 132.8 in men and women, respectively), followed by deaths from cancer (rate differences = 36.7 and 62.3 in men and women, respectively) and diabetes (rate differences = 51.2 and 29.2 in men and women, respectively). Within the class III obesity range, multivariable-adjusted hazard ratios for total deaths and deaths due to heart disease, cancer, diabetes, nephritis/nephrotic syndrome/nephrosis, chronic lower respiratory disease, and influenza/pneumonia increased with increasing BMI. Compared with normal-weight BMI, a BMI of 40-44.9, 45-49.9, 50-54.9, and 55-59.9 kg/m2 was associated with an estimated 6.5 (95% CI: 5.7-7

Published
2014

21. Genome-wide association study identifies multiple risk loci for chronic lymphocytic leukemia

Author

Berndt, SI, Skibola, CF, Joseph, V, Camp, NJ, Nieters, A, Wang, Z, Cozen, W, Monnereau, A, Wang, SS, Kelly, RS, Lan, Q, Teras, LR, Chatterjee, N, Chung, CC, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Armstrong, BK, Cocco, P, Zhang, Y, Severi, G, Zeleniuch-Jacquotte, A, Lawrence, C, Burdette, L, Yuenger, J, Hutchinson, A, Jacobs, KB, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Wang, AH, Smedby, KE, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Jones, B, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Holly, EA, Smith, MT, Jackson, RD, Tinker, LF, Benavente, Y, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Rabe, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Lanasa, MC, Spector, LG, Leis, JF, Cunningham, JM, Weinberg, JB, Morrison, VA, Caporaso, NE, Norman, AD, Linet, MS, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Giles, GG, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Offit, K, Zelenetz, A, Klein, RJ, Spinelli, JJ, Bertrand, KA, Laden, F, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Vajdic, CM, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Sampson, J, Crouch, S, Park, J-H, North, KE, Cox, A, Snowden, JA, Wright, J, Carracedo, A, Lopez-Otin, C, Bea, S, Salaverria, I, Martin-Garcia, D, Campo, E, Fraumeni, JF, de Sanjose, S, Hjalgrim, H, Cerhan, JR, Chanock, SJ, Rothman, N, Slager, SL, Berndt, SI, Skibola, CF, Joseph, V, Camp, NJ, Nieters, A, Wang, Z, Cozen, W, Monnereau, A, Wang, SS, Kelly, RS, Lan, Q, Teras, LR, Chatterjee, N, Chung, CC, Yeager, M, Brooks-Wilson, AR, Hartge, P, Purdue, MP, Birmann, BM, Armstrong, BK, Cocco, P, Zhang, Y, Severi, G, Zeleniuch-Jacquotte, A, Lawrence, C, Burdette, L, Yuenger, J, Hutchinson, A, Jacobs, KB, Call, TG, Shanafelt, TD, Novak, AJ, Kay, NE, Liebow, M, Wang, AH, Smedby, KE, Adami, H-O, Melbye, M, Glimelius, B, Chang, ET, Glenn, M, Curtin, K, Cannon-Albright, LA, Jones, B, Diver, WR, Link, BK, Weiner, GJ, Conde, L, Bracci, PM, Riby, J, Holly, EA, Smith, MT, Jackson, RD, Tinker, LF, Benavente, Y, Becker, N, Boffetta, P, Brennan, P, Foretova, L, Maynadie, M, McKay, J, Staines, A, Rabe, KG, Achenbach, SJ, Vachon, CM, Goldin, LR, Strom, SS, Lanasa, MC, Spector, LG, Leis, JF, Cunningham, JM, Weinberg, JB, Morrison, VA, Caporaso, NE, Norman, AD, Linet, MS, De Roos, AJ, Morton, LM, Severson, RK, Riboli, E, Vineis, P, Kaaks, R, Trichopoulos, D, Masala, G, Weiderpass, E, Chirlaque, M-D, Vermeulen, RCH, Travis, RC, Giles, GG, Albanes, D, Virtamo, J, Weinstein, S, Clavel, J, Zheng, T, Holford, TR, Offit, K, Zelenetz, A, Klein, RJ, Spinelli, JJ, Bertrand, KA, Laden, F, Giovannucci, E, Kraft, P, Kricker, A, Turner, J, Vajdic, CM, Ennas, MG, Ferri, GM, Miligi, L, Liang, L, Sampson, J, Crouch, S, Park, J-H, North, KE, Cox, A, Snowden, JA, Wright, J, Carracedo, A, Lopez-Otin, C, Bea, S, Salaverria, I, Martin-Garcia, D, Campo, E, Fraumeni, JF, de Sanjose, S, Hjalgrim, H, Cerhan, JR, Chanock, SJ, Rothman, N, and Slager, SL

Abstract

Genome-wide association studies (GWAS) have previously identified 13 loci associated with risk of chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL). To identify additional CLL susceptibility loci, we conducted the largest meta-analysis for CLL thus far, including four GWAS with a total of 3,100 individuals with CLL (cases) and 7,667 controls. In the meta-analysis, we identified ten independent associated SNPs in nine new loci at 10q23.31 (ACTA2 or FAS (ACTA2/FAS), P=1.22×10(-14)), 18q21.33 (BCL2, P=7.76×10(-11)), 11p15.5 (C11orf21, P=2.15×10(-10)), 4q25 (LEF1, P=4.24×10(-10)), 2q33.1 (CASP10 or CASP8 (CASP10/CASP8), P=2.50×10(-9)), 9p21.3 (CDKN2B-AS1, P=1.27×10(-8)), 18q21.32 (PMAIP1, P=2.51×10(-8)), 15q15.1 (BMF, P=2.71×10(-10)) and 2p22.2 (QPCT, P=1.68×10(-8)), as well as an independent signal at an established locus (2q13, ACOXL, P=2.08×10(-18)). We also found evidence for two additional promising loci below genome-wide significance at 8q22.3 (ODF1, P=5.40×10(-8)) and 5p15.33 (TERT, P=1.92×10(-7)). Although further studies are required, the proximity of several of these loci to genes involved in apoptosis suggests a plausible underlying biological mechanism.

Published
2013

22. Genome-wide association study identifies two susceptibility loci for osteosarcoma

Author

Savage, SA, Mirabello, L, Wang, Z, Gastier-Foster, JM, Gorlick, R, Khanna, C, Flanagan, AM, Tirabosco, R, Andrulis, IL, Wunder, JS, Gokgoz, N, Patino-Garcia, A, Sierrasesumaga, L, Lecanda, F, Kurucu, N, Ilhan, IE, Sari, N, Serra, M, Hattinger, C, Picci, P, Spector, LG, Barkauskas, DA, Marina, N, Caminada de Toledo, SR, Petrilli, AS, Amary, MF, Halai, D, Thomas, DM, Douglass, C, Meltzer, PS, Jacobs, K, Chung, CC, Berndt, SI, Purdue, MP, Caporaso, NE, Tucker, M, Rothman, N, Landi, MT, Silverman, DT, Kraft, P, Hunter, DJ, Malats, N, Kogevinas, M, Wacholder, S, Troisi, R, Helman, L, Fraumeni, JF, Yeager, M, Hoover, RN, Chanock, SJ, Savage, SA, Mirabello, L, Wang, Z, Gastier-Foster, JM, Gorlick, R, Khanna, C, Flanagan, AM, Tirabosco, R, Andrulis, IL, Wunder, JS, Gokgoz, N, Patino-Garcia, A, Sierrasesumaga, L, Lecanda, F, Kurucu, N, Ilhan, IE, Sari, N, Serra, M, Hattinger, C, Picci, P, Spector, LG, Barkauskas, DA, Marina, N, Caminada de Toledo, SR, Petrilli, AS, Amary, MF, Halai, D, Thomas, DM, Douglass, C, Meltzer, PS, Jacobs, K, Chung, CC, Berndt, SI, Purdue, MP, Caporaso, NE, Tucker, M, Rothman, N, Landi, MT, Silverman, DT, Kraft, P, Hunter, DJ, Malats, N, Kogevinas, M, Wacholder, S, Troisi, R, Helman, L, Fraumeni, JF, Yeager, M, Hoover, RN, and Chanock, SJ

Abstract

Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. To better understand the genetic etiology of osteosarcoma, we performed a multistage genome-wide association study consisting of 941 individuals with osteosarcoma (cases) and 3,291 cancer-free adult controls of European ancestry. Two loci achieved genome-wide significance: a locus in the GRM4 gene at 6p21.3 (encoding glutamate receptor metabotropic 4; rs1906953; P = 8.1 × 10⁻⁹) and a locus in the gene desert at 2p25.2 (rs7591996 and rs10208273; P = 1.0 × 10⁻⁸ and 2.9 × 10⁻⁷, respectively). These two loci warrant further exploration to uncover the biological mechanisms underlying susceptibility to osteosarcoma.

Published
2013

23. Adult height and head and neck cancer: a pooled analysis within the INHANCE Consortium

Author

Leoncini, Emanuele, Ricciardi, Walter, Cadoni, Gabriella, Arzani, Dario, Petrelli, Livia, Paludetti, Gaetano, Brennan, P, Luce, D, Stucker, I, Matsuo, K, Talamini, R, La Vecchia, C, Olshan, Af, Winn, Dm, Herrero, R, Franceschi, S, Castellsague, X, Muscat, J, Morgenstern, H, Zhang, Z, Levi, F, Dal Maso, L, Kelsey, K, Mcclean, M, Vaughan, Tl, Lazarus, P, Purdue, Mp, Hayes, Rb, Chen, C, Schwartz, Sm, Shangina, O, Koifman, S, Ahrens, W, Matos, E, Lagiou, P, Lissowska, J, Szeszenia Dabrowska, N, Fernandez, L, Menezes, A, Agudo, A, Daudt, Aw, Richiardi, L, Kjaerheim, K, Mates, D, Betka, J, Yu, G, Schantz, S, Simonato, L, Brenner, H, Conway, Di, Macfarlane, Tv, Thomson, P, Fabianova, E, Znaor, A, Rudnai, P, Healy, C, Boffetta, P, Chuang, S, Lee, Ya, Hashibe, M, Boccia, Stefania, Ricciardi, Gualtiero (ORCID:0000-0002-5655-688X), Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Paludetti, Gaetano (ORCID:0000-0003-2480-1243), Boccia, Stefania (ORCID:0000-0002-1864-749X), Leoncini, Emanuele, Ricciardi, Walter, Cadoni, Gabriella, Arzani, Dario, Petrelli, Livia, Paludetti, Gaetano, Brennan, P, Luce, D, Stucker, I, Matsuo, K, Talamini, R, La Vecchia, C, Olshan, Af, Winn, Dm, Herrero, R, Franceschi, S, Castellsague, X, Muscat, J, Morgenstern, H, Zhang, Z, Levi, F, Dal Maso, L, Kelsey, K, Mcclean, M, Vaughan, Tl, Lazarus, P, Purdue, Mp, Hayes, Rb, Chen, C, Schwartz, Sm, Shangina, O, Koifman, S, Ahrens, W, Matos, E, Lagiou, P, Lissowska, J, Szeszenia Dabrowska, N, Fernandez, L, Menezes, A, Agudo, A, Daudt, Aw, Richiardi, L, Kjaerheim, K, Mates, D, Betka, J, Yu, G, Schantz, S, Simonato, L, Brenner, H, Conway, Di, Macfarlane, Tv, Thomson, P, Fabianova, E, Znaor, A, Rudnai, P, Healy, C, Boffetta, P, Chuang, S, Lee, Ya, Hashibe, M, Boccia, Stefania, Ricciardi, Gualtiero (ORCID:0000-0002-5655-688X), Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Paludetti, Gaetano (ORCID:0000-0003-2480-1243), and Boccia, Stefania (ORCID:0000-0002-1864-749X)

Abstract

Several epidemiological studies have shown a positive association between adult height and cancer incidence. The only study conducted among women on mouth and pharynx cancer risk, however, reported an inverse association. This study aims to investigate the association between height and the risk of head and neck cancer (HNC) within a large international consortium of HNC. We analyzed pooled individual-level data from 24 case-control studies participating in the International Head and Neck Cancer Epidemiology Consortium. Odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated separately for men and women for associations between height and HNC risk. Educational level, tobacco smoking, and alcohol consumption were included in all regression models. Stratified analyses by HNC subsites were performed. This project included 17,666 cases and 28,198 controls. We found an inverse association between height and HNC (adjusted OR per 10 cm height = 0.91, 95 % CI 0.86-0.95 for men; adjusted OR = 0.86, 95 % CI 0.79-0.93 for women). In men, the estimated OR did vary by educational level, smoking status, geographic area, and control source. No differences by subsites were detected. Adult height is inversely associated with HNC risk. As height can be considered a marker of childhood illness and low energy intake, the inverse association is consistent with prior studies showing that HNC occur more frequently among deprived individuals. Further studies designed to elucidate the mechanism of such association would be warranted.

Published
2013

24. Cigarette, Cigar, and Pipe Smoking and the Risk of Head and Neck Cancers: Pooled Analysis in the International Head and Neck Cancer Epidemiology Consortium

Author

Wyss, A, Hashibe, M, Chuang, S, Lee, Ya, Zhang, Z, Yu, G, Winn, Dm, Wei, Q, Talamini, R, Szeszenia Dabrowska, N, Sturgis, Em, Smith, E, Shangina, O, Schwartz, Sm, Schantz, S, Rudnai, P, Purdue, Mp, Eluf Neto, J, Muscat, J, Morgenstern, H, Michaluart, P, Menezes, A, Matos, E, Mates, In, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Herrero, R, Hayes, Rb, Franceschi, S, Wunsch Filho, V, Fernandez, L, Fabianova, E, Daudt, Aw, Dal Maso, L, Curado, Mp, Chen, C, Castellsague, X, De Carvalho, Mb, Cadoni, Gabriella, Boccia, Stefania, Brennan, P, Boffetta, P, Olshan, Af, Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Boccia, Stefania (ORCID:0000-0002-1864-749X), Wyss, A, Hashibe, M, Chuang, S, Lee, Ya, Zhang, Z, Yu, G, Winn, Dm, Wei, Q, Talamini, R, Szeszenia Dabrowska, N, Sturgis, Em, Smith, E, Shangina, O, Schwartz, Sm, Schantz, S, Rudnai, P, Purdue, Mp, Eluf Neto, J, Muscat, J, Morgenstern, H, Michaluart, P, Menezes, A, Matos, E, Mates, In, Lissowska, J, Levi, F, Lazarus, P, La Vecchia, C, Koifman, S, Herrero, R, Hayes, Rb, Franceschi, S, Wunsch Filho, V, Fernandez, L, Fabianova, E, Daudt, Aw, Dal Maso, L, Curado, Mp, Chen, C, Castellsague, X, De Carvalho, Mb, Cadoni, Gabriella, Boccia, Stefania, Brennan, P, Boffetta, P, Olshan, Af, Cadoni, Gabriella (ORCID:0000-0001-8244-784X), and Boccia, Stefania (ORCID:0000-0002-1864-749X)

Abstract

Cigar and pipe smoking are considered risk factors for head and neck cancers, but the magnitude of effect estimates for these products has been imprecisely estimated. By using pooled data from the International Head and Neck Cancer Epidemiology (INHANCE) Consortium (comprising 13,935 cases and 18,691 controls in 19 studies from 1981 to 2007), we applied hierarchical logistic regression to more precisely estimate odds ratios and 95% confidence intervals for cigarette, cigar, and pipe smoking separately, compared with reference groups of those who had never smoked each single product. Odds ratios for cigar and pipe smoking were stratified by ever cigarette smoking. We also considered effect estimates of smoking a single product exclusively versus never having smoked any product (reference group). Among never cigarette smokers, the odds ratio for ever cigar smoking was 2.54 (95% confidence interval (CI): 1.93, 3.34), and the odds ratio for ever pipe smoking was 2.08 (95% CI: 1.55, 2.81). These odds ratios increased with increasing frequency and duration of smoking (Ptrend ≤ 0.0001). Odds ratios for cigar and pipe smoking were not elevated among ever cigarette smokers. Head and neck cancer risk was elevated for those who reported exclusive cigar smoking (odds ratio = 3.49, 95% CI: 2.58, 4.73) or exclusive pipe smoking (odds ratio = 3.71, 95% CI: 2.59, 5.33). These results suggest that cigar and pipe smoking are independently associated with increased risk of head and neck cancers

Published
2013

25. Association between adult height, genetic susceptibility and risk of glioma

Author

Kitahara, CM, Wang, SS, Melin, BS, Wang, Z, Braganza, M, Inskip, PD, Albanes, D, Andersson, U, Freeman, LEB, Buring, JE, Carreon, T, Feychting, M, Gapstur, SM, Gaziano, JM, Giles, GG, Hallmans, G, Hankinson, SE, Henriksson, R, Hsing, AW, Johansen, C, Linet, MS, McKean-Cowdin, R, Michaud, DS, Peters, U, Purdue, MP, Rothman, N, Ruder, AM, Sesso, HD, Severi, G, Shu, X-O, Stevens, VL, Visvanathan, K, Waters, MA, White, E, Wolk, A, Zeleniuch-Jacquotte, A, Zheng, W, Hoover, R, Fraumeni, JF, Chatterjee, N, Yeager, M, Chanock, SJ, Hartge, P, Rajaraman, P, Kitahara, CM, Wang, SS, Melin, BS, Wang, Z, Braganza, M, Inskip, PD, Albanes, D, Andersson, U, Freeman, LEB, Buring, JE, Carreon, T, Feychting, M, Gapstur, SM, Gaziano, JM, Giles, GG, Hallmans, G, Hankinson, SE, Henriksson, R, Hsing, AW, Johansen, C, Linet, MS, McKean-Cowdin, R, Michaud, DS, Peters, U, Purdue, MP, Rothman, N, Ruder, AM, Sesso, HD, Severi, G, Shu, X-O, Stevens, VL, Visvanathan, K, Waters, MA, White, E, Wolk, A, Zeleniuch-Jacquotte, A, Zheng, W, Hoover, R, Fraumeni, JF, Chatterjee, N, Yeager, M, Chanock, SJ, Hartge, P, and Rajaraman, P

Abstract

BACKGROUND: Some, but not all, observational studies have suggested that taller stature is associated with a significant increased risk of glioma. In a pooled analysis of observational studies, we investigated the strength and consistency of this association, overall and for major sub-types, and investigated effect modification by genetic susceptibility to the disease. METHODS: We standardized and combined individual-level data on 1354 cases and 4734 control subjects from 13 prospective and 2 case-control studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for glioma and glioma sub-types were estimated using logistic regression models stratified by sex and adjusted for birth cohort and study. Pooled ORs were additionally estimated after stratifying the models according to seven recently identified glioma-related genetic variants. RESULTS: Among men, we found a positive association between height and glioma risk (≥ 190 vs 170-174 cm, pooled OR = 1.70, 95% CI: 1.11-2.61; P-trend = 0.01), which was slightly stronger after restricting to cases with glioblastoma (pooled OR = 1.99, 95% CI: 1.17-3.38; P-trend = 0.02). Among women, these associations were less clear (≥ 175 vs 160-164 cm, pooled OR for glioma = 1.06, 95% CI: 0.70-1.62; P-trend = 0.22; pooled OR for glioblastoma = 1.36, 95% CI: 0.77-2.39; P-trend = 0.04). In general, we did not observe evidence of effect modification by glioma-related genotypes on the association between height and glioma risk. CONCLUSION: An association of taller adult stature with glioma, particularly for men and stronger for glioblastoma, should be investigated further to clarify the role of environmental and genetic determinants of height in the etiology of this disease.

Published
2012

26. History of diabetes and risk of head and neck cancer: a pooled analysis from the international head and neck cancer epidemiology consortium

Author

Stott Miller, M, Chen, Chen, Chuang, S, Lee, Ya, Boccia, Stefania, Brenner, H, Cadoni, Gabriella, Dal Maso, L, La Vecchia, C, Lazarus, P, Levi, F, Matsuo, K, Morgenstern, H, Müller, H, Muscat, J, Olshan, Af, Purdue, Mp, Serraino, D, Vaughan, Tl, Zhang, Z, Boffetta, P, Hashibe, M, Schwartz, Sm, Boccia, Stefania (ORCID:0000-0002-1864-749X), Cadoni, Gabriella (ORCID:0000-0001-8244-784X), Stott Miller, M, Chen, Chen, Chuang, S, Lee, Ya, Boccia, Stefania, Brenner, H, Cadoni, Gabriella, Dal Maso, L, La Vecchia, C, Lazarus, P, Levi, F, Matsuo, K, Morgenstern, H, Müller, H, Muscat, J, Olshan, Af, Purdue, Mp, Serraino, D, Vaughan, Tl, Zhang, Z, Boffetta, P, Hashibe, M, Schwartz, Sm, Boccia, Stefania (ORCID:0000-0002-1864-749X), and Cadoni, Gabriella (ORCID:0000-0001-8244-784X)

Abstract

Background: A history of diabetes is associated with an increased risk of several types of cancers. Whether diabetes is a risk factor for head and neck cancer (HNC) has received little attention. Methods: We pooled data from 12 case control studies including 6,448 cases and 13,747 controls, and estimated OR and 95% CI for the associations between diabetes and HNC, adjusted for age, education level, sex, race/ethnicity, study center, cigarette smoking, alcohol use, and body mass index. Results: We observed a weak association between diabetes and the incidence of HNC overall (OR, 1.09; 95% CI: 0.95-1.24). However, we observed a modest association among never smokers (OR, 1.59; 95% CI: 1.22-2.07), and no association among ever smokers (OR, 0.96; 95% CI: 0.83-1.11); likelihood ratio test for interaction P = 0.001 Conclusion: A history of diabetes was weakly associated with HNC overall, but we observed evidence of effect modification by smoking status, with a positive association among those who never smoked cigarettes. Impact: This study suggests that glucose metabolism abnormalities may be a HNC risk factor in subgroups of the population. Prospective studies incorporating biomarkers are needed to improve our understanding of the relationship between diabetes and HNC risk, possibly providing new strategies in the prevention of HNC

Published
2012

27. The association between chronic renal failure and renal cell carcinoma may differ between black and white Americans.

Author

Hofmann JN, Schwartz K, Chow WH, Ruterbusch JJ, Shuch BM, Karami S, Rothman N, Wacholder S, Graubard BI, Colt JS, Purdue MP, Hofmann, Jonathan N, Schwartz, Kendra, Chow, Wong-Ho, Ruterbusch, Julie J, Shuch, Brian M, Karami, Sara, Rothman, Nathaniel, Wacholder, Sholom, and Graubard, Barry I

Abstract

Purpose: In the United States, renal cell carcinoma (RCC) incidence is higher among blacks than among whites. Risk of RCC is elevated among end-stage renal disease patients, although no studies have looked at differences by race in the relationship between chronic renal failure and RCC.Methods: We investigated RCC risk in relation to chronic renal failure in a population-based case-control study of blacks and whites in Chicago and Detroit. Data, including information on kidney disease, were collected from interviews with 1,217 RCC cases (361 blacks, 856 whites) and 1,235 controls (523 blacks, 712 whites). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using unconditional logistic regression.Results: Risk of RCC was increased in relation to chronic renal failure (OR 4.7, 95 % CI 2.2-10.1) and dialysis (OR 18.0, 95 % CI 3.6-91). The association remained after defining exposure as those who had chronic renal failure ≥10 years prior to RCC diagnosis. Chronic renal failure was more strongly associated with RCC among blacks than among whites (OR 8.7, 95 % CI 3.3-22.9 and 2.0, 0.7-5.6, respectively; p (interaction) = 0.03) and among those without a history of diabetes relative to diabetic subjects (OR 8.3, 95 % CI 3.1-22.7 and 1.9, 0.6-5.9, respectively; p (interaction) = 0.03).Conclusions: These results suggest that chronic renal failure is a strong risk factor for RCC, particularly among black and non-diabetic subjects. Our findings of differences in risk estimates by race, to our knowledge the first such report, require replication. [ABSTRACT FROM AUTHOR]

Published
2013
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28. Body mass index and renal cell cancer: the influence of race and sex.

Author

Beebe-Dimmer JL, Colt JS, Ruterbusch JJ, Keele GR, Purdue MP, Wacholder S, Graubard BI, Davis F, Chow WH, Schwartz KL, Beebe-Dimmer, Jennifer L, Colt, Joanne S, Ruterbusch, Julie J, Keele, Gregory R, Purdue, Mark P, Wacholder, Sholom, Graubard, Barry I, Davis, Faith, Chow, Wong-Ho, and Schwartz, Kendra L

Abstract

Background: Obesity is a risk factor for renal cell (or renal) cancer. The increasing prevalence of obesity may be contributing to the rising incidence of this cancer over the past several decades. The effects of early-age obesity and change in body mass index (BMI) on renal cancer have been studied less thoroughly, and the influence of race has never been formally investigated.Methods: Using data gathered as part of a large case-control study of renal cancer (1214 cases and 1234 controls), we investigated associations with BMI at several time points, as well as with height. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression modeling. Race- and sex-stratified analyses were conducted to evaluate subgroup differences.Results: Obesity (BMI ≥ 30 kg/m) early in adulthood (OR = 1.6 [95% CI = 1.1 to 2.4]) and 5 years before diagnosis (1.6 [1.1 to 2.2]) was associated with renal cancer. The association with early-adult obesity was stronger among whites than blacks (test for interaction, P = 0.006), whereas the association with obesity near diagnosis was marginally stronger in women than men (test for interaction, P = 0.08). The strongest association with renal cancer was observed for obese whites both in early adulthood and before interview (2.6 [1.5 to 4.4]); this association was not present among blacks. Estimates of the annual excess rate of renal cancer (per 100,000 persons) attributed to both overweight and obesity (BMI > 25 kg/m) ranged from 9.9 among black men to 5.6 among white women.Conclusion: Obesity, both early and later in life, is associated with an increased risk of renal cancer. The association with early obesity seems to be stronger among whites than blacks. [ABSTRACT FROM AUTHOR]

Published
2012
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29. Cigarette smoking, alcohol intake, and thyroid cancer risk: a pooled analysis of five prospective studies in the United States.

Author

Kitahara CM, Linet MS, Beane Freeman LE, Check DP, Church TR, Park Y, Purdue MP, Schairer C, Berrington de González A, Kitahara, Cari M, Linet, Martha S, Beane Freeman, Laura E, Check, David P, Church, Timothy R, Park, Yikyung, Purdue, Mark P, Schairer, Catherine, and Berrington de González, Amy

Abstract

Objective: We examined the associations between cigarette smoking, alcohol intake, and thyroid cancer risk in a pooled analysis of five prospective studies.Methods: Data from five prospective U.S. studies were standardized and then combined into one aggregate dataset (384,433 men and 361,664 women). Pooled hazard ratios (HR) and 95 % confidence intervals (CI) for thyroid cancer were estimated from mutually adjusted models of cigarette smoking and alcohol intake, which were additionally adjusted for age, sex, education, race, marital status, body mass index, and cohort.Results: Over follow-up, 1,003 incident thyroid cancer cases (335 men and 668 women) were identified. Compared to never smokers, current smoking was associated with reduced risk of thyroid cancer (HR = 0.68, 95 % CI 0.55-0.85); this association was slightly stronger among non-drinkers (HR = 0.46, 95 % CI 0.29-0.74). No reduction in risk was observed for former, compared to never, smokers. Greater smoking intensity, duration, and pack-years were associated with further reductions in risk among former and current smokers. Alcohol intake was also inversely associated with thyroid cancer risk (≥7 drinks/week versus 0, HR = 0.72, 95 % CI 0.58-0.90, p trend = 0.002). Inverse associations with smoking and alcohol were more pronounced for papillary versus follicular tumors.Conclusion: The results of this pooled analysis suggest that both cigarette smoking and alcohol consumption are associated with reduced risks of papillary thyroid cancer and, possibly, follicular thyroid cancer. [ABSTRACT FROM AUTHOR]

Published
2012
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30. Assessing disease risk in genome-wide association studies using family history.

Author

Ghosh A, Hartge P, Purdue MP, Chanock SJ, Amundadottir L, Wang Z, Wentzensen N, Chatterjee N, Wacholder S, Ghosh, Arpita, Hartge, Patricia, Purdue, Mark P, Chanock, Stephen J, Amundadottir, Laufey, Wang, Zhaoming, Wentzensen, Nicolas, Chatterjee, Nilanjan, and Wacholder, Sholom

Abstract

We show how to use reports of cancer in family members to discover additional genetic associations or confirm previous findings in genome-wide association (GWA) studies conducted in case-control, cohort, or cross-sectional studies. Our novel family history-based approach allows economical association studies for multiple cancers, without genotyping of relatives (as required in family studies), follow-up of participants (as required in cohort studies), or oversampling of specific cancer cases (as required in case-control studies). We empirically evaluate the performance of the proposed family history-based approach in studying associations with prostate and ovarian cancers, using data from GWA studies previously conducted within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. The family history-based method may be particularly useful for investigating genetic susceptibility to rare diseases for which accruing cases may be very difficult, by using disease information from nongenotyped relatives of participants in multiple case-control and cohort studies designed primarily for other purposes. [ABSTRACT FROM AUTHOR]

Published
2012
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31. Circulating 25-hydroxyvitamin D and risk of non-Hodgkin lymphoma: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Author

Purdue MP, Freedman DM, Gapstur SM, Helzlsouer KJ, Laden F, Lim U, Maskarinec G, Rothman N, Shu X, Stevens VL, Zeleniuch-Jacquotte A, Albanes D, Bertrand K, Weinstein SJ, Yu K, Irish L, Horst RL, Hoffman-Bolton J, Giovannucci EL, and Kolonel LN

Abstract

Case-control studies generally suggesting an inverse association between sun exposure and non-Hodgkin lymphoma (NHL) have led to speculation that vitamin D may protect against lymphomagenesis. To examine this hypothesis, the authors conducted a pooled investigation of circulating 25-hydroxyvitamin D (25(OH)D) and subsequent NHL risk within 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers. The authors analyzed measurements from 1,353 cases and 1,778 controls using conditional logistic regression and other methods to estimate the association of 25(OH)D with NHL. No clear evidence of association between categories of 25(OH)D concentration and NHL was observed overall (P(trend) = 0.68) or by sex (men, P(trend) = 0.50; women, P(trend) = 0.16). Findings for other measures (continuous log(25(OH)D), categories of 25(OH)D using sex-/cohort-/season-specific quartiles as cutpoints, categories of season-adjusted residuals of predicted 25(OH)D using quartiles as cutpoints) were generally null, although some measures of increasing 25(OH)D were suggestive of an increased risk for women. Results from stratified analyses and investigations of histologic subtypes of NHL were also null. These findings do not support the hypothesis that elevated circulating 25(OH)D concentration is associated with a reduced risk of NHL. Future research investigating the biologic basis for the sunlight-NHL association should consider alternative mechanisms, such as immunologic effects. [ABSTRACT FROM AUTHOR]

Published
2010
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32. Circulating 25-hydroxyvitamin D and risk of endometrial cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Author

Zeleniuch-Jacquotte A, Gallicchio L, Hartmuller V, Helzlsouer KJ, McCullough ML, Setiawan VW, Shu X, Weinstein SJ, Weiss JM, Arslan AA, De Vivo I, Gao Y, Hayes RB, Henderson BE, Horst RL, Koenig KL, Patel AV, Purdue MP, Snyder K, and Steplowski E

Abstract

A nested case-control study, including 830 cases and 992 controls from 7 cohorts, was conducted to evaluate the association of circulating 25-hydroxyvitamin D (25(OH)D), the best indicator of vitamin D status, with risk of endometrial cancer. Matching factors included age at blood donation, date of blood donation, and race. Conditional logistic regression was used in the main analysis. The median concentration of 25(OH)D was slightly lower in cases (49.4 nmol/L) than in controls (50.8 nmol/L) (P = 0.08). However, there was no association between 25(OH)D concentration and disease risk, after adjustment for body mass index. Compared with the 50-<75 nmol/L 25(OH)D category, the body mass index-adjusted odds ratios and 95% confidence intervals were 1.08 (95% confidence interval: 0.73, 1.57) for the <25 nmol/L category and 0.90 (95% confidence interval: 0.51, 1.58) for the > or =100 nmol/L category (P(trend) = 0.99). Similarly null results were observed after further adjustment for other known risk factors and in stratified analyses. Although an effect of circulating 25(OH)D at high concentrations cannot be ruled out (the highest category of 25(OH)D was > or =100 nmol/L, and for stratified analyses, > or =75 nmol/L), these results do not support a protective role of vitamin D against endometrial cancer. [ABSTRACT FROM AUTHOR]

Published
2010
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33. Circulating 25-hydroxyvitamin D and risk of pancreatic cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Author

Stolzenberg-Solomon RZ, Jacobs EJ, Arslan AA, Qi D, Patel AV, Helzlsouer KJ, Weinstein SJ, McCullough ML, Purdue MP, Shu X, Snyder K, Virtamo J, Wilkins LR, Yu K, Zeleniuch-Jacquotte A, Zheng W, Albanes D, Cai Q, Harvey C, and Hayes R

Abstract

Results from epidemiologic studies examining pancreatic cancer risk and vitamin D intake or 25-hydroxyvitamin D (25(OH)D) concentrations (the best indicator of vitamin D derived from diet and sun) have been inconsistent. Therefore, the authors conducted a pooled nested case-control study of participants from 8 cohorts within the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP) (1974-2006) to evaluate whether prediagnostic circulating 25(OH)D concentrations were associated with the development of pancreatic cancer. In total, 952 incident pancreatic adenocarcinoma cases occurred among participants (median follow-up, 6.5 years). Controls (n = 1,333) were matched to each case by cohort, age, sex, race/ethnicity, date of blood draw, and follow-up time. Conditional logistic regression analysis was used to calculate smoking-, body mass index-, and diabetes-adjusted odds ratios and 95% confidence intervals for pancreatic cancer. Clinically relevant 25(OH)D cutpoints were compared with a referent category of 50-<75 nmol/L. No significant associations were observed for participants with lower 25(OH)D status. However, a high 25(OH)D concentration (> or =100 nmol/L) was associated with a statistically significant 2-fold increase in pancreatic cancer risk overall (odds ratio = 2.12, 95% confidence interval: 1.23, 3.64). Given this result, recommendations to increase vitamin D concentrations in healthy persons for the prevention of cancer should be carefully considered. [ABSTRACT FROM AUTHOR]

Published
2010
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34. Circulating 25-hydroxyvitamin D and risk of epithelial ovarian cancer: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Author

Zheng W, Danforth KN, Tworoger SS, Goodman MT, Arslan AA, Patel AV, McCullough ML, Weinstein SJ, Kolonel LN, Purdue MP, Shu X, Snyder K, Steplowski E, Visvanathan K, Yu K, Zeleniuch-Jacquotte A, Gao Y, Hankinson SE, Harvey C, and Hayes RB

Abstract

A role for vitamin D in ovarian cancer etiology is supported by ecologic studies of sunlight exposure, experimental mechanism studies, and some studies of dietary vitamin D intake and genetic polymorphisms in the vitamin D receptor. However, few studies have examined the association of circulating 25-hydroxyvitamin D (25(OH)D), an integrated measure of vitamin D status, with ovarian cancer risk. A nested case-control study was conducted among 7 prospective studies to evaluate the circulating 25(OH)D concentration in relation to epithelial ovarian cancer risk. Logistic regression models were used to estimate odds ratios and 95% confidence intervals among 516 cases and 770 matched controls. Compared with 25(OH)D concentrations of 50-<75 nmol/L, no statistically significant associations were observed for <37.5 (odds ratio (OR) = 1.21, 95% confidence interval (CI): 0.87, 1.70), 37.5-<50 (OR = 1.03, 95% CI: 0.75, 1.41), or > or =75 (OR = 1.11, 95% CI: 0.79, 1.55) nmol/L. Analyses stratified by tumor subtype, age, body mass index, and other variables were generally null but suggested an inverse association between 25(OH)D and ovarian cancer risk among women with a body mass index of > or =25 kg/m(2) (P(interaction) < 0.01). In conclusion, this large pooled analysis did not support an overall association between circulating 25(OH)D and ovarian cancer risk, except possibly among overweight women. [ABSTRACT FROM AUTHOR]

Published
2010
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35. Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33

Author

Hidemi Ito, Stephen K. Van Den Eeden, Abdisamad M. Ibrahim, Ching C. Lau, Preetha Rajaraman, Gloria M. Petersen, Judith Hoffman-Bolton, Colin P.N. Dinney, Chang Hyun Kang, Melinda C. Aldrich, Mark P. Purdue, Xiao-Ou Shu, William J. Blot, Sanjay Shete, Alpa V. Patel, Charles Kooperberg, Paolo Vineis, David Van Den Berg, Chao A. Hsiung, Anthony J. Swerdlow, Qing Lan, Wu Chou Su, Afshan Siddiq, Ulrike Peters, Katia Scotlandi, Sara H. Olson, Kendra Schwartz, Kelly L. Bolton, Chancellor Hohensee, Josep Lloreta, Kevin B. Jacobs, Debra T. Silverman, Rudolf Kaaks, Wei Zheng, Steven Gallinger, Junwen Wang, Angela Carta, Massimo Serra, Petra H.M. Peeters, Victoria L. Stevens, Yasushi Yatabe, Geraldine Cancel-Tassin, Joshua N. Sampson, Young Tae Kim, Graham A. Colditz, Pan-Chyr Yang, Baosen Zhou, Fredrick R. Schumacher, Nicolas Wentzensen, Evelyn Tay, Claudia Maria Hattinger, Chen Wu, Pilar Amiano, Mattias Johansson, Maxwell P. Lee, Christian P. Kratz, Michael B. Cook, Mingfeng Zhang, Kay-Tee Khaw, Jian-Min Yuan, Anne Zeleniuch-Jacquotte, Jinping Jia, Roberto Tirabosco, Jing Ma, Neil E. Caporaso, Christopher A. Haiman, Bu Tian Ji, Adrienne M. Flanagan, Neyssa Marina, Eric J. Jacobs, Sophia S. Wang, Chong-Jen Yu, Edward Giovannucci, Margaret Wrensch, Robert L. Grubb, Bin Zhu, Daniel O. Stram, Manolis Kogevinas, Margaret R. Karagas, Mazda Jenab, Alison M. Mondul, Jun Xu, Preethi S. Raj, Anders Ahlbom, Christine D. Berg, Shelley Niwa, Kala Visvanathan, Loic Le Marchand, Jorge R. Toro, Robert N. Hoover, Heather Spencer Feigelson, Michelle Brotzman, Laurence N. Kolonel, Krista A. Zanetti, Chengfeng Wang, Mary Ann Butler, Ann Truelove, Irene L. Andrulis, Hongbing Shen, H. Dean Hosgood, Ming Shyan Huang, Gee-Chen Chang, Jianjun Liu, John K. Wiencke, Stephanie J. Weinstein, Beatrice Melin, Kouya Shiraishi, Zhihua Yin, Lee E. Moore, Börje Ljungberg, Jolanta Lissowska, Elizabeth M. Gillanders, M. T. Landi, Cari M. Kitahara, Maria Feychting, Kuan-Yu Chen, Matthias Simon, Brian M. Wolpin, Hemang Parikh, Hannah P. Yang, Graham G. Giles, Alison Johnson, Demetrius Albanes, Carlos González, Brian E. Henderson, Xifeng Wu, Harvey A. Risch, Amy Hutchinson, Christopher Hautman, Constance Chen, Zhibin Hu, Donghui Li, Elio Riboli, Julie E. Buring, Curtis C. Harris, Xu Che, Núria Malats, Roger Henriksson, Rosario Tumino, Joanne S. Colt, Alfredo Carrato, Paolo Boffetta, Maria Pik Wong, Hideo Tanaka, Federico Canzian, Alan D. L. Sihoe, Chien-Jen Chen, Kenneth Muir, Chen Ying, Qincheng He, Melissa C. Southey, Marc Sanson, Victoria K. Cortessis, Sharon A. Savage, Wei Hu, Yao Tettey, Daniela S. Gerhard, Sofia Pavanello, Guangwen Cao, H. Barton Grossman, Michael Goggins, Hideo Kunitoh, Peter D. Inskip, Seth P. Lerner, Peter Kraft, David Thomas, Peng Guan, Chung Hsing Chen, I. Shou Chang, Christoffer Johansen, Roberta McKean-Cowdin, Lee J. Helman, Yuh Min Chen, Ana Patiño-García, Pär Stattin, Xiaoping Miao, Tangchun Wu, Jay S. Wunder, Ann W. Hsing, Yu-Tang Gao, Brooke L. Fridley, Tania Carreón, Charles C. Chung, Nan Hu, Yoo Jin Jung, Richard B. Biritwum, Eric J. Duell, Philip R. Taylor, Satu Männistö, Kai Yu, Meredith Yeager, Xia Pu, Vittorio Krogh, Anand P. Chokkalingam, Susan M. Gapstur, W. Ryan Diver, Yuanqing Ye, Keitaro Matsuo, Cecilia Arici, You-Lin Qiao, Alan R. Schned, Dominique S. Michaud, Joanne W. Elena, Christopher Kim, Dongxin Lin, Yun-Chul Hong, Daru Lu, Reina García-Closas, Jonine D. Figueroa, Linda M. Liao, Yi-Long Wu, Heiner Boeing, Mark Lathrop, Göran Hallmans, Elizabeth A. Holly, Carol Giffen, Andrew A. Adjei, Consol Serra, Anne Tjønneland, Joseph F. Fraumeni, Alisa M. Goldstein, Ruth C. Travis, Rebecca Troisi, Dalsu Baris, Nalan Gokgoz, Olivier Cussenot, Xiang Deng, Yeul Hong Kim, Malin Sund, Sonja I. Berndt, E. David Crawford, Edward D. Yeboah, Sook Whan Sung, Françoise Clavel-Chapelon, Woon-Puay Koh, Nilgun Kurucu, Richard B. Hayes, Ashish M. Kamat, Beata Peplonska, Laurie Burdette, Ze Zhang Tang, Alan A. Arslan, Malcolm C. Pike, Sabina Sierri, J. Michael Gaziano, Lorna H. McNeil, Katherine A. McGlynn, Ulla Vogel, Logan G. Spector, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Jae Yong Park, Jennifer Prescott, Fernando Lecanda, Margaret A. Tucker, Ti Ding, Christian C. Abnet, Jenny Chang-Claude, Dimitrios Trichopoulos, Wei-Yen Lim, Wen Tan, Nick Orr, Jin Hee Kim, Stefano Porru, Chand Khanna, Robert R. McWilliams, Zhaoming Wang, Jeong Seon Ryu, David V. Conti, Alison P. Klein, Adonina Tardón, Robert J. Klein, Rebecca J. Rodabough, Mark H. Greene, Aruna Kamineni, Jie Lin, Rachael Z. Stolzenberg-Solomon, Patricia Hartge, Susan E. Hankinson, Young-Chul Kim, In Sam Kim, Luis Sierrasesúmaga, Roel Vermeulen, Paige M. Bracci, Mariana C. Stern, Louise A. Brinton, Myron D. Gross, Yong-Bing Xiang, Chih Yi Chen, G. A. Gerald Andriole, Paul S. Meltzer, Ying-Huang Tsai, Faith G. Davis, Ulrika Andersson, Paul Brennan, Sara Lindström, Chaoyu Wang, Giuseppe Mastrangelo, Laufey T. Amundadottir, Immaculata De Vivo, Bryan A. Bassig, Elisabete Weiderpass, Takashi Kohno, Nilanjan Chatterjee, Margaret R. Spitz, Pier Alberto Bertazzi, William Wheeler, David J. Hunter, Wei Tang, Qiuyin Cai, Naomi E. Allen, Molly Schwenn, Emily White, Min Shen, Adeline Seow, Laura E. Beane Freeman, James E. Mensah, Howard D. Sesso, Anna Luisa Di Stefano, Amanda Black, Manuela Gago-Dominguez, Christine B. Ambrosone, Avima M. Ruder, Martha S. Linet, Meir J. Stampfer, Robert C. Kurtz, Donald A. Barkauskas, Lisa W. Chu, Montserrat Garcia-Closas, Jason W. Hoskins, Melissa A. Austin, Kyoung Mu Lee, Jianxin Shi, Charles S. Fuchs, Nathaniel Rothman, Richard Gorlick, Piero Picci, Gianluca Severi, Ann G. Schwartz, Jian Gu, Christopher I. Amos, Marie-Christine Boutron-Ruault, Salvatore Panico, Alicja Wolk, Sara S. Strom, Lisa Mirabello, Jin-Hu Fan, Chin-Fu Hsiao, Neal D. Freedman, Geoffrey S. Tobias, Julie M. Gastier-Foster, Wang, Z, Zhu, B, Zhang, M, Parikh, H, Jia, J, Chung, Cc, Sampson, Jn, Hoskins, Jw, Hutchinson, A, Burdette, L, Ibrahim, A, Hautman, C, Raj, P, Abnet, Cc, Adjei, Aa, Ahlbom, A, Albanes, D, Allen, Ne, Ambrosone, Cb, Aldrich, M, Amiano, P, Amos, C, Andersson, U, Andriole G., Jr, Andrulis, Il, Arici, C, Arslan, Aa, Austin, Ma, Baris, D, Barkauskas, Da, Bassig, Ba, Beane Freeman, Le, Berg, Cd, Berndt, Si, Bertazzi, Pa, Biritwum, Rb, Black, A, Blot, W, Boeing, H, Boffetta, P, Bolton, K, Boutron Ruault, Mc, Bracci, Pm, Brennan, P, Brinton, La, Brotzman, M, Bueno de Mesquita, Hb, Buring, Je, Butler, Ma, Cai, Q, Cancel Tassin, G, Canzian, F, Cao, G, Caporaso, Ne, Carrato, A, Carreon, T, Carta, A, Chang, Gc, Chang, I, Chang Claude, J, Che, X, Chen, Cj, Chen, Cy, Chen, Ch, Chen, C, Chen, Ky, Chen, Ym, Chokkalingam, Ap, Chu, Lw, Clavel Chapelon, F, Colditz, Ga, Colt, J, Conti, D, Cook, Mb, Cortessis, Vk, Crawford, Ed, Cussenot, O, Davis, Fg, De Vivo, I, Deng, X, Ding, T, Dinney, Cp, Di Stefano, Al, Diver, Wr, Duell, Ej, Elena, Jw, Fan, Jh, Feigelson, H, Feychting, M, Figueroa, Jd, Flanagan, Am, Fraumeni JF, Jr, Freedman, Nd, Fridley, Bl, Fuchs, C, Gago Dominguez, M, Gallinger, S, Gao, Yt, Gapstur, Sm, Garcia Closas, M, Garcia Closas, R, Gastier Foster, Jm, Gaziano, Jm, Gerhard, D, Giffen, Ca, Giles, Gg, Gillanders, Em, Giovannucci, El, Goggins, M, Gokgoz, N, Goldstein, Am, Gonzalez, C, Gorlick, R, Greene, Mh, Gross, M, Grossman, Hb, Grubb R., 3rd, Gu, J, Guan, P, Haiman, Ca, Hallmans, G, Hankinson, Se, Harris, Cc, Hartge, P, Hattinger, C, Hayes, Rb, He, Q, Helman, L, Henderson, Be, Henriksson, R, Hoffman Bolton, J, Hohensee, C, Holly, Ea, Hong, Yc, Hoover, Rn, Hosgood HD, 3rd, Hsiao, Cf, Hsing, Aw, Hsiung, Ca, Hu, N, Hu, W, Hu, Z, Huang, M, Hunter, Dj, Inskip, Pd, Ito, H, Jacobs, Ej, Jacobs, Kb, Jenab, M, Ji, Bt, Johansen, C, Johansson, M, Johnson, A, Kaaks, R, Kamat, Am, Kamineni, A, Karagas, M, Khanna, C, Khaw, Kt, Kim, C, Kim, I, Kim, Yh, Kim, Yc, Kim, Yt, Kang, Ch, Jung, Yj, Kitahara, Cm, Klein, Ap, Klein, R, Kogevinas, M, Koh, Wp, Kohno, T, Kolonel, Ln, Kooperberg, C, Kratz, Cp, Krogh, V, Kunitoh, H, Kurtz, Rc, Kurucu, N, Lan, Q, Lathrop, M, Lau, Cc, Lecanda, F, Lee, Km, Lee, Mp, Le Marchand, L, Lerner, Sp, Li, D, Liao, Lm, Lim, Wy, Lin, D, Lin, J, Lindstrom, S, Linet, M, Lissowska, J, Liu, J, Ljungberg, B, Lloreta, J, Lu, D, Ma, J, Malats, N, Mannisto, S, Marina, N, Mastrangelo, G, Matsuo, K, Mcglynn, Ka, McKean Cowdin, R, Mcneill, Lh, Mcwilliams, Rr, Melin, B, Meltzer, P, Mensah, Je, Miao, X, Michaud, D, Mondul, Am, Moore, Le, Muir, K, Niwa, S, Olson, Sh, Orr, N, Panico, Salvatore, Park, Jy, Patel, Av, Patino Garcia, A, Pavanello, S, Peeters, Ph, Peplonska, B, Peters, U, Petersen, Gm, Picci, P, Pike, Mc, Porru, S, Prescott, J, Pu, X, Purdue, Mp, Qiao, Yl, Rajaraman, P, Riboli, E, Risch, Ha, Rodabough, Rj, Rothman, N, Ruder, Am, Ryu, J, Sanson, M, Schned, A, Schumacher, Fr, Schwartz, Ag, Schwartz, Kl, Schwenn, M, Scotlandi, K, Seow, A, Serra, C, Serra, M, Sesso, Hd, Severi, G, Shen, H, Shen, M, Shete, S, Shiraishi, K, Shu, Xo, Siddiq, A, Sierrasesumaga, L, Sierri, S, Loon Sihoe, Ad, Silverman, Dt, Simon, M, Southey, Mc, Spector, L, Spitz, M, Stampfer, M, Stattin, P, Stern, Mc, Stevens, Vl, Stolzenberg Solomon, Rz, Stram, Do, Strom, S, Su, Wc, Sund, M, Sung, Sw, Swerdlow, A, Tan, W, Tanaka, H, Tang, W, Tang, Zz, Tardon, A, Tay, E, Taylor, Pr, Tettey, Y, Thomas, Dm, Tirabosco, R, Tjonneland, A, Tobias, G, Toro, Jr, Travis, Rc, Trichopoulos, D, Troisi, R, Truelove, A, Tsai, Yh, Tucker, Ma, Tumino, R, Van Den Berg, D, Van Den Eeden, Sk, Vermeulen, R, Vineis, P, Visvanathan, K, Vogel, U, Wang, C, Wang, J, Wang, S, Weiderpass, E, Weinstein, Sj, Wentzensen, N, Wheeler, W, White, E, Wiencke, Jk, Wolk, A, Wolpin, Bm, Wong, Mp, Wrensch, M, Wu, C, Wu, T, Wu, X, Wu, Yl, Wunder, J, Xiang, Yb, Xu, J, Yang, Hp, Yang, Pc, Yatabe, Y, Ye, Y, Yeboah, Ed, Yin, Z, Ying, C, Yu, Cj, Yu, K, Yuan, Jm, Zanetti, Ka, Zeleniuch Jacquotte, A, Zheng, W, Zhou, B, Mirabello, L, Savage, Sa, Kraft, P, Chanock, Sj, Yeager, M, Landi, Mt, Shi, J, Chatterjee, N, Amundadottir, Lt, Wang, Z., Zhu, B., Zhang, M., Parikh, H., Jia, J., Chung, C.C., Sampson, J.N., Hoskins, J.W., Hutchinson, A., Burdette, L., Ibrahim, A., Hautman, C., Raj, P.S., Abnet, C.C., Adjei, A.A., Ahlbom, A., Albanes, D., Allen, N.E., Ambrosone, C.B., Aldrich, M., Amiano, P., Amos, C., Andersson, U., Gerald Andriole, G.A., Jr., Andrulis, I.L., Arici, C., Arslan, A.A., Austin, M.A., Baris, D., Barkauskas, D.A., Bassig, B.A., Freeman, L.E.B., Berg, C.D., Berndt, S.I., Bertazzi, P.A., Biritwum, R.B., Black, A., Blot, W., Boeing, H., Boffetta, P., Bolton, K., Boutron-Ruault, M.-C., Bracci, P.M., Brennan, P., Brinton, L.A., Brotzman, M., Bueno-de-Mesquita, H.B., Buring, J.E., Butler, M.A., Cai, Q., Cancel-Tassin, G., Canzian, F., Cao, G., Caporaso, N.E., Carrato, A., Carreon, T., Carta, A., Chang, G.-C., Chang, I.-S., Chang-Claude, J., Che, X., Chen, C.-J., Chen, C.-Y., Chen, C.-H., Chen, C., Chen, K.-Y., Chen, Y.-M., Chokkalingam, A.P., Chu, L.W., Clavel-Chapelon, F., Colditz, G.A., Colt, J.S., Conti, D., Cook, M.B., Cortessis, V.K., Crawford, E.D., Cussenot, O., Davis, F.G., De Vivo, I., Deng, X., Ding, T., Dinney, C.P., Di Stefano, A.L., Diver, W.R., Duell, E.J., Elena, J.W., Fan, J.-H., Feigelson, H.S., Feychting, M., Figueroa, J.D., Flanagan, A.M., Fraumeni, J.F., Jr., Freedman, N.D., Fridley, B.L., Fuchs, C.S., Gago-Dominguez, M., Gallinger, S., Gao, Y.-T., Gapstur, S.M., Garcia-Closas, M., Garcia-Closas, R., Gastier-Foster, J.M., Gaziano, J.M., Gerhard, D.S., Giffen, C.A., Giles, G.G., Gillanders, E.M., Giovannucci, E.L., Goggins, M., Gokgoz, N., Goldstein, A.M., Gonzalez, C., Gorlick, R., Greene, M.H., Gross, M., Grossman, H.B., Grubb, R., III and Gu, J., Guan, P., Haiman, C.A., Hallmans, G., Hankinson, S.E., Harris, C.C., Hartge, P., Hattinger, C., Hayes, R.B., He, Q., Helman, L., Henderson, B.E., Henriksson, R., Hoffman-Bolton, J., Hohensee, C., Holly, E.A., Hong, Y.-C., Hoover, R.N., Dean Hosgood, H., Hsiao, C.-F., Hsing, A.W., Hsiung, C.A., Hu, N., Hu, W., Hu, Z., Huang, M.-S., Hunter, D.J., Inskip, P.D., Ito, H., Jacobs, E.J., Jacobs, K.B., Jenab, M., Ji, B.-T., Johansen, C., Johansson, M., Johnson, A., Kaaks, R., Kamat, A.M., Kamineni, A., Karagas, M., Khanna, C., Khaw, K.-T., Kim, C., Kim, I.-S., Kim, J.H., Kim, Y.H., Kim, Y.-C., Kim, Y.T., Kang, C.H., Jung, Y.J., Kitahara, C.M., Klein, A.P., Klein, R., Kogevinas, M., Koh, W.-P., Kohno, T., Kolonel, L.N., Kooperberg, C., Kratz, C.P., Krogh, V., Kunitoh, H., Kurtz, R.C., Kurucu, N., Lan, Q., Lathrop, M., Lau, C.C., Lecanda, F., Lee, K.-M., Lee, M.P., Marchand, L.L., Lerner, S.P., Li, D., Liao, L.M., Lim, W.-Y., Lin, D., Lin, J., Lindstrom, S., Linet, M.S., Lissowska, J., Liu, J., Ljungberg, B., Lloreta, J., Lu, D., Ma, J., Malats, N., Mannisto, S., Marina, N., Mastrangelo, G., Matsuo, K., McGlynn, K.A., McKean-Cowdin, R., McNeil, L.H., McWilliams, R.R., Melin, B.S., Meltzer, P.S., Mensah, J.E., Miao, X., Michaud, D.S., Mondul, A.M., Moore, L.E., Muir, K., Niwa, S., Olson, S.H., Orr, N., Panico, S., Park, J.Y., Patel, A.V., Patino-Garcia, A., Pavanello, S., Peeters, P.H.M., Peplonska, B., Peters, U., Petersen, G.M., Picci, P., Pike, M.C., Porru, S., Prescott, J., Pu, X., Purdue, M.P., Qiao, Y.-L., Rajaraman, P., Riboli, E., Risch, H.A., Rodabough, R.J., Rothman, N., Ruder, A.M., Ryu, J.-S., Sanson, M., Schned, A., Schumacher, F.R., Schwartz, A.G., Schwartz, K.L., Schwenn, M., Scotlandi, K., Seow, A., Serra, C., Serra, M., Sesso, H.D., Severi, G., Shen, H., Shen, M., Shete, S., Shiraishi, K., Shu, X.-O., Siddiq, A., Sierrasesumaga, L., Sierri, S., Sihoe, A.D.L., Silverman, D.T., Simon, M., Southey, M.C., Spector, L., Spitz, M., Stampfer, M., Stattin, P., Stern, M.C., Stevens, V.L., Stolzenberg-Solomon, R.Z., Stram, D.O., Strom, S.S., Su, W.-C., Sund, M., Sung, S.W., Swerdlow, A., Tan, W., Tanaka, H., Tang, W., Tang, Z.-Z., Tardon, A., Tay, E., Taylor, P.R., Tettey, Y., Thomas, D.M., Tirabosco, R., Tjonneland, A., Tobias, G.S., Toro, J.R., Travis, R.C., Trichopoulos, D., Troisi, R., Truelove, A., Tsai, Y.-H., Tucker, M.A., Tumino, R., Van Den Berg, D., Van Den Eeden, S.K., Vermeulen, R., Vineis, P., Visvanathan, K., Vogel, U., Wang, C., Wang, J., Wang, S.S., Weiderpass, E., Weinstein, S.J., Wentzensen, N., Wheeler, W., White, E., Wiencke, J.K., Wolk, A., Wolpin, B.M., Wong, M.P., Wrensch, M., Wu, C., Wu, T., Wu, X., Wu, Y.-L., Wunder, J.S., Xiang, Y.-B., Xu, J., Yang, H.P., Yang, P.-C., Yatabe, Y., Ye, Y., Yeboah, E.D., Yin, Z., Ying, C., Yu, C.-J., Yu, K., Yuan, J.-M., Zanetti, K.A., Zeleniuch-Jacquotte, A., Zheng, W., Zhou, B., Mirabello, L., Savage, S.A., Kraft, P., Chanock, S.J., Yeager, M., Landi, M.T., Shi, J., Chatterjee, N., and Amundadottir, L.T.

Subjects
Male, SINGLE-NUCLEOTIDE POLYMORPHISM, Genome-wide association study, Epigenesis, Genetic, Gene Frequency, Molecular Biology, Genetics, Genetics (clinical), Neoplasms, Odds Ratio, Genome-wide association studies (GWAS), Telomerase, DNA METHYLATION Author Information, Association Studies Articles, General Medicine, PANCREATIC-CANCER, PROSTATE-CANCER, Neoplasm Proteins, POSTMENOPAUSAL BREAST-CANCER, TERT PROMOTER MUTATIONS, Gene Expression Regulation, Neoplastic, 2 SUSCEPTIBILITY LOCI, DNA methylation, Chromosomes, Human, Pair 5, Female, Risk, Locus (genetics), Single-nucleotide polymorphism, TERT and CLPTM1L gene, Biology, Polymorphism, Single Nucleotide, LUNG-CANCER, Humans, Genetic Predisposition to Disease, GENOME-WIDE ASSOCIATION, Allele, Gene, Allele frequency, Alleles, Genetic association, chromosome 5p15.33, Computational Biology, Membrane Proteins, DNA Methylation, Genetic Loci, TELOMERE LENGTH, Genome-Wide Association Study
Abstract

Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 x 10(-39); Region 3: rs2853677, P = 3.30 x 10(-36) and PConditional = 2.36 x 10(-8); Region 4: rs2736098, P = 3.87 x 10(-12) and PConditional = 5.19 x 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 x 10(-6); and Region 6: rs10069690, P = 7.49 x 10(-15) and PConditional = 5.35 x 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 x 10(-18) and PConditional = 7.06 x 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

Published
2014

36. A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci

Author

Rajesh Kumar, Gerald L. Andriole, Robert L. Grubb, Monica McGrath, Amanda Black, Manuela Gago-Dominguez, Margaret A. Knowles, Francisco X. Real, Nilanjan Chatterjee, Thorunn Rafnar, Kevin B. Jacobs, Silvia Polidoro, Debra T. Silverman, Sita H. Vermeulen, Manuel Sanchez, Núria Malats, Salvatore Panico, Amy Hutchinson, William Wheeler, Carmen Navarro, Montserrat Garcia-Closas, Carlotta Sacerdote, Gabriel Valdivia, Yi-Ping Fu, Kari Stefansson, Michelle A.T. Hildebrandt, Alessandra Allione, Katja K.H. Aben, Alison Johnson, W. Ryan Diver, Laurie Burdett, Sophia C.E. Bolick, David J. Hunter, Jarmo Virtamo, Jack A. Taylor, Ludmila Prokunina-Olsson, José I Sanz-Velez, Mark P. Purdue, Fulvio Ricceri, Elio Riboli, Maria Teresa Landi, Susan M. Gapstur, Søren Besenbacher, Joseph F. Fraumeni, Olivier Cussenot, J. Alfred Witjes, Victoria K. Cortessis, Paul Brennan, Tony Fletcher, David Van Den Berg, Börje Ljungberg, Lambertus A. Kiemeney, Dalsu Baris, Mark Teo, Zongli Xu, Geraldine Cancel-Tassin, Holger Dietrich, Zhaoming Wang, Maria D. Garcia-Prats, Françoise Clavel-Chapelon, Adonina Tardón, Paolo Vineis, Peter Rudnai, Margaret R. Karagas, Naomi E. Allen, H. Bas Bueno-de-Mesquita, Molly Schwenn, Jose I. Mayordomo, Ashley C. Godfrey, Manolis Kogevinas, Silvia Selinski, Stephen J. Chanock, Jonine D. Figueroa, Alan R. Schned, Stefano Porru, Mariana C. Stern, Demetrius Albanes, Simonetta Guarrera, Patrick Sulem, Immaculata De Vivo, Hushan Yang, Robert N. Hoover, Kvetoslava Koppova, Michael J. Thun, Malcolm C. Pike, Giuseppe Matullo, D T Bishop, Neil E. Caporaso, Klaus Golka, Eugen Gurzau, Colin P.N. Dinney, Josep Lloreta, Nathaniel Rothman, Eric J. Jacobs, Simone Benhamou, Alfredo Carrato, Federico Canzian, Xifeng Wu, Consol Serra, Anne Tjønneland, Jian-Min Yuan, Meredith Yeager, Reina García-Closas, Stephanie J. Weinstein, Jan G. Hengstler, Dimitrios Trichopoulos, Remco R. R. Makkinje, Anne E. Kiltie, Bogdan Czerniak, Meng Chen, Rothman, N, Garcia Closas, M, Chatterjee, N, Malats, N, Wu, X, Figueroa, Jd, Real, Fx, Van Den Berg, D, Matullo, G, Baris, D, Thun, M, Kiemeney, La, Vineis, P, De Vivo, I, Albanes, D, Purdue, Mp, Rafnar, T, Hildebrandt, Ma, Kiltie, Ae, Cussenot, O, Golka, K, Kumar, R, Taylor, Ja, Mayordomo, Ji, Jacobs, Kb, Kogevinas, M, Hutchinson, A, Wang, Z, Fu, Yp, Prokunina Olsson, L, Burdett, L, Yeager, M, Wheeler, W, Tardón, A, Serra, C, Carrato, A, García Closas, R, Lloreta, J, Johnson, A, Schwenn, M, Karagas, Mr, Schned, A, Andriole G., Jr, Grubb R., 3rd, Black, A, Jacobs, Ej, Diver, Wr, Gapstur, Sm, Weinstein, Sj, Virtamo, J, Cortessis, Vk, Gago Dominguez, M, Pike, Mc, Stern, Mc, Yuan, Jm, Hunter, Dj, Mcgrath, M, Dinney, Cp, Czerniak, B, Chen, M, Yang, H, Vermeulen, Sh, Aben, Kk, Witjes, Ja, Makkinje, Rr, Sulem, P, Besenbacher, S, Stefansson, K, Riboli, E, Brennan, P, Panico, Salvatore, Navarro, C, Allen, Ne, Bueno de Mesquita, Hb, Trichopoulos, D, Caporaso, Nicola, Landi, Mt, Canzian, F, Ljungberg, B, Tjonneland, A, Clavel Chapelon, F, Bishop, Dt, Teo, Mt, Knowles, Ma, Guarrera, S, Polidoro, S, Ricceri, F, Sacerdote, C, Allione, A, Cancel Tassin, G, Selinski, S, Hengstler, Jg, Dietrich, H, Fletcher, T, Rudnai, P, Gurzau, E, Koppova, K, Bolick, Sc, Godfrey, A, Xu, Z, Sanz Velez, Ji, D., García Prats M, Sanchez, M, Valdivia, G, Porru, S, Benhamou, S, Hoover, Rn, Fraumeni JF, Jr, Silverman, Dt, and Chanock, Sj

Subjects
Male, Arylamine N-Acetyltransferase, Chromosomes, Human, Pair 22, Genome-wide association study, Aetiology, screening and detection [ONCOL 5], medicine.disease_cause, Genome-wide association studies, Risk Factors, genome-wide association, bladder cancer, Psychology, Genetics, Sex Characteristics, Incidence, Bladder cancer, Smoking, Chromosome Mapping, Single Nucleotide, Tag SNP, Europe, Chromosomes, Human, Pair 2, Pair 2, Female, Human, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Risk Assessment, Chromosomes, Article, Molecular epidemiology [NCEBP 1], Translational research [ONCOL 3], medicine, Humans, Family, Genetic Predisposition to Disease, Polymorphism, Pair 18, Pair 22, Genome-Wide Association Study, Neoplasm Staging, Spain, United States, Urinary Bladder Neoplasms, Cancer, Chromosome, medicine.disease, Evaluation of complex medical interventions [NCEBP 2], Carcinogenesis, Chromosomes, Human, Pair 18
Abstract

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis.

Published
2010

37. Vitamin D receptor polymorphisms and breast cancer risk: results from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium

Author

Barbara Saltzman, H. Bas Bueno-de-Mesquita, Stephen J. Chanock, Walter C. Willett, Michael J. Thun, Jakob Linseisen, Kim Overvad, Dimitrios Trichopoulos, Jeffrey Yuenger, Julie E. Buring, Eugenia E. Calle, Susan E. Hankinson, Sheila Bingham, Heather Spencer Feigelson, Laurie Burdette, Robert N. Hoover, Laurence N. Kolonel, Laure Dossus, Françoise Clavel-Chapelon, Marjorie L. McCullough, Mark P. Purdue, Anika Hüsing, Christopher A. Haiman, Regina G. Ziegler, Christine D. Berg, Goran Bergland, Salvatore Panico, Catherine A. McCarty, Rudolph Kaaks, Aurelio Barricarte, David J. Hunter, Daniel O. Stram, Magritt Brustad, Peter Kraft, James D. McKay, Loic Le Marchand, Victoria L. Stevens, David G. Cox, Elio Riboli, Mckay, Jd, Mccullough, Ml, Ziegler, Rg, Kraft, P, Saltzman, B, Riboli, E, Barricarte, A, Berg, Cd, Bergland, G, Bingham, S, Brustad, M, Bueno de Mesquita, Hb, Burdette, L, Buring, J, Calle, Ee, Chanock, Sj, Clavel Chapelon, F, Cox, Dg, Dossus, L, Feigelson, H, Haiman, Ca, Hankinson, Se, Hoover, Rn, Hunter, Dj, Husing, A, Kaaks, R, Kolonel, Ln, Le Marchand, L, Linseisen, J, Mccarty, Ca, Overvad, K, Panico, Salvatore, Purdue, Mp, Stram, Do, Stevens, Vl, Trichopoulos, D, Willett, Wc, Yuenger, J, and Thun, M. J.

Subjects
Oncology, Adult, Risk, medicine.medical_specialty, Genotype, Epidemiology, Breast Neoplasms, Calcitriol receptor, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Prostate cancer, Breast cancer, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Aged, business.industry, Cancer, Odds ratio, Middle Aged, medicine.disease, Endocrinology, Logistic Models, Case-Control Studies, Receptors, Calcitriol, Female, Breast disease, business
Abstract

Background: Vitamin D is hypothesized to lower the risk of breast cancer by inhibiting cell proliferation via the nuclear vitamin D receptor (VDR). Two common single nucleotide polymorphisms (SNP) in the VDR gene (VDR), rs1544410 (BsmI), and rs2228570 (FokI), have been inconsistently associated with breast cancer risk. Increased risk has been reported for the FokI ff genotype, which encodes a less transcriptionally active isoform of VDR, and reduced risk has been reported for the BsmI BB genotype, a SNP in strong linkage disequilibrium with a 3′-untranslated region, which may influence VDR mRNA stability. Methods: We pooled data from 6 prospective studies in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium to examine associations between these SNPs and breast cancer among >6,300 cases and 8,100 controls for each SNP using conditional logistic regression. Results: The odds ratio (OR) for the rs2228570 (FokI) ff versus FF genotype in the overall population was statistically significantly elevated [OR, 1.16; 95% confidence interval (95% CI), 1.04-1.28] but was weaker once data from the cohort with previously published positive findings were removed (OR, 1.10; 95% CI, 0.98-1.24). No association was noted between rs1544410 (BsmI) BB and breast cancer risk overall (OR, 0.98; 95% CI, 0.89-1.09), but the BB genotype was associated with a significantly lower risk of advanced breast cancer (OR, 0.74; 95% CI, 0.60-0.92). Conclusions: Although the evidence for independent contributions of these variants to breast cancer susceptibility remains equivocal, future large studies should integrate genetic variation in VDR with biomarkers of vitamin D status. (Cancer Epidemiol Biomarkers Prev 2009;18(1):297–305)

Published
2009

39. How well does a single blood sample represent long-term exposure for epidemiological studies of PFOA among men in the general population?

Author

Bartell SM, Purdue MP, Rhee J, Nøst TH, Rusiecki J, and Steenland K

Subjects
Humans, Male, Norway epidemiology, Environmental Pollutants blood, Epidemiologic Studies, Computer Simulation, Time Factors, Adult, Fluorocarbons blood, Caprylates blood, Environmental Exposure statistics & numerical data
Abstract

Many epidemiological studies use a single blood sample per participant to assess exposure, but it is unclear how well a single sample represents longer term exposure. We performed a simulation study using summary statistics for repeated serum PFOA measurements from several previous studies in men to generate plausible serum concentrations over time, taking within-subject correlations into account. Simulated serum concentrations for controls were categorized into quintiles at each time point, and used to determine the extent of misclassification at each time point compared to the "true" long-term average exposure. We then generated case counts by quintile needed to produce an odds ratio (OR) of 1.5 for the highest vs. lowest quintile categorized based on long term exposure, and used the same misclassification rates observed in the controls to simulate misclassified exposure quintiles for cases. Comparing long term vs. single baseline exposure measures for repeated serum samples collected within about 5-13 years of each other revealed similar effect estimates, although there was a small bias to the null. Trend tests across quintiles were mostly significant using either baseline or long-term exposure. For the general population sample of men in Norway, with 5 repeated measurements over 28 years, serum PFOA was substantially lower prior to 1987, and using either of the two earliest samples as the exposure metric, compared to the long term average, produced larger bias to the null and non-significant trend tests; however using later time points as the exposure metric resulted in only a small bias. Using data based on studies of men, single baseline serum samples represented rather well the mean of repeated samples collectedup to 13 years apart, but were not always reliable surrogates for average exposure over 3 decades, during which time PFOA exposure levels in the general population have changed substantially., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Scott M. Bartell has served as a compensated expert witness for PFOA medical monitoring lawsuits in New Hampshire. The terms of this arrangement were reviewed and approved by the University of California, Irvine in accordance with its conflict-of-interest policies. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2024
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40. Serum concentrations of per- and polyfluorinated substances and risk of B-cell non-Hodgkin lymphoma.

Author

Rhee J, Koponen J, Sampson JN, Keil AP, Ward MH, Hofmann JN, Huang WY, Silverman DT, Rantakokko P, and Purdue MP

Subjects
Humans, Middle Aged, Male, Female, Aged, Case-Control Studies, Aged, 80 and over, Environmental Pollutants blood, Lymphoma, B-Cell blood, Alkanesulfonic Acids blood, Environmental Exposure statistics & numerical data, Odds Ratio, Lymphoma, Non-Hodgkin blood, Lymphoma, Non-Hodgkin epidemiology, Sulfonic Acids blood, Fluorocarbons blood
Abstract

Per- and polyfluoroalkyl substances (PFAS) are persistent organic pollutants that are detectable in the serum of most U.S. adults. Some studies of highly-exposed individuals have suggested positive associations between PFAS and B-cell non-Hodgkin lymphoma (B-NHL). To investigate whether associations exist at lower exposure levels, we conducted a nested case-control study investigating serum PFAS concentrations and B-NHL within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We measured pre-diagnostic serum concentrations of five PFAS among 706 cases (age at diagnosis = 55-93 years, median 73 years) and 706 controls individually matched on age at blood draw, sex, self-reported race and ethnicity, study center, and year of blood collection (the median follow-up years = 10). We estimated odds ratios (ORs) and 95 % confidence intervals (CIs) for PFAS concentrations in relation to B-NHL, both overall and for selected histologic subtypes [diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), and marginal zone lymphoma (MZL)] using conditional logistic regression. We found no evidence of a positive association with B-NHL for any of the five PFAS. In analyses of histologic subtypes, perfluorohexane sulfonate (PFHxS) was significantly associated with DLBCL in a model adjusting for all other PFAS (OR for highest vs. lowest quintile = 2.19, 95 % CI = 1.21, 3.95; P trend  = 0.02), but not in a model without mutual adjustment (OR = 1.37, 95 % CI = 0.82, 2.29; P trend  = 0.26). We also observed an inverse association between perfluorononanoate and DLBCL (mutually-adjusted OR = 0.83, 95 % CI = 0.69, 0.99 per doubling in concentration), although the association was null among participants with blood drawn prior to 1997 (OR <1997  = 1.00, 95 % CI = 0.82, 1.21; OR ≥1997  = 0.65, 95 % CI = 0.53, 0.79; P interaction  = 0.0003). In conclusion, our findings from a prospective cohort study with PFAS serum concentrations comparable to that of the general population do not support an association with increased risk of B-NHL overall. The suggestive evidence of a positive association between PFHxS and DLBCL warrants further investigation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

Published
2024
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41. Transcriptome- and proteome-wide association studies identify genes associated with renal cell carcinoma.

Author

Dutta D, Guo X, Winter TD, Jahagirdar O, Ha E, Susztak K, Machiela MJ, Chanock SJ, and Purdue MP

Subjects
Humans, Genetic Predisposition to Disease, Gene Expression Regulation, Neoplastic, Polymorphism, Single Nucleotide, Gene Expression Profiling, Carcinoma, Renal Cell genetics, Genome-Wide Association Study, Kidney Neoplasms genetics, Transcriptome, Proteome genetics
Abstract

We performed a series of integrative analyses including transcriptome-wide association studies (TWASs) and proteome-wide association studies (PWASs) of renal cell carcinoma (RCC) to nominate and prioritize molecular targets for laboratory investigation. On the basis of a genome-wide association study (GWAS) of 29,020 affected individuals and 835,670 control individuals and prediction models trained in transcriptomic reference models, our TWAS across four kidney transcriptomes (GTEx kidney cortex, kidney tubules, TCGA-KIRC [The Cancer Genome Atlas kidney renal clear-cell carcinoma], and TCGA-KIRP [TCGA kidney renal papillary cell carcinoma]) identified 38 gene associations (false-discovery rate <5%) in at least two of four transcriptomic panels and identified 12 genes that were independent of GWAS susceptibility regions. Analyses combining TWAS associations across 48 tissues from GTEx identified associations that were replicable in tumor transcriptomes for 23 additional genes. Analyses by the two major histologic types (clear-cell RCC and papillary RCC) revealed subtype-specific associations, although at least three gene associations were common to both subtypes. PWAS identified 13 associated proteins, all mapping to GWAS-significant loci. TWAS-identified genes were enriched for active enhancer or promoter regions in RCC tumors and hypoxia-inducible factor binding sites in relevant cell lines. Using gene expression correlation, common cancers (breast and prostate) and RCC risk factors (e.g., hypertension and BMI) display genetic contributions shared with RCC. Our work identifies potential molecular targets for RCC susceptibility for downstream functional investigation., Competing Interests: Declaration of interests K.S. receives research support from Gilead, GSK, Novo Nordisk, Bayer, Regeneron, Calico, and Novartis. K.S. is on the advisory board of Jnana Therapeutics and has received consulting fees from Pfizer and Jnana. Declaration of interests for the Renal Cancer Genetics Consortium, which contributed toward acquisition of the individual-level data, can be referred to as a part of Purdue et al.(10) The other named authors in the manuscript have no competing interests to declare. It is to be noted that the individual-level data contributed by The Renal Cancer Genetics Consortium is now publicly available, and the current analyses were conducted with summary-level data only., (Published by Elsevier Inc.)

Published
2024
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42. Occupational exposure to benzene and risk of non-Hodgkin lymphoma in an extended follow-up of two population-based prospective cohorts of Chinese men and women.

Author

Bassig BA, Shu XO, Friesen MC, Vermeulen R, Purdue MP, Ji BT, Yang G, Wong JYY, Appel N, Hu W, Gao YT, Zheng W, Rothman N, and Lan Q

Subjects
Humans, Female, Male, Middle Aged, China epidemiology, Follow-Up Studies, Prospective Studies, Adult, Aged, Risk Factors, Multiple Myeloma epidemiology, Multiple Myeloma chemically induced, Multiple Myeloma etiology, Occupational Diseases epidemiology, Occupational Diseases chemically induced, Proportional Hazards Models, East Asian People, Benzene toxicity, Benzene adverse effects, Occupational Exposure adverse effects, Lymphoma, Non-Hodgkin epidemiology, Lymphoma, Non-Hodgkin chemically induced, Lymphoma, Non-Hodgkin etiology
Abstract

The carcinogenicity of benzene was reevaluated by the International Agency for Research on Cancer in 2017, with the Working Group reaffirming positive yet inconclusive associations with non-Hodgkin lymphoma (NHL). To extend our previous observation of a significant exposure-response for cumulative occupational benzene exposure and NHL risk among Chinese women in a population-based cohort in Shanghai, we extended follow-up of this cohort and pooled the data with a similarly designed population-based cohort of men in Shanghai. Cumulative exposure estimates were derived for 134,449 participants in the pooled analysis by combining ordinal job-exposure matrix intensity ratings with quantitative benzene measurements from an inspection database of Shanghai factories. Associations between benzene exposure metrics and NHL (n = 363 cases including multiple myeloma [MM]) were assessed using Cox proportional hazard models. Ever occupational exposure to benzene in the pooled population was associated with NHL risk (HR = 1.5, 95% CI = 1.2-2.0), and exposure-response relationships were observed for increasing duration (p trend  = .003) and cumulative exposure (p trend  = .003). Associations with ever exposure, duration, and cumulative exposure were similar for NHL with and without MM in the case definition, including lifetime cumulative exposures in the highest quartile (HR = 1.6, 95% CI = 1.1-2.4 with MM included; HR = 1.7, 95% CI = 1.1-2.7 with MM excluded). An elevated risk of the chronic lymphocytic leukemia subtype was suggested in the pooled analyses (HR for ever vs. never exposure = 2.3, 95% CI = 0.9-5.6). These observations provide additional support for a plausible association between occupational benzene exposure and risk of NHL., (© 2024 The Author(s). International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Published
2024
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43. Association of tea and coffee consumption and biliary tract cancer risk: The Biliary Tract Cancers Pooling Project.

Author

Huang YH, Loftfield E, Argirion I, Adami HO, Albanes D, Chan AT, Fedirko V, Fraser GE, Freedman ND, Giles GG, Hartge P, Katzke V, Knutsen SF, Lacey J Jr, Liao LM, Luo J, Milne RL, O'Brien KM, Peters U, Poynter JN, Purdue MP, Robien K, Sandin S, Sandler DP, Setiawan VW, Kang JH, Simon TG, Sinha R, VoPham T, Weinstein SJ, White E, Zhang X, Zhu B, McGlynn KA, Campbell PT, Lee MH, and Koshiol J

Subjects
Humans, Male, Female, Middle Aged, Aged, Incidence, Gallbladder Neoplasms epidemiology, Gallbladder Neoplasms etiology, Gallbladder Neoplasms prevention & control, Risk Factors, Adult, Bile Duct Neoplasms epidemiology, Bile Duct Neoplasms etiology, Coffee, Tea, Biliary Tract Neoplasms epidemiology, Biliary Tract Neoplasms etiology
Abstract

Background and Aims: Tea and coffee are widely consumed beverages worldwide. We evaluated their association with biliary tract cancer (BTC) incidence., Approach and Results: We pooled data from 15 studies in the Biliary Tract Cancers Pooling Project to evaluate associations between tea and coffee consumption and biliary tract cancer development. We categorized participants as nondrinkers (0 cup/day), moderate drinkers (>0 and <3 cups/day), and heavy drinkers (≥3 cups/day). We estimated multivariable HRs and 95% CIs using Cox models. During 29,911,744 person-years of follow-up, 851 gallbladder, 588 intrahepatic bile duct, 753 extrahepatic bile duct, and 458 ampulla of Vater cancer cases were diagnosed. Individuals who drank tea showed a statistically significantly lower incidence rate of gallbladder cancer (GBC) relative to tea nondrinkers (HR=0.77; 95% CI, 0.64-0.91), and intrahepatic bile duct cancer (IHBDC) had an inverse association (HR=0.81; 95% CI, 0.66-1.00). However, no associations were observed for extrahepatic bile duct cancer (EHBDC) or ampulla of Vater cancer (AVC). In contrast, coffee consumption was positively associated with GBC, with a higher incidence rate for individuals consuming more coffee (HR<3 cups/day =1.29; 95% CI, 1.01-1.66; HR≥3 cups/day =1.49; 95% CI, 1.11-1.99, Ptrend=0.01) relative to coffee nondrinkers. However, there was no association between coffee consumption and GBC when restricted to coffee drinkers. There was little evidence of associations between coffee consumption and other biliary tract cancers., Conclusions: Tea consumption was associated with a lower incidence of GBC and possibly IHBDC. Further research is warranted to replicate the observed positive association between coffee and GBC., (Copyright © 2023 American Association for the Study of Liver Diseases.)

Published
2024
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44. Multi-ancestry genome-wide association study of kidney cancer identifies 63 susceptibility regions.

Author

Purdue MP, Dutta D, Machiela MJ, Gorman BR, Winter T, Okuhara D, Cleland S, Ferreiro-Iglesias A, Scheet P, Liu A, Wu C, Antwi SO, Larkin J, Zequi SC, Sun M, Hikino K, Hajiran A, Lawson KA, Cárcano F, Blanchet O, Shuch B, Nepple KG, Margue G, Sundi D, Diver WR, Folgueira MAAK, van Bokhoven A, Neffa F, Brown KM, Hofmann JN, Rhee J, Yeager M, Cole NR, Hicks BD, Manning MR, Hutchinson AA, Rothman N, Huang WY, Linehan WM, Lori A, Ferragu M, Zidane-Marinnes M, Serrano SV, Magnabosco WJ, Vilas A, Decia R, Carusso F, Graham LS, Anderson K, Bilen MA, Arciero C, Pellegrin I, Ricard S, Scelo G, Banks RE, Vasudev NS, Soomro N, Stewart GD, Adeyoju A, Bromage S, Hrouda D, Gibbons N, Patel P, Sullivan M, Protheroe A, Nugent FI, Fournier MJ, Zhang X, Martin LJ, Komisarenko M, Eisen T, Cunningham SA, Connolly DC, Uzzo RG, Zaridze D, Mukeria A, Holcatova I, Hornakova A, Foretova L, Janout V, Mates D, Jinga V, Rascu S, Mijuskovic M, Savic S, Milosavljevic S, Gaborieau V, Abedi-Ardekani B, McKay J, Johansson M, Phouthavongsy L, Hayman L, Li J, Lungu I, Bezerra SM, Souza AG, Sares CTG, Reis RB, Gallucci FP, Cordeiro MD, Pomerantz M, Lee GM, Freedman ML, Jeong A, Greenberg SE, Sanchez A, Thompson RH, Sharma V, Thiel DD, Ball CT, Abreu D, Lam ET, Nahas WC, Master VA, Patel AV, Bernhard JC, Freedman ND, Bigot P, Reis RM, Colli LM, Finelli A, Manley BJ, Terao C, Choueiri TK, Carraro DM, Houlston R, Eckel-Passow JE, Abbosh PH, Ganna A, Brennan P, Gu J, and Chanock SJ

Subjects
Humans, Case-Control Studies, Von Hippel-Lindau Tumor Suppressor Protein genetics, White People genetics, Black People, Carcinoma, Renal Cell genetics, Genetic Predisposition to Disease, Genome-Wide Association Study, Kidney Neoplasms genetics, Polymorphism, Single Nucleotide, Quantitative Trait Loci
Abstract

Here, in a multi-ancestry genome-wide association study meta-analysis of kidney cancer (29,020 cases and 835,670 controls), we identified 63 susceptibility regions (50 novel) containing 108 independent risk loci. In analyses stratified by subtype, 52 regions (78 loci) were associated with clear cell renal cell carcinoma (RCC) and 6 regions (7 loci) with papillary RCC. Notably, we report a variant common in African ancestry individuals ( rs7629500 ) in the 3' untranslated region of VHL, nearly tripling clear cell RCC risk (odds ratio 2.72, 95% confidence interval 2.23-3.30). In cis-expression quantitative trait locus analyses, 48 variants from 34 regions point toward 83 candidate genes. Enrichment of hypoxia-inducible factor-binding sites underscores the importance of hypoxia-related mechanisms in kidney cancer. Our results advance understanding of the genetic architecture of kidney cancer, provide clues for functional investigation and enable generation of a validated polygenic risk score with an estimated area under the curve of 0.65 (0.74 including risk factors) among European ancestry individuals., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Published
2024
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45. Geographic variation of mutagenic exposures in kidney cancer genomes.

Author

Senkin S, Moody S, Díaz-Gay M, Abedi-Ardekani B, Cattiaux T, Ferreiro-Iglesias A, Wang J, Fitzgerald S, Kazachkova M, Vangara R, Le AP, Bergstrom EN, Khandekar A, Otlu B, Cheema S, Latimer C, Thomas E, Atkins JR, Smith-Byrne K, Cortez Cardoso Penha R, Carreira C, Chopard P, Gaborieau V, Keski-Rahkonen P, Jones D, Teague JW, Ferlicot S, Asgari M, Sangkhathat S, Attawettayanon W, Świątkowska B, Jarmalaite S, Sabaliauskaite R, Shibata T, Fukagawa A, Mates D, Jinga V, Rascu S, Mijuskovic M, Savic S, Milosavljevic S, Bartlett JMS, Albert M, Phouthavongsy L, Ashton-Prolla P, Botton MR, Silva Neto B, Bezerra SM, Curado MP, Zequi SC, Reis RM, Faria EF, de Menezes NS, Ferrari RS, Banks RE, Vasudev NS, Zaridze D, Mukeriya A, Shangina O, Matveev V, Foretova L, Navratilova M, Holcatova I, Hornakova A, Janout V, Purdue MP, Rothman N, Chanock SJ, Ueland PM, Johansson M, McKay J, Scelo G, Chanudet E, Humphreys L, de Carvalho AC, Perdomo S, Alexandrov LB, Stratton MR, and Brennan P

Subjects
Female, Humans, Male, Aristolochic Acids adverse effects, Genome, Human genetics, Genomics, Hypertension epidemiology, Incidence, Japan epidemiology, Obesity epidemiology, Risk Factors, Romania epidemiology, Serbia epidemiology, Thailand epidemiology, Tobacco Smoking adverse effects, Tobacco Smoking genetics, Carcinoma, Renal Cell genetics, Carcinoma, Renal Cell epidemiology, Carcinoma, Renal Cell chemically induced, Environmental Exposure adverse effects, Environmental Exposure analysis, Geography, Kidney Neoplasms genetics, Kidney Neoplasms epidemiology, Kidney Neoplasms chemically induced, Mutagens adverse effects, Mutation
Abstract

International differences in the incidence of many cancer types indicate the existence of carcinogen exposures that have not yet been identified by conventional epidemiology make a substantial contribution to cancer burden 1 . In clear cell renal cell carcinoma, obesity, hypertension and tobacco smoking are risk factors, but they do not explain the geographical variation in its incidence 2 . Underlying causes can be inferred by sequencing the genomes of cancers from populations with different incidence rates and detecting differences in patterns of somatic mutations. Here we sequenced 962 clear cell renal cell carcinomas from 11 countries with varying incidence. The somatic mutation profiles differed between countries. In Romania, Serbia and Thailand, mutational signatures characteristic of aristolochic acid compounds were present in most cases, but these were rare elsewhere. In Japan, a mutational signature of unknown cause was found in more than 70% of cases but in less than 2% elsewhere. A further mutational signature of unknown cause was ubiquitous but exhibited higher mutation loads in countries with higher incidence rates of kidney cancer. Known signatures of tobacco smoking correlated with tobacco consumption, but no signature was associated with obesity or hypertension, suggesting that non-mutagenic mechanisms of action underlie these risk factors. The results of this study indicate the existence of multiple, geographically variable, mutagenic exposures that potentially affect tens of millions of people and illustrate the opportunities for new insights into cancer causation through large-scale global cancer genomics., (© 2024. The Author(s).)

Published
2024
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46. Advisory Group recommendations on priorities for the IARC Monographs.

Author

Berrington de González A, Masten SA, Bhatti P, Fortner RT, Peters S, Santonen T, Yakubovskaya MG, Barouki R, Barros SBM, Barupal D, Beane Freeman LE, Calaf GM, Dillner J, El Rhazi K, Fritschi L, Fukushima S, Godderis L, Kogevinas M, Lachenmeier DW, Mandrioli D, Muchengeti MM, Niemeier RT, Pappas JJ, Pi J, Purdue MP, Riboli E, Rodríguez T, Schlünssen V, Benbrahim-Tallaa L, de Conti A, Facchin C, Pasqual E, Wedekind R, Ahmadi A, Chittiboyina S, Herceg Z, Kulasingam S, Lauby-Secretan B, MacLehose R, Sanaa M, Schüz J, Suonio E, Zavadil J, Mattock H, Madia F, and Schubauer-Berigan MK

Subjects
Humans, Advisory Committees, Health Priorities, Neoplasms therapy
Published
2024
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47. The Mutographs biorepository: A unique genomic resource to study cancer around the world.

Author

Perdomo S, Abedi-Ardekani B, de Carvalho AC, Ferreiro-Iglesias A, Gaborieau V, Cattiaux T, Renard H, Chopard P, Carreira C, Spanu A, Nikmanesh A, Cardoso Penha RC, Antwi SO, Ashton-Prolla P, Canova C, Chitapanarux T, Cox R, Curado MP, de Oliveira JC, Dzamalala C, Fabianova E, Ferri L, Fitzgerald R, Foretova L, Gallinger S, Goldstein AM, Holcatova I, Huertas A, Janout V, Jarmalaite S, Kaneva R, Kowalski LP, Kulis T, Lagiou P, Lissowska J, Malekzadeh R, Mates D, McCorrmack V, Menya D, Mhatre S, Mmbaga BT, de Moricz A, Nyirády P, Ognjanovic M, Papadopoulou K, Polesel J, Purdue MP, Rascu S, Rebolho Batista LM, Reis RM, Ribeiro Pinto LF, Rodríguez-Urrego PA, Sangkhathat S, Sangrajrang S, Shibata T, Stakhovsky E, Świątkowska B, Vaccaro C, Vasconcelos de Podesta JR, Vasudev NS, Vilensky M, Yeung J, Zaridze D, Zendehdel K, Scelo G, Chanudet E, Wang J, Fitzgerald S, Latimer C, Moody S, Humphreys L, Alexandrov LB, Stratton MR, and Brennan P

Subjects
Humans, Genomics, Databases, Factual, Delivery of Health Care, Biological Specimen Banks, Neoplasms diagnosis
Abstract

Large-scale biorepositories and databases are essential to generate equitable, effective, and sustainable advances in cancer prevention, early detection, cancer therapy, cancer care, and surveillance. The Mutographs project has created a large genomic dataset and biorepository of over 7,800 cancer cases from 30 countries across five continents with extensive demographic, lifestyle, environmental, and clinical information. Whole-genome sequencing is being finalized for over 4,000 cases, with the primary goal of understanding the causes of cancer at eight anatomic sites. Genomic, exposure, and clinical data will be publicly available through the International Cancer Genome Consortium Accelerating Research in Genomic Oncology platform. The Mutographs sample and metadata biorepository constitutes a legacy resource for new projects and collaborations aiming to increase our current research efforts in cancer genomic epidemiology globally., Competing Interests: Declaration of interests M.R.S. is founder of, consultant to, and stockholder in Quotient Therapeutics. L.B.A. is a compensated consultant and has equity interest in io9, LLC, and Genome Insight. His spouse is an employee of Biotheranostics, Inc. L.B.A. is also an inventor of a US patent 10,776,718 for source identification by non-negative matrix factorization. L.B.A. declares US provisional applications with serial numbers 63/289,601; 63/269,033; and 63/483,237. L.B.A. also declares US provisional applications with serial numbers 63/366,392; 63/367,846; 63/412,835; and 63/492,348., (Copyright © 2024. Published by Elsevier Inc.)

Published
2024
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48. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysis.

Author

Yarmolinsky J, Robinson JW, Mariosa D, Karhunen V, Huang J, Dimou N, Murphy N, Burrows K, Bouras E, Smith-Byrne K, Lewis SJ, Galesloot TE, Kiemeney LA, Vermeulen S, Martin P, Albanes D, Hou L, Newcomb PA, White E, Wolk A, Wu AH, Le Marchand L, Phipps AI, Buchanan DD, Zhao SS, Gill D, Chanock SJ, Purdue MP, Davey Smith G, Brennan P, Herzig KH, Järvelin MR, Amos CI, Hung RJ, Dehghan A, Johansson M, Gunter MJ, Tsilidis KK, and Martin RM

Subjects
Adult, Humans, Mendelian Randomization Analysis, Risk, Inflammation genetics, Polymorphism, Single Nucleotide, Genome-Wide Association Study, Neoplasms epidemiology, Neoplasms genetics
Abstract

Background: Tumour-promoting inflammation is a "hallmark" of cancer and conventional epidemiological studies have reported links between various inflammatory markers and cancer risk. The causal nature of these relationships and, thus, the suitability of these markers as intervention targets for cancer prevention is unclear., Methods: We meta-analysed 6 genome-wide association studies of circulating inflammatory markers comprising 59,969 participants of European ancestry. We then used combined cis-Mendelian randomization and colocalisation analysis to evaluate the causal role of 66 circulating inflammatory markers in risk of 30 adult cancers in 338,294 cancer cases and up to 1,238,345 controls. Genetic instruments for inflammatory markers were constructed using genome-wide significant (P < 5.0 × 10 -8 ) cis-acting SNPs (i.e., in or ±250 kb from the gene encoding the relevant protein) in weak linkage disequilibrium (LD, r 2  < 0.10). Effect estimates were generated using inverse-variance weighted random-effects models and standard errors were inflated to account for weak LD between variants with reference to the 1000 Genomes Phase 3 CEU panel. A false discovery rate (FDR)-corrected P-value ("q-value") <0.05 was used as a threshold to define "strong evidence" to support associations and 0.05 ≤ q-value < 0.20 to define "suggestive evidence". A colocalisation posterior probability (PPH 4 ) >70% was employed to indicate support for shared causal variants across inflammatory markers and cancer outcomes. Findings were replicated in the FinnGen study and then pooled using meta-analysis., Findings: We found strong evidence to support an association of genetically-proxied circulating pro-adrenomedullin concentrations with increased breast cancer risk (OR: 1.19, 95% CI: 1.10-1.29, q-value = 0.033, PPH 4  = 84.3%) and suggestive evidence to support associations of interleukin-23 receptor concentrations with increased pancreatic cancer risk (OR: 1.42, 95% CI: 1.20-1.69, q-value = 0.055, PPH 4  = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53-0.81, q-value = 0.067, PPH 4  = 81.8%), and interleukin-1 receptor-like 1 concentrations with decreased triple-negative breast cancer risk (OR: 0.92, 95% CI: 0.88-0.97, q-value = 0.15, PPH 4  = 85.6%). These findings were replicated in pooled analyses with the FinnGen study. Though suggestive evidence was found to support an association of macrophage migration inhibitory factor concentrations with increased bladder cancer risk (OR: 2.46, 95% CI: 1.48-4.10, q-value = 0.072, PPH 4  = 76.1%), this finding was not replicated when pooled with the FinnGen study. For 22 of 30 cancer outcomes examined, there was little evidence (q-value ≥0.20) that any of the 66 circulating inflammatory markers examined were associated with cancer risk., Interpretation: Our comprehensive joint Mendelian randomization and colocalisation analysis of the role of circulating inflammatory markers in cancer risk identified potential roles for 4 circulating inflammatory markers in risk of 4 site-specific cancers. Contrary to reports from some prior conventional epidemiological studies, we found little evidence of association of circulating inflammatory markers with the majority of site-specific cancers evaluated., Funding: Cancer Research UK (C68933/A28534, C18281/A29019, PPRCPJT∖100005), World Cancer Research Fund (IIG&#95;FULL&#95;2020&#95;022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC&#95;UU&#95;00011/1, MC&#95;UU&#95;00011/3, MC&#95;UU&#95;00011/6, and MC&#95;UU&#95;00011/4), Academy of Finland Project 326291, European Union's Horizon 2020 grant agreement no. 848158 (EarlyCause), French National Cancer Institute (INCa SHSESP20, 2020-076), Versus Arthritis (21173, 21754, 21755), National Institutes of Health (U19 CA203654), National Cancer Institute (U19CA203654)., Competing Interests: Declaration of interests GDS reports Scientific Advisory Board Membership for Relation Therapeutics and Insitro. Where authors are identified as personnel of the International Agency for Research on Cancer/World Health Organization, the authors alone are responsible for the views expressed in this article and they do not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer/World Health Organization., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Published
2024
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49. Associations of per- and polyfluoroalkyl substances and nonalcoholic fatty liver disease in the United States adult population, 2003-2018.

Author

Momo HD, Alvarez CS, Purdue MP, Graubard BI, and McGlynn KA

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder worldwide and a leading cause of liver-related mortality. Prior studies have linked per- and polyfluoroalkyl substances (PFAS) exposure to liver dysfunction and alterations in metabolic pathways, but the extent of a PFAS-NAFLD relationship is unclear. Thus, the aim of the current study was to examine whether there were associations between PFAS exposures and NAFLD in the US adult population over a 16-year period., Methods: Data from 10,234 persons who participated in the National Health and Nutrition Examination Survey between 2003 and 2018 were analyzed. Odds ratios and 95% confidence intervals were calculated using multivariable logistic regression for the associations between PFAS and NAFLD, defined by the Hepatic Steatosis Index (NAFLD-HSI), the Fatty Liver Index (NAFLD-FLI), and by Transient Elastography with Controlled Attenuation Parameter (NAFLD-TE-CAP)., Results: Overall, there was a significant inverse association between total PFAS and NAFLD-HSI ( P -trend = 0.04). Significant inverse associations were also found between perfluorohexane sulfonic acid (PFHxS) and NAFLD-HSI ( P -trend = 0.04), and NAFLD-FLI ( P -trend = 0.03). Analysis by time period, 2003-2010 versus 2011-2018, found that while inverse associations were more apparent during the latter period when total PFAS ( P -trend = 0.02), PFHxS ( P -trend = 0.04), and perfluorooctanoic acid (PFOA) ( P -trend = 0.03) were inversely associated with NAFLD-HSI and PFOA was inversely associated with NAFLD-FLI ( P -trend = 0.05), there were no significant interaction effects. No significant associations between the PFAS and NAFLD-TE-CAP were found., Conclusions: The current study found no evidence of a positive association between the most common PFAS and NAFLD in the US population., Competing Interests: The authors declare that they have no conflicts of interest with regard to the content of this report.

Published
2024
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50. Observational and genetic associations between cardiorespiratory fitness and cancer: a UK Biobank and international consortia study.

Author

Watts EL, Gonzales TI, Strain T, Saint-Maurice PF, Bishop DT, Chanock SJ, Johansson M, Keku TO, Le Marchand L, Moreno V, Newcomb PA, Newton CC, Pai RK, Purdue MP, Ulrich CM, Smith-Byrne K, Van Guelpen B, Day FR, Wijndaele K, Wareham NJ, Matthews CE, Moore SC, and Brage S

Subjects
Male, Humans, Biological Specimen Banks, UK Biobank, Risk Factors, Cardiorespiratory Fitness, Breast Neoplasms epidemiology, Breast Neoplasms genetics, Colorectal Neoplasms epidemiology, Colorectal Neoplasms genetics, Colorectal Neoplasms diagnosis
Abstract

Background: The association of fitness with cancer risk is not clear., Methods: We used Cox proportional hazards models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of lung, colorectal, endometrial, breast, and prostate cancer in a subset of UK Biobank participants who completed a submaximal fitness test in 2009-12 (N = 72,572). We also investigated relationships using two-sample Mendelian randomisation (MR), odds ratios (ORs) were estimated using the inverse-variance weighted method., Results: After a median of 11 years of follow-up, 4290 cancers of interest were diagnosed. A 3.5 ml O 2 ⋅min -1 ⋅kg -1 total-body mass increase in fitness (equivalent to 1 metabolic equivalent of task (MET), approximately 0.5 standard deviation (SD)) was associated with lower risks of endometrial (HR = 0.81, 95% CI: 0.73-0.89), colorectal (0.94, 0.90-0.99), and breast cancer (0.96, 0.92-0.99). In MR analyses, a 0.5 SD increase in genetically predicted O 2 ⋅min -1 ⋅kg -1 fat-free mass was associated with a lower risk of breast cancer (OR = 0.92, 95% CI: 0.86-0.98). After adjusting for adiposity, both the observational and genetic associations were attenuated., Discussion: Higher fitness levels may reduce risks of endometrial, colorectal, and breast cancer, though relationships with adiposity are complex and may mediate these relationships. Increasing fitness, including via changes in body composition, may be an effective strategy for cancer prevention., (© 2023. The Author(s).)

Published
2024
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