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207 results on '"Stella Koutros"'

1. A PSA SNP associates with cellular function and clinical outcome in men with prostate cancer

Author: Srilakshmi Srinivasan, Thomas Kryza, Nathalie Bock, Brian W. C. Tse, Kamil A. Sokolowski, Panchadsaram Janaththani, Achala Fernando, Leire Moya, Carson Stephens, Ying Dong, Joan Röhl, Saeid Alinezhad, Ian Vela, Joanna L. Perry-Keene, Katie Buzacott, Robert Nica, The IMPACT Study, Manuela Gago-Dominguez, The PROFILE Study Steering Committee, Johanna Schleutker, Christiane Maier, Kenneth Muir, Catherine M. Tangen, Henrik Gronberg, Nora Pashayan, Demetrius Albanes, Alicja Wolk, Janet L. Stanford, Sonja I. Berndt, Lorelei A. Mucci, Stella Koutros, Olivier Cussenot, Karina Dalsgaard Sorensen, Eli Marie Grindedal, Ruth C. Travis, Christopher A. Haiman, Robert J. MacInnis, Ana Vega, Fredrik Wiklund, David E. Neal, Manolis Kogevinas, Kathryn L. Penney, Børge G. Nordestgaard, Hermann Brenner, Esther M. John, Marija Gamulin, Frank Claessens, Olle Melander, Anders Dahlin, Pär Stattin, Göran Hallmans, Christel Häggström, Robert Johansson, Elin Thysell, Ann-Charlotte Rönn, Weiqiang Li, Nigel Brown, Goce Dimeski, Benjamin Shepherd, Tokhir Dadaev, Mark N. Brook, Amanda B. Spurdle, Ulf-Håkan Stenman, Hannu Koistinen, Zsofia Kote-Jarai, Robert J. Klein, Hans Lilja, Rupert C. Ecker, Rosalind Eeles, The Practical Consortium, The Australian Prostate Cancer BioResource, Judith Clements, and Jyotsna Batra
Subjects: Science
Abstract: Abstract Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.536 T > C; Ile163Thr-substitution in PSA) is associated with reduced prostate cancer risk, however, the functional relevance is unknown. Here, we identify that the SNP variant-induced change in PSA biochemical activity mediates prostate cancer pathogenesis. The ‘Thr’ PSA variant leads to small subcutaneous tumours, supporting reduced prostate cancer risk. However, ‘Thr’ PSA also displays higher metastatic potential with pronounced osteolytic activity in an experimental metastasis in-vivo model. Biochemical characterisation of this PSA variant demonstrates markedly reduced proteolytic activity that correlates with differences in in-vivo tumour burden. The SNP is associated with increased risk for aggressive disease and prostate cancer-specific mortality in three independent cohorts, highlighting its critical function in mediating metastasis. Carriers of this SNP allele have reduced serum total PSA and a higher free/total PSA ratio that could contribute to late biopsy decisions and delay in diagnosis. Our results provide a molecular explanation for the prominent 19q13.3 KLK locus, rs17632542 SNP, association with a spectrum of prostate cancer clinical outcomes.
Published: 2024
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2. Worker exit and suicide and overdose mortality in a cohort of male non-metal mine workers

Author: Hilary L. Colbeth, Jacqueline M. Ferguson, Sally Picciotto, Stella Koutros, Debra T. Silverman, and Ellen A. Eisen
Subjects: Deaths of despair, Mining, Job loss, Age-adjusted mortality rates, Cox proportional hazards, Mental healing, RZ400-408, Public aspects of medicine, RA1-1270
Abstract: Background: Suicides, overdoses, and drug-related liver diseases (deaths of despair) are greatly elevated in the mining and extraction industries compared to other industries. To better understand the drivers of these deaths, we examined suicide or overdose mortality in relation to age at worker exit among a retrospective cohort of 11,009 male mine workers from the Diesel Exhaust in Miners Study II. Methods: We calculated age-adjusted mortality rates (1947–2015) and estimated hazard ratios (HRs) and 95% Confidence Intervals (CI) for suicide or overdose death in relation to age at worker exit (leaving work). The mining industry curtailed its workforce in the early 1980s due to economic downturn; therefore, separate models were fit for worker exit pre- and post-1980. Results: Suicide deaths peaked between 1980 and 1989 at 67.2 per 100,000, more than double the rate in the general population. The hazard rate for suicide or overdose was 2.56 times higher for inactive versus actively employed workers (95% CI: 1.88, 3.50). Based on 187 suicides or overdoses, associations between younger age at worker exit and suicide or overdose death were null or protective before 1980. However post-1980, those who exited between ages 30–39 years had an elevated risk of death HR = 1.33, 95% CI (0.70, 2.53) and those who exited before age 30 had a HR for suicide or overdose of 1.57 (0.83, 2.96) compared to those who exited work after age 55. Conclusion: Worker exit may contribute to the elevated mortality from suicide or overdose among male mine workers, particularly among younger age groups.
Published: 2024
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3. Diesel exhaust and respiratory dust exposure in miners and chronic obstructive pulmonary disease (COPD) mortality in DEMS II

Author: Andreas M. Neophytou, Jacqueline M. Ferguson, Sadie Costello, Sally Picciotto, John R. Balmes, Stella Koutros, Debra T. Silverman, and Ellen A. Eisen
Subjects: Diesel exhaust, Respiratory dust, COPD mortality, Survivor bias, Environmental sciences, GE1-350
Abstract: Background: Diesel exhaust and respirable dust exposures in the mining industry have not been studied in depth with respect to non-malignant respiratory disease including chronic obstructive pulmonary disease (COPD), with most available evidence coming from other settings. Objectives: To assess the relationship between occupational diesel exhaust and respirable dust exposures and COPD mortality, while addressing issues of survivor bias in exposed miners. Methods: The study population consisted of 11,817 male workers from the Diesel Exhaust in Miners Study II, followed from 1947 to 2015, with 279 observed COPD deaths. We fit Cox proportional hazards models for the relationship between respirable elemental carbon (REC) and respirable dust (RD) exposure and COPD mortality. To address healthy worker survivor bias, we leveraged the parametric g-formula to assess effects of hypothetical interventions on both exposures. Results: Cox models yielded elevated estimates for the associations between average intensity of REC and RD and COPD mortality, with hazard ratios (HR) corresponding to an interquartile range width increase in exposure of 1.46 (95 % confidence interval (CI): 1.12, 1.91) and 1.20 (95 % CI: 0.96, 1.49), respectively for each exposure. HRs for cumulative exposures were negative for both REC and RD. Based on results from the parametric g-formula, the risk ratio (RR) for COPD mortality comparing risk under an intervention eliminating REC to the observed risk was 0.85 (95 % CI: 0.55, 1.06), equivalent to an attributable risk of 15 %. The corresponding RR comparing risk under an intervention eliminating RD to the observed risk was 0.93 (95 % CI: 0.56, 1.31). Conclusions: Our findings, based on data from a cohort of nonmetal miners, are suggestive of an increased risk of COPD mortality associated with REC and RD, as well as evidence of survivor bias in this population leading to negative associations between cumulative exposures and COPD mortality in traditional regression analysis.
Published: 2024
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4. A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry

Author: Pooja Middha, Xiaoliang Wang, Sabine Behrens, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Thaïs Baert, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Javier Benitez, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Daniele Campa, Federico Canzian, Angel Carracedo, Jose E. Castelao, Stephen J. Chanock, Georgia Chenevix-Trench, CTS Consortium, Emilie Cordina-Duverger, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Laure Dossus, Pierre-Antoine Dugué, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine D. Figueroa, Olivia Fletcher, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Graham G. Giles, Anna González-Neira, Felix Grassmann, Anne Grundy, Pascal Guénel, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Susan E. Hankinson, Elaine F. Harkness, Bernd Holleczek, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, David J. Hunter, Christian Ingvar, ABCTB Investigators, kConFab Investigators, Karolin Isaksson, Helena Jernström, Esther M. John, Michael E. Jones, Rudolf Kaaks, Renske Keeman, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Susanna Larsson, Loic Le Marchand, Flavio Lejbkowicz, Shuai Li, Martha Linet, Jolanta Lissowska, Maria Elena Martinez, Tabea Maurer, Anna Marie Mulligan, Claire Mulot, Rachel A. Murphy, William G. Newman, Sune F. Nielsen, Børge G. Nordestgaard, Aaron Norman, Katie M. O’Brien, Janet E. Olson, Alpa V. Patel, Ross Prentice, Erika Rees-Punia, Gad Rennert, Valerie Rhenius, Kathryn J. Ruddy, Dale P. Sandler, Christopher G. Scott, Mitul Shah, Xiao-Ou Shu, Ann Smeets, Melissa C. Southey, Jennifer Stone, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Katarzyna Tomczyk, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Sophia S. Wang, Clarice R. Weinberg, Hans Wildiers, Walter Willett, Stacey J. Winham, Alicja Wolk, Xiaohong R. Yang, M. Pilar Zamora, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul D. P. Pharoah, Montserrat García-Closas, Marjanka K. Schmidt, Peter Kraft, Roger L. Milne, Sara Lindström, Douglas F. Easton, and Jenny Chang-Claude
Subjects: Breast cancer, Gene-environment interactions, Genetic epidemiology, European ancestry, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genome-wide studies of gene–environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. Methods Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene–environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. Results Assuming a 1 × 10–5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability
Published: 2023
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5. Association between circulating inflammatory markers and adult cancer risk: a Mendelian randomization analysisResearch in context

Author: James Yarmolinsky, Jamie W. Robinson, Daniela Mariosa, Ville Karhunen, Jian Huang, Niki Dimou, Neil Murphy, Kimberley Burrows, Emmanouil Bouras, Karl Smith-Byrne, Sarah J. Lewis, Tessel E. Galesloot, Lambertus A. Kiemeney, Sita Vermeulen, Paul Martin, Demetrius Albanes, Lifang Hou, Polly A. Newcomb, Emily White, Alicja Wolk, Anna H. Wu, Loïc Le Marchand, Amanda I. Phipps, Daniel D. Buchanan, Sizheng Steven Zhao, Dipender Gill, Stephen J. Chanock, Mark P. Purdue, George Davey Smith, Paul Brennan, Karl-Heinz Herzig, Marjo-Riitta Järvelin, Chris I. Amos, Rayjean J. Hung, Abbas Dehghan, Mattias Johansson, Marc J. Gunter, Kostas K. Tsilidis, Richard M. Martin, Maria Teresa Landi, Victoria Stevens, Ying Wang, Demetrios Albanes, Neil Caporaso, Christopher I. Amos, Sanjay Shete, Heike Bickeböller, Angela Risch, Richard Houlston, Stephen Lam, Adonina Tardon, Chu Chen, Stig E. Bojesen, H-Erich Wichmann, David Christiani, Gadi Rennert, Susanne Arnold, John K. Field, Loic Le Marchand, Olle Melander, Hans Brunnström, Geoffrey Liu, Angeline Andrew, Hongbing Shen, Shan Zienolddiny, Kjell Grankvist, Mikael Johansson, M. Dawn Teare, Yun-Chul Hong, Jian-Min Yuan, Philip Lazarus, Matthew B. Schabath, Melinda C. Aldrich, Rosalind A. Eeles, Christopher A. Haiman, Zsofia Kote-Jarai, Fredrick R. Schumacher, Sara Benlloch, Ali Amin Al Olama, Kenneth R. Muir, Sonja I. Berndt, David V. Conti, Fredrik Wiklund, Stephen Chanock, Catherine M. Tangen, Jyotsna Batra, Judith A. Clements, Henrik Grönberg, Nora Pashayan, Johanna Schleutker, Stephanie J. Weinstein, Catharine M.L. West, Lorelei A. Mucci, Géraldine Cancel-Tassin, Stella Koutros, Karina Dalsgaard Sørensen, Eli Marie Grindedal, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Sue Ann Ingles, Barry S. Rosenstein, Yong-Jie Lu, Graham G. Giles, Robert J. MacInnis, Adam S. Kibel, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanfrod, Cezary Cybulski, Børge G. Nordestgaard, Sune F. Nielsen, Hermann Brenner, Christiane Maier, Christopher J. Logothetis, Esther M. John, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Jose Esteban Castelao, Monique J. Roobol, Florence Menegaux, Kay-Tee Khaw, Lisa Cannon-Albright, Hardev Pandha, Stephen N. Thibodeau, David J. Hunter, Peter Kraft, William J. Blot, and Elio Riboli
Subjects: Inflammation, Cancer, Mendelian randomization, Genetic epidemiology, Medicine, Medicine (General), R5-920
Abstract: Summary: 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 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, PPH4 = 73.9%), prothrombin concentrations with decreased basal cell carcinoma risk (OR: 0.66, 95% CI: 0.53–0.81, q-value = 0.067, PPH4 = 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, PPH4 = 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, PPH4 = 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_FULL_2020_022), National Institute for Health Research (NIHR202411, BRC-1215-20011), Medical Research Council (MC_UU_00011/1, MC_UU_00011/3, MC_UU_00011/6, and MC_UU_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).
Published: 2024
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6. Aggregation tests identify new gene associations with breast cancer in populations with diverse ancestry

Author: Stefanie H. Mueller, Alvina G. Lai, Maria Valkovskaya, Kyriaki Michailidou, Manjeet K. Bolla, Qin Wang, Joe Dennis, Michael Lush, Zomoruda Abu-Ful, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Annelie Augustinsson, Thais Baert, Laura E. Beane Freeman, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, Natalia V. Bogdanova, Stig E. Bojesen, Bernardo Bonanni, Hermann Brenner, Sara Y. Brucker, Saundra S. Buys, Jose E. Castelao, Tsun L. Chan, Jenny Chang-Claude, Stephen J. Chanock, Ji-Yeob Choi, Wendy K. Chung, NBCS Collaborators, Sarah V. Colonna, CTS Consortium, Sten Cornelissen, Fergus J. Couch, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Laure Dossus, Miriam Dwek, Diana M. Eccles, Arif B. Ekici, A. Heather Eliassen, Christoph Engel, D. Gareth Evans, Peter A. Fasching, Olivia Fletcher, Henrik Flyger, Manuela Gago-Dominguez, Yu-Tang Gao, Montserrat García-Closas, José A. García-Sáenz, Jeanine Genkinger, Aleksandra Gentry-Maharaj, Felix Grassmann, Pascal Guénel, Melanie Gündert, Lothar Haeberle, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Per Hall, Elaine F. Harkness, Patricia A. Harrington, Jaana M. Hartikainen, Mikael Hartman, Alexander Hein, Weang-Kee Ho, Maartje J. Hooning, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, David J. Hunter, Dezheng Huo, ABCTB Investigators, Hidemi Ito, Motoki Iwasaki, Anna Jakubowska, Wolfgang Janni, Esther M. John, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Daehee Kang, Elza K. Khusnutdinova, Sung-Won Kim, Cari M. Kitahara, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Allison W. Kurian, Ava Kwong, James V. Lacey, Diether Lambrechts, Loic Le Marchand, Jingmei Li, Martha Linet, Wing-Yee Lo, Jirong Long, Artitaya Lophatananon, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Keitaro Matsuo, Dimitrios Mavroudis, Usha Menon, Kenneth Muir, Rachel A. Murphy, Heli Nevanlinna, William G. Newman, Dieter Niederacher, Katie M. O’Brien, Nadia Obi, Kenneth Offit, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Sue K. Park, Alpa V. Patel, Achal Patel, Charles M. Perou, Julian Peto, Paul D. P. Pharoah, Dijana Plaseska-Karanfilska, Nadege Presneau, Brigitte Rack, Paolo Radice, Dhanya Ramachandran, Muhammad U. Rashid, Gad Rennert, Atocha Romero, Kathryn J. Ruddy, Matthias Ruebner, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Michael O. Schneider, Christopher Scott, Mitul Shah, Priyanka Sharma, Chen-Yang Shen, Xiao-Ou Shu, Jacques Simard, Harald Surowy, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Soo Hwang Teo, Lauren R. Teras, Amanda E. Toland, Rob A. E. M. Tollenaar, Diana Torres, Gabriela Torres-Mejía, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Joseph Vijai, Clarice R. Weinberg, Camilla Wendt, Robert Winqvist, Alicja Wolk, Anna H. Wu, Taiki Yamaji, Xiaohong R. Yang, Jyh-Cherng Yu, Wei Zheng, Argyrios Ziogas, Elad Ziv, Alison M. Dunning, Douglas F. Easton, Harry Hemingway, Ute Hamann, and Karoline B. Kuchenbaecker
Subjects: Breast cancer susceptibility, Diverse ancestry, Rare variants, Gene regulation, Genome-wide association study, Medicine, Genetics, QH426-470
Abstract: Abstract Background Low-frequency variants play an important role in breast cancer (BC) susceptibility. Gene-based methods can increase power by combining multiple variants in the same gene and help identify target genes. Methods We evaluated the potential of gene-based aggregation in the Breast Cancer Association Consortium cohorts including 83,471 cases and 59,199 controls. Low-frequency variants were aggregated for individual genes’ coding and regulatory regions. Association results in European ancestry samples were compared to single-marker association results in the same cohort. Gene-based associations were also combined in meta-analysis across individuals with European, Asian, African, and Latin American and Hispanic ancestry. Results In European ancestry samples, 14 genes were significantly associated (q
Published: 2023
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7. Common variants in breast cancer risk loci predispose to distinct tumor subtypes

Author: Thomas U. Ahearn, Haoyu Zhang, Kyriaki Michailidou, Roger L. Milne, Manjeet K. Bolla, Joe Dennis, Alison M. Dunning, Michael Lush, Qin Wang, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Adinda Baten, Heiko Becher, Sabine Behrens, Javier Benitez, Marina Bermisheva, Carl Blomqvist, Stig E. Bojesen, Bernardo Bonanni, Anne-Lise Børresen-Dale, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Thomas Brüning, Barbara Burwinkel, Saundra S. Buys, Federico Canzian, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Georgia Chenevix-Trench, Christine L. Clarke, NBCS Collaborators, J. Margriet Collée, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Peter Devilee, Thilo Dörk, Miriam Dwek, Diana M. Eccles, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Giuseppe Floris, Manuela Gago-Dominguez, Susan M. Gapstur, José A. García-Sáenz, Mia M. Gaudet, Graham G. Giles, Mark S. Goldberg, Anna González-Neira, Grethe I. Grenaker Alnæs, Mervi Grip, Pascal Guénel, Christopher A. Haiman, Per Hall, Ute Hamann, Elaine F. Harkness, Bernadette A. M. Heemskerk-Gerritsen, Bernd Holleczek, Antoinette Hollestelle, Maartje J. Hooning, Robert N. Hoover, John L. Hopper, Anthony Howell, ABCTB Investigators, kConFab/AOCS Investigators, Milena Jakimovska, Anna Jakubowska, Esther M. John, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Saila Kauppila, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Vessela N. Kristensen, Ute Krüger, Katerina Kubelka-Sabit, Allison W. Kurian, Kyriacos Kyriacou, Diether Lambrechts, Derrick G. Lee, Annika Lindblom, Martha Linet, Jolanta Lissowska, Ana Llaneza, Wing-Yee Lo, Robert J. MacInnis, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, Maria Elena Martinez, Catriona McLean, Alfons Meindl, Usha Menon, Heli Nevanlinna, William G. Newman, Jesse Nodora, Kenneth Offit, Håkan Olsson, Nick Orr, Tjoung-Won Park-Simon, Alpa V. Patel, Julian Peto, Guillermo Pita, Dijana Plaseska-Karanfilska, Ross Prentice, Kevin Punie, Katri Pylkäs, Paolo Radice, Gad Rennert, Atocha Romero, Thomas Rüdiger, Emmanouil Saloustros, Sarah Sampson, Dale P. Sandler, Elinor J. Sawyer, Rita K. Schmutzler, Minouk J. Schoemaker, Ben Schöttker, Mark E. Sherman, Xiao-Ou Shu, Snezhana Smichkoska, Melissa C. Southey, John J. Spinelli, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Diana Torres, Melissa A. Troester, Celine M. Vachon, Carolien H. M. van Deurzen, Elke M. van Veen, Philippe Wagner, Clarice R. Weinberg, Camilla Wendt, Jelle Wesseling, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Fergus J. Couch, Jacques Simard, Peter Kraft, Douglas F. Easton, Paul D. P. Pharoah, Marjanka K. Schmidt, Montserrat García-Closas, and Nilanjan Chatterjee
Subjects: Breast cancer, Etiologic heterogeneity, Genetic predisposition, Common breast cancer susceptibility variants, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear. Methods Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes. Results Eighty-five of 173 variants were associated with at least one tumor feature (false discovery rate
Published: 2022
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8. Rare germline copy number variants (CNVs) and breast cancer risk

Author: Joe Dennis, Jonathan P. Tyrer, Logan C. Walker, Kyriaki Michailidou, Leila Dorling, Manjeet K. Bolla, Qin Wang, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Natalia N. Antonenkova, Volker Arndt, Kristan J. Aronson, Laura E. Beane Freeman, Matthias W. Beckmann, Sabine Behrens, Javier Benitez, Marina Bermisheva, Natalia V. Bogdanova, Stig E. Bojesen, Hermann Brenner, Jose E. Castelao, Jenny Chang-Claude, Georgia Chenevix-Trench, Christine L. Clarke, NBCS Collaborators, J. Margriet Collée, CTS Consortium, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Peter Devilee, Thilo Dörk, Laure Dossus, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Lin Fritschi, Marike Gabrielson, Manuela Gago-Dominguez, Montserrat García-Closas, Graham G. Giles, Anna González-Neira, Pascal Guénel, Eric Hahnen, Christopher A. Haiman, Per Hall, Antoinette Hollestelle, Reiner Hoppe, John L. Hopper, Anthony Howell, ABCTB Investigators, kConFab/AOCS Investigators, Agnes Jager, Anna Jakubowska, Esther M. John, Nichola Johnson, Michael E. Jones, Audrey Jung, Rudolf Kaaks, Renske Keeman, Elza Khusnutdinova, Cari M. Kitahara, Yon-Dschun Ko, Veli-Matti Kosma, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Katerina Kubelka-Sabit, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Martha Linet, Alicja Ogrodniczak, Arto Mannermaa, Siranoush Manoukian, Sara Margolin, Dimitrios Mavroudis, Roger L. Milne, Taru A. Muranen, Rachel A. Murphy, Heli Nevanlinna, Janet E. Olson, Håkan Olsson, Tjoung-Won Park-Simon, Charles M. Perou, Paolo Peterlongo, Dijana Plaseska-Karanfilska, Katri Pylkäs, Gad Rennert, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Marjanka K. Schmidt, Rita K. Schmutzler, Rana Shibli, Ann Smeets, Penny Soucy, Melissa C. Southey, Anthony J. Swerdlow, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Mary Beth Terry, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Camilla Wendt, Robert Winqvist, Alicja Wolk, Xiaohong R. Yang, Wei Zheng, Argyrios Ziogas, Jacques Simard, Alison M. Dunning, Paul D. P. Pharoah, and Douglas F. Easton
Subjects: Biology (General), QH301-705.5
Abstract: Dennis et al. investigate potential breast cancer associations with rare germline copy number variants (CNVs) by conducting a genome-wide analysis in a large breast cancer case-control dataset. The authors detected associations with exonic deletions in established breast cancer susceptibility genes and suggestive associations for a number of non-coding CNVs.
Published: 2022
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9. Association of germline genetic variants with breast cancer-specific survival in patient subgroups defined by clinic-pathological variables related to tumor biology and type of systemic treatment

Author: Anna Morra, Maria Escala-Garcia, Jonathan Beesley, Renske Keeman, Sander Canisius, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Paul L. Auer, Annelie Augustinsson, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Sabine Behrens, Stig E. Bojesen, Manjeet K. Bolla, Hermann Brenner, Thomas Brüning, Saundra S. Buys, Bette Caan, Daniele Campa, Federico Canzian, Jose E. Castelao, Jenny Chang-Claude, Stephen J. Chanock, Ting-Yuan David Cheng, Christine L. Clarke, NBCS Collaborators, Sarah V. Colonna, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Mary B. Daly, Joe Dennis, Thilo Dörk, Laure Dossus, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Arif B. Ekici, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Henrik Flyger, Lin Fritschi, Manuela Gago-Dominguez, José A. García-Sáenz, Graham G. Giles, Mervi Grip, Pascal Guénel, Melanie Gündert, Eric Hahnen, Christopher A. Haiman, Niclas Håkansson, Per Hall, Ute Hamann, Steven N. Hart, Jaana M. Hartikainen, Arndt Hartmann, Wei He, Maartje J. Hooning, Reiner Hoppe, John L. Hopper, Anthony Howell, David J. Hunter, ABCTB Investigators, kConFab Investigators, Agnes Jager, Anna Jakubowska, Wolfgang Janni, Esther M. John, Audrey Y. Jung, Rudolf Kaaks, Machteld Keupers, Cari M. Kitahara, Stella Koutros, Peter Kraft, Vessela N. Kristensen, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Loic Le Marchand, Annika Lindblom, Martha Linet, Robert N. Luben, Jan Lubiński, Michael Lush, Arto Mannermaa, Mehdi Manoochehri, Sara Margolin, John W. M. Martens, Maria Elena Martinez, Dimitrios Mavroudis, Kyriaki Michailidou, Roger L. Milne, Anna Marie Mulligan, Taru A. Muranen, Heli Nevanlinna, William G. Newman, Sune F. Nielsen, Børge G. Nordestgaard, Andrew F. Olshan, Håkan Olsson, Nick Orr, Tjoung-Won Park-Simon, Alpa V. Patel, Bernard Peissel, Paolo Peterlongo, Dijana Plaseska-Karanfilska, Karolina Prajzendanc, Ross Prentice, Nadege Presneau, Brigitte Rack, Gad Rennert, Hedy S. Rennert, Valerie Rhenius, Atocha Romero, Rebecca Roylance, Matthias Ruebner, Emmanouil Saloustros, Elinor J. Sawyer, Rita K. Schmutzler, Andreas Schneeweiss, Christopher Scott, Mitul Shah, Snezhana Smichkoska, Melissa C. Southey, Jennifer Stone, Harald Surowy, Anthony J. Swerdlow, Rulla M. Tamimi, William J. Tapper, Lauren R. Teras, Mary Beth Terry, Rob A. E. M. Tollenaar, Ian Tomlinson, Melissa A. Troester, Thérèse Truong, Celine M. Vachon, Qin Wang, Amber N. Hurson, Robert Winqvist, Alicja Wolk, Argyrios Ziogas, Hiltrud Brauch, Montserrat García-Closas, Paul D. P. Pharoah, Douglas F. Easton, Georgia Chenevix-Trench, and Marjanka K. Schmidt
Subjects: Common germline genetic variants, Breast cancer-specific survival, Patient subgroups, Tumor biology, Systemic treatment, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Abstract Background Given the high heterogeneity among breast tumors, associations between common germline genetic variants and survival that may exist within specific subgroups could go undetected in an unstratified set of breast cancer patients. Methods We performed genome-wide association analyses within 15 subgroups of breast cancer patients based on prognostic factors, including hormone receptors, tumor grade, age, and type of systemic treatment. Analyses were based on 91,686 female patients of European ancestry from the Breast Cancer Association Consortium, including 7531 breast cancer-specific deaths over a median follow-up of 8.1 years. Cox regression was used to assess associations of common germline variants with 15-year and 5-year breast cancer-specific survival. We assessed the probability of these associations being true positives via the Bayesian false discovery probability (BFDP
Published: 2021
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10. Polygenic hazard score is associated with prostate cancer in multi-ethnic populations

Author: Minh-Phuong Huynh-Le, Chun Chieh Fan, Roshan Karunamuni, Wesley K. Thompson, Maria Elena Martinez, Rosalind A. Eeles, Zsofia Kote-Jarai, Kenneth Muir, Johanna Schleutker, Nora Pashayan, Jyotsna Batra, Henrik Grönberg, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Sune F. Nielsen, Børge G. Nordestgaard, Fredrik Wiklund, Catherine M. Tangen, Graham G. Giles, Alicja Wolk, Demetrius Albanes, Ruth C. Travis, William J. Blot, Wei Zheng, Maureen Sanderson, Janet L. Stanford, Lorelei A. Mucci, Catharine M. L. West, Adam S. Kibel, Olivier Cussenot, Sonja I. Berndt, Stella Koutros, Karina Dalsgaard Sørensen, Cezary Cybulski, Eli Marie Grindedal, Florence Menegaux, Kay-Tee Khaw, Jong Y. Park, Sue A. Ingles, Christiane Maier, Robert J. Hamilton, Stephen N. Thibodeau, Barry S. Rosenstein, Yong-Jie Lu, Stephen Watya, Ana Vega, Manolis Kogevinas, Kathryn L. Penney, Chad Huff, Manuel R. Teixeira, Luc Multigner, Robin J. Leach, Lisa Cannon-Albright, Hermann Brenner, Esther M. John, Radka Kaneva, Christopher J. Logothetis, Susan L. Neuhausen, Kim De Ruyck, Hardev Pandha, Azad Razack, Lisa F. Newcomb, Jay H. Fowke, Marija Gamulin, Nawaid Usmani, Frank Claessens, Manuela Gago-Dominguez, Paul A. Townsend, William S. Bush, Monique J. Roobol, Marie-Élise Parent, Jennifer J. Hu, Ian G. Mills, Ole A. Andreassen, Anders M. Dale, Tyler M. Seibert, UKGPCS collaborators, APCB (Australian Prostate Cancer BioResource), NC-LA PCaP Investigators, The IMPACT Study Steering Committee and Collaborators, Canary PASS Investigators, The Profile Study Steering Committee, and The PRACTICAL Consortium
Subjects: Science
Abstract: A polygenic hazard score (PHS1) improves prostate cancer screening accuracy in European patients. Here, the authors test the performance of a version compatible with OncoArray genotypes (PHS2) in a multi-ethnic dataset and find that it risk-stratifies men for any, aggressive, and fatal prostate cancer.
Published: 2021
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11. Pesticide exposure and risk of aggressive prostate cancer among private pesticide applicators

Author: Larissa A. Pardo, Laura E. Beane Freeman, Catherine C. Lerro, Gabriella Andreotti, Jonathan N. Hofmann, Christine G. Parks, Dale P. Sandler, Jay H. Lubin, Aaron Blair, and Stella Koutros
Subjects: Pesticide, Aggressive prostate cancer (PCa), Organodithioate insecticides, Pesticide applicators, Industrial medicine. Industrial hygiene, RC963-969, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Prostate cancer (PCa) is one of the most commonly diagnosed cancers among men in developed countries; however, little is known about modifiable risk factors. Some studies have implicated organochlorine and organophosphate insecticides as risk factors (particularly the organodithioate class) and risk of clinically significant PCa subtypes. However, few studies have evaluated other pesticides. We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators in North Carolina and Iowa, to extend our previous work and evaluate 39 additional pesticides and aggressive PCa. Methods We used Cox proportional hazards models, with age as the time scale, to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between ever use of individual pesticides and 883 cases of aggressive PCa (distant stage, poorly differentiated grade, Gleason score ≥ 7, or fatal prostate cancer) diagnosed between 1993 and 2015. All models adjusted for birth year, state, family history of PCa, race, and smoking status. We conducted exposure-response analyses for pesticides with reported lifetime years of use. Results There was an increased aggressive PCa risk among ever users of the organodithioate insecticide dimethoate (n = 54 exposed cases, HR = 1.37, 95% CI = 1.04, 1.80) compared to never users. We observed an inverse association between aggressive PCa and the herbicide triclopyr (n = 35 exposed cases, HR = 0.68, 95% CI = 0.48, 0.95), with the strongest inverse association for those reporting durations of use above the median (≥ 4 years; n = 13 exposed cases, HR=0.44, 95% CI=0.26, 0.77). Conclusion Few additional pesticides were associated with prostate cancer risk after evaluation of extended data from this large cohort of private pesticide applicators.
Published: 2020
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12. Publisher Correction: Shared heritability and functional enrichment across six solid cancers

Author: Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R. Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H. M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, and Sara Lindström
Subjects: Science
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Published: 2019
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13. Non-Hodgkin lymphoma risk and organophosphate and carbamate insecticide use in the north American pooled project

Author: Stella Koutros, Shelley A. Harris, John J. Spinelli, Aaron Blair, John R. McLaughlin, Shelia Hoar Zahm, Sungduk Kim, Paul S. Albert, Linda Kachuri, Manisha Pahwa, Kenneth P. Cantor, Dennis D. Weisenburger, Punam Pahwa, Larissa A. Pardo, James A. Dosman, Paul A. Demers, and Laura E. Beane Freeman
Subjects: Environmental sciences, GE1-350
Abstract: Organophosphates and carbamates have been among the most commonly used insecticides, with both agricultural and residential uses. Previous studies have suggested associations of non-Hodgkin lymphoma (NHL) with some of these chemicals; however, many studies have been limited in their ability to evaluate associations with lymphoma subtypes. We evaluated the use of eleven organophosphate and two carbamate insecticides in association with NHL in the North American Pooled Project, which includes data from case-control studies in the United States and Canada (1690 cases/5131 controls). We used unconditional logistic regression adjusting for potential confounders, including use of other pesticides, to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between these chemicals and NHL overall, and NHL subtypes, i.e., follicular (FL), diffuse large B-cell (DLBCL), small lymphocytic lymphoma (SLL) and others. Ever use of malathion was associated with increased risk of NHL overall (OR = 1.43; 95% CI: 1.14–1.81) compared with never users. Categories using tertiles of duration (12 yrs) also showed a significant exposure-response for increasing years of use of malathion and risk of NHL (OR12vsUnex = 1.55 (1.05, 2.28, p-trend
Published: 2019
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14. Shared heritability and functional enrichment across six solid cancers

Author: Xia Jiang, Hilary K. Finucane, Fredrick R. Schumacher, Stephanie L. Schmit, Jonathan P. Tyrer, Younghun Han, Kyriaki Michailidou, Corina Lesseur, Karoline B. Kuchenbaecker, Joe Dennis, David V. Conti, Graham Casey, Mia M. Gaudet, Jeroen R. Huyghe, Demetrius Albanes, Melinda C. Aldrich, Angeline S. Andrew, Irene L. Andrulis, Hoda Anton-Culver, Antonis C. Antoniou, Natalia N. Antonenkova, Susanne M. Arnold, Kristan J. Aronson, Banu K. Arun, Elisa V. Bandera, Rosa B. Barkardottir, Daniel R. Barnes, Jyotsna Batra, Matthias W. Beckmann, Javier Benitez, Sara Benlloch, Andrew Berchuck, Sonja I. Berndt, Heike Bickeböller, Stephanie A. Bien, Carl Blomqvist, Stefania Boccia, Natalia V. Bogdanova, Stig E. Bojesen, Manjeet K. Bolla, Hiltrud Brauch, Hermann Brenner, James D. Brenton, Mark N. Brook, Joan Brunet, Hans Brunnström, Daniel D. Buchanan, Barbara Burwinkel, Ralf Butzow, Gabriella Cadoni, Trinidad Caldés, Maria A. Caligo, Ian Campbell, Peter T. Campbell, Géraldine Cancel-Tassin, Lisa Cannon-Albright, Daniele Campa, Neil Caporaso, André L. Carvalho, Andrew T. Chan, Jenny Chang-Claude, Stephen J. Chanock, Chu Chen, David C. Christiani, Kathleen B. M. Claes, Frank Claessens, Judith Clements, J. Margriet Collée, Marcia Cruz Correa, Fergus J. Couch, Angela Cox, Julie M. Cunningham, Cezary Cybulski, Kamila Czene, Mary B. Daly, Anna deFazio, Peter Devilee, Orland Diez, Manuela Gago-Dominguez, Jenny L. Donovan, Thilo Dörk, Eric J. Duell, Alison M. Dunning, Miriam Dwek, Diana M. Eccles, Christopher K. Edlund, Digna R Velez Edwards, Carolina Ellberg, D. Gareth Evans, Peter A. Fasching, Robert L. Ferris, Triantafillos Liloglou, Jane C. Figueiredo, Olivia Fletcher, Renée T. Fortner, Florentia Fostira, Silvia Franceschi, Eitan Friedman, Steven J. Gallinger, Patricia A. Ganz, Judy Garber, José A. García-Sáenz, Simon A. Gayther, Graham G. Giles, Andrew K. Godwin, Mark S. Goldberg, David E. Goldgar, Ellen L. Goode, Marc T. Goodman, Gary Goodman, Kjell Grankvist, Mark H. Greene, Henrik Gronberg, Jacek Gronwald, Pascal Guénel, Niclas Håkansson, Per Hall, Ute Hamann, Freddie C. Hamdy, Robert J. Hamilton, Jochen Hampe, Aage Haugen, Florian Heitz, Rolando Herrero, Peter Hillemanns, Michael Hoffmeister, Estrid Høgdall, Yun-Chul Hong, John L. Hopper, Richard Houlston, Peter J. Hulick, David J. Hunter, David G. Huntsman, Gregory Idos, Evgeny N. Imyanitov, Sue Ann Ingles, Claudine Isaacs, Anna Jakubowska, Paul James, Mark A. Jenkins, Mattias Johansson, Mikael Johansson, Esther M. John, Amit D. Joshi, Radka Kaneva, Beth Y. Karlan, Linda E. Kelemen, Tabea Kühl, Kay-Tee Khaw, Elza Khusnutdinova, Adam S. Kibel, Lambertus A. Kiemeney, Jeri Kim, Susanne K. Kjaer, Julia A. Knight, Manolis Kogevinas, Zsofia Kote-Jarai, Stella Koutros, Vessela N. Kristensen, Jolanta Kupryjanczyk, Martin Lacko, Stephan Lam, Diether Lambrechts, Maria Teresa Landi, Philip Lazarus, Nhu D. Le, Eunjung Lee, Flavio Lejbkowicz, Heinz-Josef Lenz, Goska Leslie, Davor Lessel, Jenny Lester, Douglas A. Levine, Li Li, Christopher I. Li, Annika Lindblom, Noralane M. Lindor, Geoffrey Liu, Fotios Loupakis, Jan Lubiński, Lovise Maehle, Christiane Maier, Arto Mannermaa, Loic Le Marchand, Sara Margolin, Taymaa May, Lesley McGuffog, Alfons Meindl, Pooja Middha, Austin Miller, Roger L. Milne, Robert J. MacInnis, Francesmary Modugno, Marco Montagna, Victor Moreno, Kirsten B. Moysich, Lorelei Mucci, Kenneth Muir, Anna Marie Mulligan, Katherine L. Nathanson, David E. Neal, Andrew R. Ness, Susan L. Neuhausen, Heli Nevanlinna, Polly A. Newcomb, Lisa F. Newcomb, Finn Cilius Nielsen, Liene Nikitina-Zake, Børge G. Nordestgaard, Robert L. Nussbaum, Kenneth Offit, Edith Olah, Ali Amin Al Olama, Olufunmilayo I. Olopade, Andrew F. Olshan, Håkan Olsson, Ana Osorio, Hardev Pandha, Jong Y. Park, Nora Pashayan, Michael T. Parsons, Tanja Pejovic, Kathryn L. Penney, Wilbert H M. Peters, Catherine M. Phelan, Amanda I. Phipps, Dijana Plaseska-Karanfilska, Miranda Pring, Darya Prokofyeva, Paolo Radice, Kari Stefansson, Susan J. Ramus, Leon Raskin, Gad Rennert, Hedy S. Rennert, Elizabeth J. van Rensburg, Marjorie J. Riggan, Harvey A. Risch, Angela Risch, Monique J. Roobol, Barry S. Rosenstein, Mary Anne Rossing, Kim De Ruyck, Emmanouil Saloustros, Dale P. Sandler, Elinor J. Sawyer, Matthew B. Schabath, Johanna Schleutker, Marjanka K. Schmidt, V. Wendy Setiawan, Hongbing Shen, Erin M. Siegel, Weiva Sieh, Christian F. Singer, Martha L. Slattery, Karina Dalsgaard Sorensen, Melissa C. Southey, Amanda B. Spurdle, Janet L. Stanford, Victoria L. Stevens, Sebastian Stintzing, Jennifer Stone, Karin Sundfeldt, Rebecca Sutphen, Anthony J. Swerdlow, Eloiza H. Tajara, Catherine M. Tangen, Adonina Tardon, Jack A. Taylor, M. Dawn Teare, Manuel R. Teixeira, Mary Beth Terry, Kathryn L. Terry, Stephen N. Thibodeau, Mads Thomassen, Line Bjørge, Marc Tischkowitz, Amanda E. Toland, Diana Torres, Paul A. Townsend, Ruth C. Travis, Nadine Tung, Shelley S. Tworoger, Cornelia M. Ulrich, Nawaid Usmani, Celine M. Vachon, Els Van Nieuwenhuysen, Ana Vega, Miguel Elías Aguado-Barrera, Qin Wang, Penelope M. Webb, Clarice R. Weinberg, Stephanie Weinstein, Mark C. Weissler, Jeffrey N. Weitzel, Catharine M. L. West, Emily White, Alice S. Whittemore, H-Erich Wichmann, Fredrik Wiklund, Robert Winqvist, Alicja Wolk, Penella Woll, Michael Woods, Anna H. Wu, Xifeng Wu, Drakoulis Yannoukakos, Wei Zheng, Shanbeh Zienolddiny, Argyrios Ziogas, Kristin K. Zorn, Jacqueline M. Lane, Richa Saxena, Duncan Thomas, Rayjean J. Hung, Brenda Diergaarde, James McKay, Ulrike Peters, Li Hsu, Montserrat García-Closas, Rosalind A. Eeles, Georgia Chenevix-Trench, Paul J. Brennan, Christopher A. Haiman, Jacques Simard, Douglas F. Easton, Stephen B. Gruber, Paul D. P. Pharoah, Alkes L. Price, Bogdan Pasaniuc, Christopher I. Amos, Peter Kraft, and Sara Lindström
Subjects: Science
Abstract: Similarities in cancers can be studied to interrogate their etiology. Here, the authors use genome-wide association study summary statistics from six cancer types based on 296,215 cases and 301,319 controls of European ancestry, showing that solid tumours arising from different tissues share a degree of common germline genetic basis.
Published: 2019
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15. Author Correction: Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Author: Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Kan Wang, Xin Sheng, Ali Amin Al Olama, Fredrick R. Schumacher, Sue A. Ingles, Koveela Govindasami, Sara Benlloch, Sonja I. Berndt, Demetrius Albanes, Stella Koutros, Kenneth Muir, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith Clements, Henrik Gronberg, Nora Pashayan, Johanna Schleutker, Alicja Wolk, Catharine West, Lorelei Mucci, Peter Kraft, Géraldine Cancel-Tassin, Karina D. Sorensen, Lovise Maehle, Eli M. Grindedal, Sara S. Strom, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Barry Rosenstein, Yong-Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Jeanette T. Bensen, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Hermann Brenner, Christiane Maier, Jeri Kim, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago-Dominguez, Monique J. Roobol, Florence Menegaux, Kay-Tee Khaw, Lisa A. Cannon-Albright, Hardev Pandha, Stephen N. Thibodeau, Daniel J. Schaid, The PRACTICAL Consortium, Fredrik Wiklund, Stephen J. Chanock, Douglas F. Easton, Rosalind A. Eeles, Zsofia Kote-Jarai, David V. Conti, and Christopher A. Haiman
Subjects: Science
Abstract: The original version of this Article contained an error in the spelling of the author Manuela Gago-Dominguez, which was incorrectly given as Manuela G. Dominguez. This has now been corrected in both the PDF and HTML versions of the Article.
Published: 2019
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16. Pesticide exposure and incident thyroid cancer among male pesticide applicators in agricultural health study

Author: Catherine C. Lerro, Laura E. Beane Freeman, Curt T. DellaValle, Gabriella Andreotti, Jonathan N. Hofmann, Stella Koutros, Christine G. Parks, Srishti Shrestha, Michael C.R. Alavanja, Aaron Blair, Jay H. Lubin, Dale P. Sandler, and Mary H. Ward
Subjects: Pesticides, Thyroid cancer, Agriculture, Epidemiology, Environmental sciences, GE1-350
Abstract: Background: Many pesticides are known to have thyroid-disrupting properties. However, few studies have evaluated the association between specific pesticide ingredients and risk of thyroid cancer. We investigated self-reported pesticide use and incident thyroid cancer in the Agricultural Health Study (AHS), a large cohort of occupationally-exposed male pesticide applicators. Methods: The AHS is a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. At enrollment (1993–1997) and follow-up (1999–2005), participants reported use of 50 pesticides. We characterized exposure as ever use (44 pesticides with ≥5 exposed cases) and by cumulative intensity-weighted lifetime days (22 pesticides with ≥10 exposed cases), a metric that accounts for factors that influence exposure. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression for incident thyroid (n = 85 cases) cancer among male participants using follow-up through 2014/2015. Results: Use of the fungicide metalaxyl (HR = 2.03, CI:1.16–3.52) and the organochlorine insecticide lindane (HR = 1.74, CI:1.06–2.84) was associated with increased risk of thyroid cancer. The herbicide chlorimuron-ethyl was inversely associated with risk when we restricted to papillary thyroid cancer, the most common subtype (HR = 0.52, CI:0.28–0.96). High use of the insecticide carbaryl (>median intensity-weighted days) was inversely associated with thyroid cancer (HR = 0.20, CI:0.08–0.53, ptrend = 0.001). Conclusions: In this large cohort study, we observed increased risk of thyroid cancer associated with use of metalaxyl and lindane, and an inverse association with carbaryl. More work is needed to understand the potential role of these chemicals in thyroid carcinogenesis.
Published: 2021
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17. Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes

Author: Stella Koutros, Manolis Kogevinas, Melissa C. Friesen, Patricia A. Stewart, Dalsu Baris, Margaret R. Karagas, Molly Schwenn, Alison Johnson, G.M. Monawar Hosain, Consol Serra, Adonina Tardon, Alfredo Carrato, Reina Garcia-Closas, Lee E. Moore, Michael L. Nickerson, Stephen M. Hewitt, Petra Lenz, Alan R. Schned, Josep Lloreta, Yves Allory, Haoyu Zhang, Nilanjan Chatterjee, Montserrat Garcia-Closas, Nathaniel Rothman, Núria Malats, and Debra T. Silverman
Subjects: Environmental sciences, GE1-350
Abstract: Background: The International Agency for Research on Cancer (IARC) classifies diesel engine exhaust as carcinogenic to humans based on sufficient evidence for lung cancer. IARC noted, however, an increased risk of bladder cancer (based on limited evidence). Objective: To evaluate the association between quantitative, lifetime occupational diesel exhaust exposure and risk of urothelial cell carcinoma of the bladder (UBC) overall and according to pathological subtypes. Methods: Data from personal interviews with 1944 UBC cases, as well as formalin-fixed paraffin-embedded tumor tissue blocks, and 2135 controls were pooled from two case-control studies conducted in the U.S. and Spain. Lifetime occupational histories combined with exposure-oriented questions were used to estimate cumulative exposure to respirable elemental carbon (REC), a primary surrogate for diesel exhaust. Unconditional logistic regression and two-stage polytomous logistic regression were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for smoking and other risk factors. Results: Exposure to cumulative REC was associated with an increased risk of UBC; workers with cumulative REC >396 μg/m3-years had an OR of 1.61 (95% CI, 1.08–2.40). At this level of cumulative exposure, similar results were observed in the U.S. and Spain, OR = 1.75 (95% CI, 0.97–3.15) and OR = 1.54 (95% CI, 0.89–2.68), respectively. In lagged analysis, we also observed a consistent increased risk among workers with cumulative REC >396 μg/m3-years (range of ORs = 1.52–1.93) for all lag intervals evaluated (5–40 years). When we accounted for tumor subtypes defined by stage and grade, a significant association between diesel exhaust exposure and UBC was apparent (global test for association p = 0.0019). Conclusions: Combining data from two large epidemiologic studies, our results provide further evidence that diesel exhaust exposure increases the risk of UBC. Keywords: Bladder cancer, Diesel exhaust, Occupation
Published: 2020
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18. Germline variation at 8q24 and prostate cancer risk in men of European ancestry

Author: Marco Matejcic, Edward J. Saunders, Tokhir Dadaev, Mark N. Brook, Kan Wang, Xin Sheng, Ali Amin Al Olama, Fredrick R. Schumacher, Sue A. Ingles, Koveela Govindasami, Sara Benlloch, Sonja I. Berndt, Demetrius Albanes, Stella Koutros, Kenneth Muir, Victoria L. Stevens, Susan M. Gapstur, Catherine M. Tangen, Jyotsna Batra, Judith Clements, Henrik Gronberg, Nora Pashayan, Johanna Schleutker, Alicja Wolk, Catharine West, Lorelei Mucci, Peter Kraft, Géraldine Cancel-Tassin, Karina D. Sorensen, Lovise Maehle, Eli M. Grindedal, Sara S. Strom, David E. Neal, Freddie C. Hamdy, Jenny L. Donovan, Ruth C. Travis, Robert J. Hamilton, Barry Rosenstein, Yong-Jie Lu, Graham G. Giles, Adam S. Kibel, Ana Vega, Jeanette T. Bensen, Manolis Kogevinas, Kathryn L. Penney, Jong Y. Park, Janet L. Stanford, Cezary Cybulski, Børge G. Nordestgaard, Hermann Brenner, Christiane Maier, Jeri Kim, Manuel R. Teixeira, Susan L. Neuhausen, Kim De Ruyck, Azad Razack, Lisa F. Newcomb, Davor Lessel, Radka Kaneva, Nawaid Usmani, Frank Claessens, Paul A. Townsend, Manuela Gago-Dominguez, Monique J. Roobol, Florence Menegaux, Kay-Tee Khaw, Lisa A. Cannon-Albright, Hardev Pandha, Stephen N. Thibodeau, Daniel J. Schaid, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Fredrik Wiklund, Stephen J. Chanock, Douglas F. Easton, Rosalind A. Eeles, Zsofia Kote-Jarai, David V. Conti, and Christopher A. Haiman
Subjects: Science
Abstract: Chromosome 8q24 is known to be a major susceptibility region for prostate cancer risk. Here the authors analyze genetic data across the 8q24 region from 71,535 prostate cancer patients identifying 12 risk loci, three previously unreported, highlighting the contribution of germline variation at this locus.
Published: 2018
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19. Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants

Author: Tokhir Dadaev, Edward J. Saunders, Paul J. Newcombe, Ezequiel Anokian, Daniel A. Leongamornlert, Mark N. Brook, Clara Cieza-Borrella, Martina Mijuskovic, Sarah Wakerell, Ali Amin Al Olama, Fredrick R. Schumacher, Sonja I. Berndt, Sara Benlloch, Mahbubl Ahmed, Chee Goh, Xin Sheng, Zhuo Zhang, Kenneth Muir, Koveela Govindasami, Artitaya Lophatananon, Victoria L. Stevens, Susan M. Gapstur, Brian D. Carter, Catherine M. Tangen, Phyllis Goodman, Ian M. Thompson, Jyotsna Batra, Suzanne Chambers, Leire Moya, Judith Clements, Lisa Horvath, Wayne Tilley, Gail Risbridger, Henrik Gronberg, Markus Aly, Tobias Nordström, Paul Pharoah, Nora Pashayan, Johanna Schleutker, Teuvo L. J. Tammela, Csilla Sipeky, Anssi Auvinen, Demetrius Albanes, Stephanie Weinstein, Alicja Wolk, Niclas Hakansson, Catharine West, Alison M. Dunning, Neil Burnet, Lorelei Mucci, Edward Giovannucci, Gerald Andriole, Olivier Cussenot, Géraldine Cancel-Tassin, Stella Koutros, Laura E. Beane Freeman, Karina Dalsgaard Sorensen, Torben Falck Orntoft, Michael Borre, Lovise Maehle, Eli Marie Grindedal, David E. Neal, Jenny L. Donovan, Freddie C. Hamdy, Richard M. Martin, Ruth C. Travis, Tim J. Key, Robert J. Hamilton, Neil E. Fleshner, Antonio Finelli, Sue Ann Ingles, Mariana C. Stern, Barry Rosenstein, Sarah Kerns, Harry Ostrer, Yong-Jie Lu, Hong-Wei Zhang, Ninghan Feng, Xueying Mao, Xin Guo, Guomin Wang, Zan Sun, Graham G. Giles, Melissa C. Southey, Robert J. MacInnis, Liesel M. FitzGerald, Adam S. Kibel, Bettina F. Drake, Ana Vega, Antonio Gómez-Caamaño, Laura Fachal, Robert Szulkin, Martin Eklund, Manolis Kogevinas, Javier Llorca, Gemma Castaño-Vinyals, Kathryn L. Penney, Meir Stampfer, Jong Y. Park, Thomas A. Sellers, Hui-Yi Lin, Janet L. Stanford, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Elaine A. Ostrander, Milan S. Geybels, Børge G. Nordestgaard, Sune F. Nielsen, Maren Weisher, Rasmus Bisbjerg, Martin Andreas Røder, Peter Iversen, Hermann Brenner, Katarina Cuk, Bernd Holleczek, Christiane Maier, Manuel Luedeke, Thomas Schnoeller, Jeri Kim, Christopher J. Logothetis, Esther M. John, Manuel R. Teixeira, Paula Paulo, Marta Cardoso, Susan L. Neuhausen, Linda Steele, Yuan Chun Ding, Kim De Ruyck, Gert De Meerleer, Piet Ost, Azad Razack, Jasmine Lim, Soo-Hwang Teo, Daniel W. Lin, Lisa F. Newcomb, Davor Lessel, Marija Gamulin, Tomislav Kulis, Radka Kaneva, Nawaid Usmani, Chavdar Slavov, Vanio Mitev, Matthew Parliament, Sandeep Singhal, Frank Claessens, Steven Joniau, Thomas Van den Broeck, Samantha Larkin, Paul A. Townsend, Claire Aukim-Hastie, Manuela Gago-Dominguez, Jose Esteban Castelao, Maria Elena Martinez, Monique J. Roobol, Guido Jenster, Ron H. N. van Schaik, Florence Menegaux, Thérèse Truong, Yves Akoli Koudou, Jianfeng Xu, Kay-Tee Khaw, Lisa Cannon-Albright, Hardev Pandha, Agnieszka Michael, Andrzej Kierzek, Stephen N. Thibodeau, Shannon K. McDonnell, Daniel J. Schaid, Sara Lindstrom, Constance Turman, Jing Ma, David J. Hunter, Elio Riboli, Afshan Siddiq, Federico Canzian, Laurence N. Kolonel, Loic Le Marchand, Robert N. Hoover, Mitchell J. Machiela, Peter Kraft, The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium, Matthew Freedman, Fredrik Wiklund, Stephen Chanock, Brian E. Henderson, Douglas F. Easton, Christopher A. Haiman, Rosalind A. Eeles, David V. Conti, and Zsofia Kote-Jarai
Subjects: Science
Abstract: Prostate cancer (PrCa) involves a large heritable genetic component. Here, the authors perform multivariate fine-mapping of known PrCa GWAS loci, identifying variants enriched for biological function, explaining more familial relative risk, and with potential application in clinical risk profiling.
Published: 2018
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20. A prospective study of cancer risk among Agricultural Health Study farm spouses associated with personal use of organochlorine insecticides

Author: Lydia M. Louis, Catherine C. Lerro, Melissa C. Friesen, Gabriella Andreotti, Stella Koutros, Dale P. Sandler, Aaron Blair, Mark G. Robson, and Laura E. Beane Freeman
Subjects: Agricultural Health Study, Cancer, Farm spouses, Organochlorine, Pesticide, Industrial medicine. Industrial hygiene, RC963-969, Public aspects of medicine, RA1-1270
Abstract: Abstract Background Organochlorine insecticides (OCs) have historically been used worldwide to control insects, although most have now been banned in developed countries. Evidence for an association between OC exposures and cancer predominantly comes from occupational and population based-studies among men. We evaluated the association between the use of specific OCs and cancer among the female spouses of pesticide applicators in the Agricultural Health Study. Methods At enrollment (1993–1997), spouses of private applicators in the cohort provided information about their own use of pesticides, including seven OCs (aldrin, chlordane, dieldrin, DDT, heptachlor, lindane, and toxaphene), and information on potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% confidence intervals (CIs) for cancers (n ≥ 3 exposed cases) reported to state cancer registries from enrollment through 2012 (North Carolina) and 2013 (Iowa), and use of the individual OCs, as well as use of any of the specific OCs. Results Among 28,909 female spouses, 2191 (7.58%) reported ever use of at least one OC, of whom 287 were diagnosed with cancer. Most cancers were not associated with OC use. Risk of glioma was increased among users of at least one OC (Nexposed = 11, RR = 3.52, 95% CI 1.72–7.21) and specifically among lindane users (Nexposed = 3, RR = 4.45, 95% CI 1.36–14.55). Multiple myeloma was associated with chlordane (Nexposed = 6, RR = 2.71, 95% CI 1.12–6.55). Based on 3 exposed cases each, there were also positive associations between pancreatic cancer and lindane, and ER-PR- breast cancer and dieldrin. No other associations with breast cancer were found. Conclusions Overall, there were some associations with OC use and cancer incidence, however we were limited by the small number of exposed cancer cases. Future research should attempt to expand on these findings by assessing environmental sources of OC exposures, to fully evaluate the role of OC exposures on cancer risk in women.
Published: 2017
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21. Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Author: Ghislaine Scelo, Mark P. Purdue, Kevin M. Brown, Mattias Johansson, Zhaoming Wang, Jeanette E. Eckel-Passow, Yuanqing Ye, Jonathan N. Hofmann, Jiyeon Choi, Matthieu Foll, Valerie Gaborieau, Mitchell J. Machiela, Leandro M. Colli, Peng Li, Joshua N. Sampson, Behnoush Abedi-Ardekani, Celine Besse, Helene Blanche, Anne Boland, Laurie Burdette, Amelie Chabrier, Geoffroy Durand, Florence Le Calvez-Kelm, Egor Prokhortchouk, Nivonirina Robinot, Konstantin G. Skryabin, Magdalena B. Wozniak, Meredith Yeager, Gordana Basta-Jovanovic, Zoran Dzamic, Lenka Foretova, Ivana Holcatova, Vladimir Janout, Dana Mates, Anush Mukeriya, Stefan Rascu, David Zaridze, Vladimir Bencko, Cezary Cybulski, Eleonora Fabianova, Viorel Jinga, Jolanta Lissowska, Jan Lubinski, Marie Navratilova, Peter Rudnai, Neonila Szeszenia-Dabrowska, Simone Benhamou, Geraldine Cancel-Tassin, Olivier Cussenot, Laura Baglietto, Heiner Boeing, Kay-Tee Khaw, Elisabete Weiderpass, Borje Ljungberg, Raviprakash T. Sitaram, Fiona Bruinsma, Susan J. Jordan, Gianluca Severi, Ingrid Winship, Kristian Hveem, Lars J. Vatten, Tony Fletcher, Kvetoslava Koppova, Susanna C. Larsson, Alicja Wolk, Rosamonde E. Banks, Peter J. Selby, Douglas F. Easton, Paul Pharoah, Gabriella Andreotti, Laura E. Beane Freeman, Stella Koutros, Demetrius Albanes, Satu Männistö, Stephanie Weinstein, Peter E. Clark, Todd L. Edwards, Loren Lipworth, Susan M. Gapstur, Victoria L. Stevens, Hallie Carol, Matthew L. Freedman, Mark M. Pomerantz, Eunyoung Cho, Peter Kraft, Mark A. Preston, Kathryn M. Wilson, J. Michael Gaziano, Howard D. Sesso, Amanda Black, Neal D. Freedman, Wen-Yi Huang, John G. Anema, Richard J. Kahnoski, Brian R. Lane, Sabrina L. Noyes, David Petillo, Bin Tean Teh, Ulrike Peters, Emily White, Garnet L. Anderson, Lisa Johnson, Juhua Luo, Julie Buring, I-Min Lee, Wong-Ho Chow, Lee E. Moore, Christopher Wood, Timothy Eisen, Marc Henrion, James Larkin, Poulami Barman, Bradley C. Leibovich, Toni K. Choueiri, G. Mark Lathrop, Nathaniel Rothman, Jean-Francois Deleuze, James D. McKay, Alexander S. Parker, Xifeng Wu, Richard S. Houlston, Paul Brennan, and Stephen J. Chanock
Subjects: Science
Abstract: Risk for renal cell carcinoma (RCC) is higher when there are first-degree family members with the disease. Here, Scelo and colleagues perform a genome-wide association meta-analysis and new genome-wide scan to identify seven new loci with significant RCC association.
Published: 2017
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22. The influence of obesity-related factors in the etiology of renal cell carcinoma-A mendelian randomization study.

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

Author: Srishti Shrestha, Freya Kamel, David M Umbach, Laura E Beane Freeman, Stella Koutros, Michael Alavanja, Dale P Sandler, and Honglei Chen
Subjects: Medicine, Science
Abstract: Few studies have evaluated the presence of multiple nonmotor symptoms (NMS) in relation to Parkinson disease (PD). Therefore, we examined cross-sectional associations between individual and multiple NMS and PD in the Agricultural Health Study.20,473 male farmers and 16,259 female spouses provided information on six NMS (reduced sense of smell, dream-enacting behavior, daytime sleepiness, infrequent bowel movement, depression, and anxiety) in the cohort's 2013-2015 follow-up survey. 191 men and 68 women reported physician-diagnosed PD. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multivariable logistic regression models separately by sex.NMS were each associated with PD, with the strongest association for reduced sense of smell in men and dream-enacting behavior in women. The number of NMS showed a strong dose-response relationship with PD, particularly in men. ORs were 5.5 (95% CI 3.4-8.8) for one, 17 (95% CI 10.4-28.0) for two, and 53.4 (95% CI 33.2-86.1) for three or more NMS in men; the corresponding ORs were 4.6 (95% CI 2.3-9.5), 6.7 (95% CI 2.9-15.6), and 23.6 (95% CI 10.7-52.4) in women (PNMS-interaction-with-sex = 0.07).The number of NMS was associated with PD in a dose-response manner and the association appeared stronger in men than in women. These findings should be further investigated in population-based prospective studies.
Published: 2017
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24. Sex Steroid Hormone Gene Variants, Pesticide Use and the Risk of Prostate Cancer: A Nested Case-Control Study within the Agricultural Health Study

Author: Carol H Christensen, Kathryn Hughes Barry, Gabriella Andreotti, Michael CR Alavanja, Michael B Cook, Scott P. Kelly, Laurie A. Burdette, Meredith Yeager, Laura E. Beane Freeman, Sonja I. Berndt, and Stella Koutros
Subjects: Pesticides, prostate cancer, Interaction, Single nucleotide polymorphism, sex steroid hormones, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract: Experimental and epidemiologic investigations suggest that certain pesticides may alter sex steroid hormone synthesis, metabolism or regulation and the risk of hormone-related cancers. Here we evaluated whether single nucleotide polymorphisms (SNPs) involved in hormone homeostasis alter the effect of pesticide exposure on prostate cancer risk. We evaluated pesticide–SNP interactions between 39 pesticides and SNPs with respect to prostate cancer among 776 cases and 1444 controls nested in the Agricultural Health Study cohort. In these interactions, we included candidate SNPs involved in hormone synthesis, metabolism and regulation (N=1100), as well as SNPs associated with circulating sex steroid concentrations as identified by genome-wide association studies (N=17). Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP–pesticide interactions were calculated using a likelihood ratio test. We translated p-values for interaction into q-values, which reflected the false discovery rate, to account for multiple comparisons. We observed a significant interaction, which was robust to multiple comparison testing, between the herbicide dicamba and rs8192166 in the testosterone metabolizing gene SRD5A1 (p-interaction=4.0x10-5; q-value=0.03), such that men with two copies of the wild-type genotype CC had a reduced risk of prostate cancer associated with low use of dicamba (OR=0.62 95% CI: 0.41, 0.93), and high use of dicamba (OR=0.44, 95% CI: 0.29, 0.68), compared to those who reported no use of dicamba; in contrast, there was no significant association between dicamba and prostate cancer among those carrying one or two copies of the variant T allele at rs8192166. In addition, interactions between two organophosphate insecticides and SNPs related to estradiol metabolism were observed to result in an increased risk of prostate cancer. While replication is needed, these data suggest both agonistic or antagonistic effects on circulating hormones, due to the combination of exposure to pesticides and genetic susceptibility, may impact prostate cancer risk.
Published: 2016
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25. Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study.

Author: Gabriella Andreotti, Jane A Hoppin, Lifang Hou, Stella Koutros, Shahinaz M Gadalla, Sharon A Savage, Jay Lubin, Aaron Blair, Mirjam Hoxha, Andrea Baccarelli, Dale Sandler, Michael Alavanja, and Laura E Beane Freeman
Subjects: Medicine, Science
Abstract: Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.
Published: 2015
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26. Non-hodgkin lymphoma risk and insecticide, fungicide and fumigant use in the agricultural health study.

Author: Michael C R Alavanja, Jonathan N Hofmann, Charles F Lynch, Cynthia J Hines, Kathryn H Barry, Joseph Barker, Dennis W Buckman, Kent Thomas, Dale P Sandler, Jane A Hoppin, Stella Koutros, Gabriella Andreotti, Jay H Lubin, Aaron Blair, and Laura E Beane Freeman
Subjects: Medicine, Science
Abstract: Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993-97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999-2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.
Published: 2014
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27. Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis.

Author: Pei-Hsuan Weng, Yi-Ling Huang, John H Page, Jen-Hau Chen, Jianfeng Xu, Stella Koutros, Sonja Berndt, Stephen Chanock, Meredith Yeager, John S Witte, Rosalind A Eeles, Douglas F Easton, David E Neal, Jenny Donovan, Freddie C Hamdy, Kenneth R Muir, Graham Giles, Gianluca Severi, Jeffrey R Smith, Carmela R Balistreri, Irene M Shui, and Yen-Ching Chen
Subjects: Medicine, Science
Abstract: Toll-like receptor 4 (TLR4) is one of the best known TLR members expressed on the surface of several leukocytes and tissue cells and has a key function in detecting pathogen and danger-associated molecular patterns. The role of TLR4 in the pathophysiology of several age-related diseases is also well recognized, such as prostate cancer (PCa). TLR4 polymorphisms have been related to PCa risk, but the relationship between TLR4 genotypes and aggressive PCa risk has not been evaluated by any systematic reviews.We performed a systematic review and meta-analysis of candidate-gene and genome-wide association studies analyzing this relationship and included only white population. Considering appropriate criteria, only nine studies were analyzed in the meta-analysis, including 3,937 aggressive PCa and 7,382 controls.Using random effects model, no significant association was found in the ten TLR4 SNPs reported by at least four included studies under any inheritance model (rs2737191, rs1927914, rs10759932, rs1927911, rs11536879, rs2149356, rs4986790, rs11536889, rs7873784, and rs1554973). Pooled estimates from another ten TLR4 SNPs reported by three studies also showed no significant association (rs10759930, rs10116253, rs11536869, rs5030717, rs4986791, rs11536897, rs1927906, rs913930, rs1927905, and rs7045953). Meta-regression revealed that study type was not a significant source of between-study heterogeneity.TLR4 polymorphisms were not significantly associated with the risk of aggressive PCa.
Published: 2014
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28. Genetic susceptibility loci, pesticide exposure and prostate cancer risk.

Author: Stella Koutros, Sonja I Berndt, Kathryn Hughes Barry, Gabriella Andreotti, Jane A Hoppin, Dale P Sandler, Meredith Yeager, Laurie A Burdett, Jeffrey Yuenger, Michael C R Alavanja, and Laura E Beane Freeman
Subjects: Medicine, Science
Abstract: Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44-8.15) (P-interaction= 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction= 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.
Published: 2013
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29. The Interaction between Pesticide Use and Genetic Variants Involved in Lipid Metabolism on Prostate Cancer Risk

Author: Gabriella Andreotti, Stella Koutros, Sonja I. Berndt, Kathryn Hughes Barry, Lifang Hou, Jane A. Hoppin, Dale P. Sandler, Jay H. Lubin, Laurie A. Burdette, Jeffrey Yuenger, Meredith Yeager, Laura E. Beane Freeman, and Michael C. R. Alavanja
Subjects: Medicine
Abstract: Background. Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods. In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results. We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion. Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.
Published: 2012
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30. Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Nicole Gonzalez, Nina Rao, Michael Dean, Donghyuk Lee, Amber N. Hurson, Dalsu Baris, Molly Schwenn, Alison Johnson, Ludmila Prokunina-Olsson, Melissa C. Friesen, Bin Zhu, Nathaniel Rothman, Debra T. Silverman, and Stella Koutros
Subjects: Oncology, Epidemiology
Abstract: Background: Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors. Methods: Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study. Using data on 797 cases and 1,418 controls, two-stage polytomous logistic regression was used to evaluate etiologic heterogeneity between bladder cancer subtypes and quantitative, lifetime estimates of respirable elemental carbon (REC), a surrogate for diesel exposure. Poisson regression was used to evaluate associations between REC and mutational signatures. Results: We observed significant heterogeneity in the diesel-bladder cancer risk relationship, with a strong positive association among cases with high-grade, nonmuscle invasive TP53-mutated tumors compared with controls [ORTop Tertile vs.Unexposed, 4.8; 95% confidence interval (CI), 2.2–10.5; Ptrend Conclusions: The relationship between diesel exhaust and bladder cancer was heterogeneous based on the presence of TP53 mutations in tumors, further supporting the link between PAH exposure and TP53 mutations in carcinogenesis. Future studies that can identify nitro-PAH signatures in exposed tumors are warranted to add human data supporting the link between diesel and bladder cancer. Impact: This study provides additional insight into the etiology and possible mechanisms related to diesel exhaust-induced bladder cancer.
Published: 2023

31. Diet quality, common genetic polymorphisms, and bladder cancer risk in a New England population-based study

Author: Reno C. Leeming, Stella Koutros, Margaret R. Karagas, Dalsu Baris, Molly Schwenn, Alison Johnson, Michael S. Zens, Alan R. Schned, Nathaniel Rothman, Debra T. Silverman, and Michael N. Passarelli
Subjects: Nutrition and Dietetics, Medicine (miscellaneous)
Published: 2022

32. Supplemental Table 7 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: Cosine similarities for all signatures
Published: 2023

33. Supplemental Table 3 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: Case-case associations between REC and TP53 mutation, NEBCS
Published: 2023

34. Supplemental Table 4 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: specific TP53 mutations and ever diesel
Published: 2023

35. Data from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: Background:Diesel exhaust is a complex mixture, including polycyclic aromatic hydrocarbons (PAH) and nitrated PAHs (nitro-PAH), many of which are potent mutagens and possible bladder carcinogens. To explore the association between diesel exposure and bladder carcinogenesis, we examined the relationship between exposure and somatic mutations and mutational signatures in bladder tumors.Methods:Targeted sequencing was conducted in bladder tumors from the New England Bladder Cancer Study. Using data on 797 cases and 1,418 controls, two-stage polytomous logistic regression was used to evaluate etiologic heterogeneity between bladder cancer subtypes and quantitative, lifetime estimates of respirable elemental carbon (REC), a surrogate for diesel exposure. Poisson regression was used to evaluate associations between REC and mutational signatures.Results:We observed significant heterogeneity in the diesel-bladder cancer risk relationship, with a strong positive association among cases with high-grade, nonmuscle invasive TP53-mutated tumors compared with controls [ORTop Tertile vs.Unexposed, 4.8; 95% confidence interval (CI), 2.2–10.5; Ptrend Pheterogeneity = 0.002]. In muscle-invasive tumors, we observed a positive association between diesel exposure and the nitro-PAH signatures of 1,6-dintropyrene (RR, 1.93; 95% CI, 1.28–2.92) and 3-nitrobenzoic acid (RR, 1.97; 95% CI, 1.33–2.92).Conclusions:The relationship between diesel exhaust and bladder cancer was heterogeneous based on the presence of TP53 mutations in tumors, further supporting the link between PAH exposure and TP53 mutations in carcinogenesis. Future studies that can identify nitro-PAH signatures in exposed tumors are warranted to add human data supporting the link between diesel and bladder cancer.Impact:This study provides additional insight into the etiology and possible mechanisms related to diesel exhaust-induced bladder cancer.
Published: 2023

36. Supplemental Table 6 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: Ever diesel and nitro-PAH signatures adjusted for smoking
Published: 2023

37. Supplemental Table 5 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: REC and nitro-PAH signatures in New England
Published: 2023

38. Supplemental Table 1 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: Genes on panel
Published: 2023

39. Supplemental Table 2 from Nitrated Polycyclic Aromatic Hydrocarbon (Nitro-PAH) Signatures and Somatic Mutations in Diesel Exhaust-Exposed Bladder Tumors

Author: Stella Koutros, Debra T. Silverman, Nathaniel Rothman, Bin Zhu, Melissa C. Friesen, Ludmila Prokunina-Olsson, Alison Johnson, Molly Schwenn, Dalsu Baris, Amber N. Hurson, Donghyuk Lee, Michael Dean, Nina Rao, and Nicole Gonzalez
Abstract: study characteristics
Published: 2023

40. Supplementary Tables 1-3 from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author: Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang
Abstract: Supplementary Table 1. Sample Size of each participated study, by case-control status and genotype platform. Supplementary Table 2. Association between fourteen environmental factors and the risk of breast cancer. Supplementary Table 3. Interactions between genes and fourteen environmental factors.
Published: 2023

41. Data from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author: Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang
Abstract: Genome-wide association studies (GWAS) have identified more than 200 susceptibility loci for breast cancer, but these variants explain less than a fifth of the disease risk. Although gene–environment interactions have been proposed to account for some of the remaining heritability, few studies have empirically assessed this.We obtained genotype and risk factor data from 46,060 cases and 47,929 controls of European ancestry from population-based studies within the Breast Cancer Association Consortium (BCAC). We built gene expression prediction models for 4,864 genes with a significant (P < 0.01) heritable component using the transcriptome and genotype data from the Genotype-Tissue Expression (GTEx) project. We leveraged predicted gene expression information to investigate the interactions between gene-centric genetic variation and 14 established risk factors in association with breast cancer risk, using a mixed-effects score test.After adjusting for number of tests using Bonferroni correction, no interaction remained statistically significant. The strongest interaction observed was between the predicted expression of the C13orf45 gene and age at first full-term pregnancy (PGXE = 4.44 × 10−6).In this transcriptome-informed genome-wide gene–environment interaction study of breast cancer, we found no strong support for the role of gene expression in modifying the associations between established risk factors and breast cancer risk.Our study suggests a limited role of gene–environment interactions in breast cancer risk.
Published: 2023

42. Supplementary Information from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author: Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang
Abstract: Funding and acknowledgements.
Published: 2023

43. Supplementary Figure 1 from A Genome-Wide Gene-Based Gene–Environment Interaction Study of Breast Cancer in More than 90,000 Women

Author: Sara Lindström, Jenny Chang-Claude, Peter Kraft, Li Hsu, Roger L. Milne, Douglas F. Easton, Håkan Olsson, Sophia Wang, James V. Lacey, Nick Orr, Anthony J. Swerdlow, Jack A. Taylor, Dale P. Sandler, Alicja Wolk, Kamila Czene, Per Hall, Anthony Howell, D. Gareth Evans, Rose Yang, Thomas Ahearn, Jonine Figueroa, Montserrat García-Closas, Heather Eliassen, Rulla Tamimi, Cheng Peng, Michael I. Love, Melissa A. Troester, Jirong Long, Wei Zheng, Mark S. Goldberg, Jacques Simard, Stacey Winham, Christopher Scott, Gertraud Maskarinec, Christopher A. Haiman, Graham G. Giles, Heiko Becher, Audrey Jung, Veli-Matti Kosma, Arto Mannermaa, Sabine Behrens, Wing-Yee Lo, Reiner Hoppe, Volker Arndt, Hermann Brenner, Rudolf Kaaks, Federico Canzian, James M. Hodge, Lauren R. Teras, Thérèse Truong, Pascal Guénel, Kristan Aronson, Rachel A. Murphy, Rana Shibli, Gad Rennert, Jennifer Stone, Laura E. Beane Freeman, Stella Koutros, Melissa C. Southey, John L. Hopper, Paul D.P. Pharoah, Kyriaki Michailidou, Qin Wang, Michael Lush, Alison M. Dunning, Joe Dennis, Manjeet K. Bolla, Yu-Ru Su, Pooja Middha Kapoor, Hongjie Chen, and Xiaoliang Wang
Abstract: Quantile-Quantile plot (Q-Q plot) of the aMiSTi p-values for each set of the GxE interactions.
Published: 2023

44. MP22-13 OCCUPATIONAL EXPOSURE TO ORGANIC SOLVENTS AND RISK OF BLADDER CANCER

Author: Shuai Xie, Melissa Friesen, Dalsu Barus, Molly Schwenn, Nathaniel Rothman, Alison Johnson, Margaret Karagas, Debra Silverman, and Stella Koutros
Subjects: Urology
Published: 2023

45. Supplemental Table 1, Supplemental Table 2 from Tobacco Use and Cancer Risk in the Agricultural Health Study

Author: Laura Beane Freeman, Dale P. Sandler, Michael C. Alavanja, Patricia Hartge, Stella Koutros, Catherine C. Lerro, Debra T. Silverman, Neal D. Freedman, and Gabriella Andreotti
Abstract: Supplemental Table 1. Prevalence of tobacco use by gender; Supplemental Table 2. Cigarette Smoking Characteristics among exclusive cigarette and dual tobacco users
Published: 2023

46. Data from Tobacco Use and Cancer Risk in the Agricultural Health Study

Author: Laura Beane Freeman, Dale P. Sandler, Michael C. Alavanja, Patricia Hartge, Stella Koutros, Catherine C. Lerro, Debra T. Silverman, Neal D. Freedman, and Gabriella Andreotti
Abstract: Background: Cigarettes are well known to cause cancer, but less is known about the risks of other tobacco products and use of more than one product.Methods: We examined cancer incidence in relation to exclusive use of six tobacco products [cigarettes, other combustibles (pipe, cigar, cigarillo), and smokeless tobacco (chewing tobacco, snuff)] in the Agricultural Health Study. We also examined the added cancer risks associated with use of cigarettes and other tobacco products.Results: In our study population of 84,015, ever use of smokeless tobacco was higher than the general United States population, whereas cigarette use was lower and other combustible product use was about the same. The strongest associations for exclusive ever use were for lung cancer [cigarettes HR = 15.48; 95% confidence interval (CI), 11.95–20.06; other combustible tobacco HR = 3.44; 95% CI, 1.53–7.71; smokeless tobacco HR = 2.21; 95% CI, 1.11–4.42]. Compared with exclusive cigarette smokers, cigarette smokers who additionally ever-used another combustible product had higher risks of smoking-related cancers (HR = 1.16; 95% CI, 1.04–1.30), especially among those who smoked cigarettes for more than 15 years.Conclusions and Impact: Cigarette smokers who additionally ever used smokeless tobacco had cancer risks similar to exclusive cigarette smokers. Users of cigarettes and other combustible tobacco may have higher risks of certain cancers than exclusive cigarette users. Cancer Epidemiol Biomarkers Prev; 26(5); 769–78. ©2016 AACR.
Published: 2023

47. Data from Targeted Deep Sequencing of Bladder Tumors Reveals Novel Associations between Cancer Gene Mutations and Mutational Signatures with Major Risk Factors

Author: Michael Dean, Nathaniel Rothman, Debra T. Silverman, Ludmila Prokunina-Olsson, Montserrat Garcia-Closas, Kristine Jones, Alison Johnson, Molly Schwenn, Dalsu Baris, Larissa A. Pardo, Bin Zhu, Donghyuk Lee, Michael L. Nickerson, Lee E. Moore, Nina Rao, and Stella Koutros
Abstract: Purpose:Exome- and whole-genome sequencing of muscle-invasive bladder cancer has revealed important insights into the molecular landscape; however, there are few studies of non–muscle-invasive bladder cancer with detailed risk factor information.Experimental Design:We examined the relationship between smoking and other bladder cancer risk factors and somatic mutations and mutational signatures in bladder tumors. Targeted sequencing of frequently mutated genes in bladder cancer was conducted in 322 formalin-fixed paraffin-embedded bladder tumors from a population-based case–control study. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI), evaluating mutations and risk factors. We used SignatureEstimation to extract four known single base substitution mutational signatures and Poisson regression to calculate risk ratios (RR) and 95% CIs, evaluating signatures and risk factors.Results:Non-silent KDM6A mutations were more common in females than males (OR = 1.83; 95% CI, 1.05–3.19). There was striking heterogeneity in the relationship between smoking status and established single base substitution signatures: current smoking status was associated with greater ERCC2-Signature mutations compared with former (P = 0.024) and never smoking (RR = 1.40; 95% CI, 1.09–1.80; P = 0.008), former smoking was associated with greater APOBEC-Signature13 mutations (P = 0.05), and never smoking was associated with greater APOBEC-Signature2 mutations (RR = 1.54; 95% CI, 1.17–2.01; P = 0.002). There was evidence that smoking duration (the component most strongly associated with bladder cancer risk) was associated with ERCC2-Signature mutations and APOBEC-Signature13 mutations among current (Ptrend = 0.005) and former smokers (P = 0.0004), respectively.Conclusions:These data quantify the contribution of bladder cancer risk factors to mutational burden and suggest different signature enrichments among never, former, and current smokers.
Published: 2023

48. Supplementary Table 3 from Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer

Author: Michael C.R. Alavanja, Meredith Yeager, Jeffrey Yuenger, Laura A. Burdette, Qizhai Li, Kai Yu, Jane A. Hoppin, Dale P. Sandler, Jay H. Lubin, Gabriella Andreotti, Sonja I. Berndt, Laura E. Beane Freeman, and Stella Koutros
Abstract: Supplementary Table 3 from Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Published: 2023

49. Supplementary Table 1 from Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer

Author: Michael C.R. Alavanja, Meredith Yeager, Jeffrey Yuenger, Laura A. Burdette, Qizhai Li, Kai Yu, Jane A. Hoppin, Dale P. Sandler, Jay H. Lubin, Gabriella Andreotti, Sonja I. Berndt, Laura E. Beane Freeman, and Stella Koutros
Abstract: Supplementary Table 1 from Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Published: 2023

50. Supplementary Table 2 from Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer

Author: Michael C.R. Alavanja, Meredith Yeager, Jeffrey Yuenger, Laura A. Burdette, Qizhai Li, Kai Yu, Jane A. Hoppin, Dale P. Sandler, Jay H. Lubin, Gabriella Andreotti, Sonja I. Berndt, Laura E. Beane Freeman, and Stella Koutros
Abstract: Supplementary Table 2 from Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer
Published: 2023

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