234 results on '"Alan A. Arslan"'
Search Results
2. A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
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Øivind Midttun, Arve Ulvik, Klaus Meyer, Hana Zahed, Graham G. Giles, Jonas Manjer, Malte Sandsveden, Arnulf Langhammer, Elin Pettersen Sørgjerd, Annelie F. Behndig, Mikael Johansson, Neal D. Freedman, Wen-Yi Huang, Chu Chen, Ross Prentice, Victoria L. Stevens, Ying Wang, Loïc Le Marchand, Stephanie J. Weinstein, Qiuyin Cai, Alan A. Arslan, Yu Chen, Xiao-Ou Shu, Wei Zheng, Jian-Min Yuan, Woon-Puay Koh, Kala Visvanathan, Howard D. Sesso, Xuehong Zhang, J. Michael Gaziano, Anouar Fanidi, Hilary A. Robbins, Paul Brennan, Mattias Johansson, and Per M. Ueland
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Medicine ,Science - Abstract
Abstract Circulating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan–NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.
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- 2023
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3. World Trade Center Exposure, DNA Methylation Changes, and Cancer: A Review of Current Evidence
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Stephanie Tuminello, Emelie Nguyen, Nedim Durmus, Ramazan Alptekin, Muhammed Yilmaz, Maria Cecilia Crisanti, Matija Snuderl, Yu Chen, Yongzhao Shao, Joan Reibman, Emanuela Taioli, and Alan A. Arslan
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World Trade Center ,epigenetics ,DNA methylation ,breast cancer ,prostate cancer ,Genetics ,QH426-470 ,Biotechnology ,TP248.13-248.65 - Abstract
Introduction: Known carcinogens in the dust and fumes from the destruction of the World Trade Center (WTC) towers on 9 November 2001 included metals, asbestos, and organic pollutants, which have been shown to modify epigenetic status. Epigenome-wide association analyses (EWAS) using uniform (Illumina) methodology have identified novel epigenetic profiles of WTC exposure. Methods: We reviewed all published data, comparing differentially methylated gene profiles identified in the prior EWAS studies of WTC exposure. This included DNA methylation changes in blood-derived DNA from cases of cancer-free “Survivors” and those with breast cancer, as well as tissue-derived DNA from “Responders” with prostate cancer. Emerging molecular pathways related to the observed DNA methylation changes in WTC-exposed groups were explored and summarized. Results: WTC dust exposure appears to be associated with DNA methylation changes across the genome. Notably, WTC dust exposure appears to be associated with increased global DNA methylation; direct dysregulation of cancer genes and pathways, including inflammation and immune system dysregulation; and endocrine system disruption, as well as disruption of cholesterol homeostasis and lipid metabolism. Conclusion: WTC dust exposure appears to be associated with biologically meaningful DNA methylation changes, with implications for carcinogenesis and development of other chronic diseases.
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- 2023
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4. Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults
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Hana Zahed, Mattias Johansson, Per M. Ueland, Øivind Midttun, Roger L. Milne, Graham G. Giles, Jonas Manjer, Malte Sandsveden, Arnulf Langhammer, Elin Pettersen Sørgjerd, Kjell Grankvist, Mikael Johansson, Neal D. Freedman, Wen-Yi Huang, Chu Chen, Ross Prentice, Victoria L. Stevens, Ying Wang, Loic Le Marchand, Lynne R. Wilkens, Stephanie J. Weinstein, Demetrius Albanes, Qiuyin Cai, William J. Blot, Alan A. Arslan, Anne Zeleniuch-Jacquotte, Xiao-Ou Shu, Wei Zheng, Jian-Min Yuan, Woon-Puay Koh, Kala Visvanathan, Howard D. Sesso, Xuehong Zhang, J. Michael Gaziano, Anouar Fanidi, David Muller, Paul Brennan, Florence Guida, and Hilary A. Robbins
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Medicine ,Science - Abstract
Abstract Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p
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- 2021
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5. Genomic signature of parity in the breast of premenopausal women
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Julia Santucci-Pereira, Anne Zeleniuch-Jacquotte, Yelena Afanasyeva, Hua Zhong, Michael Slifker, Suraj Peri, Eric A. Ross, Ricardo López de Cicco, Yubo Zhai, Theresa Nguyen, Fathima Sheriff, Irma H. Russo, Yanrong Su, Alan A. Arslan, Pal Bordas, Per Lenner, Janet Åhman, Anna Stina Landström Eriksson, Robert Johansson, Göran Hallmans, Paolo Toniolo, and Jose Russo
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Gene expression profiling ,Pregnancy ,Breast differentiation ,Parous and nulliparous breast transcriptome ,Immune response ,Breast cancer risk ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women. Methods Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues. Results Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues. Conclusions Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.
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- 2019
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6. Genetically Determined Height and Risk of Non-hodgkin Lymphoma
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Amy Moore, Eleanor Kane, Zhaoming Wang, Orestis A. Panagiotou, Lauren R. Teras, Alain Monnereau, Nicole Wong Doo, Mitchell J. Machiela, Christine F. Skibola, Susan L. Slager, Gilles Salles, Nicola J. Camp, Paige M. Bracci, Alexandra Nieters, Roel C. H. Vermeulen, Joseph Vijai, Karin E. Smedby, Yawei Zhang, Claire M. Vajdic, Wendy Cozen, John J. Spinelli, Henrik Hjalgrim, Graham G. Giles, Brian K. Link, Jacqueline Clavel, Alan A. Arslan, Mark P. Purdue, Lesley F. Tinker, Demetrius Albanes, Giovanni M. Ferri, Thomas M. Habermann, Hans-Olov Adami, Nikolaus Becker, Yolanda Benavente, Simonetta Bisanzi, Paolo Boffetta, Paul Brennan, Angela R. Brooks-Wilson, Federico Canzian, Lucia Conde, David G. Cox, Karen Curtin, Lenka Foretova, Susan M. Gapstur, Hervé Ghesquières, Martha Glenn, Bengt Glimelius, Rebecca D. Jackson, Qing Lan, Mark Liebow, Marc Maynadie, James McKay, Mads Melbye, Lucia Miligi, Roger L. Milne, Thierry J. Molina, Lindsay M. Morton, Kari E. North, Kenneth Offit, Marina Padoan, Alpa V. Patel, Sara Piro, Vignesh Ravichandran, Elio Riboli, Silvia de Sanjose, Richard K. Severson, Melissa C. Southey, Anthony Staines, Carolyn Stewart, Ruth C. Travis, Elisabete Weiderpass, Stephanie Weinstein, Tongzhang Zheng, Stephen J. Chanock, Nilanjan Chatterjee, Nathaniel Rothman, Brenda M. Birmann, James R. Cerhan, and Sonja I. Berndt
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non-Hodgkin lymphoma ,height ,genetics ,chronic lymphocytic leukemia ,diffuse large B-cell lymphoma ,follicular lymphoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00–1.17, p = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01–1.31, p = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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- 2020
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7. Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer
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Alison P. Klein, Brian M. Wolpin, Harvey A. Risch, Rachael Z. Stolzenberg-Solomon, Evelina Mocci, Mingfeng Zhang, Federico Canzian, Erica J. Childs, Jason W. Hoskins, Ashley Jermusyk, Jun Zhong, Fei Chen, Demetrius Albanes, Gabriella Andreotti, Alan A. Arslan, Ana Babic, William R. Bamlet, Laura Beane-Freeman, Sonja I. Berndt, Amanda Blackford, Michael Borges, Ayelet Borgida, Paige M. Bracci, Lauren Brais, Paul Brennan, Hermann Brenner, Bas Bueno-de-Mesquita, Julie Buring, Daniele Campa, Gabriele Capurso, Giulia Martina Cavestro, Kari G. Chaffee, Charles C. Chung, Sean Cleary, Michelle Cotterchio, Frederike Dijk, Eric J. Duell, Lenka Foretova, Charles Fuchs, Niccola Funel, Steven Gallinger, J. Michael M. Gaziano, Maria Gazouli, Graham G. Giles, Edward Giovannucci, Michael Goggins, Gary E. Goodman, Phyllis J. Goodman, Thilo Hackert, Christopher Haiman, Patricia Hartge, Manal Hasan, Peter Hegyi, Kathy J. Helzlsouer, Joseph Herman, Ivana Holcatova, Elizabeth A. Holly, Robert Hoover, Rayjean J. Hung, Eric J. Jacobs, Krzysztof Jamroziak, Vladimir Janout, Rudolf Kaaks, Kay-Tee Khaw, Eric A. Klein, Manolis Kogevinas, Charles Kooperberg, Matthew H. Kulke, Juozas Kupcinskas, Robert J. Kurtz, Daniel Laheru, Stefano Landi, Rita T. Lawlor, I.-Min Lee, Loic LeMarchand, Lingeng Lu, Núria Malats, Andrea Mambrini, Satu Mannisto, Roger L. Milne, Beatrice Mohelníková-Duchoňová, Rachel E. Neale, John P. Neoptolemos, Ann L. Oberg, Sara H. Olson, Irene Orlow, Claudio Pasquali, Alpa V. Patel, Ulrike Peters, Raffaele Pezzilli, Miquel Porta, Francisco X. Real, Nathaniel Rothman, Ghislaine Scelo, Howard D. Sesso, Gianluca Severi, Xiao-Ou Shu, Debra Silverman, Jill P. Smith, Pavel Soucek, Malin Sund, Renata Talar-Wojnarowska, Francesca Tavano, Mark D. Thornquist, Geoffrey S. Tobias, Stephen K. Van Den Eeden, Yogesh Vashist, Kala Visvanathan, Pavel Vodicka, Jean Wactawski-Wende, Zhaoming Wang, Nicolas Wentzensen, Emily White, Herbert Yu, Kai Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Peter Kraft, Donghui Li, Stephen Chanock, Ofure Obazee, Gloria M. Petersen, and Laufey T. Amundadottir
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Science - Abstract
Genetic variants associated with susceptibility to pancreatic cancer have been identified using genome wide association studies (GWAS). Here, the authors combine data from over 9000 patients and perform a meta-analysis to identify five novel loci linked to pancreatic cancer.
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- 2018
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8. Factors associated with cesarean delivery rates: a single-institution experience
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Spencer McClelland, Naomi Gorfinkle, Alan A. Arslan, Maria Teresa Benedetto-Anzai, Teresa Cheon, and Yuzuru Anzai
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Cesarean delivery ,Cesarean section ,Reduction ,Forceps ,Provider volume ,Medicine - Abstract
Abstract Background The aim of this study was to identify factors associated with variability in Cesarean delivery (CD) rates amongst providers at a single institution. Methods A retrospective cohort analysis was carried out on all births at NYU Langone Medical Center from 2005–2013. Data was collected for subjects and linked to diagnosis codes for singleton and twin deliveries. Descriptive characteristics were generated for all deliveries, and inferential analysis was performed including multiple covariates for singleton deliveries in the 2010–2013 cohort, including both univariate and multivariate regression analyses to identify factors associated with higher CD rates. Results 37,692 deliveries were identified at our institution during the study period, performed by 88 unique providers. The mean CD rate was 29.6%, with a range for individual physicians from 9.9% to 75.6%. In multivariate regression analysis, CD rate was directly correlated with average patient age, physician male gender, proportion of high-risk deliveries, and Maternal-Fetal Medicine specialty, and it was inversely correlated with total number of deliveries by physician and forceps delivery rate. There was no significant difference in CD rates between group and solo practices. Within the same group practice, each member’s CD rate was strongly correlated with the average CD rate of the group. Conclusion Our study demonstrates the wide range of CD rates for providers practicing within the same institution and reiterates the association of CD rates with patient age, high-risk pregnancy, and provider volume. Among operative vaginal deliveries, forceps delivery rate was associated with lower CD rates whereas vacuum delivery rate was not. Despite these findings, practice patterns within individual practices appear to contribute significantly to the wide range of CD rates.
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- 2017
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9. Female chromosome X mosaicism is age-related and preferentially affects the inactivated X chromosome
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Mitchell J. Machiela, Weiyin Zhou, Eric Karlins, Joshua N. Sampson, Neal D. Freedman, Qi Yang, Belynda Hicks, Casey Dagnall, Christopher Hautman, Kevin B. Jacobs, Christian C. Abnet, Melinda C. Aldrich, Christopher Amos, Laufey T. Amundadottir, Alan A. Arslan, Laura E. Beane-Freeman, Sonja I. Berndt, Amanda Black, William J. Blot, Cathryn H. Bock, Paige M. Bracci, Louise A. Brinton, H Bas Bueno-de-Mesquita, Laurie Burdett, Julie E. Buring, Mary A. Butler, Federico Canzian, Tania Carreón, Kari G. Chaffee, I-Shou Chang, Nilanjan Chatterjee, Chu Chen, Constance Chen, Kexin Chen, Charles C. Chung, Linda S. Cook, Marta Crous Bou, Michael Cullen, Faith G. Davis, Immaculata De Vivo, Ti Ding, Jennifer Doherty, Eric J. Duell, Caroline G. Epstein, Jin-Hu Fan, Jonine D. Figueroa, Joseph F. Fraumeni, Christine M. Friedenreich, Charles S. Fuchs, Steven Gallinger, Yu-Tang Gao, Susan M. Gapstur, Montserrat Garcia-Closas, Mia M. Gaudet, J. Michael Gaziano, Graham G. Giles, Elizabeth M. Gillanders, Edward L. Giovannucci, Lynn Goldin, Alisa M. Goldstein, Christopher A. Haiman, Goran Hallmans, Susan E. Hankinson, Curtis C. Harris, Roger Henriksson, Elizabeth A. Holly, Yun-Chul Hong, Robert N. Hoover, Chao A. Hsiung, Nan Hu, Wei Hu, David J. Hunter, Amy Hutchinson, Mazda Jenab, Christoffer Johansen, Kay-Tee Khaw, Hee Nam Kim, Yeul Hong Kim, Young Tae Kim, Alison P. Klein, Robert Klein, Woon-Puay Koh, Laurence N. Kolonel, Charles Kooperberg, Peter Kraft, Vittorio Krogh, Robert C. Kurtz, Andrea LaCroix, Qing Lan, Maria Teresa Landi, Loic Le Marchand, Donghui Li, Xiaolin Liang, Linda M. Liao, Dongxin Lin, Jianjun Liu, Jolanta Lissowska, Lingeng Lu, Anthony M. Magliocco, Nuria Malats, Keitaro Matsuo, Lorna H. McNeill, Robert R. McWilliams, Beatrice S. Melin, Lisa Mirabello, Lee Moore, Sara H. Olson, Irene Orlow, Jae Yong Park, Ana Patiño-Garcia, Beata Peplonska, Ulrike Peters, Gloria M. Petersen, Loreall Pooler, Jennifer Prescott, Ludmila Prokunina-Olsson, Mark P. Purdue, You-Lin Qiao, Preetha Rajaraman, Francisco X. Real, Elio Riboli, Harvey A. Risch, Benjamin Rodriguez-Santiago, Avima M. Ruder, Sharon A. Savage, Fredrick Schumacher, Ann G. Schwartz, Kendra L. Schwartz, Adeline Seow, Veronica Wendy Setiawan, Gianluca Severi, Hongbing Shen, Xin Sheng, Min-Ho Shin, Xiao-Ou Shu, Debra T. Silverman, Margaret R. Spitz, Victoria L. Stevens, Rachael Stolzenberg-Solomon, Daniel Stram, Ze-Zhong Tang, Philip R. Taylor, Lauren R. Teras, Geoffrey S. Tobias, David Van Den Berg, Kala Visvanathan, Sholom Wacholder, Jiu-Cun Wang, Zhaoming Wang, Nicolas Wentzensen, William Wheeler, Emily White, John K. Wiencke, Brian M. Wolpin, Maria Pik Wong, Chen Wu, Tangchun Wu, Xifeng Wu, Yi-Long Wu, Jay S. Wunder, Lucy Xia, Hannah P. Yang, Pan-Chyr Yang, Kai Yu, Krista A. Zanetti, Anne Zeleniuch-Jacquotte, Wei Zheng, Baosen Zhou, Regina G. Ziegler, Luis A. Perez-Jurado, Neil E. Caporaso, Nathaniel Rothman, Margaret Tucker, Michael C. Dean, Meredith Yeager, and Stephen J. Chanock
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Science - Abstract
It is unclear how often genetic mosaicism of chromosome X arises. Here, the authors examine women with cancer and cancer-free controls and show that X chromosome mosaicism occurs more frequently than on autosomes, especially on the inactive X chromosome, but is not linked to non-haematologic cancer risk
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- 2016
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10. Global Breast Cancer: The Lessons to Bring Home
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Silvia C. Formenti, Alan A. Arslan, and Susan M. Love
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Breast cancer is the most common cancer affecting women globally. This paper discusses the current progress in breast cancer in Western countries and focuses on important differences of this disease in low- and middle-income countries (LMCs). It introduces several arguments for applying caution before globalizing some of the US-adopted practices in the screening and management of the disease. Finally, it suggests that studies of breast cancer in LMCs might offer important insights for a more effective management of the problem both in developing as well as developed countries.
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- 2012
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11. Cohort Profile
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Katie M. O'Brien, Michael J. Orlich, Alpa V. Patel, Kim Robien, Alicja Wolk, Roger L. Milne, Susanna C. Larsson, Melissa A. Merritt, Brian D. Carter, Sven Sandin, Julie R. Palmer, Alan A. Arslan, Leo J. Schouten, Shelley S. Tworoger, Michael Jones, Anne Zeleniuch-Jacquotte, Nicolas Wentzensen, Sarah R. Irvin, Hilde Langseth, Britton Trabert, I-Min Lee, Maria Elena Martinez, Graham G. Giles, Lynn Rosenberg, Victoria A. Kirsh, Julie E. Buring, Mary K. Townsend, Rudolf Kaaks, James V. Lacey, Jian-Min Yuan, Kala Visvanathan, Giske Ursin, Jenny N. Poynter, Synnove F. Knutsen, Thomas E. Rohan, Ulrike Peters, Renée T. Fortner, Elisabete Weiderpass, V. Wendy Setiawan, Anthony J. Swerdlow, Woon-Puay Koh, Piet A. van den Brandt, Dale P. Sandler, Epidemiologie, and RS: GROW - R1 - Prevention
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Ovarian Neoplasms ,Oncology ,RISK ,medicine.medical_specialty ,Epidemiology ,business.industry ,MORTALITY ,MEDLINE ,General Medicine ,Carcinoma, Ovarian Epithelial ,medicine.disease ,Cohort Studies ,Online Only ,Internal medicine ,Cohort ,Humans ,Medicine ,Female ,business ,Ovarian cancer ,POWDER - Published
- 2022
12. Supplementary Data from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3
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Rachael Stolzenberg-Solomon, Alison P. Klein, Nilanjan Chatterjee, Peter Kraft, Harvey A. Risch, Brian M. Wolpin, Gloria M. Petersen, Eric J. Jacobs, Donghui Li, Laufey T. Amundadottir, Anne Zeleniuch-Jacquotte, Fangcheng Yuan, Herbert Yu, Lynne R. Wilkens, Nicolas Wentzensen, Jean Wactawski-Wende, Stephen K. Van Den Eeden, Antonia Trichopoulou, Anne Tjonneland, Ian M. Thompson, Oliver Strobel, Victoria L. Stevens, Debra T. Silverman, Howard D. Sesso, Ghislaine Scelo, Nathaniel Rothman, Elio Riboli, Kari G. Rabe, Miquel Porta, Ulrike Peters, Salvatore Panico, Ann L. Oberg, Kimmie Ng, Roger L. Milne, Núria Malats, I-Min Lee, Robert C. Kurtz, Rayjean J. Hung, Robert N. Hoover, Elizabeth A. Holly, Manal M. Hassan, Patricia Hartge, Michael G. Goggins, Edward L. Giovannucci, J. Michael Gaziano, Charles S. Fuchs, Eric J. Duell, Erica J. Childs, Stephen J. Chanock, Daniele Campa, Julie E. Buring, Bas Bueno-de-Mesquita, Amanda L. Blackford, Sonja I. Berndt, William R. Bamlet, Ana Babic, Gabriella Andreotti, Demetrius Albanes, Wei Zheng, Emily White, Kala Visvanathan, Xiao-Ou Shu, Rachel E. Neale, Loic Le Marchand, Charles Kooperberg, Phyllis J. Goodman, Graham G. Giles, Steven Gallinger, Mengmeng Du, Federico Canzian, Paul Brennan, Paige M. Bracci, Laura E. Beane-Freeman, Alan A. Arslan, William Wheeler, Prosenjit Kundu, and Evelina Mocci
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Supplemental figures 1 and 2. Supplemental tables 1-7.
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- 2023
13. Data from Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium
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Renée T. Fortner, Rudolf Kaaks, Shelley S. Tworoger, Nicolas Wentzensen, Britton Trabert, Melissa A. Merritt, Sabina Rinaldi, Ruth C. Travis, Annika Idahl, Eric J. Duell, Elisabete Weiderpass, N. Charlotte Onland-Moret, Giovanna Masala, Antonia Trichopoulou, Laure Dossus, Anne Tjønneland, I-Min Lee, Julie E. Buring, Kathy Helzlsouer, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Alan A. Arslan, Matti Lehtinen, Helena Schock, Elizabeth M. Poole, and Jennifer Ose
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Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case–control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02–1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03–1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60–0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC. Cancer Res; 77(14); 3951–60. ©2017 AACR.
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- 2023
14. Supplemental Table from HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
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Christine F. Skibola, Patricia Hartge, Nathaniel Rothman, Stephen J. Chanock, Peter Kraft, Yawei Zhang, Anne Kricker, Eve Roman, Martyn T. Smith, Angela Brooks-Wilson, Qing Lan, Richard K. Severson, Scott Davis, Anthony Staines, Lenka Foretova, Paulo Bofetta, Gilles Salles, Hervé Ghesquières, David G. Cox, Alain Monnereau, Jacqueline Clavel, Karen Curtin, Martha Glenn, Nicola J. Camp, Lucia Conde, Bengt Glimelius, Mads Melbye, Hans-Olov Adami, Mark P. Purdue, Alan A. Arslan, Jacob Musinsky, Kenneth Offit, Roger L. Milne, Melissa C. Southey, Graham G. Giles, Nicole Wong Doo, Andrew L. Feldman, Giancarlo Latte, Maria Grazia Ennas, Corrado Magnani, Brian K. Link, Marie-Hélène Delfau-Larue, James McKay, Paul Brennan, Yolanda Benavente, Elio Riboli, Rudolph Kaaks, Ruth C. Travis, Stephanie J. Lax, W. Ryan Diver, Lauren R. Teras, Stephanie J. Weinstein, Demetrius Albanes, Pierluigi Cocco, Marc Maynadie, Dennis Weisenburger, Eleanor Kane, Elizabeth A. Holly, Nikolaus Becker, Christopher R. Flowers, Brenda M. Birmann, Tongzhang Zheng, John J. Spinelli, Jennifer Turner, Elizabeth E. Brown, Wendy Cozen, Silvia de Sanjose, Alexandra Nieters, Martha S. Linet, Claire M. Vajdic, Ora Paltiel, Roel Vermeulen, Lindsay M. Morton, Joseph Vijai, Henrik Hjalgrim, Karin E. Smedby, James R. Cerhan, Jenna Voutsinas, Paige M. Bracci, Susan L. Slager, Sonja I. Berndt, Mary Carrington, and Sophia S. Wang
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SUPPLEMENTAL TABLE: Effect of homozygosity at the three HLA class I loci -A, -B and -C and five HLA class I loci -DRB1, DQA1, DQB1, DPA1, and DPB1 on susceptibility to four NHL subtypes (DLBCL, FL, CLL/SLL, and MZL) stratified by GWAS platform (analyses adjusted for sex, age, and ancestry/principal components)
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- 2023
15. Data from High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium
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Shelley S. Tworoger, Anne Zeleniuch-Jacquotte, Nicolas Wentzensen, Kala Visvanathan, Carla H. van Gils, Rosario Tumino, Antonia Trichopoulou, Anne Tjonneland, J. Ramón Quirós, Melissa A. Merritt, Anthony M. Magliocco, Marina Kvaskoff, Rudolf Kaaks, Annika Idahl, Patricia Hartge, Inger T. Gram, Renée T. Fortner, Laure Dossus, Alan A. Arslan, Naomi E. Allen, Britton Trabert, Elizabeth M. Poole, Mary K. Townsend, Adrianne R. Mallen, and Lauren C. Peres
- Abstract
Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case–control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with 10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10–84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07–10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82–2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36–11.57; Pheterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (Pinteraction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 1.62–6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma.Significance:C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.
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- 2023
16. Supplementary Table 2 from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)
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Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert
- Abstract
Associations between continuous total lifetime number of ovulatory cycles and ovarian cancer by tumor aggressiveness considering mutual adjustment for LOC component factors: duration of oral contraceptive use and pregnancies, Ovarian Cancer Cohort Consortium (OC3).
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- 2023
17. Data from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)
- Author
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Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert
- Abstract
Repeated exposure to the acute proinflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2,045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted HRs between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (Significance:Although ovarian cancer is rare, risk of most ovarian cancers doubles as the number of lifetime ovulatory cycles increases from approximately 300 to 500. Thus, identifying an important area for cancer prevention research.
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- 2023
18. Supplementary Material (Table S1-S3, Figure S1-S2) from High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer: Results from the Ovarian Cancer Cohort Consortium
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Shelley S. Tworoger, Anne Zeleniuch-Jacquotte, Nicolas Wentzensen, Kala Visvanathan, Carla H. van Gils, Rosario Tumino, Antonia Trichopoulou, Anne Tjonneland, J. Ramón Quirós, Melissa A. Merritt, Anthony M. Magliocco, Marina Kvaskoff, Rudolf Kaaks, Annika Idahl, Patricia Hartge, Inger T. Gram, Renée T. Fortner, Laure Dossus, Alan A. Arslan, Naomi E. Allen, Britton Trabert, Elizabeth M. Poole, Mary K. Townsend, Adrianne R. Mallen, and Lauren C. Peres
- Abstract
Table S1. Association between CRP and ovarian cancer risk by OC3 study Table S2. Association between CRP and ovarian cancer risk for various sensitivity analyses, including exclusion of PLCO, exclusion of women diagnosed within 2 years of blood draw, additional adjustment for aspirin use, and exclusion of women with cardiovascular disease Table S3. Association between CRP and ovarian cancer risk by time between blood draw and diagnosis Figure S1. Restricted cubic splines of the association between CRP and ovarian cancer risk using two approaches to identify CRP outliers Figure S2. Restricted cubic splines of the association between CRP and risk of serous and non-serous ovarian cancer
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- 2023
19. Data from HLA Class I and II Diversity Contributes to the Etiologic Heterogeneity of Non-Hodgkin Lymphoma Subtypes
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Christine F. Skibola, Patricia Hartge, Nathaniel Rothman, Stephen J. Chanock, Peter Kraft, Yawei Zhang, Anne Kricker, Eve Roman, Martyn T. Smith, Angela Brooks-Wilson, Qing Lan, Richard K. Severson, Scott Davis, Anthony Staines, Lenka Foretova, Paulo Bofetta, Gilles Salles, Hervé Ghesquières, David G. Cox, Alain Monnereau, Jacqueline Clavel, Karen Curtin, Martha Glenn, Nicola J. Camp, Lucia Conde, Bengt Glimelius, Mads Melbye, Hans-Olov Adami, Mark P. Purdue, Alan A. Arslan, Jacob Musinsky, Kenneth Offit, Roger L. Milne, Melissa C. Southey, Graham G. Giles, Nicole Wong Doo, Andrew L. Feldman, Giancarlo Latte, Maria Grazia Ennas, Corrado Magnani, Brian K. Link, Marie-Hélène Delfau-Larue, James McKay, Paul Brennan, Yolanda Benavente, Elio Riboli, Rudolph Kaaks, Ruth C. Travis, Stephanie J. Lax, W. Ryan Diver, Lauren R. Teras, Stephanie J. Weinstein, Demetrius Albanes, Pierluigi Cocco, Marc Maynadie, Dennis Weisenburger, Eleanor Kane, Elizabeth A. Holly, Nikolaus Becker, Christopher R. Flowers, Brenda M. Birmann, Tongzhang Zheng, John J. Spinelli, Jennifer Turner, Elizabeth E. Brown, Wendy Cozen, Silvia de Sanjose, Alexandra Nieters, Martha S. Linet, Claire M. Vajdic, Ora Paltiel, Roel Vermeulen, Lindsay M. Morton, Joseph Vijai, Henrik Hjalgrim, Karin E. Smedby, James R. Cerhan, Jenna Voutsinas, Paige M. Bracci, Susan L. Slager, Sonja I. Berndt, Mary Carrington, and Sophia S. Wang
- Abstract
A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend < 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes.Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.
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- 2023
20. Supplementary Tables S1-S5, Figure S1 from Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium
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Renée T. Fortner, Rudolf Kaaks, Shelley S. Tworoger, Nicolas Wentzensen, Britton Trabert, Melissa A. Merritt, Sabina Rinaldi, Ruth C. Travis, Annika Idahl, Eric J. Duell, Elisabete Weiderpass, N. Charlotte Onland-Moret, Giovanna Masala, Antonia Trichopoulou, Laure Dossus, Anne Tjønneland, I-Min Lee, Julie E. Buring, Kathy Helzlsouer, Kala Visvanathan, Anne Zeleniuch-Jacquotte, Alan A. Arslan, Matti Lehtinen, Helena Schock, Elizabeth M. Poole, and Jennifer Ose
- Abstract
Supplementary Table S1 provides details on each of the participating studies, including recruitment period, fasting status at blood collection and storage temperature of blood specimens, number of matched controls per case, and the matching criteria employed in each study. Supplementary Table S2 shows the blood sample fraction available, the assays used for androgen measurement, and laboratory coefficients of variation. Supplementary Table S3 includes the geometric means of hormone concentrations by cohort after log2 transformation and standardization. Supplementary Table S4 provides the case characteristics for each of the participating cohorts. Supplementary Table S4 shows the odds ratios (ORs) and 95% confidence intervals (95% CIs) for quintiles of androgen concentrations and overall invasive EOC and serous invasive EOC. Supplementary Figure S1 is a forest plot showing the odds ratios (ORs) and 95% confidence intervals (95% CIs) for a doubling of androgen concentration and Type I EOC in a sensitivity analysis restricted to EOC cases with grade data.
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- 2023
21. Data from Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk
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Rachael Stolzenberg-Solomon, Alison P. Klein, Kai Yu, Harvey A. Risch, Brian M. Wolpin, Gloria M. Petersen, Donghui Li, Laufey T. Amundadottir, Eric J. Duell, Jianxin Shi, Anne Zeleniuch-Jacquotte, Herbert Yu, Lynne R. Wilkens, Nicolas Wentzensen, Xiaoliang Wang, Jean Wactawski-Wende, Ian M. Thompson, Debra T. Silverman, Howard D. Sesso, Nathaniel Rothman, Francisco X. Real, Kari G. Rabe, Miquel Porta, Ann L. Oberg, Kimmie Ng, Neil Murphy, Roger L. Milne, Nuria Malats, I-Min Lee, Robert C. Kurtz, Holger Kirsten, Verena Katzke, Robert N. Hoover, Elizabeth A. Holly, Manal M. Hassan, Patricia Hartge, Thilo Hackert, Michael G. Goggins, J. Michael Gaziano, Charles S. Fuchs, Stephen J. Chanock, Peter T. Campbell, Julie E. Buring, Bas Bueno-de-Mesquita, Paul Brennan, Sonja I. Berndt, William R. Bamlet, Ana Babic, Gabriella Andreotti, Pilar Amiano, Demetrius Albanes, Wei Zheng, Emily White, Kala Visvanathan, Xiao-Ou Shu, Ghislaine Scelo, Jonas Rosendahl, Rachel E. Neale, Loic Le Marchand, Charles Kooperberg, Phyllis J. Goodman, Graham G. Giles, Steven Gallinger, Mengmeng Du, Federico Canzian, Paige Bracci, Laura E. Beane Freeman, Alan A. Arslan, Lei Song, William Wheeler, Elizabeth A. Platz, Han Zhang, Naomi Walsh, Rayjean J. Hung, and Fangcheng Yuan
- Abstract
Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10−6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC.Significance:The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
- Published
- 2023
22. Supplementary Table 1 from The Risk of Ovarian Cancer Increases with an Increase in the Lifetime Number of Ovulatory Cycles: An Analysis from the Ovarian Cancer Cohort Consortium (OC3)
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Nicolas Wentzensen, Anne Zeleniuch-Jacquotte, Alicja Wolk, Lynne R. Wilkens, Kala Visvanathan, Piet A. van den Brandt, Antonia Trichopoulou, Ruth C. Travis, Anthony J. Swerdlow, Veronica W. Setiawan, Leo J. Schouten, Catherine Schairer, Dale P. Sandler, Thomas E. Rohan, Kim Robien, Elio Riboli, Jenny N. Poynter, Ulrike Peters, Alpa V. Patel, Kim Overvad, N. Charlotte Onland-Moret, Roger L. Milne, I-Min Lee, James V. Lacey, Marina Kvaskoff, Synnove F. Knutsen, Victoria A. Kirsh, Rudolf Kaaks, Michael E. Jones, Annika Idahl, Judith Hoffman Bolton, Holly R. Harris, Inger T. Gram, Graham G. Giles, Mia M. Gaudet, Gary E. Fraser, Laure Dossus, Julie E. Buring, Louise A. Brinton, Leslie Bernstein, Alan A. Arslan, Pilar Amiano, Emily White, Patricia Hartge, Edwin S. Iversen, Renée T. Fortner, Mary K. Townsend, Katie M. O'Brien, Shelley S. Tworoger, and Britton Trabert
- Abstract
Summary of 20 Ovarian Cancer Cohort Consortium (OC3) cohorts included in analysis of lifetime ovulatory cycles (LOC) and incident ovarian cancer.
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- 2023
23. Data from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3
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Rachael Stolzenberg-Solomon, Alison P. Klein, Nilanjan Chatterjee, Peter Kraft, Harvey A. Risch, Brian M. Wolpin, Gloria M. Petersen, Eric J. Jacobs, Donghui Li, Laufey T. Amundadottir, Anne Zeleniuch-Jacquotte, Fangcheng Yuan, Herbert Yu, Lynne R. Wilkens, Nicolas Wentzensen, Jean Wactawski-Wende, Stephen K. Van Den Eeden, Antonia Trichopoulou, Anne Tjonneland, Ian M. Thompson, Oliver Strobel, Victoria L. Stevens, Debra T. Silverman, Howard D. Sesso, Ghislaine Scelo, Nathaniel Rothman, Elio Riboli, Kari G. Rabe, Miquel Porta, Ulrike Peters, Salvatore Panico, Ann L. Oberg, Kimmie Ng, Roger L. Milne, Núria Malats, I-Min Lee, Robert C. Kurtz, Rayjean J. Hung, Robert N. Hoover, Elizabeth A. Holly, Manal M. Hassan, Patricia Hartge, Michael G. Goggins, Edward L. Giovannucci, J. Michael Gaziano, Charles S. Fuchs, Eric J. Duell, Erica J. Childs, Stephen J. Chanock, Daniele Campa, Julie E. Buring, Bas Bueno-de-Mesquita, Amanda L. Blackford, Sonja I. Berndt, William R. Bamlet, Ana Babic, Gabriella Andreotti, Demetrius Albanes, Wei Zheng, Emily White, Kala Visvanathan, Xiao-Ou Shu, Rachel E. Neale, Loic Le Marchand, Charles Kooperberg, Phyllis J. Goodman, Graham G. Giles, Steven Gallinger, Mengmeng Du, Federico Canzian, Paul Brennan, Paige M. Bracci, Laura E. Beane-Freeman, Alan A. Arslan, William Wheeler, Prosenjit Kundu, and Evelina Mocci
- Abstract
Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10–8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82–0.93; former smokers 1.00, 95% CI, 0.91–1.07; current smokers 1.25, 95% CI 1.12–1.40, Pinteraction = 3.08 × 10–9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings.Significance:This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
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- 2023
24. Supplementary table 8 from Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3
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Rachael Stolzenberg-Solomon, Alison P. Klein, Nilanjan Chatterjee, Peter Kraft, Harvey A. Risch, Brian M. Wolpin, Gloria M. Petersen, Eric J. Jacobs, Donghui Li, Laufey T. Amundadottir, Anne Zeleniuch-Jacquotte, Fangcheng Yuan, Herbert Yu, Lynne R. Wilkens, Nicolas Wentzensen, Jean Wactawski-Wende, Stephen K. Van Den Eeden, Antonia Trichopoulou, Anne Tjonneland, Ian M. Thompson, Oliver Strobel, Victoria L. Stevens, Debra T. Silverman, Howard D. Sesso, Ghislaine Scelo, Nathaniel Rothman, Elio Riboli, Kari G. Rabe, Miquel Porta, Ulrike Peters, Salvatore Panico, Ann L. Oberg, Kimmie Ng, Roger L. Milne, Núria Malats, I-Min Lee, Robert C. Kurtz, Rayjean J. Hung, Robert N. Hoover, Elizabeth A. Holly, Manal M. Hassan, Patricia Hartge, Michael G. Goggins, Edward L. Giovannucci, J. Michael Gaziano, Charles S. Fuchs, Eric J. Duell, Erica J. Childs, Stephen J. Chanock, Daniele Campa, Julie E. Buring, Bas Bueno-de-Mesquita, Amanda L. Blackford, Sonja I. Berndt, William R. Bamlet, Ana Babic, Gabriella Andreotti, Demetrius Albanes, Wei Zheng, Emily White, Kala Visvanathan, Xiao-Ou Shu, Rachel E. Neale, Loic Le Marchand, Charles Kooperberg, Phyllis J. Goodman, Graham G. Giles, Steven Gallinger, Mengmeng Du, Federico Canzian, Paul Brennan, Paige M. Bracci, Laura E. Beane-Freeman, Alan A. Arslan, William Wheeler, Prosenjit Kundu, and Evelina Mocci
- Abstract
Supplemental Table 8. Enrichment in regulatory regions for rs842357 and related SNPs
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- 2023
25. Supplementary Tables 1-3 from Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium
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Charles S. Fuchs, Patricia Hartge, Anne Zeleniuch-Jacquotte, Kai Yu, Jean Wactawski-Wende, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Geoffrey S. Tobias, Gilles Thomas, Nadia Slimani, Xiao-Ou Shu, Maria-José Sanchéz, Aleksandar Rajkovic, Alpa V. Patel, Kim Overvad, Dominique S. Michaud, Julie B. Mendelsohn, Shannon M. Lynch, Charles Kooperberg, Kevin Jacobs, Amy Hutchinson, David J. Hunter, Robert N. Hoover, Susan E. Hankinson, Göran Hallmans, Edward L. Giovannucci, John Michael Gaziano, Sandra Clipp, Stephen J. Chanock, Federico Canzian, Julie E. Buring, Marie-Christine Boutron-Ruault, Garnet Anderson, Laufey Amundadottir, Naomi E. Allen, Demetrius Albanes, Wei Zheng, Gloria Petersen, Andrea LaCroix, Eric J. Jacobs, Alan A. Arslan, Rachael Z. Stolzenberg-Solomon, Emily Steplowski, H. Bas Bueno-de-Mesquita, Kathy Helzlsouer, Myron Gross, Peter Kraft, and Brian M. Wolpin
- Abstract
Supplementary Tables 1-3 from Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium
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- 2023
26. Data from Pancreatic Cancer Risk and ABO Blood Group Alleles: Results from the Pancreatic Cancer Cohort Consortium
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Charles S. Fuchs, Patricia Hartge, Anne Zeleniuch-Jacquotte, Kai Yu, Jean Wactawski-Wende, Jarmo Virtamo, Paolo Vineis, Dimitrios Trichopoulos, Geoffrey S. Tobias, Gilles Thomas, Nadia Slimani, Xiao-Ou Shu, Maria-José Sanchéz, Aleksandar Rajkovic, Alpa V. Patel, Kim Overvad, Dominique S. Michaud, Julie B. Mendelsohn, Shannon M. Lynch, Charles Kooperberg, Kevin Jacobs, Amy Hutchinson, David J. Hunter, Robert N. Hoover, Susan E. Hankinson, Göran Hallmans, Edward L. Giovannucci, John Michael Gaziano, Sandra Clipp, Stephen J. Chanock, Federico Canzian, Julie E. Buring, Marie-Christine Boutron-Ruault, Garnet Anderson, Laufey Amundadottir, Naomi E. Allen, Demetrius Albanes, Wei Zheng, Gloria Petersen, Andrea LaCroix, Eric J. Jacobs, Alan A. Arslan, Rachael Z. Stolzenberg-Solomon, Emily Steplowski, H. Bas Bueno-de-Mesquita, Kathy Helzlsouer, Myron Gross, Peter Kraft, and Brian M. Wolpin
- Abstract
A recent genome-wide association study (PanScan) identified significant associations at the ABO gene locus with risk of pancreatic cancer, but the influence of specific ABO genotypes remains unknown. We determined ABO genotypes (OO, AO, AA, AB, BO, and BB) in 1,534 cases and 1,583 controls from 12 prospective cohorts in PanScan, grouping participants by genotype-derived serologic blood type (O, A, AB, and B). Adjusted odds ratios (ORs) for pancreatic cancer by ABO alleles were calculated using logistic regression. Compared with blood type O, the ORs for pancreatic cancer in subjects with types A, AB, and B were 1.38 [95% confidence interval (95% CI), 1.18–1.62], 1.47 (95% CI, 1.07–2.02), and 1.53 (95% CI, 1.21–1.92), respectively. The incidence rates for blood types O, A, AB, and B were 28.9, 39.9, 41.8, and 44.5 cases per 100,000 subjects per year. An increase in risk was noted with the addition of each non-O allele. Compared with OO genotype, subjects with AO and AA genotype had ORs of 1.33 (95% CI, 1.13–1.58) and 1.61 (95% CI, 1.22–2.18), whereas subjects with BO and BB genotypes had ORs of 1.45 (95% CI, 1.14–1.85) and 2.42 (1.28–4.57). The population attributable fraction for non-O blood type was 19.5%. In a joint model with smoking, current smokers with non-O blood type had an adjusted OR of 2.68 (95% CI, 2.03–3.54) compared with nonsmokers of blood type O. We concluded that ABO genotypes were significantly associated with pancreatic cancer risk. Cancer Res; 70(3); 1015–23
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- 2023
27. Estimation of Urinary Frequency: Does Question Phrasing Matter?
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Cheonguen Oh, Scott W. Smilen, D. Pape, Christina Escobar, Dora Jericevic, Victor W. Nitti, Benjamin M. Brucker, Rachael D. Sussman, R. Palmerola, Nirit Rosenblum, and Alan A. Arslan
- Subjects
Adult ,Male ,medicine.medical_specialty ,Time Factors ,Urinary Incontinence, Stress ,Urology ,Patient interview ,media_common.quotation_subject ,Urinary system ,Population ,030232 urology & nephrology ,Urination ,Interviews as Topic ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Numeracy ,medicine ,Humans ,Nocturia ,Prospective Studies ,Medical History Taking ,education ,Prospective cohort study ,Aged ,media_common ,Aged, 80 and over ,Estimation ,education.field_of_study ,Urinary Bladder, Overactive ,business.industry ,Reproducibility of Results ,Urinary Incontinence, Urge ,Middle Aged ,Diaries as Topic ,030220 oncology & carcinogenesis ,Physical therapy ,Female ,Symptom Assessment ,medicine.symptom ,business ,Prostatism - Abstract
To evaluate if question phrasing and patient numeracy impact estimation of urinary frequency.We conducted a prospective study looking at reliability of a patient interview in assessing urinary frequency. Prior to completing a voiding diary, patients estimated daytime, and nighttime frequency in 3 ways: (1) how many times they urinated (2) how many hours they waited in between urinations (3) how many times they urinated over the course of 4 hours. Numeracy was assessed using the Lipkus Numeracy Scale.Seventy-one patients completed the study. Correlation of estimates from questions 1, 2, and 3 to the diary were not statistically different. Prediction of nighttime frequency was better than daytime for all questions (correlation coefficients 0.751, 0.754, and 0.670 vs 0.596, 0.575, and 0.460). When compared to the diary, Question 1 underestimated (8.5 vs 9.7, P = .014) while Question 2 overestimated (11.8 vs 9.7, P = .027) recorded voids on a diary. All questions overpredicted nighttime frequency with 2.6, 2.9, and 3.9 predicted versus 1.6 recorded voids (P.001). Although not statistically significant, for each question, the predicted frequency of numerate patients was more correlated to the diary than those of innumerate patients.When compared to a voiding diary for daytime urinary frequency, asking patients how many times they urinated underestimated, and asking patients how many hours they waited between urinations overestimated the number recorded voids. Regardless of phrasing, patients overestimated nighttime urination. Patients in our functional urology population have limited numeracy, which may impact accuracy of urinary frequency estimation.
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- 2021
28. Prolactin and Risk of Epithelial Ovarian Cancer
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Annika Idahl, Patrick M. Sluss, Susan E. Hankinson, Laura D. Kubzansky, Cassandra A. Hathaway, Eva Lundin, Mary K. Townsend, Anne Zeleniuch-Jacquotte, Megan S. Rice, Alan A. Arslan, Shelley S. Tworoger, Göran Hallmans, I-Min Lee, and Julie E. Buring
- Subjects
Adult ,Oncology ,medicine.medical_specialty ,Epidemiology ,Carcinoma, Ovarian Epithelial ,Logistic regression ,Article ,Body Mass Index ,Risk Factors ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Aged ,Ovarian Neoplasms ,business.industry ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Prolactin ,Causality ,Postmenopause ,Premenopause ,Quartile ,Case-Control Studies ,Female ,business ,Ovarian cancer ,Body mass index - Abstract
Background: Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. Methods: We conducted a pooled case–control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype. Results: Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (Ptrend = 0.045; OR, quartile 4 vs. 1 = 1.34; 95% CI = 0.97–1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR = 1.38; 95% CI = 0.74–2.58; Ptrend = 0.32 and OR = 1.41; 95% CI = 0.93–2.13; Ptrend = 0.08, respectively; Pheterogeneity = 0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI ≥ 25 kg/m2, but not BMI < 25 kg/m2 (corresponding OR = 2.68; 95% CI = 1.56–4.59; Ptrend < 0.01 and OR = 0.90; 95% CI = 0.58–1.40; Ptrend = 0.98, respectively; Pheterogeneity < 0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis. Conclusions: We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI ≥ 25 kg/m2. Impact: This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.
- Published
- 2021
29. Smoking Modifies Pancreatic Cancer Risk Loci on 2q21.3
- Author
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Mengmeng Du, Rachael Z. Stolzenberg-Solomon, Herbert Yu, Paige M. Bracci, Antonia Trichopoulou, Anne Tjønneland, Eric J. Duell, Bas Bueno-de-Mesquita, Alison P. Klein, Graham G. Giles, Fangcheng Yuan, Howard D. Sesso, Federico Canzian, Sonja I. Berndt, I-Min Lee, Ghislaine Scelo, Lynne R. Wilkens, Jean Wactawski-Wende, Nicolas Wentzensen, Kari G. Rabe, Laufey T. Amundadottir, Eric J. Jacobs, Victoria L. Stevens, Phyllis J. Goodman, Harvey A. Risch, Edward Giovannucci, Evelina Mocci, Stephen K. Van Den Eeden, Stephen J. Chanock, Ann L. Oberg, Gloria M. Petersen, Rayjean J. Hung, Robert C. Kurtz, Xiao-Ou Shu, Charles Kooperberg, Charles S. Fuchs, Nilanjan Chatterjee, Nathaniel Rothman, Ulrike Peters, Núria Malats, Kimmie Ng, Ian M. Thompson, Roger L. Milne, William Wheeler, Paul Brennan, Emily White, J. Michael Gaziano, Steven Gallinger, Prosenjit Kundu, Wei Zheng, Miquel Porta, Brian M. Wolpin, Kala Visvanathan, Loic Le Marchand, Elio Riboli, Oliver Strobel, Michael Goggins, Daniele Campa, Salvatore Panico, Rachel E. Neale, Laura E. Beane Freeman, Gabriella Andreotti, Debra T. Silverman, Ana Babic, Erica J. Childs, Donghui Li, Julie E. Buring, Patricia Hartge, Manal M. Hassan, Alan A. Arslan, Robert N. Hoover, Amanda L. Blackford, Anne Zeleniuch-Jacquotte, Demetrius Albanes, William R. Bamlet, Peter Kraft, and Elizabeth A. Holly
- Subjects
0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,Genotype ,Quantitative Trait Loci ,Polymorphism, Single Nucleotide ,Article ,Chromosomes ,Germline ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Pancreatic cancer ,Internal medicine ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Polymorphism ,Genetic association ,business.industry ,Cyclin T ,Carcinoma ,Smoking ,Membrane Proteins ,Colocalization ,Single Nucleotide ,medicine.disease ,Pancreatic Neoplasms ,030104 developmental biology ,Pancreatic Ductal ,Chromosomes, Human, Pair 2 ,030220 oncology & carcinogenesis ,Pair 2 ,Expression quantitative trait loci ,Carcinoma, Pancreatic Ductal ,Genome-Wide Association Study ,business ,Human - Abstract
Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10–8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82–0.93; former smokers 1.00, 95% CI, 0.91–1.07; current smokers 1.25, 95% CI 1.12–1.40, Pinteraction = 3.08 × 10–9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high linkage disequilibrium with rs1818613 (r2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. Significance: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.
- Published
- 2021
30. Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk
- Author
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Núria Malats, Paul Brennan, Veronica Wendy Setiawan, Yaohua Yang, Jirong Long, Thilo Hackert, Xiaoliang Wang, Charles Kooperberg, Michael Goggins, Manal M. Hassan, I-Min Lee, Elizabeth A. Holly, Graham G. Giles, Roger L. Milne, Brian M. Wolpin, Miquel Porta, Verena Katske, Sonja I. Berndt, Herbert Yu, Laura E. Beane Freeman, Kari G. Rabe, Jean Wactawski-Wende, Robert N. Hoover, Stephen J. Chanock, Paige M. Bracci, Fei Ye, Ann L. Oberg, Wei Zheng, Anne Zeleniuch-Jacquotte, Lauren K. Brais, Samuel O. Antwi, Pilar Amiano, Nicolas Wentzensen, J. Michael Gaziano, Dalia Ghoneim, Jingjing Zhu, Rachel E. Neale, Charles S. Fuchs, Nathaniel Rothman, Ghislaine Scelo, Philip C Haycock, Alison P. Klein, Neil Murphy, Harvey A. Risch, Nikhil K. Khankari, Lynne R. Wilkens, Laufey T. Amundadottir, Peter Kraft, Mengmeng Du, Eric J. Jacobs, Federico Canzian, Ian M. Thompson, Alan A. Arslan, Howard D. Sesso, Emily White, Eric J. Duell, Gloria M. Petersen, Phyllis J. Goodman, Stolzenberg-Solomon R, Xiao-Ou Shu, Harvey J. Murff, Priya Duggal, Kathy J. Helzlsouer, Steven Gallinger, Demetrius Albanes, Bas Bueno-de-Mesquita, William R. Bamlet, Kai Yu, Gabriella Andreotti, Lang Wu, Peter T. Campbell, Robert C. Kurtz, Debra T. Silverman, Ana Babic, Julie E. Buring, Kala Visvanathan, and Loic Le Marchand
- Subjects
Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Epidemiology ,Linoleic acid ,Article ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,Fatty Acids, Omega-6 ,Internal medicine ,Pancreatic cancer ,Mendelian randomization ,Humans ,Medicine ,Aged ,chemistry.chemical_classification ,business.industry ,Mendelian Randomization Analysis ,Odds ratio ,Middle Aged ,medicine.disease ,Confidence interval ,Pancreatic Neoplasms ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Cohort ,Female ,business ,Polyunsaturated fatty acid - Abstract
Background: Whether circulating polyunsaturated fatty acid (PUFA) levels are associated with pancreatic cancer risk is uncertain. Mendelian randomization (MR) represents a study design using genetic instruments to better characterize the relationship between exposure and outcome. Methods: We utilized data from genome-wide association studies within the Pancreatic Cancer Cohort Consortium and Pancreatic Cancer Case–Control Consortium, involving approximately 9,269 cases and 12,530 controls of European descent, to evaluate associations between pancreatic cancer risk and genetically predicted plasma n-6 PUFA levels. Conventional MR analyses were performed using individual-level and summary-level data. Results: Using genetic instruments, we did not find evidence of associations between genetically predicted plasma n-6 PUFA levels and pancreatic cancer risk [estimates per one SD increase in each PUFA-specific weighted genetic score using summary statistics: linoleic acid odds ratio (OR) = 1.00, 95% confidence interval (CI) = 0.98–1.02; arachidonic acid OR = 1.00, 95% CI = 0.99–1.01; and dihomo-gamma-linolenic acid OR = 0.95, 95% CI = 0.87–1.02]. The OR estimates remained virtually unchanged after adjustment for covariates, using individual-level data or summary statistics, or stratification by age and sex. Conclusions: Our results suggest that variations of genetically determined plasma n-6 PUFA levels are not associated with pancreatic cancer risk. Impact: These results suggest that modifying n-6 PUFA levels through food sources or supplementation may not influence risk of pancreatic cancer.
- Published
- 2020
31. Characteristics of Women with Lung Adenocarcinoma in the World Trade Center Environmental Health Center
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Elaine Shum, Nedim Durmus, Sultan Pehlivan, Yuting Lu, Yian Zhang, Alan A. Arslan, Yongzhao Shao, and Joan Reibman
- Subjects
Lung Neoplasms ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Adenocarcinoma of Lung ,Dust ,complex mixtures ,humanities ,respiratory tract diseases ,Humans ,Female ,New York City ,September 11 Terrorist Attacks ,World Trade Center (WTC) ,WTC Environmental Health Center ,September 11 ,lung cancer ,lung adenocarcinoma ,women ,smoking ,biomarker ,Environmental Health - Abstract
The destruction of the World Trade Center towers on 11 September 2001 exposed local residents, workers, and individuals in the area (Survivors) to dust and fumes that included known and suspected carcinogens. Given the potential for inhalation of toxic substances and the long latency after exposure, the incidence of lung cancer is expected to increase in WTC-exposed individuals. We describe the characteristics of women WTC Survivors with lung adenocarcinoma who were enrolled in the WTC Environmental Health Center (WTC EHC) between May 2002 and July 2021. A total of 173 women in WTC EHC had a diagnosis of any type of lung cancer, representing 10% of all cancers in women. Most of the lung cancers (87%) were non-small cell carcinomas, with adenocarcinoma (77%) being the most common subtype. Nearly half (46%) of these patients were exposed to dust clouds on 11 September 2001. Race and ethnicity varied by smoking status, as follows: 44% of Asian women compared with 29% of non-Hispanic White women were never-smokers (p < 0.001). There was no significant difference between the pathologic characteristics of adenocarcinomas between never and ever smokers. We also summarize EGFR, ALK, KRAS, ROS-1 and BRAF mutation status stratified by smoking, race and ethnicity. The identification of a relatively high proportion of women never-smokers with lung cancer warrants further investigation into the role of WTC dust exposure.
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- 2022
32. Neighborhood walkability and sex steroid hormone levels in women
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Sandra India-Aldana, Andrew G. Rundle, Tess V. Clendenen, James W. Quinn, Alan A. Arslan, Yelena Afanasyeva, Karen L. Koenig, Mengling Liu, Kathryn M. Neckerman, Lorna E. Thorpe, Anne Zeleniuch-Jacquotte, and Yu Chen
- Subjects
Estradiol ,Dehydroepiandrosterone Sulfate ,Estrone ,Androstenedione ,Dehydroepiandrosterone ,Biochemistry ,Cross-Sectional Studies ,Sex Hormone-Binding Globulin ,Androgens ,Humans ,Female ,Testosterone ,Gonadal Steroid Hormones ,General Environmental Science - Abstract
Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels.We conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women.We included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors.In premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results.Our findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.
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- 2022
33. Design and methodological considerations for biomarker discovery and validation in the Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) Program
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Hilary A Robbins, Karine Alcala, Elham Khodayari Moez, Florence Guida, Sera Thomas, Hana Zahed, Matthew Warkentin, Karl Smith-Byrne, Yonathan Brhane, David Muller, Demetrius Albanes, Melinda C Aldrich, Alan A Arslan, Julie Bassett, Christine D Berg, Qiuyin Cai, Chu Chen, Michael PA Davies, Brenda Diergaarde, John K Field, Neal D Freedman, Wen-Yi Huang, Mikael Johansson, Michael Jones, Woon-Puay Koh, Stephen Lam, Qing Lan, Arnulf Langhammer, Linda M Liao, Geoffrey Liu, Reza Malekzadeh, Roger L Milne, Luis M Montuenga, Thomas Rohan, Howard D Sesso, Gianluca Severi, Mahdi Sheikh, Rashmi Sinha, Xiao-Ou Shu, Victoria L Stevens, Martin C Tammemägi, Lesley F Tinker, Kala Visvanathan, Ying Wang, Renwei Wang, Stephanie J Weinstein, Emily White, David Wilson, Jian-Min Yuan, Xuehong Zhang, Wei Zheng, Christopher I Amos, Paul Brennan, Mattias Johansson, and Rayjean J Hung
- Abstract
The Integrative Analysis of Lung Cancer Etiology and Risk (INTEGRAL) program is an NCI-funded initiative with an objective to develop tools to optimize lung cancer screening. Here, we describe the rationale and design for the Risk Biomarker and Nodule Malignancy projects within INTEGRAL. The overarching goal of these projects is to systematically investigate circulating protein markers to include on a panel for use (i) pre-LDCT, to identify people likely to benefit from screening, and (ii) post-LDCT, to differentiate benign versus malignant nodules. To identify informative proteins, the Risk Biomarker project measured 1,161 proteins in a nested-case control study within 2 prospective cohorts (n=252 lung cancer cases and 252 controls) and replicated associations for a subset of proteins in 4 cohorts (n=479 cases and 479 controls). Eligible participants had any history of smoking and cases were diagnosed within 3 years of blood draw. The Nodule Malignancy project measured 1,077 proteins among participants with a heavy smoking history within 4 LDCT screening studies (n=425 cases within 5 years of blood draw, 398 benign-nodule controls, and 430 nodule-free controls). The INTEGRAL panel will enable absolute quantification of 21 proteins. We will evaluate its lung cancer discriminative performance in the Risk Biomarker project using a case-cohort study including 14 cohorts (n=1,696 cases and 2,926 subcohort representatives), and in the Nodule Malignancy project within 5 LDCT screening studies (n=675 cases, 648 benign-nodule controls, and 680 nodule-free controls). Future progress to advance lung cancer early detection biomarkers will require carefully designed validation, translational, and comparative studies.
- Published
- 2022
34. Genome-Wide Association Study Data Reveal Genetic Susceptibility to Chronic Inflammatory Intestinal Diseases and Pancreatic Ductal Adenocarcinoma Risk
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Brian M. Wolpin, Fangcheng Yuan, Lynne R. Wilkens, Núria Malats, Alan A. Arslan, Verena Katzke, Charles Kooperberg, Manal M. Hassan, Kimmie Ng, Robert N. Hoover, Naomi Walsh, Nicolas Wentzensen, Bas Bueno-de-Mesquita, Rachael Z. Stolzenberg-Solomon, Sonja I. Berndt, Holger Kirsten, Alison P. Klein, Patricia Hartge, Steven Gallinger, Demetrius Albanes, Wei Zheng, Stephen J. Chanock, Federico Canzian, Ann L. Oberg, Paige M. Bracci, I-Min Lee, Kala Visvanathan, Loic Le Marchand, Herbert Yu, Ian M. Thompson, Anne Zeleniuch-Jacquotte, Eric J. Duell, Han Zhang, Jonas Rosendahl, William R. Bamlet, Paul Brennan, Rayjean J. Hung, Kari G. Rabe, Thilo Hackert, Lei Song, Xiaoliang Wang, Elizabeth A. Holly, Howard D. Sesso, Jean Wactawski-Wende, Rachel E. Neale, Laura E. Beane Freeman, Phyllis J. Goodman, Harvey A. Risch, Jianxin Shi, Charles S. Fuchs, Nathaniel Rothman, Gabriella Andreotti, Roger L. Milne, Robert C. Kurtz, Neil Murphy, Francisco X. Real, Miquel Porta, J. Michael Gaziano, William Wheeler, Pilar Amiano, Emily White, Debra T. Silverman, Ana Babic, Kai Yu, Ghislaine Scelo, Laufey T. Amundadottir, Mengmeng Du, Gloria M. Petersen, Peter T. Campbell, Xiao-Ou Shu, Graham G. Giles, Michael Goggins, Elizabeth A. Platz, Donghui Li, and Julie E. Buring
- Subjects
0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Cholangitis, Sclerosing ,Genome-wide association study ,Disease ,Inflammatory bowel disease ,Gastroenterology ,Article ,Primary sclerosing cholangitis ,03 medical and health sciences ,0302 clinical medicine ,Crohn Disease ,Pancreatitis, Chronic ,Internal medicine ,Genetic predisposition ,medicine ,Humans ,Genetic Predisposition to Disease ,Colitis ,business.industry ,Inflammatory Bowel Diseases ,medicine.disease ,Ulcerative colitis ,digestive system diseases ,Pancreatic Neoplasms ,Celiac Disease ,030104 developmental biology ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Chronic Disease ,Pancreatitis ,Colitis, Ulcerative ,business ,Carcinoma, Pancreatic Ductal ,Genome-Wide Association Study - Abstract
Registry-based epidemiologic studies suggest associations between chronic inflammatory intestinal diseases and pancreatic ductal adenocarcinoma (PDAC). As genetic susceptibility contributes to a large proportion of chronic inflammatory intestinal diseases, we hypothesize that the genomic regions surrounding established genome-wide associated variants for these chronic inflammatory diseases are associated with PDAC. We examined the association between PDAC and genomic regions (±500 kb) surrounding established common susceptibility variants for ulcerative colitis, Crohn's disease, inflammatory bowel disease, celiac disease, chronic pancreatitis, and primary sclerosing cholangitis. We analyzed summary statistics from genome-wide association studies data for 8,384 cases and 11,955 controls of European descent from two large consortium studies using the summary data-based adaptive rank truncated product method to examine the overall association of combined genomic regions for each inflammatory disease group. Combined genomic susceptibility regions for ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis were associated with PDAC at P values < 0.05 (0.0040, 0.0057, 0.011, and 3.4 × 10−6, respectively). After excluding the 20 PDAC susceptibility regions (±500 kb) previously identified by GWAS, the genomic regions for ulcerative colitis, Crohn disease, and inflammatory bowel disease remained associated with PDAC (P = 0.0029, 0.0057, and 0.0098, respectively). Genomic regions for celiac disease (P = 0.22) and primary sclerosing cholangitis (P = 0.078) were not associated with PDAC. Our results support the hypothesis that genomic regions surrounding variants associated with inflammatory intestinal diseases, particularly, ulcerative colitis, Crohn disease, inflammatory bowel disease, and chronic pancreatitis are associated with PDAC. Significance: The joint effects of common variants in genomic regions containing susceptibility loci for inflammatory bowel disease and chronic pancreatitis are associated with PDAC and may provide insights to understanding pancreatic cancer etiology.
- Published
- 2020
35. Genome-Wide Gene–Diabetes and Gene–Obesity Interaction Scan in 8,255 Cases and 11,900 Controls from PanScan and PanC4 Consortia
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Sonja I. Berndt, Elizabeth A. Holly, Anne Zeleniuch-Jacquotte, Gloria M. Petersen, Herbert Yu, Xiao-Ou Shu, Steven Gallinger, Eric J. Jacobs, Eric J. Duell, Anne Tjønneland, Federico Canzian, Howard D. Sesso, William R. Bamlet, Rachel E. Neale, Peter Kraft, Jean Wactawski-Wende, J. Michael Gaziano, Harvey A. Risch, Gabriella Andreotti, Graham G. Giles, Robert C. Kurtz, Kari G. Rabe, Bas Bueno-de-Mesquita, Erica J. Childs, Ghislaine Scelo, Patricia Hartge, Robert N. Hoover, Phyllis J. Goodman, Amanda L. Blackford, Laufey T. Amundadottir, Hong Wei Tang, Alan A. Arslan, Mengmeng Du, Demetrius Albanes, Lai Jiang, Michael Goggins, Rachael Z. Stolzenberg-Solomon, Paige M. Bracci, Antonia Trichopoulou, Charles S. Fuchs, Nathaniel Rothman, I. Min Lee, Ian M. Thompson, Rayjean J. Hung, Nilanjan Chatterjee, Paul Brennan, Peng Wei, Emily White, Laura E. Beane Freeman, Roger L. Milne, Miquel Porta, Wei Zheng, Daniele Campa, Lynne R. Wilkens, Donghui Li, Stephen J. Chanock, Ann L. Oberg, Julie E. Buring, Ulrike Peters, Irene Orlow, Debra T. Silverman, Ana Babic, Nicolas Wentzensen, Brian M. Wolpin, Kala Visvanathan, Loic Le Marchand, Núria Malats, Manal H. Hassam, Charles Kooperberg, Kimmie Ng, and Alison P. Klein
- Subjects
Male ,0301 basic medicine ,Epidemiology ,Population ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Pancreatic cancer ,Diabetes Mellitus ,medicine ,Humans ,SNP ,Obesity ,education ,Genetics ,education.field_of_study ,medicine.disease ,Minor allele frequency ,030104 developmental biology ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Body mass index ,Genome-Wide Association Study - Abstract
Background: Obesity and diabetes are major modifiable risk factors for pancreatic cancer. Interactions between genetic variants and diabetes/obesity have not previously been comprehensively investigated in pancreatic cancer at the genome-wide level. Methods: We conducted a gene–environment interaction (GxE) analysis including 8,255 cases and 11,900 controls from four pancreatic cancer genome-wide association study (GWAS) datasets (Pancreatic Cancer Cohort Consortium I–III and Pancreatic Cancer Case Control Consortium). Obesity (body mass index ≥30 kg/m2) and diabetes (duration ≥3 years) were the environmental variables of interest. Approximately 870,000 SNPs (minor allele frequency ≥0.005, genotyped in at least one dataset) were analyzed. Case–control (CC), case-only (CO), and joint-effect test methods were used for SNP-level GxE analysis. As a complementary approach, gene-based GxE analysis was also performed. Age, sex, study site, and principal components accounting for population substructure were included as covariates. Meta-analysis was applied to combine individual GWAS summary statistics. Results: No genome-wide significant interactions (departures from a log-additive odds model) with diabetes or obesity were detected at the SNP level by the CC or CO approaches. The joint-effect test detected numerous genome-wide significant GxE signals in the GWAS main effects top hit regions, but the significance diminished after adjusting for the GWAS top hits. In the gene-based analysis, a significant interaction of diabetes with variants in the FAM63A (family with sequence similarity 63 member A) gene (significance threshold P < 1.25 × 10−6) was observed in the meta-analysis (PGxE = 1.2 ×10−6, PJoint = 4.2 ×10−7). Conclusions: This analysis did not find significant GxE interactions at the SNP level but found one significant interaction with diabetes at the gene level. A larger sample size might unveil additional genetic factors via GxE scans. Impact: This study may contribute to discovering the mechanism of diabetes-associated pancreatic cancer.
- Published
- 2020
36. Associations between Genetically Predicted Blood Protein Biomarkers and Pancreatic Cancer Risk
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Rachael Z. Stolzenberg-Solomon, Eric J. Duell, Paige M. Bracci, Charles Kooperberg, Gloria M. Petersen, Xiao-Ou Shu, Herbert Yu, Federico Canzian, Steven Gallinger, Graham G. Giles, Verena Katzke, Harvey A. Risch, Qiuyin Cai, Stephen K. Van Den Eeden, Chong Wu, Jiandong Bao, Lang Wu, Alison P. Klein, Xingyi Guo, Laura E. Beane Freeman, Núria Malats, Ghislaine Scelo, Wei Zheng, Emily White, Alan A. Arslan, Rachel E. Neale, Mengmeng Du, Xiang Shu, Duo Liu, Phyllis J. Goodman, Donghui Li, Jingjing Zhu, Jirong Long, Christopher A. Haiman, Kala Visvanathan, Loic Le Marchand, and Roger L. Milne
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Pancreatic ductal adenocarcinoma ,endocrine system diseases ,Protein biomarkers ,Epidemiology ,Quantitative trait locus ,Article ,European descent ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Pancreatic cancer ,Biomarkers, Tumor ,Humans ,Medicine ,business.industry ,Blood Proteins ,medicine.disease ,Blood proteins ,digestive system diseases ,030104 developmental biology ,030220 oncology & carcinogenesis ,Cohort ,Biomarker (medicine) ,business ,Carcinoma, Pancreatic Ductal - Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with few known risk factors and biomarkers. Several blood protein biomarkers have been linked to PDAC in previous studies, but these studies have assessed only a limited number of biomarkers, usually in small samples. In this study, we evaluated associations of circulating protein levels and PDAC risk using genetic instruments. Methods: To identify novel circulating protein biomarkers of PDAC, we studied 8,280 cases and 6,728 controls of European descent from the Pancreatic Cancer Cohort Consortium and the Pancreatic Cancer Case-Control Consortium, using genetic instruments of protein quantitative trait loci. Results: We observed associations between predicted concentrations of 38 proteins and PDAC risk at an FDR of < 0.05, including 23 of those proteins that showed an association even after Bonferroni correction. These include the protein encoded by ABO, which has been implicated as a potential target gene of PDAC risk variant. Eight of the identified proteins (LMA2L, TM11D, IP-10, ADH1B, STOM, TENC1, DOCK9, and CRBB2) were associated with PDAC risk after adjusting for previously reported PDAC risk variants (OR ranged from 0.79 to 1.52). Pathway enrichment analysis showed that the encoding genes for implicated proteins were significantly enriched in cancer-related pathways, such as STAT3 and IL15 production. Conclusions: We identified 38 candidates of protein biomarkers for PDAC risk. Impact: This study identifies novel protein biomarker candidates for PDAC, which if validated by additional studies, may contribute to the etiologic understanding of PDAC development.
- Published
- 2020
37. The rising relative and absolute incidence of uterine cancer in specific populations
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Lee E Buenconsejo-Lum, Yi-Ju A. Chen, Roland Matthews, Alan A. Arslan, Kareem Hamed Khozaim, Giuseppe Del Priore, and Ianeta Timoteo-Liaina
- Subjects
Adult ,medicine.medical_specialty ,Databases, Factual ,Samoa ,Uterine Cervical Neoplasms ,03 medical and health sciences ,0302 clinical medicine ,Uterine cancer ,medicine ,Humans ,Obesity ,030212 general & internal medicine ,Lung cancer ,Retrospective Studies ,030219 obstetrics & reproductive medicine ,business.industry ,Obstetrics ,Incidence ,Incidence (epidemiology) ,Obstetrics and Gynecology ,Cancer ,General Medicine ,Middle Aged ,Non-communicable disease ,medicine.disease ,American samoa ,Uterine Neoplasms ,Pacific islanders ,Female ,business - Abstract
OBJECTIVE To assess the contemporary incidence of cancers using American Samoa as a learning set for insights into similar populations. METHODS A retrospective observational analysis of de-identified data held in public-access databases (2004-2014) and data on uterine cancer from a hospital, both in American Samoa (2015-2016). RESULTS There were 341 new cases of cancer in 2004-2014 (111 per 100 000 women/year), including breast (20.2%), uterine (19.4%), and cervical (5.0%); and 287 in 2011-2015 (103 per 100 000 women/year), including uterine (24.0%), breast (18.5%), and cervical (5.2%). Uterine cancer increased from 21.4 to 60.3 per 100 000 women/year, becoming the most common cancer in American Samoa. In 2011-2015, the incidence-rate ratio of uterine cancer to other cancers in American Samoa was 1.3-, 3.8-, 4.6-, 7.7-, and 23-fold higher than breast, colon, cervical, ovarian, and lung cancer, respectively. Among the most recent cases (n=33), median age was 55 years (10 [30.3%]
- Published
- 2020
38. Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer
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Stephanie Tuminello, Yian Zhang, Lei Yang, Nedim Durmus, Matija Snuderl, Adriana Heguy, Anne Zeleniuch-Jacquotte, Yu Chen, Yongzhao Shao, Joan Reibman, and Alan A. Arslan
- Subjects
Cytoskeletal Proteins ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Humans ,Breast Neoplasms ,Female ,New York City ,DNA Methylation ,September 11 Terrorist Attacks ,skin and connective tissue diseases ,complex mixtures ,humanities ,environmental exposure ,epigenome-wide association study ,exposure assessment ,methylation ,pathway analysis ,World Trade Center ,9/11 ,breast cancer - Abstract
Breast cancer represents the most common cancer diagnosis among World Trade Center (WTC)-exposed community members, residents, and cleanup workers enrolled in the WTC Environmental Health Center (WTC EHC). The primary aims of this study were (1) to compare blood DNA methylation profiles of WTC-exposed community members with breast cancer and WTC-unexposed pre-diagnostic breast cancer blood samples, and (2) to compare the DNA methylation differences among the WTC EHC breast cancer cases and WTC-exposed cancer-free controls. Gene pathway enrichment analyses were further conducted. There were significant differences in DNA methylation between WTC-exposed breast cancer cases and unexposed prediagnostic breast cancer cases. The top differentially methylated genes were Intraflagellar Transport 74 (IFT74), WD repeat-containing protein 90 (WDR90), and Oncomodulin (OCM), which are commonly upregulated in tumors. Probes associated with established tumor suppressor genes (ATM, BRCA1, PALB2, and TP53) were hypermethylated among WTC-exposed breast cancer cases compared to the unexposed group. When comparing WTC EHC breast cancer cases vs. cancer-free controls, there appeared to be global hypomethylation among WTC-exposed breast cancer cases compared to exposed controls. Functional pathway analysis revealed enrichment of several gene pathways in WTC-exposed breast cancer cases including endocytosis, proteoglycans in cancer, regulation of actin cytoskeleton, axon guidance, focal adhesion, calcium signaling, cGMP-PKG signaling, mTOR, Hippo, and oxytocin signaling. The results suggest potential epigenetic links between WTC exposure and breast cancer in local community members enrolled in the WTC EHC program.
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- 2022
39. Characteristics of Cancers in Community Members Exposed to the World Trade Center Disaster at a Young Age
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Rebecca Lynn Florsheim, Qiao Zhang, Nedim Durmus, Yian Zhang, Sultan Pehlivan, Alan A. Arslan, Yongzhao Shao, and Joan Reibman
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Adult ,Disasters ,Neoplasms ,Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health ,Humans ,Dust ,Environmental Exposure ,Gases ,September 11 Terrorist Attacks ,World Trade Center ,WTC survivors ,environmental exposure ,cancer ,cancer characteristics ,young adult ,children - Abstract
The destruction of the World Trade Center (WTC) towers on 11 September 2001 (9/11) released tons of dust and smoke into the atmosphere, exposing hundreds of thousands of community members (survivors) and responders to carcinogens. The WTC Environmental Health Center (WTC EHC) is a federally designated surveillance and treatment program for community members who were present in the New York City disaster area on 9/11 or during the months that followed. WTC EHC enrollment requires exposure to the WTC dust and fumes and a federally certifiable medical condition, which includes most solid and blood cancers. Several studies have described the prevalence and characteristics of cancers in responders and survivors exposed to the WTC dust and fumes as adults. Cancers in those exposed at a young age warrant specific investigation since environmental toxin exposure at a younger age may change cancer risk. We describe the characteristics of 269 cancer patients with 278 cancer diagnoses among WTC EHC enrollees who were young in age (aged 0 to 30) on 9/11. These include 215 patients with a solid tumor (79.9%) and 54 with a lymphoid and/or hematopoietic cancer (20.1%). Among them, 9 patients had a known second primary cancer. A total of 23 different types of cancer were identified, including cancer types rare for this age group. Many were diagnosed in individuals lacking traditional cancer-specific risk factors such as tobacco use. The current study is the first to report specifically on cancer characteristics of younger enrollees in the WTC EHC program.
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- 2022
40. Neighborhood Walkability and Sex Hormone Levels in Women
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Lorna E. Thorpe, Anne Zeleniuch Jacquotte, Yu Chen, Yelena Afanasyeva, Tess V. Clendenen, Alan A. Arslan, Mengling Liu, Andrew Rundle, James W. Quinn, Sandra India Aldana, and Karen L. Koenig
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Sex hormone-binding globulin ,biology ,Neighborhood walkability ,biology.protein ,General Earth and Planetary Sciences ,Psychology ,General Environmental Science ,Demography - Published
- 2021
41. Breast Cancer Characteristics in the Population of Survivors Participating in the World Trade Center Environmental Health Center Program 2002–2019
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Nedim Durmus, Y. Zhang, Adrienne Addessi, Sultan Pehlivan, Yongzhao Shao, Joan Reibman, Freya Schnabel, and Alan A. Arslan
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Male ,medicine.medical_specialty ,exposure assessment ,Health, Toxicology and Mutagenesis ,Population ,environmental exposure ,Breast Neoplasms ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,9/11 ,Environmental health ,Epidemiology ,medicine ,Humans ,030212 general & internal medicine ,world trade center ,Survivors ,education ,education.field_of_study ,business.industry ,Public Health, Environmental and Occupational Health ,World trade center ,Cancer ,Luminal a ,Environmental exposure ,medicine.disease ,humanities ,030220 oncology & carcinogenesis ,Carcinogens ,Medicine ,Female ,New York City ,September 11 Terrorist Attacks ,Primary breast cancer ,business ,Environmental Health - Abstract
The destruction of World Trade Center on 11 September 2001 exposed local community members to a complex mixture of known carcinogens and potentially carcinogenic substances. To date, breast cancer has not been characterized in detail in the WTC-exposed civilian populations. The cancer characteristics of breast cancer patients were derived from the newly developed Pan-Cancer Database at the WTC Environmental Health Center (WTC EHC). We used the Surveillance, Epidemiology, and End Results (SEER) Program breast cancer data as a reference source. Between May 2002 and 31 December 2019, 2840 persons were diagnosed with any type of cancer at the WTC EHC, including 601 patients with a primary breast cancer diagnosis (592 women and 9 men). There was a higher proportion of grade 3 (poorly differentiated) tumors (34%) among the WTC EHC female breast cancers compared to that of the SEER-18 data (25%). Compared to that of the SEER data, female breast cancers in the WTC EHC had a lower proportion of luminal A (88% and 65%, respectively), higher proportion of luminal B (13% and 15%, respectively), and HER-2-enriched (5.5% and 7%, respectively) subtypes. These findings suggest considerable differences in the breast cancer characteristics and distribution of breast cancer intrinsic subtypes in the WTC-exposed civilian population compared to that of the general population. This is important because of the known effect of molecular subtypes on breast cancer prognosis.
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- 2021
42. Is high vitamin B12 status a cause of lung cancer?
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Alan A. Arslan, Woon-Puay Koh, Ben Michael Brumpton, Stig E. Bojesen, Mark P. Purdue, Neil E. Caporaso, William J. Blot, Yong-Bing Xiang, Allison M. Hodge, Meir J. Stampfer, Jonas Manjer, Tricia L Larose, I-Min Lee, Gianluca Severi, Robert Carreras-Torres, Rayjean J. Hung, Mikael Johansson, J. Michael Gaziano, Julie E. Buring, Christopher A. Haiman, Per Magne Ueland, S. M. Arnold, Paul Brennan, Qing Lan, Qiuyin Cai, Honglan Li, Howard D. Sesso, Renwei Wang, Kala Visvanathan, Loic Le Marchand, Ulrika Ericson, Edward Giovannucci, Ross L. Prentice, Anouar Fanidi, Christopher I. Amos, Yu-Tang Gao, Demetrius Albanes, Judith Hoffman-Bolton, Xiao-Ou Shu, Caroline L Relton, Stephanie A. Smith-Warner, Mattias Johansson, Jian-Min Yuan, Graham G. Giles, Wei Zheng, Stephanie J. Weinstein, Arnulf Langhammer, Kjell Grankvist, Anne Zeleniuch-Jacquotte, Xuehong Zhang, Neal D. Freedman, Lynne R. Wilkens, Victoria L. Stevens, Øivind Midttun, Mary Pettinger, and Marjorie L. McCullough
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Adult ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Single-nucleotide polymorphism ,Polymorphism, Single Nucleotide ,Gastroenterology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Mendelian randomization ,Humans ,Medicine ,Prospective Studies ,Vitamin B12 ,Lung cancer ,Aged ,business.industry ,Smoking ,Odds ratio ,Mendelian Randomization Analysis ,Middle Aged ,medicine.disease ,Confidence interval ,Vitamin B 12 ,lung cancer ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Etiology ,Biomarker (medicine) ,Female ,ICEP ,business - Abstract
Vitamin B supplementation can have side effects for human health, including cancer risk. We aimed to elucidate the role of vitamin B12 in lung cancer aetiology via direct measurements of pre‐diagnostic circulating vitamin B12 concentrations in a nested case‐control study, complemented with a Mendelian randomization (MR) approach in an independent case‐control sample. We used pre‐diagnostic biomarker data from 5,183 case‐control pairs nested within 20 prospective cohorts, and genetic data from 29,266 cases and 56,450 controls.Exposures included directly measured circulating vitamin B12 in pre‐diagnostic blood samples from the nested case‐control study, and 8 single nucleotide polymorphisms associated with vitamin B12 concentrations in the MR study.Our main outcome of interest was increased risk for lung cancer, overall and by histological subtype, per increase in circulating vitamin B12 concentrations.We found circulating vitamin B12 to be positively associated with overall lung cancer risk in a dose response fashion (odds ratio for a doubling in B12 [ORlog2B12] = 1.15, 95% confidence interval (95%CI) = 1.06‐1.25). The MR analysis based on 8 genetic variants also indicated that genetically determined higher vitamin B12 concentrations were positively associated with overall lung cancer risk (OR per 150 pmol/L standard deviation increase in B12 [ORSD]= 1.08, 95%CI= 1.00‐1.16).Considering the consistency of these two independent and complementary analyses, these findings support the hypothesis that high vitamin B12 status increases the risk of lung cancer.
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- 2019
43. Screening for uterine cancer
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Thomas F Chavez, Feng Xia Yan, Regina Lee, Jeffrey Hines, Yiju Amy Chen, Peter Baltrus, Roland Matthews, Alan A Arslan, James Lillard, and Giuseppe Del Priore
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Cancer Research ,Oncology - Abstract
e18578 Background: Endometrial cancer is the most common gynecologic malignancy. Historically, endometrial cancer would present at an early stage without disseminated disease. Presently, in certain populations endometrial cancer presents at a late stage and carries a mortality rate similar or even greater to that of ovarian cancer. This increase is tied to the increasing prevalence of risk factors and worsening disparities. Owing to data and trends from decades long past, routine endometrial cancer screening is not recommended by any gynecologic or oncologic society. It is now time to revisit the discussion on endometrial cancer screening in the modern era of the disease. In our community with advanced stage and 60% 5-year mortality, endometrial biopsy is a reasonable approach for those at highest risk for disease and the worse outcomes. Methods: Using nationally available datasets on endometrial cancer (NHANES, PLCO), we analyzed the most common risk factors associated with endometrial cancer to develop a risk assessment nomogram. The variables were age, body-mass index, race, concomitant medication usage (specifically hormone use), race, and prior obstetrical history. We bootstrapped our risk calculations to exclude data from the most recent year and used those cases as our testing set to test the ability of the nomogram to correctly predict endometrial cancer in those patients with known disease. We also tested our nomogram against unpublished endometrial cancer data from the population of an Atlanta safety net hospital. Results: For each learning data set (ie the bootstrapped patients from the NHANES and PLCO data), the association with the candidate variables was as expected. The magnitude of the associations was also consistent with previously reported univariate analyses. In the population of interest, there were 342994 women with 1076 (67.4/100,000) uterine cancers over 5 yrs (2015-20). The incidence rate ratio of cancer with the presence of known risk factors already contained in the population EMR was approximately 6x and 15:1 (15 high risk women identified with 1 expected cancer). Conclusions: Our nomogram was able to accurately predict the presence of cancer in patients included in both the national databases as well as the local safety net hospital community. Using a 100% sensitivity goal yielded a PPV of 6.7%. With these promising retrospective results, we intend to apply our risk assessment model in the clinical setting with a prospective study design to predict asymptomatic endometrial disease in at-risk patients, selecting those for further clinical investigation including triage to soliciting symptoms, ordering ultrasound or even performing endometrial sampling using shared decision making. Further directions for research include the results and subsequent effects on stage at diagnosis and survival of these additional clinical investigations in asymptomatic women identified as high-risk by this nomogram.
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- 2022
44. Agnostic Pathway/Gene Set Analysis of Genome-Wide Association Data Identifies Associations for Pancreatic Cancer
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Paula L. Hyland, Sonja I. Berndt, Michelle Cotterchio, Rayjean J. Hung, Stephen K. Van Den Eeden, Núria Malats, Sara H. Olson, Rachel E. Neale, Eric A. Klein, Gloria M. Petersen, Eric J. Duell, Ann L. Oberg, Naomi Walsh, Robert C. Kurtz, Kari G Chaffee, Anne Zeleniuch-Jacquotte, Elisabete Weiderpass, Elizabeth A Holly, Brian M. Wolpin, Vladimir Janout, Lauren K. Brais, Paul Brennan, Qi Yang, Federico Canzian, Patricia Hartge, Han Zhang, Irene Collins, Peter Kraft, S. Chanock, Satu Männistö, PanScan, Christopher A. Haiman, Erica J. Childs, Wei Zheng, Robert N. Hoover, Malin Sund, Ayelet Borgida, Joseph M. Herman, Rachael Z. Stolzenberg-Solomon, Harvey A. Risch, Gabriella Andreotti, Oliver Strobel, Julie E. Buring, Kala Visvanathan, Ivana Holcatova, Nicholas J. Wareham, Paige M. Bracci, Nathaniel Rothman, Zhaoming Wang, Alison P Klein, Howard D. Sesso, Graham G. Giles, Gary E. Goodman, Edward Giovannucci, Michael Goggins, Emily White, Demetrius Albanes, Phyllis J. Goodman, Sean Cleary, Roger L. Milne, Francisco X. Real, Kathy J. Helzlsouer, Miquel Porta, Charles S. Fuchs, B. Bueno-de-Mesquita, Thilo Hackert, Lingeng Lu, Ghislaine Scelo, Marie-Christine Boutron-Ruault, Ana Babic, Herbert Yu, Laura Beane-Freeman, PanC consortia, J. Michael Gaziano, Laufey T. Amundadottir, Mark D Thornquist, I-Min Lee, Ulrike Peters, Mingfeng Zhang, Donghui Li, Eric J. Jacobs, Evelina Mocci, William Wheeler, Kai Yu, William R. Bamlet, Gianluca Severi, Xiao O. Shu, Alpa V. Patel, Alan A. Arslan, Charles Kooperberg, D. Silverman, Daniel Laheru, Irene Orlow, Steven Gallinger, J. Wactawski-Wende, Geoffrey S Tobias, Loic LeMarchand, Nicolas Wentzensen, Lenka Foretová, Manal Hasan, and Department of Medical and Clinical Genetics
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EXPRESSION ,Developmental genetics ,Cancer Research ,GENES ,SUSCEPTIBILITY LOCI ,Pàncrees -- Genètica ,3122 Cancers ,Genome-wide association study ,Single-nucleotide polymorphism ,Computational biology ,VARIANTS ,Biology ,Polymorphism, Single Nucleotide ,Genome ,03 medical and health sciences ,Pàncrees -- Malalties ,0302 clinical medicine ,Pancreatic cancer ,ENDOTHELIN ,medicine ,Humans ,BREAST-CANCER ,Genetic Predisposition to Disease ,TRANSCRIPTOME ,Gene ,Càncer de pàncrees ,Pancreas cancer ,Pàncrees -- Càncer ,Genetic association ,Models, Statistical ,RECEPTOR ,MUTATIONS ,Case-control study ,Articles ,medicine.disease ,3. Good health ,Pancreatic Neoplasms ,Oncology ,Case-Control Studies ,030220 oncology & carcinogenesis ,Meta-analysis ,METASTASIS ,Carcinoma, Pancreatic Ductal ,Genome-Wide Association Study ,Genètica del desenvolupament - Abstract
Background: Genome-wide association studies (GWAS) identify associations of individual single-nucleotide polymorphisms (SNPs) with cancer risk but usually only explain a fraction of the inherited variability. Pathway analysis of genetic variants is a powerful tool to identify networks of susceptibility genes. Methods: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided. Results: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P
- Published
- 2018
45. Lung Cancer Characteristics in Male and Female Community Members Exposed to the Dust and Fumes from the World Trade Center Towers
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Nedim Durmus, Daniel H. Sterman, Yongzhao Shao, Rachel Corona, Sultan Pehlivan, Y. Zhang, Joan Reibman, Ian J. Henderson, and Alan A. Arslan
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Geography ,Environmental health ,World trade center ,medicine ,Lung cancer ,medicine.disease - Published
- 2021
46. Lung Cancer Characteristics in the World Trade Center Environmental Health Center
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Nedim Durmus, Ian J. Henderson, Joan Reibman, Rachel Corona, Daniel H. Sterman, Sultan Pehlivan, Y. Zhang, Alan A. Arslan, and Yongzhao Shao
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Lung Diseases ,Male ,Tobacco use ,Lung Neoplasms ,Demographics ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,010501 environmental sciences ,01 natural sciences ,complex mixtures ,Smoking history ,Article ,03 medical and health sciences ,0302 clinical medicine ,Adverse health effect ,Environmental health ,medicine ,Humans ,cancer characteristics ,030212 general & internal medicine ,Lung cancer ,0105 earth and related environmental sciences ,WTC Environmental Health Center ,September 11th ,business.industry ,lcsh:R ,Public Health, Environmental and Occupational Health ,World trade center ,Cancer ,Dust ,Middle Aged ,medicine.disease ,humanities ,World Trade Center ,respiratory tract diseases ,lung cancer ,Adenocarcinoma ,Female ,New York City ,September 11 Terrorist Attacks ,business ,Environmental Health - Abstract
The destruction of the World Trade Center (WTC) towers on 11 September 2001 resulted in acute and chronic dust and fume exposures to community members, including local workers and residents, with well-described aerodigestive adverse health effects. This study aimed to characterize lung cancer in the WTC Environmental Health Center (WTC EHC) focusing on gender and smoking history. WTC EHC patients undergo an initial evaluation that includes WTC exposure information, demographics, and tobacco use. Detailed cancer characteristics are recorded from pathology reports. As of 31 December 2019, 248 WTC EHC patients had a diagnosis of lung cancer. More patients with lung cancer were women (57%) compared to men (43%). Many cases (47% women, 51% men) reported acute dust cloud exposure. Thirty-seven percent of lung cancer cases with available smoking history were never-smokers (≤1 pack-years) and 42% had a ≤5 pack-year history. The median age of cancer diagnosis in never-smoking women was 61 years compared to 66 years in men. Adenocarcinoma was more common in never-smokers compared to ever-smokers (72% vs. 65%) and in women compared to men (70% vs. 65%). We provide an initial description of lung cancers in local community members with documented exposure to the WTC dust and fumes.
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- 2021
47. The Development of a WTC Environmental Health Center Pan-Cancer Database
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Rachel Corona, Yongzhao Shao, Maria-Elena Fernandez-Beros, Adrienne Addessi, Sheila Smyth-Giambanco, Sultan Pehlivan, Nedim Durmus, Sharon A. Abbott, Y. Zhang, Alan A. Arslan, Joan Reibman, and Lisette Umana
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cancer incidence ,Databases, Factual ,Health, Toxicology and Mutagenesis ,Population ,lcsh:Medicine ,computer.software_genre ,complex mixtures ,Article ,clinical cancer database ,03 medical and health sciences ,0302 clinical medicine ,Neoplasms ,Environmental health ,Humans ,Medicine ,Survivors ,030212 general & internal medicine ,WTC survivors ,education ,WTC Environmental Health Center ,education.field_of_study ,September 11th ,Database ,Pan cancer ,business.industry ,lcsh:R ,Public Health, Environmental and Occupational Health ,World trade center ,Cancer ,biomarkers ,medicine.disease ,030210 environmental & occupational health ,Mental health ,humanities ,Cancer incidence ,Biomarker (medicine) ,New York City ,September 11 Terrorist Attacks ,business ,Environmental Health ,computer ,Clinical record - Abstract
(1) Background: Recent studies have reported elevated risks of multiple cancers in the World Trade Center (WTC) affected community members (also called WTC “Survivors”). The large variety of WTC-cancers created a need to develop a comprehensive cancer database. This paper describes the development of a pan-cancer database at the WTC Environmental Health Center (EHC) Data Center. (2) Methods: A new REDCap-based pan-cancer database was created using the pathology reports and available biomarker data of confirmed cancer cases after review by a cancer epidemiologist, a pathologist, physicians and biostatisticians. (3) Results: The WTC EHC pan-cancer database contains cancer characteristics and emerging biomarker information for cancers of individuals enrolled in the WTC EHC and diagnosed after 11 September 2001 and up to 31 December 2019 obtained from WTC EHC clinical records, pathological reports and state cancer registries. As of 31 December 2019, the database included 3440 cancer cases with cancer characteristics and biomarker information. (4) Conclusions: This evolving database represents an important resource for the scientific community facilitating future research about the etiology, heterogeneity, characteristics and outcomes of cancers and comorbid mental health conditions, cancer economics and gene–environment interaction in the unique population of WTC survivors.
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- 2021
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48. Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults
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Woon-Puay Koh, Mattias Johansson, Jian-Min Yuan, Kjell Grankvist, Howard D. Sesso, Demetrius Albanes, Elin Pettersen Sørgjerd, Mikael Johansson, Xiao-Ou Shu, Graham G. Giles, Kala Visvanathan, Loic Le Marchand, Paul Brennan, Malte Sandsveden, Ross L. Prentice, Alan A. Arslan, Qiuyin Cai, Neal D. Freedman, Roger L. Milne, Jonas Manjer, J. Michael Gaziano, Hilary A. Robbins, Lynne R. Wilkens, Victoria L. Stevens, Hana Zahed, Florence Guida, Chu Chen, Wen Yi Huang, Anne Zeleniuch-Jacquotte, Stephanie J. Weinstein, Per Magne Ueland, Arnulf Langhammer, Xuehong Zhang, Wei Zheng, Ying Wang, William J. Blot, Anouar Fanidi, David C. Muller, and Øivind Midttun
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Male ,0301 basic medicine ,Epidemiology ,Science ,medicine.medical_treatment ,Population ,Physiology ,Renal function ,Kidney ,Article ,Body Mass Index ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Humans ,education ,Kynurenine ,Aged ,Aged, 80 and over ,Inflammation ,Creatinine ,education.field_of_study ,Cancer och onkologi ,Multidisciplinary ,business.industry ,Smoking ,Vitamins ,Middle Aged ,Carbon ,B vitamins ,C-Reactive Protein ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,Cancer and Oncology ,Cohort ,Medicine ,Smoking cessation ,Biomarker (medicine) ,Female ,Smoking Cessation ,business ,Body mass index ,Biomarkers - Abstract
Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40–80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was − 0.91 standard-deviations lower in women than men (95%CI − 0.98; − 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p
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- 2021
49. A multilayered post-GWAS assessment on genetic susceptibility to pancreatic cancer
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Manuel Hidalgo, D Easton, William Greenhalf, Paige M. Bracci, Víctor Manuel Barberá, Alan A. Arslan, Enrique Dominguez-Munoz, Isabel Adoración Martín-Antoniano, Luis Arnes, L. Ilzarbe, Rita T. Lawlor, Stephen J. Chanock, Marc A. Marti-Renom, Luis Muñoz-Bellvís, LT Amundadottir, BM Wolpin, M Gunter, F.X. Real, L Beane-Freeman, Josefina Mora, Jörg Kleeff, PJ Goodman, Tatjana Crnogorac-Jurcevic, Juan Antonio Rodríguez, B Kong, K Visvanathan, Harvey A. Risch, S Gallinger, Debra T. Silverman, O Lao, Joaquim Balsells, Damian O'Driscoll, M O’Rorke, Núria Malats, D Albanes, A. Carrato, Epicuro Investigators, Eithne Costello, RZ Stolzenberg-Solomon, Esther Molina-Montes, PanGenEU Study Investigators, Xavier Molero, RE Neale, Paulina Gomez-Rubio, Thornquist, Weimin Ye, Nathanial Rothman, Xiao-Ou Shu, Laura C. Alonso, Ulrike Peters, Mirari Marquez, Wei Zheng, Aldo Scarpa, Ll Cecchini, Thomas M. Gress, Alison P. Klein, F Canzian, D Li, Adonina Tardón, A Farré, Manolis Kogevinas, M Garcia-Closas, GM Petersen, B Bueno-de-Mesquita, Mar Iglesias, MJ Sánchez, José Perea, Christoph W. Michalski, M Du, Linda Sharp, JM Gaziano, Matthias Löhr, J Yu, L LeMarchand, J Buring, E. López de Maturana, Paul Brennan, Malats, Núria [0000-0003-2538-3784], Apollo - University of Cambridge Repository, Institut Català de la Salut, [López de Maturana E, Alonso L, Molina-Montes E, Martín-Antoniano IA] Genetic and Molecular Epidemiology Group, Spanish National Cancer Research Center (CNIO), C/Melchor Fernandez Almagro 3, 28029 Madrid, Spain. CIBERONC, Madrid, Spain. [Rodríguez JA, Lao O] CNAG-CRG, Centre for Genomic Regulation (CRG), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain. [Molero X, Balsells J] Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall d’Hebron Institut de Recerca (VHIR), Barcelona, Spain. Universitat Autònoma de Barcelona, Bellaterra, Spain. CIBEREHD, Barcelona, Spain, and Vall d'Hebron Barcelona Hospital Campus
- Subjects
Genetic Phenomena::Genotype::Genetic Predisposition to Disease [PHENOMENA AND PROCESSES] ,Complex disease ,lcsh:Medicine ,Genome-wide association study ,Genome ,Linkage Disequilibrium ,European descent ,0302 clinical medicine ,Gene Regulatory Networks ,neoplasias::neoplasias por localización::neoplasias del sistema digestivo::neoplasias pancreáticas [ENFERMEDADES] ,Genetics (clinical) ,0303 health sciences ,Phenotype ,3. Good health ,ddc ,030220 oncology & carcinogenesis ,Molecular Medicine ,Malalties congènites ,Signal Transduction ,Prioritization ,Pancreatic cancer risk ,Investigative Techniques::Epidemiologic Methods::Epidemiologic Research Design::Genome-Wide Association Study [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,lcsh:QH426-470 ,Systems biology ,In silico ,Computational biology ,Biology ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Cell Line, Tumor ,Pancreatic cancer ,Genetics ,Biomarkers, Tumor ,Genetic predisposition ,medicine ,Genetic susceptibility ,Humans ,Computer Simulation ,Genetic Predisposition to Disease ,Genome-wide association analysis ,Molecular Biology ,Gene ,Spatial analysis ,fenómenos genéticos::genotipo::predisposición genética a la enfermedad [FENÓMENOS Y PROCESOS] ,030304 developmental biology ,Neoplasms::Neoplasms by Site::Digestive System Neoplasms::Pancreatic Neoplasms [DISEASES] ,Pàncrees - Càncer ,Local indices of genome spatial autocorrelation ,Genome, Human ,3D genomic structure ,Research ,lcsh:R ,Reproducibility of Results ,medicine.disease ,Human genetics ,Pancreatic Neoplasms ,lcsh:Genetics ,técnicas de investigación::métodos epidemiológicos::diseño de la investigación epidemiológica::estudio de asociación genómica completa [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Genome-Wide Association Study - Abstract
The work was partially supported by Fondo de Investigaciones Sanitarias (FIS), Instituto de Salud Carlos III, Spain (PI061614, PI11/01542, PI0902102, PI12/01635, PI12/00815, PI15/01573, PI18/01347); Red Temática de Investigación Cooperativa en Cáncer, Spain (RD12/0036/0034, RD12/0036/ 0050, RD12/0036/0073); Spanish Ministerio de Ciencia, Innovación y Universidades (BFU2017-85926-P), López de Maturana, E., Rodríguez, J.A., Alonso, L., Lao, O., Molina-Montes, E., Martín-Antoniano, I.A., Gómez-Rubio, P., Lawlor, R., Carrato, A., Hidalgo, M., Iglesias, M., Molero, X., Löhr, M., Michalski, C., Perea, J., O’Rorke, M., Barberà, V.M., Tardón, A., Farré, A., Muñoz-Bellvís, L., Crnogorac-Jurcevic, T., Domínguez-Muñoz, E., Gress, T., Greenhalf, W., Sharp, L., Arnes, L., Cecchini, L., Balsells, J., Costello, E., Ilzarbe, L., Kleeff, J., Kong, B., Márquez, M., Mora, J., O’Driscoll, D., Scarpa, A., Ye, W., Yu, J., García-Closas, M., Kogevinas, M., Rothman, N., Silverman, D.T., Albanes, D., Arslan, A.A., Beane-Freeman, L., Bracci, P.M., Brennan, P., Bueno-de-Mesquita, B., Buring, J., Canzian, F., Du, M., Gallinger, S., Gaziano, J.M., Goodman, P.J., Gunter, M., LeMarchand, L., Li, D., Neale, R.E., Peters, U., Petersen, G.M., Risch, H.A., Sánchez, M.J., Shu, X.-O., Thornquist, M.D., Visvanathan, K., Zheng, W., Chanock, S.J., Easton, D., Wolpin, B.M., Stolzenberg-Solomon, R.Z., Klein, A.P., Amundadottir, L.T., Marti-Renom, M.A., Real, F.X., Malats, N., PanGenEU Investigators, SBC/EPICURO Investigators
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- 2021
50. Genome-wide homozygosity and risk of four non-Hodgkin lymphoma subtypes
- Author
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Joseph Vijai, Henrik Hjalgrim, Roger L. Milne, Simonetta Bisanzi, Rebecca D. Jackson, Graham G. Giles, Mark Liebow, John J. Spinelli, Stephanie J. Weinstein, Wendy Cozen, Susan M. Gapstur, Michael Dean, Paolo Boffetta, Pierluigi Cocco, Paige M. Bracci, Nicola J. Camp, Amy Moore, Herve Ghesquieres, Federico Canzian, James McKay, Thomas M. Habermann, Nikolaus Becker, Kari E. North, Demetrius Albanes, Alain Monnereau, Marc Maynadié, Lesley F. Tinker, Christine F. Skibola, Vignesh Ravichandran, Susan L. Slager, Karin E. Smedby, Ruth C. Travis, Jacqueline Clavel, Lucia Miligi, Melissa C. Southey, Mary Carrington, Claire M. Vajdic, Karen Curtin, David G. Cox, Roel Vermeulen, Elio Riboli, Eleanor Kane, Weiyin Zhou, Nathaniel Rothman, Mitchell J. Machiela, Yolanda Benavente, Alan A. Arslan, Meredith Yeager, Paul Brennan, Tongzhang Zheng, Elisabete Weiderpass, Moara Machado, Qing Lan, Alpa V. Patel, James R. Cerhan, Sonja I. Berndt, Neil E. Caporaso, Silvia de Sanjosé, Stephen J. Chanock, Nicole Wong Doo, Lauren R. Teras, Sara Piro, Lenka Foretova, Chi Gao, Gilles Salles, Immaculata De Vivo, Alexandra Nieters, Bengt Glimelius, Sophia S. Wang, Richard K. Severson, Mads Melbye, Hans-Olov Adami, Yawei Zhang, Carolyn Stewart, Lucia Conde, Brenda M. Birmann, Angela Brooks-Wilson, Thierry Jo Molina, Kenneth Offit, Brian K. Link, Martha Glenn, Anthony Staines, Moore, Amy, Machiela, Mitchell J, Machado, Moara, Wang, Sophia S, Kane, Eleanor, Slager, Susan L, Zhou, Weiyin, Carrington, Mary, Lan, Qing, Milne, Roger L, Birmann, Brenda M, Adami, Hans-Olov, Albanes, Demetriu, Arslan, Alan A, Becker, Nikolau, Benavente, Yolanda, Bisanzi, Simonetta, Boffetta, Paolo, Bracci, Paige M, Brennan, Paul, Brooks-Wilson, Angela R, Canzian, Federico, Caporaso, Neil, Clavel, Jacqueline, Cocco, Pierluigi, Conde, Lucia, Cox, David G, Cozen, Wendy, Curtin, Karen, De Vivo, Immaculata, de Sanjose, Silvia, Foretova, Lenka, Gapstur, Susan M, Ghesquières, Hervè, Giles, Graham G, Glenn, Martha, Glimelius, Bengt, Gao, Chi, Habermann, Thomas M, Hjalgrim, Henrik, Jackson, Rebecca D, Liebow, Mark, Link, Brian K, Maynadie, Marc, McKay, Jame, Melbye, Mad, Miligi, Lucia, Molina, Thierry J, Monnereau, Alain, Nieters, Alexandra, North, Kari E, Offit, Kenneth, Patel, Alpa V, Piro, Sara, Ravichandran, Vignesh, Riboli, Elio, Salles, Gille, Severson, Richard K, Skibola, Christine F, Smedby, Karin E, Southey, Melissa C, Spinelli, John J, Staines, Anthony, Stewart, Carolyn, Teras, Lauren R, Tinker, Lesley F, Travis, Ruth C, Vajdic, Claire M, Vermeulen, Roel C H, Vijai, Joseph, Weiderpass, Elisabete, Weinstein, Stephanie, Doo, Nicole Wong, Zhang, Yawei, Zheng, Tongzhang, Chanock, Stephen J, Rothman, Nathaniel, Cerhan, James R, Dean, Michael, Camp, Nicola J, Yeager, Meredith, and Berndt, Sonja I
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Genetics ,Chronic lymphocytic leukemia ,diffuse large B-cell lymphoma ,Follicular lymphoma ,Single-nucleotide polymorphism ,Runs of Homozygosity ,Biology ,medicine.disease ,marginal zone lymphoma ,Article ,follicular lymphoma ,immune system diseases ,hemic and lymphatic diseases ,Genetic variation ,medicine ,chronic lymphocytic leukemia ,homozygosity ,Diffuse large B-cell lymphoma ,Inbreeding ,Non-Hodgkin lymphoma ,Genetic association - Abstract
Aim: Recessive genetic variation is thought to play a role in non-Hodgkin lymphoma (NHL) etiology. Runs of homozygosity (ROH), defined based on long, continuous segments of homozygous SNPs, can be used to estimate both measured and unmeasured recessive genetic variation. We sought to examine genome-wide homozygosity and NHL risk.Methods: We used data from eight genome-wide association studies of four common NHL subtypes: 3061 chronic lymphocytic leukemia (CLL), 3814 diffuse large B-cell lymphoma (DLBCL), 2784 follicular lymphoma (FL), and 808 marginal zone lymphoma (MZL) cases, as well as 9374 controls. We examined the effect of homozygous variation on risk by: (1) estimating the fraction of the autosome containing runs of homozygosity (FROH); (2) calculating an inbreeding coefficient derived from the correlation among uniting gametes (F3); and (3) examining specific autosomal regions containing ROH. For each, we calculated beta coefficients and standard errors using logistic regression and combined estimates across studies using random-effects meta-analysis.Results: We discovered positive associations between FROH and CLL (β = 21.1, SE = 4.41, P = 1.6 × 10 -6) and FL (β = 11.4, SE = 5.82, P = 0.02) but not DLBCL ( P = 1.0) or MZL ( P = 0.91). For F3, we observed an association with CLL (β = 27.5, SE = 6.51, P = 2.4 × 10 -5). We did not find evidence of associations with specific ROH, suggesting that the associations observed with FROH and F3 for CLL and FL risk were not driven by a single region of homozygosity. Conclusion: Our findings support the role of recessive genetic variation in the etiology of CLL and FL; additional research is needed to identify the specific loci associated with NHL risk.
- Published
- 2021
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