Zhanmo Ni, Prosenjit Kundu, David F McKean, William Wheeler, Demetrius Albanes, Gabriella Andreotti, Samuel O Antwi, Alan A Arslan, William R Bamlet, Laura E Beane-Freeman, Sonja I Berndt, Paige M Bracci, Paul Brennan, Julie E Buring, Stephen J Chanock, Steven Gallinger, J M Gaziano, Graham G Giles, Edward L Giovannucci, Michael G Goggins, Phyllis J Goodman, Christopher A Haiman, Manal M Hassan, Elizabeth A Holly, Rayjean J Hung, Verena Katzke, Charles Kooperberg, Peter Kraft, Loic LeMarchand, Donghui Li, Marjorie L McCullough, Roger L Milne, Steven C Moore, Rachel E Neale, Ann L Oberg, Alpa V Patel, Ulrike Peters, Kari G Rabe, Harvey A Risch, Xiao-Ou Shu, Karl Smith-Byrne, Kala Visvanathan, Jean Wactawski-Wende, Emily White, Brian M Wolpin, Herbert Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Jun Zhong, Laufey T Amundadottir, Rachael Z Stolzenberg-Solomon, Alison P Klein
{"title":"进行全基因组分析，评估大量饮酒是否会改变 SNP 与胰腺癌风险之间的关联。","authors":"Zhanmo Ni, Prosenjit Kundu, David F McKean, William Wheeler, Demetrius Albanes, Gabriella Andreotti, Samuel O Antwi, Alan A Arslan, William R Bamlet, Laura E Beane-Freeman, Sonja I Berndt, Paige M Bracci, Paul Brennan, Julie E Buring, Stephen J Chanock, Steven Gallinger, J M Gaziano, Graham G Giles, Edward L Giovannucci, Michael G Goggins, Phyllis J Goodman, Christopher A Haiman, Manal M Hassan, Elizabeth A Holly, Rayjean J Hung, Verena Katzke, Charles Kooperberg, Peter Kraft, Loic LeMarchand, Donghui Li, Marjorie L McCullough, Roger L Milne, Steven C Moore, Rachel E Neale, Ann L Oberg, Alpa V Patel, Ulrike Peters, Kari G Rabe, Harvey A Risch, Xiao-Ou Shu, Karl Smith-Byrne, Kala Visvanathan, Jean Wactawski-Wende, Emily White, Brian M Wolpin, Herbert Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Jun Zhong, Laufey T Amundadottir, Rachael Z Stolzenberg-Solomon, Alison P Klein","doi":"10.1158/1055-9965.EPI-24-0096","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.</p><p><strong>Methods: </strong>We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted.</p><p><strong>Results: </strong>A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004).</p><p><strong>Conclusions: </strong>We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer.</p><p><strong>Impact: </strong>This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.</p>","PeriodicalId":9458,"journal":{"name":"Cancer Epidemiology Biomarkers & Prevention","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Genome-Wide Analysis to Assess if Heavy Alcohol Consumption Modifies the Association between SNPs and Pancreatic Cancer Risk.\",\"authors\":\"Zhanmo Ni, Prosenjit Kundu, David F McKean, William Wheeler, Demetrius Albanes, Gabriella Andreotti, Samuel O Antwi, Alan A Arslan, William R Bamlet, Laura E Beane-Freeman, Sonja I Berndt, Paige M Bracci, Paul Brennan, Julie E Buring, Stephen J Chanock, Steven Gallinger, J M Gaziano, Graham G Giles, Edward L Giovannucci, Michael G Goggins, Phyllis J Goodman, Christopher A Haiman, Manal M Hassan, Elizabeth A Holly, Rayjean J Hung, Verena Katzke, Charles Kooperberg, Peter Kraft, Loic LeMarchand, Donghui Li, Marjorie L McCullough, Roger L Milne, Steven C Moore, Rachel E Neale, Ann L Oberg, Alpa V Patel, Ulrike Peters, Kari G Rabe, Harvey A Risch, Xiao-Ou Shu, Karl Smith-Byrne, Kala Visvanathan, Jean Wactawski-Wende, Emily White, Brian M Wolpin, Herbert Yu, Anne Zeleniuch-Jacquotte, Wei Zheng, Jun Zhong, Laufey T Amundadottir, Rachael Z Stolzenberg-Solomon, Alison P Klein\",\"doi\":\"10.1158/1055-9965.EPI-24-0096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.</p><p><strong>Methods: </strong>We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted.</p><p><strong>Results: </strong>A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004).</p><p><strong>Conclusions: </strong>We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer.</p><p><strong>Impact: </strong>This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.</p>\",\"PeriodicalId\":9458,\"journal\":{\"name\":\"Cancer Epidemiology Biomarkers & Prevention\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2024-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Epidemiology Biomarkers & Prevention\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1158/1055-9965.EPI-24-0096\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Epidemiology Biomarkers & Prevention","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1158/1055-9965.EPI-24-0096","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
Genome-Wide Analysis to Assess if Heavy Alcohol Consumption Modifies the Association between SNPs and Pancreatic Cancer Risk.
Background: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.
Methods: We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted.
Results: A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004).
Conclusions: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer.
Impact: This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.
期刊介绍：
Cancer Epidemiology, Biomarkers & Prevention publishes original peer-reviewed, population-based research on cancer etiology, prevention, surveillance, and survivorship. The following topics are of special interest: descriptive, analytical, and molecular epidemiology; biomarkers including assay development, validation, and application; chemoprevention and other types of prevention research in the context of descriptive and observational studies; the role of behavioral factors in cancer etiology and prevention; survivorship studies; risk factors; implementation science and cancer care delivery; and the science of cancer health disparities. Besides welcoming manuscripts that address individual subjects in any of the relevant disciplines, CEBP editors encourage the submission of manuscripts with a transdisciplinary approach.
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