Citations 2
Mendelian Randomization Analysis of n-6 Polyunsaturated Fatty Acid Levels and Pancreatic Cancer Risk
Ghoneim, Dalia, Zhu, Jingjing , Murff, Harvey J. , Ye, Fei , Khankari, Nikhil K. , Haycock, Philip , Antwi, Samuel O. , Yang, Yaohua , Arslan, Alan A. , Bracci, Paige M. , Du, Mengmeng , Gallinger, Steven , Goodman, Phyllis J. , Scélo, Ghislaine , Visvanathan, Kala , Andreotti, Gabriella , Babić, Ana , Berndt, Sonja I. , Brennan, Paul , Bueno‐de‐Mesquita, Bas , Buring, Julie E. , Rabe, Kari G. , Duggal, Priya , Fuchs, Charles S. , Gaziano, J. Michael , Hackert, Thilo , Hassan, Manal M. , Helzlsouer, Kathy J. , Holly, Elizabeth A. , Hoover, Robert N. , Katske, Verena, Kurtz, Robert C. , Lee, I‐Min , Murphy, Neil , Oberg, Ann L. , Porta, Miquel , Rothman, Nathaniel , Sesso, Howard D. , Wactawski‐Wende, Jean , Wentzensen, Nicolas , Wolpin, Brian M. , Jacobs, Eric J. , Petersen, Gloria M. , Stolzenberg-Solomon, Rachel Z., Wu, Lang , Haycock, Philip , Arslan, Alan A , Canzian, Federico , Giles, Graham G , Visvanathan, Kala , Bamlet, William R , Brennan, Paul , Chaffee, Kari G. , Hackert, Thilo , Katzke, Verena , Malats, Nuria , Milne, Roger L , Oberg, Ann L , Sesso, Howard D , Wactawski-Wende, Jean , Yu, Herbert , Duell, Eric J , Amundadottir, Laufey , Klein, Alison P , Antwi, Samuel O , Murphy, Neil , Porta, Miquel , Duggal, Priya , Zheng, Wei , Long, Jirong , Setiawan, Veronica Wendy , Wilkens, Lynne R. , Freeman, Laura E. Beane , Canzian, Federico , Giles, Graham G. , Kooperberg, Charles , Marchand, Loı̈c Le , Neale, Rachel Ε. , White, Emily , Albanes, Demetrius , Amiano, Pilar , Bamlet, William R. , Brais, Lauren K , Campbell, Peter T. , Chanock, Stephen Jacob , Goggins, Michael , Malats, Núria , Milne, Roger L. , Rothman, Nathaniel , Silverman, Debra T. , Thompson, Ian M. , Wang, Xiaoliang , Yu, Kai , Zeleniuch‐Jacquotte, Anne , Duell, Eric J. , Risch, Harvey A. , Ámundadóttir, Laufey T. , Kraft, Peter , Klein, Alison P. , Shu, Xiao‐Ou , Yang, Yaohua
Cancer Epidemiology, Biomarkers & Prevention | September 23, 2020 | Volume: 29 | Issue: 12 | Pages: 2735-2739
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.
Mendelian Randomization of Circulating Polyunsaturated Fatty Acids and Colorectal Cancer Risk
Khankari, Nikhil K. , Banbury, Barbara L. , Borges, Maria Carolina , Haycock, Philip , Arndt, Volker , Berndt, Sonja I. , Brenner, Hermann , Casey, Graham , Chang‐Claude, Jenny , Conti, David V. , English, Dallas R. , Figueiredo, Jane C. , Giovannucci, Edward L. , Gunter, Marc J. , Hampe, Jochen , Hoffmeister, Michael , Joshi, Amit D. , Lemire, Mathieu , Li, Li , Lindblom, Annika , Martín, Vicente , Moreno, Vı́ctor , Offit, Kenneth, Rennert, Gad , Schafmayer, Clemens , Schmit, Stephanie L. , Slattery, Martha L. , Thibodeau, Stephen N. , Weinstein, Stephanie J. , Win, Aung Ko , Woods, Michael O. , Wu, Anna H. , Murff, Harvey J. , Gruber, Stephen B. , Peters, Ulrike , Brenner, Hermann , Borges, Maria C , Arndt, Volker , Brenner, Hermann , Chang-Claude, Jenny , English, Dallas R , Giles, Graham G , Hoffmeister, Michael , Martín, Vicente , Moreno, Victor , Pharoah, Paul D P , Rennert, Gad , Sakoda, Lori C , Slattery, Martha L , Weinstein, Stephanie J , Win, Aung K , Wolk, Alicja , Denny, Joshua C , Gunter, Marc J , Haycock, Philip , Brenner, Hermann , Hampe, Jochen , Conti, David V , Lindblom, Annika , Albanes, Demetrius , Bezieau, Stéphane , Campbell, Peter T. , Chan, Andrew T. , Cotterchio, Michelle , Giles, Graham G. , Hopper, John L. , Jenkins, Mark A. , Marchand, Loı̈c Le , Li, Christopher I , Newcomb, Polly A. , Pharoah, Paul D.P. , Sakoda, Lori C. , Song, Mingyang , Ulrich, Cornelia M. , White, Emily , Wolk, Alicja , Cai, Qiuyin , Denny, Joshua C. , Edwards, Todd L. , Zheng, Wei
Cancer Epidemiology, Biomarkers & Prevention | February 12, 2020 | Volume: 29 | Issue: 4 | Pages: 860-870
Abstract Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93–0.98; P = 5.2 × 10−4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92–0.97; P = 5.4 × 10−5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03–1.08; P = 3.3 × 10−5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01–1.07; P = 2.5 × 10−3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01–1.06; P = 1.2 × 10−2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.