Browsing by Author "Prentice, Ross L."

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    Beyond GWAS of Colorectal Cancer: Evidence of Interaction with Alcohol Consumption and Putative Causal Variant for the 10q24.2 Region
    (American Association for Cancer Research, 2022) Jordahl, Kristina M.; Shcherbina, Anna; Kim, Andre E.; Su, Yu-Ru; Lin, Yi; Wang, Jun; Qu, Conghui; Albanes, Demetrius; Arndt, Volker; Baurley, James W.; Berndt, Sonja I.; Bien, Stephanie A.; Bishop, D. Timothy; Bouras, Emmanouil; Brenner, Hermann; Buchanan, Daniel D.; Budiarto, Arif; Campbell, Peter T.; Carreras-Torres, Robert; Casey, Graham; Cenggoro, Tjeng Wawan; Chan, Andrew T.; Conti, David V.; Dampier, Christopher H.; Devall, Matthew A.; Díez-Obrero, Virginia; Dimou, Niki; Drew, David A.; Figueiredo, Jane C.; Gallinger, Steven; Giles, Graham G.; Gruber, Stephen B.; Gsur, Andrea; Gunter, Marc J.; Hampel, Heather; Harlid, Sophia; Harrison, Tabitha A.; Hidaka, Akihisa; Hoffmeister, Michael; Huyghe, Jeroen R.; Jenkins, Mark A.; Joshi, Amit D.; Keku, Temitope O.; Larsson, Susanna C.; Le Marchand, Loic; Lewinger, Juan Pablo; Li, Li; Mahesworo, Bharuno; Moreno, Victor; Morrison, John L.; Murphy, Neil; Nan, Hongmei; Nassir, Rami; Newcomb, Polly A.; Obón-Santacana, Mireia; Ogino, Shuji; Ose, Jennifer; Pai, Rish K.; Palmer, Julie R.; Papadimitriou, Nikos; Pardamean, Bens; Peoples, Anita R.; Pharoah, Paul D. P.; Platz, Elizabeth A.; Potter, John D.; Prentice, Ross L.; Rennert, Gad; Ruiz-Narvaez, Edward; Sakoda, Lori C.; Scacheri, Peter C.; Schmit, Stephanie L.; Schoen, Robert E.; Slattery, Martha L.; Stern, Mariana C.; Tangen, Catherine M.; Thibodeau, Stephen N.; Thomas, Duncan C.; Tian, Yu; Tsilidis, Konstantinos K.; Ulrich, Cornelia M.; van Duijnhoven, Franzel J. B.; Van Guelpen, Bethany; Visvanathan, Kala; Vodicka, Pavel; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Zemlianskaia, Natalia; Chang-Claude, Jenny; Gauderman, W. James; Hsu, Li; Kundaje, Anshul; Peters, Ulrike; Epidemiology, Richard M. Fairbanks School of Public Health
    Background: Currently known associations between common genetic variants and colorectal cancer explain less than half of its heritability of 25%. As alcohol consumption has a J-shape association with colorectal cancer risk, nondrinking and heavy drinking are both risk factors for colorectal cancer. Methods: Individual-level data was pooled from the Colon Cancer Family Registry, Colorectal Transdisciplinary Study, and Genetics and Epidemiology of Colorectal Cancer Consortium to compare nondrinkers (≤1 g/day) and heavy drinkers (>28 g/day) with light-to-moderate drinkers (1-28 g/day) in GxE analyses. To improve power, we implemented joint 2df and 3df tests and a novel two-step method that modifies the weighted hypothesis testing framework. We prioritized putative causal variants by predicting allelic effects using support vector machine models. Results: For nondrinking as compared with light-to-moderate drinking, the hybrid two-step approach identified 13 significant SNPs with pairwise r2 > 0.9 in the 10q24.2/COX15 region. When stratified by alcohol intake, the A allele of lead SNP rs2300985 has a dose-response increase in risk of colorectal cancer as compared with the G allele in light-to-moderate drinkers [OR for GA genotype = 1.11; 95% confidence interval (CI), 1.06-1.17; OR for AA genotype = 1.22; 95% CI, 1.14-1.31], but not in nondrinkers or heavy drinkers. Among the correlated candidate SNPs in the 10q24.2/COX15 region, rs1318920 was predicted to disrupt an HNF4 transcription factor binding motif. Conclusions: Our study suggests that the association with colorectal cancer in 10q24.2/COX15 observed in genome-wide association study is strongest in nondrinkers. We also identified rs1318920 as the putative causal regulatory variant for the region. Impact: The study identifies multifaceted evidence of a possible functional effect for rs1318920.
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    Genome-Wide Interaction Analysis of Genetic Variants With Menopausal Hormone Therapy for Colorectal Cancer Risk
    (Oxford, 2022) Tian, Yu; Kim, Andre E.; Bien, Stephanie A.; Lin, Yi; Qu, Conghui; Harrison, Tabitha A.; Carreras-Torres, Robert; Díez-Obrero, Virginia; Dimou, Niki; Drew , David A.; Hidaka, Akihisa; Huyghe, Jeroen R.; Jordahl, Kristina M.; Morrison , John; Murphy, Neil; Obón-Santacana, Mireia; Ulrich, Cornelia M.; Ose, Jennifer; Peoples, Anita R.; Ruiz-Narvaez, Edward A.; Shcherbina, Anna; Stern , Mariana C.; Su, Yu-Ru; van Duijnhoven, Franzel J. B.; Arndt, Volker; Baurley, James W.; Berndt, Sonja I.; Bishop, D. Timothy; Brenner, Hermann; Buchanan, Daniel D.; Chan, Andrew T.; Figueiredo, Jane C.; Gallinger, Steven; Gruber, Stephen B.; Harlid, Sophia; Hoffmeister, Michael; Jenkins, Mark A.; Joshi, Amit D.; Keku, Temitope O.; Larsson, Susanna C.; Marchand, Loic Le; Li, Li; Giles, Graham G.; Milne, Roger L.; Nan, Hongmei; Nassir, Rami; Ogino, Shuji; Budiarto, Arif; Platz, Elizabeth A.; Potter, John D.; Prentice, Ross L.; Rennert, Gad; Sakoda, Lori C.; Schoen, Robert E.; Slattery, Martha L.; Thibodeau, Stephen N.; Van Guelpen, Bethany; Visvanathan, Kala; White, Emily; Wolk, Alicja; Woods, Michael O.; Wu, Anna H.; Campbell, Peter T.; Casey, Graham; Conti, David V.; Gunter, Marc J.; Kundaje, Anshul; Lewinger, Juan Pablo; Moreno, Victor; Newcomb, Polly A.; Pardamean, Bens; Thomas, Duncan C.; Tsilidis, Konstantinos K.; Peters, Ulrike; Gauderman, W. James; Hsu, Li; Chang-Claude, Jenny; Community and Global Health, Richard M. Fairbanks School of Public Health
    Background: The use of menopausal hormone therapy (MHT) may interact with genetic variants to influence colorectal cancer (CRC) risk. Methods: We conducted a genome-wide, gene-environment interaction between single nucleotide polymorphisms and the use of any MHT, estrogen only, and combined estrogen-progestogen therapy with CRC risk, among 28 486 postmenopausal women (11 519 CRC patients and 16 967 participants without CRC) from 38 studies, using logistic regression, 2-step method, and 2– or 3–degree-of-freedom joint test. A set-based score test was applied for rare genetic variants. Results: The use of any MHT, estrogen only and estrogen-progestogen were associated with a reduced CRC risk (odds ratio [OR] = 0.71, 95% confidence interval [CI] = 0.64 to 0.78; OR = 0.65, 95% CI = 0.53 to 0.79; and OR = 0.73, 95% CI = 0.59 to 0.90, respectively). The 2-step method identified a statistically significant interaction between a GRIN2B variant rs117868593 and MHT use, whereby MHT-associated CRC risk was statistically significantly reduced in women with the GG genotype (OR = 0.68, 95% CI = 0.64 to 0.72) but not within strata of GC or CC genotypes. A statistically significant interaction between a DCBLD1 intronic variant at 6q22.1 (rs10782186) and MHT use was identified by the 2–degree-of-freedom joint test. The MHT-associated CRC risk was reduced with increasing number of rs10782186-C alleles, showing odds ratios of 0.78 (95% CI = 0.70 to 0.87) for TT, 0.68 (95% CI = 0.63 to 0.73) for TC, and 0.66 (95% CI = 0.60 to 0.74) for CC genotypes. In addition, 5 genes in rare variant analysis showed suggestive interactions with MHT (2-sided P < 1.2 × 10−4). Conclusion: Genetic variants that modify the association between MHT and CRC risk were identified, offering new insights into pathways of CRC carcinogenesis and potential mechanisms involved.