Citations 2
A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
Aglago, Elom K. , Kim, Andre E. , Lin, Yi , Qu, Conghui , Evangelou, Marina , Yu, Ren , Morrison, John L. , Albanes, Demetrius , Arndt, Volker , Barry, Elizabeth L. , Baurley, James W. , Berndt, Sonja I. , Bishop, D. Timothy , Bouras, Emmanouil , Brenner, Hermann , Casey, Graham , Chang‐Claude, Jenny , Díez‐Obrero, Virginia , Figueiredo, Jane C. , Gallinger, Steven , Gruber, Stephen B. , Gsur, Andrea , Harlid, Sophia , Harrison, Tabitha A. , Hoffmeister, Michael , Huyghe, Jeroen R. , Jordahl, Kristina M. , Joshi, Amit D. , Kundaje, Anshul , Li, Li , Mandic, Marko , Obón‐Santacana, Mireia , Nan, Hongmei , Nassir, Rami , Ose, Jennifer , Pai, Rish K. , Papadimitriou, Nikos , Prentice, Ross L. , Scacheri, Peter C. , Schmit, Stephanie L. , Slattery, Martha L. , Thibodeau, Stephen N. , Thomas, Duncan C. , Duijnhoven, Fränzel J.B. van , Guelpen, Bethany Van , Visvanathan, Kala , Vodička, Pavel , White, Emily , Woods, Michael O. , Wu, Anna H. , Zemlianskaia, Natalia , Gauderman, W. James , Peters, Ulrike , Kim, Andre E , Ren, Yu , Morrison, John L , Bien, Stephanie A , Bishop, D Timothy , Bouras, Emmanouil , Brenner, Hermann , Buchanan, Daniel D , Budiarto, Arif , Carreras-Torres, Robert , Casey, Graham , Cenggoro, Tjeng Wawan , Chan, Andrew T , Chang-Claude, Jenny , Chen, Xuechen , Conti, David V , Devall, Matthew A M , Diez-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 , Hidaka, Akihisa , Harrison, Tabitha A , Hoffmeister, Michael , Huyghe, Jeroen R , Jenkins, Mark A , Jordahl, Kristina M , Joshi, Amit D , Kawaguchi, Eric , Keku, Temitope O , Kundaje, Anshul , Larsson, Susanna C , Marchand, Loïc Le , Lewinger, Juan Pablo , Li, Li , Lynch, Brigid M , Mahesworo, Bharuno , Mandic, Marko , Obón-Santacana, Mireia , Moreno, Victor , Murphy, Neil , Nan, Hongmei , Nassir, Rami , Newcomb, Polly A. , Ogino, Shuji , Ose, Jennifer , Pai, R K , Palmer, Julie R , Papadimitriou, Nikos , Pardamean, Bens , Peoples, Anita R , 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 , Shcherbina, Anna , Slattery, Martha L , Stern, Mariana Carla , Su, Yu-Ru , Tangen, Catherine M , Thibodeau, Stephen N , Thomas, Duncan C , Tian, Yu , Ulrich, Cornelia M , van Duijnhoven, Fränzel J B , Van Guelpen, Bethany , Visvanathan, Kala , Vodicka, Pavel , Wang, Jun , White, Emily , Wolk, Alicja , Woods, Michael O , Wu, Anna H. , Zemlianskaia, Natalia , Hsu, Li , Gauderman, W James , Peters, Ulrike , Tsilidis, Konstantinos K , Campbell, Peter T , Arndt, Volker , Aglago, Elom K , Albanes, Demetrius , Qu, Conghui , Bien, Stephanie A. , Buchanan, Daniel D. , Carreras‐Torres, Robert , Chan, Andrew T. , Conti, David V. , Dimou, Niki , Drew, David A. , Giles, Graham G. , Gunter, Marc J. , Hampel, Heather , Hidaka, Akihisa , Jenkins, Mark A. , Larsson, Susanna C. , Marchand, Loı̈c Le , Lewinger, Juan Pablo , Moreno, Vı́ctor , Murphy, Neil , Palmer, Julie R. , Pardamean, Bens , Potter, John D. , Rennert, Gad , Sakoda, Lori C. , Schoen, Robert E. , Shcherbina, Anna , Tangen, Catherine M. , Tian, Yu , Ulrich, Cornelia M. , Wolk, Alicja , Tsilidis, Konstantinos K. , Campbell, Peter T.
Cancer Research | May 30, 2023 | Volume: 83 | Issue: 15 | Pages: 2572-2583
Abstract Colorectal cancer risk can be impacted by genetic, environmental, and lifestyle factors, including diet and obesity. Gene-environment interactions (G × E) can provide biological insights into the effects of obesity on colorectal cancer risk. Here, we assessed potential genome-wide G × E interactions between body mass index (BMI) and common SNPs for colorectal cancer risk using data from 36,415 colorectal cancer cases and 48,451 controls from three international colorectal cancer consortia (CCFR, CORECT, and GECCO). The G × E tests included the conventional logistic regression using multiplicative terms (one degree of freedom, 1DF test), the two-step EDGE method, and the joint 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher colorectal cancer risk. The two-step approach revealed a statistically significant G×BMI interaction located within the Formin 1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This SNP was also identified by the 3DF test, with a suggestive statistical significance in the 1DF test. Among participants with the CC genotype of rs58349661, overweight and obesity categories were associated with higher colorectal cancer risk, whereas null associations were observed across BMI categories in those with the TT genotype. Using data from three large international consortia, this study discovered a locus in the FMN1/GREM1 gene region that interacts with BMI on the association with colorectal cancer risk. Further studies should examine the potential mechanisms through which this locus modifies the etiologic link between obesity and colorectal cancer. Significance: This gene-environment interaction analysis revealed a genetic locus in FMN1/GREM1 that interacts with body mass index in colorectal cancer risk, suggesting potential implications for precision prevention strategies.
Body mass index and molecular subtypes of colorectal cancer
Murphy, Neil , Newton, Christina C. , Papadimitriou, Nikos , Hoffmeister, Michael , Phipps, Amanda I. , Harrison, Tabitha A. , Aglago, Elom K. , Berndt, Sonja I. , Brenner, Hermann , Cao, Yin , Chang‐Claude, Jenny , French, Amy J. , Gallinger, Steven , Georgeson, Peter , Giannakis, Marios , Gruber, Stephen B. , Harlid, Sophia , Huang, Wen‐Yi , Laskar, Ruhina Shirin , Mandic, Marko , Nowak, Johnathan A., Obón‐Santacana, Mireia , Steinfelder, Robert S. , Thibodeau, Stephen N. , Trinh, Quang M. , Tsilidis, Kostas K, Guelpen, Bethany Van , Wang, Xiaoliang , Woods, Michael O. , Zaidi, Syed Hassan Ejaz , Gunter, Marc J. , Peters, Ulrike , Song, Mingyang , Song, Mingyang , Hoffmeister, Michael , Harrison, Tabitha A , Brenner, Hermann , Cao, Yin , Chen, Xuechen , Drew, David A , Harlid, Sophia , Huang, Wen-Yi , Marchand, Loïc Le , Limburg, Paul, Sun, Wei , Ugai, Tomotaka , Van Guelpen, Bethany , Wang, Xiaoliang , Woods, Michael O , Gunter, Marc J , Murphy, Neil , Song, Mingyang , Aglago, Elom K , Obón-Santacana, Mireia , Papadimitriou, Nikos , Mandic, Marko , Trinh, Quang M , Georgeson, Peter , Newcomb, Polly A. , Buchanan, Daniel D. , Chan, Andrew T. , Cheng, Iona C. , Dimou, Niki , Drew, David A. , Farris, Alton B. , Giles, Graham G. , Hsu, Li , Jenkins, Mark A. , Marchand, Loı̈c Le , Limburg, Paul J. , Lin, Yi , Ogino, Shuji , Qu, Conghui , Sakoda, Lori C. , Schoen, Robert E. , Southey, Melissa C. , Stadler, Zsofia , Sun, Wei , Toland, Amanda Ewart , Tsilidis, Kostas K, Campbell, Peter T.
JNCI: Journal of the National Cancer Institute | November 26, 2022 | Volume: 115 | Issue: 2 | Pages: 165-173
Abstract Background Obesity is an established risk factor for colorectal cancer (CRC), but the evidence for the association is inconsistent across molecular subtypes of the disease. Methods We pooled data on body mass index (BMI), tumor microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, and Jass classification types for 11 872 CRC cases and 11 013 controls from 11 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for covariables. Results Higher BMI was associated with increased CRC risk (OR per 5 kg/m2 = 1.18, 95% CI = 1.15 to 1.22). The positive association was stronger for men than women but similar across tumor subtypes defined by individual molecular markers. In analyses by Jass type, higher BMI was associated with elevated CRC risk for types 1-4 cases but not for type 5 CRC cases (considered familial-like/Lynch syndrome microsatellite instability-H, CpG island methylator phenotype-low or negative, BRAF-wild type, KRAS-wild type, OR = 1.04, 95% CI = 0.90 to 1.20). This pattern of associations for BMI and Jass types was consistent by sex and design of contributing studies (cohort or case-control). Conclusions In contrast to previous reports with fewer study participants, we found limited evidence of heterogeneity for the association between BMI and CRC risk according to molecular subtype, suggesting that obesity influences nearly all major pathways involved in colorectal carcinogenesis. The null association observed for the Jass type 5 suggests that BMI is not a risk factor for the development of CRC for individuals with Lynch syndrome.