A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk

Elom K. Aglago, Andre Kim, Yi Lin, Conghui Qu, Marina Evangelou, Yu Ren, John Morrison, Demetrius Albanes, Volker Arndt, Elizabeth L. Barry, James W. Baurley, Sonja I. Berndt, Stephanie A. Bien, D. Timothy Bishop, Emmanouil Bouras, Hermann Brenner, Daniel D. Buchanan, Arif Budiarto, Robert Carreras-Torres, Graham CaseyTjeng Wawan Cenggoro, Andrew T. Chan, Jenny Chang-Claude, Xuechen Chen, David V. Conti, Matthew Devall, Virginia Diez-Obrero, Niki Dimou, David Drew, Jane C. Figueiredo, Steven Gallinger, Graham G. Giles, Stephen B. Gruber, Andrea Gsur, Marc J. Gunter, Heather Hampel, Sophia Harlid, Akihisa Hidaka, Tabitha A. Harrison, Michael Hoffmeister, Jeroen R. Huyghe, Mark A. Jenkins, Kristina Jordahl, Amit D. Joshi, Eric S. Kawaguchi, Temitope O. Keku, Anshul Kundaje, Susanna C. Larsson, Loic Le Marchand, Juan Pablo Lewinger, Li Li, Brigid M. Lynch, Bharuno Mahesworo, Marko Mandic, Mireia Obón-Santacana, Victor Moreno, Neil Murphy, Hongmei Nan, Rami Nassir, Polly A. Newcomb, Shuji Ogino, Jennifer Ose, Rish K. Pai, Julie R. Palmer, Nikos Papadimitriou, Bens Pardamean, Anita R. Peoples, Elizabeth A. Platz, John D. Potter, Ross L. Prentice, Gad Rennert, Edward Ruiz-Narvaez, Lori C. Sakoda, Peter C. Scacheri, Stephanie L. Schmit, Robert E. Schoen, Anna Shcherbina, Martha L. Slattery, Mariana C. Stern, Yu Ru Su, Catherine M. Tangen, Stephen N. Thibodeau, Duncan C. Thomas, Yu Tian, Cornelia M. Ulrich, Franzel J.B. van Duijnhoven, Bethany Van Guelpen, Kala Visvanathan, Pavel Vodicka, Jun Wang, Emily White, Alicja Wolk, Michael O. Woods, Anna H. Wu, Natalia Zemlianskaia, Li Hsu, W. James Gauderman, Ulrike Peters, Konstantinos K. Tsilidis, Peter T. Campbell, L. Hsu, W. J. Gauderman, U. Peters, K. K. Tsilidis, P. T. Campbell

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Abstract

Colorectal cancer risk can be impacted by genetic, environ-SNP was also identified by the 3DF test, with a suggestive statimental, and lifestyle factors, including diet and obesity. Genestical significance in the 1DF test. Among participants with the environment interactions (G × E) can provide biological insights CC genotype of rs58349661, overweight and obesity categories into the effects of obesity on colorectal cancer risk. Here, we were associated with higher colorectal cancer risk, whereas null assessed potential genome-wide G × E interactions between body associations were observed across BMI categories in those with mass index (BMI) and common SNPs for colorectal cancer risk the TT genotype. Using data from three large international using data from 36,415 colorectal cancer cases and 48,451 con-consortia, this study discovered a locus in the FMN1/GREM1 trols from three international colorectal cancer consortia (CCFR, gene region that interacts with BMI on the association with CORECT, and GECCO). The G × E tests included the convencolorectal cancer risk. Further studies should examine the potentional logistic regression using multiplicative terms (one degree tial mechanisms through which this locus modifies the etiologic of freedom, 1DF test), the two-step EDGE method, and the joint link between obesity and colorectal cancer. 3DF test, each of which is powerful for detecting G × E interactions under specific conditions. BMI was associated with higher Significance: This gene-environment interaction analysis colorectal cancer risk. The two-step approach revealed a statisrevealed a genetic locus in FMN1/GREM1 that interacts with body tically significant G×BMI interaction located within the Formin mass index in colorectal cancer risk, suggesting potential implica-1/Gremlin 1 (FMN1/GREM1) gene region (rs58349661). This tions for precision prevention strategies.

Original languageEnglish
Pages (from-to)2572-2583
Number of pages12
JournalCancer Research
Volume83
Issue number15
DOIs
StatePublished - 1 Aug 2023
Externally publishedYes

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