A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk.
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Date
2023-08-01
Open Access Location
Journal Title
Journal ISSN
Volume Title
Publisher
American Association for Cancer Research
Rights
(c) 2023 The Author/s
CC BY 4.0
CC BY 4.0
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.
Description
Keywords
Humans, Body Mass Index, Risk Factors, Obesity, Genetic Loci, Colorectal Neoplasms, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Genome-Wide Association Study, Intercellular Signaling Peptides and Proteins
Citation
Aglago EK, Kim A, Lin Y, Qu C, Evangelou M, Ren Y, Morrison J, Albanes D, Arndt V, Barry EL, Baurley JW, Berndt SI, Bien SA, Bishop DT, Bouras E, Brenner H, Buchanan DD, Budiarto A, Carreras-Torres R, Casey G, Cenggoro TW, Chan AT, Chang-Claude J, Chen X, Conti DV, Devall M, Diez-Obrero V, Dimou N, Drew D, Figueiredo JC, Gallinger S, Giles GG, Gruber SB, Gsur A, Gunter MJ, Hampel H, Harlid S, Hidaka A, Harrison TA, Hoffmeister M, Huyghe JR, Jenkins MA, Jordahl K, Joshi AD, Kawaguchi ES, Keku TO, Kundaje A, Larsson SC, Marchand LL, Lewinger JP, Li L, Lynch BM, Mahesworo B, Mandic M, Obón-Santacana M, Moreno V, Murphy N, Nan H, Nassir R, Newcomb PA, Ogino S, Ose J, Pai RK, Palmer JR, Papadimitriou N, Pardamean B, Peoples AR, Platz EA, Potter JD, Prentice RL, Rennert G, Ruiz-Narvaez E, Sakoda LC, Scacheri PC, Schmit SL, Schoen RE, Shcherbina A, Slattery ML, Stern MC, Su Y-R, Tangen CM, Thibodeau SN, Thomas DC, Tian Y, Ulrich CM, van Duijnhoven FJ, Van Guelpen B, Visvanathan K, Vodicka P, Wang J, White E, Wolk A, Woods MO, Wu AH, Zemlianskaia N, Hsu L, Gauderman WJ, Peters U, Tsilidis KK, Campbell PT. (2023). A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk.. Cancer Res. 83. 15. (pp. 2572-2583).