A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
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A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk. / Aglago, Elom K.; Kim, Andre; Lin, Yi; Qu, Conghui; Evangelou, Marina; Ren, Yu; Morrison, John; Albanes, Demetrius; Arndt, Volker; Barry, Elizabeth L.; Baurley, James W.; Berndt, Sonja I.; 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; Diez-Obrero, Virginia; Dimou, Niki; Drew, David; 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; Joshi, Amit D.; Kawaguchi, Eric S.; Keku, Temitope O.; Kundaje, Anshul; Larsson, Susanna C.; Marchand, Loic 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, Rish 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 C.; Su, Yu Ru; Tangen, Catherine M.; Thibodeau, Stephen N.; Thomas, Duncan C.; Tian, Yu; Ulrich, Cornelia M.; van Duijnhoven, Franzel Jb; 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.
In: Cancer Research, Vol. 83, No. 15, 2023, p. 2572-2583.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - A Genetic Locus within the FMN1/GREM1 Gene Region Interacts with Body Mass Index in Colorectal Cancer Risk
AU - Aglago, Elom K.
AU - Kim, Andre
AU - Lin, Yi
AU - Qu, Conghui
AU - Evangelou, Marina
AU - Ren, Yu
AU - Morrison, John
AU - Albanes, Demetrius
AU - Arndt, Volker
AU - Barry, Elizabeth L.
AU - Baurley, James W.
AU - Berndt, Sonja I.
AU - Bien, Stephanie A.
AU - Bishop, D. Timothy
AU - Bouras, Emmanouil
AU - Brenner, Hermann
AU - Buchanan, Daniel D.
AU - Budiarto, Arif
AU - Carreras-Torres, Robert
AU - Casey, Graham
AU - Cenggoro, Tjeng Wawan
AU - Chan, Andrew T.
AU - Chang-Claude, Jenny
AU - Chen, Xuechen
AU - Conti, David V.
AU - Devall, Matthew
AU - Diez-Obrero, Virginia
AU - Dimou, Niki
AU - Drew, David
AU - Figueiredo, Jane C.
AU - Gallinger, Steven
AU - Giles, Graham G.
AU - Gruber, Stephen B.
AU - Gsur, Andrea
AU - Gunter, Marc J.
AU - Hampel, Heather
AU - Harlid, Sophia
AU - Hidaka, Akihisa
AU - Harrison, Tabitha A.
AU - Hoffmeister, Michael
AU - Huyghe, Jeroen R.
AU - Jenkins, Mark A.
AU - Jordahl, Kristina
AU - Joshi, Amit D.
AU - Kawaguchi, Eric S.
AU - Keku, Temitope O.
AU - Kundaje, Anshul
AU - Larsson, Susanna C.
AU - Marchand, Loic Le
AU - Lewinger, Juan Pablo
AU - Li, Li
AU - Lynch, Brigid M.
AU - Mahesworo, Bharuno
AU - Mandic, Marko
AU - Obón-Santacana, Mireia
AU - Moreno, Victor
AU - Murphy, Neil
AU - Nan, Hongmei
AU - Nassir, Rami
AU - Newcomb, Polly A.
AU - Ogino, Shuji
AU - Ose, Jennifer
AU - Pai, Rish K.
AU - Palmer, Julie R.
AU - Papadimitriou, Nikos
AU - Pardamean, Bens
AU - Peoples, Anita R.
AU - Platz, Elizabeth A.
AU - Potter, John D.
AU - Prentice, Ross L.
AU - Rennert, Gad
AU - Ruiz-Narvaez, Edward
AU - Sakoda, Lori C.
AU - Scacheri, Peter C.
AU - Schmit, Stephanie L.
AU - Schoen, Robert E.
AU - Shcherbina, Anna
AU - Slattery, Martha L.
AU - Stern, Mariana C.
AU - Su, Yu Ru
AU - Tangen, Catherine M.
AU - Thibodeau, Stephen N.
AU - Thomas, Duncan C.
AU - Tian, Yu
AU - Ulrich, Cornelia M.
AU - van Duijnhoven, Franzel Jb
AU - Van Guelpen, Bethany
AU - Visvanathan, Kala
AU - Vodicka, Pavel
AU - Wang, Jun
AU - White, Emily
AU - Wolk, Alicja
AU - Woods, Michael O.
AU - Wu, Anna H.
AU - Zemlianskaia, Natalia
AU - Hsu, Li
AU - Gauderman, W. James
AU - Peters, Ulrike
AU - Tsilidis, Konstantinos K.
AU - Campbell, Peter T.
N1 - Publisher Copyright: ©2023 The Authors; Published by the American Association for Cancer Research.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.1158/0008-5472.CAN-22-3713
DO - 10.1158/0008-5472.CAN-22-3713
M3 - Journal article
C2 - 37249599
AN - SCOPUS:85166391630
VL - 83
SP - 2572
EP - 2583
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 15
ER -
ID: 362319958