Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response

dc.contributor.authorCarreras-Torres, Robert
dc.contributor.authorKim, Andre E.
dc.contributor.authorLin, Yi
dc.contributor.authorDíez-Obrero, Virginia
dc.contributor.authorBien, Stephanie A.
dc.contributor.authorQu, Conghui
dc.contributor.authorWang, Jun
dc.contributor.authorDimou, Niki
dc.contributor.authorAglago, Elom K.
dc.contributor.authorAlbanes, Demetrius
dc.contributor.authorArndt, Volker
dc.contributor.authorBaurley, James W.
dc.contributor.authorBerndt, Sonja I.
dc.contributor.authorBézieau, Stéphane
dc.contributor.authorBishop, D. Timothy
dc.contributor.authorBouras, Emmanouil
dc.contributor.authorBrenner, Hermann
dc.contributor.authorBudiarto, Arif
dc.contributor.authorCampbell, Peter T.
dc.contributor.authorCasey, Graham
dc.contributor.authorChan, Andrew T.
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorChen, Xuechen
dc.contributor.authorConti, David V.
dc.contributor.authorDampier, Christopher H.
dc.contributor.authorDevall, Matthew A. M.
dc.contributor.authorDrew, David A.
dc.contributor.authorFigueiredo, Jane C.
dc.contributor.authorGallinger, Steven
dc.contributor.authorGiles, Graham G.
dc.contributor.authorGruber, Stephen B.
dc.contributor.authorGsur, Andrea
dc.contributor.authorGunter, Marc J.
dc.contributor.authorHarrison, Tabitha A.
dc.contributor.authorHidaka, Akihisa
dc.contributor.authorHoffmeister, Michael
dc.contributor.authorHuyghe, Jeroen R.
dc.contributor.authorJenkins, Mark A.
dc.contributor.authorJordahl, Kristina M.
dc.contributor.authorKawaguchi, Eric
dc.contributor.authorKeku, Temitope O.
dc.contributor.authorKundaje, Anshul
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorLewinger, Juan Pablo
dc.contributor.authorLi, Li
dc.contributor.authorMahesworo, Bharuno
dc.contributor.authorMorrison, John L.
dc.contributor.authorMurphy, Neil
dc.contributor.authorNan, Hongmei
dc.contributor.authorNassir, Rami
dc.contributor.authorNewcomb, Polly A.
dc.contributor.authorObón-Santacana, Mireia
dc.contributor.authorOgino, Shuji
dc.contributor.authorOse, Jennifer
dc.contributor.authorPai, Rish K.
dc.contributor.authorPalmer, Julie R.
dc.contributor.authorPapadimitriou, Nikos
dc.contributor.authorPardamean, Bens
dc.contributor.authorPeoples, Anita R.
dc.contributor.authorPharoah, Paul D. P.
dc.contributor.authorPlatz, Elizabeth A.
dc.contributor.authorRennert, Gad
dc.contributor.authorRuiz-Narvaez, Edward
dc.contributor.authorSakoda, Lori C.
dc.contributor.authorScacheri, Peter C.
dc.contributor.authorSchmit, Stephanie L.
dc.contributor.authorSchoen, Robert E.
dc.contributor.authorShcherbina, Anna
dc.contributor.authorSlattery, Martha L.
dc.contributor.authorStern, Mariana C.
dc.contributor.authorSu, Yu-Ru
dc.contributor.authorTangen, Catherine M.
dc.contributor.authorThomas, Duncan C.
dc.contributor.authorTian, Yu
dc.contributor.authorTsilidis, Konstantinos K.
dc.contributor.authorUlrich, Cornelia M.
dc.contributor.authorvan Duijnhoven, Fränzel J. B.
dc.contributor.authorVan Guelpen, Bethany
dc.contributor.authorVisvanathan, Kala
dc.contributor.authorVodicka, Pavel
dc.contributor.authorWawan Cenggoro, Tjeng
dc.contributor.authorWeinstein, Stephanie J.
dc.contributor.authorWhite, Emily
dc.contributor.authorWolk, Alicja
dc.contributor.authorWoods, Michael O.
dc.contributor.authorHsu, Li
dc.contributor.authorPeters, Ulrike
dc.contributor.authorMoreno, Victor
dc.contributor.authorGauderman, W. James
dc.contributor.departmentEpidemiology, Richard M. Fairbanks School of Public Health
dc.date.accessioned2024-09-30T13:42:19Z
dc.date.available2024-09-30T13:42:19Z
dc.date.issued2023
dc.description.abstractBackground: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population subgroups may have increased susceptibility to smoking-related effects on colorectal cancer. Methods: A genome-wide interaction scan was performed including 33,756 colorectal cancer cases and 44,346 controls from three genetic consortia. Results: Evidence of an interaction was observed between smoking status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 × 10-8), with higher associated risk in subjects carrying the GG genotype [OR, 1.25; 95% confidence interval (CI), 1.20-1.30] compared with the other genotypes (OR <1.17 for GA and AA). Among ever smokers, we observed interactions between smoking intensity (increase in 10 cigarettes smoked per day) and two loci on 6p21.33 (rs4151657, P = 1.72 × 10-8) and 8q24.23 (rs7005722, P = 2.88 × 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12; 95% CI, 1.09-1.16) compared with the other genotypes (OR <1.06 for TC and CC). Similarly, higher risk was observed among subjects carrying the rs7005722 AA genotype (OR, 1.17; 95% CI, 1.07-1.28) compared with the other genotypes (OR <1.13 for AC and CC). Functional annotation revealed that SNPs in 3p12.1 and 6p21.33 loci were located in regulatory regions, and were associated with expression levels of nearby genes. Genetic models predicting gene expression revealed that smoking parameters were associated with lower colorectal cancer risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33). Conclusions: Our study identified novel genetic loci that may modulate the risk for colorectal cancer of smoking status and intensity, linked to tumor suppression and immune response. Impact: These findings can guide potential prevention treatments.
dc.eprint.versionAuthor's manuscript
dc.identifier.citationCarreras-Torres R, Kim AE, Lin Y, et al. Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response. Cancer Epidemiol Biomarkers Prev. 2023;32(3):315-328. doi:10.1158/1055-9965.EPI-22-0763
dc.identifier.urihttps://hdl.handle.net/1805/43663
dc.language.isoen_US
dc.publisherAmerican Association for Cancer Research
dc.relation.isversionof10.1158/1055-9965.EPI-22-0763
dc.relation.journalCancer Epidemiology Biomarkers and Prevention
dc.rightsPublisher Policy
dc.sourcePMC
dc.subjectColorectal neoplasms
dc.subjectGenetic predisposition to disease
dc.subjectInflammation
dc.subjectSmoking
dc.titleGenome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response
dc.typeArticle
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