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

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Carreras-Torres, R. - Kim, A.E. - Lin, Y. - Diez-Obrero, V. - Bien, S.A. - Qu, C. - Wang, J. - Dimou, N. - Aglago, E.K. - Albanes, D. - Arndt, V. - Baurley, J.W. - Berndt, S. I. - Bezieau, S. - Bishop, D.T. - Bouras, E. - Brenner, H. - Budiarto, A. - Campbell, P.T. - Casey, B. - Chan, A.T. - Chang-Claude, J. - Chen, X. - Conti, D.V. - Dampier, Ch.H. - Vodička, Pavel … celkem 89 autorů
Genome-wide Interaction Study with Smoking for Colorectal Cancer Risk Identifies Novel Genetic Loci Related to Tumor Suppression, Inflammation, and Immune Response.
Cancer Epidemiology Biomarkers & Prevention. Roč. 32, č. 3 (2023), s. 315-328. ISSN 1055-9965. E-ISSN 1538-7755
Grant CEP: GA ČR(CZ) GA21-27902S; GA ČR(CZ) GA20-03997S; GA MZd(CZ) NV18-03-00199; GA MZd(CZ) NV19-09-00237
Institucionální podpora: RVO:68378041
Klíčová slova: environment interaction * association scan * complement * epithelium * driven
Obor OECD: Human genetics
Impakt faktor: 3.8, rok: 2022
Způsob publikování: Open access
https://aacrjournals.org/cebp/article-abstract/32/3/315/718496/Genome-wide-Interaction-Study-with-Smoking-for?redirectedFrom=fulltext

Background: Tobacco smoking is an established risk factor for colorectal cancer. However, genetically defined population sub-groups 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 smok-ing status (ever vs. never smokers) and a locus on 3p12.1 (rs9880919, P = 4.58 x 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 x 10-8) and 8q24.23 (rs7005722, P = 2.88 x 10-8). Subjects carrying the rs4151657 TT genotype showed higher risk (OR, 1.12, 95% CI, 1.09-1.16) com-pared 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.
Trvalý link: https://hdl.handle.net/11104/0350864