% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX 0.99 or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{CarrerasTorres:186491, author = {R. Carreras-Torres and A. E. Kim and Y. Lin and V. Díez-Obrero and S. A. Bien and C. Qu and J. Wang and N. Dimou and E. K. Aglago and D. Albanes and V. Arndt$^*$ and J. W. Baurley and S. I. Berndt and S. Bézieau and D. T. Bishop and E. Bouras and H. Brenner$^*$ and A. Budiarto and P. T. Campbell and G. Casey and A. T. Chan and J. Chang-Claude$^*$ and X. Chen$^*$ and D. V. Conti and C. H. Dampier and M. A. Devall and D. A. Drew and J. C. Figueiredo and S. Gallinger and G. G. Giles and S. B. Gruber and A. Gsur and M. J. Gunter and T. A. Harrison and A. Hidaka and M. Hoffmeister$^*$ and J. R. Huyghe and M. A. Jenkins and K. M. Jordahl and E. Kawaguchi and T. O. Keku and A. Kundaje and L. Le Marchand and J. P. Lewinger and L. Li and B. Mahesworo and J. L. Morrison and N. Murphy and H. Nan and R. Nassir and P. A. Newcomb and M. Obón-Santacana and S. Ogino and J. Ose and R. K. Pai and J. R. Palmer and N. Papadimitriou and B. Pardamean and A. R. Peoples and P. D. P. Pharoah and E. A. Platz and G. Rennert and E. Ruiz-Narvaez and L. C. Sakoda and P. C. Scacheri and S. L. Schmit and R. E. Schoen and A. Shcherbina and M. L. Slattery and M. C. Stern and Y.-R. Su and C. M. Tangen and D. C. Thomas and Y. Tian and K. K. Tsilidis and C. M. Ulrich and F. J. B. van Duijnhoven and B. Van Guelpen and K. Visvanathan and P. Vodicka and T. W. Cenggoro and S. J. Weinstein and E. White and A. Wolk and M. O. Woods and L. Hsu and U. Peters and V. Moreno and W. J. Gauderman}, title = {{G}enome-wide interaction study with smoking for colorectal cancer risk identifies novel genetic loci related to tumor suppression, inflammation and immune response.}, journal = {Cancer epidemiology, biomarkers $\&$ prevention}, volume = {32}, number = {3}, issn = {1055-9965}, address = {Philadelphia, Pa.}, publisher = {AACR}, reportid = {DKFZ-2022-03212}, pages = {315-328}, year = {2023}, note = {2023 Mar 6;32(3):315-328}, abstract = {Tobacco smoking is an established risk factor for colorectal cancer (CRC). However, genetically-defined population subgroups may have increased susceptibility to smoking-related effects on CRC.A genome-wide interaction scan was performed including 33,756 CRC cases and 44,346 controls from three genetic consortia.Evidence of an interaction was observed between smoking status (ever vs never smokers) and a locus on 3p12.1 (rs9880919, p=4.58x10-8), with higher associated risk in subjects carrying the GG genotype (OR 1.25, $95\%CI$ 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=1.72x10-8) and 8q24.23 (rs7005722, p=2.88x10-8). 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 CRC risk with higher expression levels of CADM2 (3p12.1) and ATF6B (6p21.33).Our study identified novel genetic loci that may modulate the risk for CRC of smoking status and intensity, linked to tumor suppression and immune response.These findings can guide potential prevention treatments.}, cin = {C071 / C070 / C020}, ddc = {610}, cid = {I:(DE-He78)C071-20160331 / I:(DE-He78)C070-20160331 / I:(DE-He78)C020-20160331}, pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)}, pid = {G:(DE-HGF)POF4-313}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid:36576985}, doi = {10.1158/1055-9965.EPI-22-0763}, url = {https://inrepo02.dkfz.de/record/186491}, }