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000154276 1001_ $$0P:(DE-He78)6e02c183f41e45a5867dec393fb4616a$$aAmitay, Efrat$$b0$$eFirst author
000154276 245__ $$aSmoking, alcohol consumption and colorectal cancer risk by molecular pathological subtypes and pathways.
000154276 260__ $$aEdinburgh$$bNature Publ. Group$$c2020
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000154276 520__ $$aSmoking and alcohol increase risk for colorectal malignancies. However, colorectal cancer (CRC) is a heterogenic disease and associations with the molecular pathological pathways are unclear.This population-based case-control study includes 2444 cases with first-diagnosis CRC and 2475 controls. Tumour tissue was analysed for MSI (microsatellite instability), CIMP (CpG island methylator phenotype), BRAF (B-Raf proto-oncogene serine/threonine kinase gene) and KRAS (Kirsten rat sarcoma viral oncogene homologue gene) mutations. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated for associations between alcohol and smoking and CRC molecular subtypes and pathways.Current smoking showed higher ORs for MSI-high (OR = 2.79, 95% CI: 1.86-4.18) compared to MSS (OR = 1.41, 1.14-1.75, p-heterogeneity (p-het) = 0.001), BRAF-mutated (mut) (OR = 2.40, 1.41-4.07) compared to BRAF-wild type (wt) (OR = 1.52, 1.24-1.88, p-het = 0.074), KRAS-wt (OR = 1.70, 1.36-2.13) compared to KRAS-mut (OR = 1.26, 0.95-1.68, p-het = 0.039) and CIMP-high (OR = 2.01, 1.40-2.88) compared to CIMP-low/negative CRC (OR = 1.50, 1.22-1.85, p-het=0.101). Current smoking seemed more strongly associated with sessile serrated pathway (CIMP-high + BRAF-mut; OR = 2.39, 1.27-4.52) than with traditional pathway CRC (MSS + CIMP-low/negative + BRAF-wt; OR = 1.50, 1.16-1.94) and no association was observed with alternate pathway CRC (MSS + CIMP-low/negative + KRAS-wt; OR = 1.08, 0.77-1.43). No heterogeneity was observed in alcohol consumption association by molecular subtypes.In this large case-control study, smoking was more strongly associated with MSI-high and KRAS-wt CRC and with cases showing features of the sessile serrated pathway. Association patterns were less clear for alcohol consumption.
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000154276 7001_ $$0P:(DE-He78)7d7ee36ed0313bbc4c91bc3df5950107$$aCarr, Prudence R$$b1
000154276 7001_ $$0P:(DE-He78)bbfe0ebad1e3b608bca2b49d4f86bd09$$aJansen, Lina$$b2
000154276 7001_ $$aRoth, Wilfried$$b3
000154276 7001_ $$0P:(DE-He78)9b2a61b2abe4a64ca23b6783b7c4fe63$$aAlwers, Elizabeth$$b4
000154276 7001_ $$aHerpel, Esther$$b5
000154276 7001_ $$0P:(DE-He78)028ee60cca729028708496826f077b58$$aKloor, Matthias$$b6
000154276 7001_ $$aBläker, Hendrik$$b7
000154276 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b8
000154276 7001_ $$0P:(DE-He78)90d5535ff896e70eed81f4a4f6f22ae2$$aBrenner, Hermann$$b9
000154276 7001_ $$0P:(DE-He78)6c5d058b7552d071a7fa4c5e943fff0f$$aHoffmeister, Michael$$b10$$eLast author
000154276 773__ $$0PERI:(DE-600)2002452-6$$a10.1038/s41416-020-0803-0$$n11$$p1604-1610$$tBritish journal of cancer$$v122$$x1532-1827$$y2020
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