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@ARTICLE{Amitay:154276,
author = {E. Amitay$^*$ and P. R. Carr$^*$ and L. Jansen$^*$ and W.
Roth and E. Alwers$^*$ and E. Herpel and M. Kloor and H.
Bläker and J. Chang-Claude$^*$ and H. Brenner$^*$ and M.
Hoffmeister$^*$},
title = {{S}moking, alcohol consumption and colorectal cancer risk
by molecular pathological subtypes and pathways.},
journal = {British journal of cancer},
volume = {122},
number = {11},
issn = {1532-1827},
address = {Edinburgh},
publisher = {Nature Publ. Group},
reportid = {DKFZ-2020-00703},
pages = {1604-1610},
year = {2020},
note = {2020 May;122(11):1604-1610#EA:C070#LA:C070#},
abstract = {Smoking 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.},
cin = {C070 / C120 / HD01 / C020},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32225169},
doi = {10.1038/s41416-020-0803-0},
url = {https://inrepo02.dkfz.de/record/154276},
}