Cigarette smoking and genetic alterations in sporadic colon carcinomas.
Cigarette smoking has been inconsistently associated with colon cancer risk. To evaluate the hypothesis that smoking is primarily linked to a specific colon tumor subgroup(s), we assessed associations between smoking and the occurrence of mutations in the APC, K-ras and p53 genes, p53 overexpression, and microsatellite instability (MSI) in a Dutch population-based case-control study on sporadic colon carcinomas. The study population consisted of 176 cases and 249 controls. Smoking status (never, ever), number of cigarettes smoked per day (never, <15, > or =15), total years of smoking (never, < or =30, >30), and years since first started smoking (never, < or =35, >35) were all evaluated. Cigarette smoking status was significantly differently related to p53 overexpression-positive (p53(pos)) tumors compared with p53 overexpression-negative (p53(neg)) tumors (p53(pos) versus p53(neg), OR 0.4, 95% CI 0.2-0.9), as well as to tumors with transversion mutations in APC, K-ras or p53 (transv(+)) compared with tumors without transversion mutations in one of these genes (transv(-)) (transv(+) versus transv(-), OR 2.5, 95% CI 1.0-5.9). Positive associations were observed with p53(neg) tumors and transv(+) tumors when compared with the population-based controls (ever versus transv(-), OR 1.5, 95% CI 0.9-2.8 and OR 2.2, 95% CI 0.9-5.6, respectively), inverse associations with p53(pos) tumors and transv(-) tumors (ever versus never, OR 0.5, 95% CI 0.3-1.0 and OR 0.8, 95% CI 0.5-1.3, respectively). Similar patterns of association were observed for the other smoking variables evaluated. In addition, although statistically non-significant, smoking was more notably positively associated with tumors that exhibit K-ras mutations, especially K-ras transversion mutations, than with tumors without K-ras mutations. An inverse relationship between smoking and the occurrence of APC mutations was suggested, whereas no clear associations were observed with MSI. Our data suggest that smoking-related colon cancers develop through a p53(neg) pathway and that smoking particularly results in colon carcinomas with transversion mutations.
Diergaarde
Brenda
B
Division of Human Nutrition and Epidemiology, Wageningen University, PO Box 8129, 6700 EV Wageningen, The Netherlands.
Vrieling
Alina
A
van Kraats
Annemieke A
AA
van Muijen
Goos N P
GN
Kok
Frans J
FJ
Kampman
Ellen
E
D001483:Base Sequence; D016022:Case-Control Studies; D003043:Cocarcinogenesis; D003110:Colonic Neoplasms / Q000209:etiology* / Q000235:genetics*; D017931:DNA Primers; D005260:Female; D017491:Genes, APC; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation; D016133:Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*
D017931:DNA Primers