Japanese Journal of Clinical Oncology 32:196-201 (2002)
© 2002 Foundation for Promotion of Cancer Research
Increased Frequency of p53 Mutation in Sporadic Colorectal Cancer from Cigarette Smokers
1 Hereditary Tumor Research Project, 4 Department of Surgery and 3 Department of Pathology, Tokyo Metropolitan Komagome Hospital, Tokyo and 2 Institute of Molecular Oncology, Showa University, Tokyo, Japan
Background: Cigarette smoking has been shown to increase the risk of colorectal cancer. However, the relation between smoking and genetic alterations has not been clarified in this type of cancer.
Methods: Mutations of p53, APC, ß-catenin and K-ras-2 genes were analyzed in colorectal carcinomas from 28 smokers and 33 non-smokers. Frequencies and types of mutations were compared between smokers and non-smokers.
Results: The frequency of carcinomas with p53 mutation was higher in smokers (20/28, 71%) than in non-smokers (15/33, 45%) (P = 0.037). The common type of mutation was single-base substitution including G:C to A:T transition in both groups (68% in smokers and 67% in non-smokers). With respect to G:C to A:T transitions, mutation at CpG sites was less frequent in smokers (9/15, 60%) than in non-smokers (10/10, 100%), whereas mutation at non-CpG sites was more frequent in smokers (6/16, 40%) than in non-smokers (0/10, 0%) (P = 0.028). The frequency of APC mutation was not significantly different between smokers (14/28, 50%) and non-smokers (15/33, 45%). No ß-catenin mutation was detected in carcinomas from smokers. K-ras-2 mutation occurred in smokers at a similar frequency (9/28, 32%) to that in non-smokers (13/33, 39%). Concerning pathological aspects, Dukes’ A carcinomas were less frequent in smokers (11%) than in non-smokers (33%), whereas Dukes’ D carcinomas were more frequent in smokers (25%) than in non-smokers (15%).
Conclusion: The present results suggest that an increased frequency of p53 gene mutation, including G:C to A:T transitions at non-CpG sites, is associated with an increased risk of colorectal carcinogenesis in cigarette smokers.
+ For reprints and all correspondence: Michiko Miyaki, Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, 3–18–22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan. E-mail: mmiyaki@opal.famille.ne.jp
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