Increased frequency of p53 mutation in sporadic colorectal cancer from cigarette smokers.
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, beta-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 beta-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%).


CONCLUSIONS
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.
Hereditary Tumor Research Project, Tokyo Metropolitan Komagome Hospital, Japan. mmiyaki@opal.famille.ne.jp
Michiko
M
Miyaki
Takeru
T
Iijima
Reiko
R
Ishii
Yumi
Y
Kita
Morio
M
Koike
Toshio
T
Kuroki
Takeo
T
Mori
D002277:Carcinoma / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics*; D003598:Cytoskeletal Proteins / Q000235:genetics; D005787:Gene Frequency; D017491:Genes, APC; D016158:Genes, p53; D011905:Genes, ras; D006801:Humans; D008297:Male; D009154:Mutation; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin