Cigarette smoking, genetic polymorphisms and colorectal cancer risk: the Fukuoka Colorectal Cancer Study.
BACKGROUND
It is uncertain whether smoking is related to colorectal cancer risk. Cytochrome P-450 CYP1A1, glutathione-S-transferase (GST) and NAD(P)H:quinone oxidoreductase 1 (NQO1) are important enzymes in the metabolism of tobacco carcinogens, and functional genetic polymorphisms are known for these enzymes. We investigated the relation of cigarette smoking and related genetic polymorphisms to colorectal cancer risk, with special reference to the interaction between smoking and genetic polymorphism.


METHODS
We used data from the Fukuoka Colorectal Cancer Study, a population-based case-control study, including 685 cases and 778 controls who gave informed consent to genetic analysis. Interview was conducted to assess lifestyle factors, and DNA was extracted from buffy coat.


RESULTS
In comparison with lifelong nonsmokers, the odds ratios (OR) of colorectal cancer for <400, 400-799 and > or = 800 cigarette-years were 0.65 (95% confidence interval [CI], 0.45-0.89), 1.16 (0.83-1.62) and 1.14 (0.73-1.77), respectively. A decreased risk associated with light smoking was observed only for colon cancer, and rectal cancer showed an increased risk among those with > or = 400 cigarette-years (OR 1.60, 95% CI 1.04-2.45). None of the polymorphisms under study was singly associated with colorectal cancer risk. Of the gene-gene interactions studied, the composite genotype of CYP1A1*2A or CYP1A1*2C and GSTT1 polymorphisms was associated with a decreased risk of colorectal cancer, showing a nearly statistically significant (Pinteraction = 0.06) or significant interaction (Pinteraction = 0.02). The composite genotypes of these two polymorphisms, however, showed no measurable interaction with cigarette smoking in relation to colorectal cancer risk.


CONCLUSIONS
Cigarette smoking may be associated with increased risk of rectal cancer, but not of colon cancer. The observed interactions between CYP1A1 and GSTT1 polymorphisms warrant further confirmation.
Department of Preventive Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. hoirun@phealth.med.kyushu-u.ac.jp
Hoirun
H
Nisa
Suminori
S
Kono
Guang
G
Yin
Kengo
K
Toyomura
Jun
J
Nagano
Ryuichi
R
Mibu
Masao
M
Tanaka
Yoshihiro
Y
Kakeji
Yoshihiko
Y
Maehara
Takeshi
T
Okamura
Koji
K
Ikejiri
Kitaroh
K
Futami
Takafumi
T
Maekawa
Yohichi
Y
Yasunami
Kenji
K
Takenaka
Hitoshi
H
Ichimiya
Reiji
R
Terasaka
D000230:Adenocarcinoma / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D015810:Linkage Disequilibrium; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D055815:Young Adult
D019363:Cytochrome P-450 CYP1A1; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase