CYP1A1 genetic polymorphisms and in situ colorectal cancer.
Numerous studies have associated colorectal adenoma with smoking and large bowel cancer with consumption of foods potentially containing polycyclic aromatic hydrocarbons. Enhanced metabolic activation of polycyclic aromatic hydrocarbons has recently been observed in homozygotes for a MspI mutation in the 3'-end of CYP1A1. We conducted a population-based case-control study to investigate whether CYP1A1 polymorphisms were related to colorectal cancer risk. Using polymerase chain reaction-based methods, we assessed the frequency of the MspI polymorphism in the 3'-end of CYP1A1 and another mutation in exon 7 of the gene (Ile-Val polymorphism) among 43 patients with in situ adenocarcinoma of the large bowel and 129 population controls. Homozygosity for the MspI mutant genotype was found to be positively associated with in situ colorectal cancer in Japanese (P = 0.008) and Hawaiians/part-Hawaiians (P < 0.001), whereas the study lacked power to detect a similar association in Caucasians. The odds ratio for the homozygous variant genotype compared to the heterozygous and wild-type genotypes was 7.9 (95% confidence interval, 1.4-44.4) in Japanese. A similar association was suggested for the exon 7 mutation homozygosity in Japanese, as the two polymorphisms are in genetic disequilibrium. Thus, this study suggests a potentially important role for CYP1A1 and polycyclic aromatic hydrocarbons in the etiology of colorectal cancer in populations with a high gene frequency.
Sivaraman
L
L
Molecular Carcinogenesis Program, Cancer Research Center of Hawaii, University of Hawaii, Honolulu 96813.
Leatham
M P
MP
Yee
J
J
Wilkens
L R
LR
Lau
A F
AF
Le Marchand
L
L
D000328:Adult; D000368:Aged; D001483:Base Sequence; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011083:Polycyclic Compounds / Q000378:metabolism; D012150:Polymorphism, Restriction Fragment Length
D011083:Polycyclic Compounds; D003577:Cytochrome P-450 Enzyme System