Relationship between genetic polymorphism of CYP1A1 at codon 462 (Ile462Val) in colorectal cancer.
OBJECTIVE
The enzyme cytochrome P450 plays an important role in the metabolization and detoxification of various compounds. CYP1A1 is a polymorphic enzyme and some of its alleles have been correlated with an increased risk of developing various types of cancer. The aim of this study was to investigate the incidence of the polymorphism A-->G (Ile462Val, exon 7) in colorectal cancer patients and the correlation of this polymorphism with others risk factors.


METHODS
114 Brazilian patients with colorectal cancer were matched by age and sex to 114 healthy individuals. DNA was extracted from peripheral blood and the genotypes of the polymorphisms were assessed by PCR-restriction fragment length polymorphism.


RESULTS
In the case group 64 subjects were male, 53 were alcohol users and 68 were smokers. In the control group 61 were male, 67 were alcohol users and 53 smokers. There were 14 subjects with wild-type homozygous A/A, 97 with heterozygous A/G, and 3 with homozygous mutated G/G in the cancer group versus 81 subjects with wild-type homozygous A/A and 33 with heterozygous A/G in the control group. The presence of the G allele (OR 5.14, 95%CI 3.15-10.80) was associated with an increased risk of colorectal cancer (p=0.001). The prevalence of smokers was higher in the cancer group (p=0.047, OR 1.71, 95%CI 1.03-3.11).


CONCLUSIONS
These results suggest a positive association between the A-->G polymorphism and the risk of colorectal cancer. In addition, smoking was also a colorectal cancer risk. We did not find any correlation between this polymorphism and sex, grade of differentiation, stage, or evolution of the disease.
Pereira Serafim
P V
PV
Oncology Group/Gastroenterology Division, Universidade Federal de São Paulo/UNIFESP, São Paulo - Brazil.
Cotrim Guerreiro da Silva
I D
ID
Manoukias Forones
N
N
D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D019943:Amino Acid Substitution; D054458:Amplified Fragment Length Polymorphism Analysis; D001483:Base Sequence; D001938:Brazil; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000209:etiology / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D017931:DNA Primers; D004273:DNA, Neoplasm; D019363:Cytochrome P-450 CYP1A1