The association between a functional CYP1A1 polymorphism and colorectal neoplasia risk in post menopausal women.
BACKGROUND
The impact of estrogen on risk of colorectal neoplasia is uncertain. Carriers of the AA and CA genotype allele of the C4887A polymorphism of the CYP1A1 gene have enhanced estrogen metabolism relative to carriers of the CC genotype.


OBJECTIVE
This study examined whether this genetic marker of enhanced estrogen catabolism segregated with colorectal neoplasia (CRN) in postmenopausal women.


METHODS
We enrolled hormone negative postmenopausal women having screening or surveillance colonoscopy. Demographic and medical data were gathered. Blood was collected and analyzed for CYP1A1 polymorphisms of the C4887A allele by PCR-RFLP. Colonoscopy and pathology data were gathered from hospital databases.


RESULTS
One hundred sixty-eight women were enrolled in the study. Twenty-one subjects (12.5%) carried at least one A allele, and 147 subjects (87.5%) carried the CC alleles for the C4887A polymorphism of the CYP1A1 gene. Seventy subjects (41.7%) had CRN and 98 subjects (58.3%) did not have CRN. Of the subjects who carried the A allele, 57% had CRN as compared to 39% of those who carried the CC allele; the association was not statistically significant (P = 0.16). In a multivariate logistic regression analysis, age, BMI, current tobacco use, and first degree relative with CRN were independent risk factors for CRN but the C4887A polymorphisms remained not statistically significant (P = 0.35).


CONCLUSIONS
Carriers of the A allele of the C4887A polymorphism have enhanced estrogen catabolism and lower free estradiol. Our results suggest, however, that inherent estrogen metabolism as determined by C4887A polymorphisms is not associated with CRN risk.
Early
Dayna S
DS
Division of Gastroenterology, Washington University in St. Louis,St. Louis, MO, USA. dearly@im.wustl.edu
Gao
Feng
F
Ha
Christina Y
CY
Nagler
Anne
A
Cole
Elizabeth
E
Gorbe
Elizabeth
E
Napoli
Nicola
N
Armamento-Villareal
Reina
R
D000368:Aged; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D005663:Furans; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D017698:Postmenopause; D012307:Risk Factors; D013876:Thiophenes
C516387:3,4-bis-(2,4,5-trimethyl-thiophen-3-yl)furan-2,5-dione; D004967:Estrogens; D005663:Furans; D013876:Thiophenes; D019363:Cytochrome P-450 CYP1A1