Polymorphisms in CYP1A1 and breast carcinoma risk in a population-based case-control study of Chinese women.
BACKGROUND
Cytochrome P450 1A1 (CYP1A1) is involved in the 2-hydroxylation of estrogen, the hormone that plays a critical role in the etiology of breast carcinoma.


METHODS
The authors evaluated common polymorphisms in the CYP1A1 gene in relation to breast carcinoma risk in a large population-based case-control study among Chinese women, the Shanghai Breast Cancer Study. Because the CYP1A1*3 and CYP1A1*4 alleles were not detected in the study population, analyses were performed for CYP1A1*2A (T-->C transition in the 3' noncoding region) and CYP1A1*2C (A-->G transition in exon 7, resulting in a substitution of Val for Ile) in 1134 patients with breast carcinoma and 1227 controls.


RESULTS
The frequencies of the variant allele were 38.3% and 38.8% among cases and controls (P = 0.91), respectively, for the CYP1A1*2A polymorphism, and 23.1% and 24.8% (P = 0.26) for the CYP1A1*2C polymorphism. Homozygosity for both variant alleles in these 2 polymorphic sites (CYP1A1*2B) was associated with a borderline significant odds ratio (OR) of 0.71 (95% confidence interval [CI], 0.47-1.06). The reduced risk was more pronounced among postmenopausal women with long duration (> 30 yrs) of menstruation (OR = 0.43; 95% CI, 0.19-0.99) or among women with a low waist-to-hip ratio (OR = 0.52; 95% CI, 0.28-0.94).


CONCLUSIONS
Results from the current study suggest that homozygosity for the CYP1A1*2A and CYP1A1*2C alleles in the CYP1A1 gene may be associated with a reduced risk for breast carcinoma, particularly among lean women with long-term endogenous estrogen exposure.
Boyapati
Sonia M
SM
Department of Medicine, Center for Health Services Research, Vanderbilt Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
Shu
Xiao Ou
XO
Gao
Yu-Tang
YT
Cai
Qiuyin
Q
Jin
Fan
F
Zheng
Wei
W
D001943:Breast Neoplasms / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D004967:Estrogens / Q000008:administration & dosage; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D012307:Risk Factors; D049629:Waist-Hip Ratio
D004967:Estrogens; D019363:Cytochrome P-450 CYP1A1