High penetrance genes such as BRCA1 or BRCA2 account for only a small proportion of
familial breast cancer in Chinese population.
Estrogen has been proposed to participate in the proliferation and
carcinogenesis of
breast cancer. To investigate the association between genetic polymorphisms in genes encoding
estrogen metabolizing,
estrogen biosynthesizing
enzyme and
estrogen receptor and the
breast cancer risk in BRCA1/BRCA2 negative Shanghai women, we conducted a case-control study including 114 cases with early-onset
breast cancer or affected relatives and 121 healthy controls. The genotypes of
estrogen receptor alpha (
ERalpha),
aromatase (
CYP19), and
catechol-O-methyltransferase (COMT) genes were analyzed by direct
DNA-sequencing. Compared with H/H genotype of COMT Val158Met, COMT Val158Met L/L genotype was associated with a nonsignificantly elevated risk of
breast cancer (OR: 3.72; 95% CI: 0.99-13.96, P=0.051). There was no statistically significant difference in genotype frequency of the
ERalpha PvuII,
ERalpha XbaI and
CYP19 Arg264Cys polymorphism between controls and cases. When stratified by menopausal status, COMT Val158Met L/L (OR: 11.94; 95% CI: 1.48-96.03, P=0.02) and
ERalpha PvuII P/p genotypes (OR: 2.67; 95% CI: 1.01-7.05, P=0.048) were associated with a significantly elevated risk of
breast cancer in premenopausal women, and there was a association between
ERalpha XbaI x/x genotype and the nonsignificantly increased risk of
breast cancer in premenopausal women (OR: 6.88; 95% CI: 0.80-59.15, P=0.079). The multigenic analysis showed maybe these high risk genotypes had combined effect on
breast cancer risk. Our findings suggest that polymorphism of genes involving
estrogen-metabolizing pathway,
estrogen- biosynthesizing pathway and
estrogen receptor pathway may play an important role in the etiology of BRCA1/2 negative
breast cancer with hereditary predisposing factors.