Insulin-like growth factor-I gene polymorphism and breast cancer risk in Chinese women

The evidence that high circulating levels of insulin-like growth factor-I (IGF-I) are associated with an increased risk of breast cancer among premenopausal women lends credence to the hypothesis that genetic polymorphisms in the IGF-I gene may be involved in the disease. A population-based case-control study was conducted to assess the association of IGF-I gene polymorphisms [(CA)n repeats in the promoter region] with breast cancer risk and plasma IGF-I level in Chinese women. The study included 1,041 incident breast cancer cases diagnosed from August 1996 through March 1998 in Shanghai and 1,086 randomly selected, age frequency-matched controls from the general population. Although no relation between plasma IGF-I levels and IGF-I genotypes was found, women who carried the genotypes containing the (CA)17 or (CA)19 allele were associated with a significantly decreased (OR = 0.80, 95% CI: 0.64-1.00) or increased (OR = 1.23, 95% CI: 1.04-1.47) risk of breast cancer, respectively, and women who carried the genotypes containing any of the 4 rare alleles, (CA)11, (CA)13, (CA)16 and (CA)23, were associated with a nonsignificantly increased risk of breast cancer (OR = 1.92, 95% CI: 0.92-4.02) compared to those who did not carry the specific alleles. The associations with the (CA)17 or (CA)19 allele were predominantly present among premenopausal women and in a dose-response manner. The meta-analysis results indicated that IGF-I genotypes containing the (CA)19 were consistently associated with increased risk of breast cancer across studies (overall OR = 1.22, 95% CI: 1.06-1.41, p for heterogeneity test = 0.524). The findings of this study support the hypothesis that IGF-I gene polymorphisms may be a significant genetic factor for breast cancer susceptibility.