Impact of the IGFBP3 A-202C polymorphism on susceptibility and clinicopathologic features of breast cancer

Abstract

Background: Insulin-like growth factor binding protein 3 (IGFBP3) plays an important role in cellular proliferation, differentiation, apoptosis, and mammary carcinogenesis. Genetic variations in IGFBP3 have been identified to influence the circulating IGFBP3 level. The present study determined the impact of an important promoter polymorphism (A-202C, rs2854744) on susceptibility and progression of breast cancer in a Chinese population.

Methods: We genotyped the IGFBP3 A-202C polymorphism in a case-control study involving 465 breast cancer patients and 799 age-matched, cancer-free controls using the TaqMan method. Logistic regression was used to assess the genetic association between the occurrence and progression of breast cancer.

Results: Compared with the wild genotype (-202AA), we found a statistically significant increased risk of breast cancer associated with the variant genotypes (CC vs. AA: OR=2.00, 95% CI=1.25-3.21; AC+CC vs. AA: OR=1.34, 95% CI=1.06-1.70). In the stratified analysis, the increased risk was more apparent among the subgroups of older subjects (OR=1.70, 95% CI=1.20-2.42). Furthermore, we found that patients carrying variant genotypes (AC+CC) had a significantly greater prevalence of large tumor size (OR=1.72, 95% CI=1.13-2.64; P=0.021).

Conclusion: Our results suggest that the functional IGFBP3 A-202C polymorphism may influence the susceptibility and progression of breast cancer in the Chinese population.

Keywords: Breast cancer; IGFBP3; Polymorphism; Progression; Susceptibility.