IGF-1 (CA)n repeat and -202A/C IGFBP-3 polymorphisms and the risk of breast cancer in African-American and Latina women Free

A27

Insulin-like growth factor-1 (IGF-1) is a powerful mitogen that is intimately involved in the proliferation of both normal and malignant breast epithelial cells. The actions of IGF-1 are regulated by a family of IGF binding proteins (IGFBPs). The IGFBP-3 is the most abundant in circulation and its binding to IGF-1 regulates both breast epithelial and stromal cell proliferation and apoptosis. We had previously demonstrated that high plasma levels of IGF-1 and low serum levels of IGFBP-3 are associated with an increased risk of breast cancer and with poor prognosis in African American women. IGF-1 and IGFBP-3 both have an important polymorphic site in their promoter region, (CA)n repeat and A/C, respectively, which may affect their expression pattern. The AA cohort is known to be a high risk group for poor survival from breast cancer. The biological or genetic factors that could contribute to the disparity are poorly understood in minority populations compared to Caucasians. In our current study, we hypothesized that CA repeat polymorphism in IGF-1 and the -202A/C polymorphism in IGFBP-3 may influence the risk of breast cancer development and perhaps in the prognosis of the disease. In our case-control study, we screened a cohort of 455 subjects for IGF-1 and IGFBP-3 polymorphisms. IGF-1 CA repeat polymorphism was analyzed by the PCR-GenScan method while -202A/C IGFBP-3 polymorphism was detected by the PCR-RFLP (Restriction fragment length polymorphism) method. The (CA)19 repeat allele of IGF-1 was the most common allele in both cases and controls. Non-19/non-19 repeat genotypes were more frequent in African-Americans as compared to the Latina group. In a multivariate analysis of IGF-1 genotypes, African Americans showed a 3-fold increased risk (OR=3.2 at 95%, CI=0.9-11.6, p=0.07) with non-19/non-19 genotype. In comparison, Latinas had more than 9-fold increased risk (OR=9.6 at 95%, CI=1.4-52.0, p=0.02). The IGFBP-3 polymorphism pattern showed a significant difference between the two ethnic groups (in both controls and cases). Latinas had a greater distribution of the CC genotype. However, there was no significant association with breast cancer risk. In summary, our study suggests an important association of the IGF-1 non19/non19 CA repeat with breast cancer. Further studies with larger number of study subjects will help us to validate the role of IGF-1 and IGFBP3 polymorphisms in minority populations.