Gene polymorphisms and their association with diabetes and hypertension in African American and Latina breast cancer patients Free

A32

Epidemiological studies have shown that African American (AA) and Latina women with breast cancer have poor outcome. The poor outcome is significantly associated with comorbid conditions, especially diabetes and hypertension. In our study, we have postulated that African-American and Latina women with comorbid diseases will have a poor outcome, and this may be influenced by the IGF-1 axis. IGF-1, insulin-like growth factor 1, is a potent mitogen which regulates growth of breast epithelial and stromal cells. Conversely, IGFBP-3, insulin-like growth factor binding protein 3, inhibits IGF-1 action and contributes to cellular apoptosis. We have hypothesized that African American and Latina women with breast cancer, in addition to comorbid diseases may be predisposed to IGF-1 and/or IGFBP-3 promoter polymorphisms. We studied 286 subjects (106 AA and 180 Latina), which included 111 cases and 175 control. DNA was extracted from blood samples and IGF-1 and IGFBP-3 genotyping was performed by PCR-GenScan and PCR-RFLP methods respectively. Our results demonstrated that 47% of breast cancer patients have comorbidities (diabetes and/or hypertension) as compared to 26% of controls (p≤0.0001). This study also found a significant difference in the distribution of IGF-1 genotypes between the two ethnic groups with African-Americans having the greatest occurrence of the non-19/non-19 genotype at 19% vs. 3% of the Latina subjects (p≤0.0001). Also, there was a significant association (p=0.02) between the non-19/non-19 genotype in cases (15%) vs. controls (5%). The association of comorbidities with the IGF-1 non-19/non-19 genotype was also significant (p = 0.042). No significant association was found with the IGFBP-3 polymorphism and cancer or comorbidities. There was however, a significant difference (p≤0.0001) in the distribution of the IGFBP-3 genotype with Latina patients having the highest occurrence of the CC genotype (51%) vs. African-Americans (32%). In summary, our study demonstrated a significant association of IGF-1 polymorphism and breast cancer and with further link to comorbid diseases. The African American cohort had the greatest association between the IGF-1 genotype, hypertension, and breast cancer.