title: IGF gene polymorphisms and breast cancer in African-American and Hispanic women.
abstract: Previous studies from our group and others have shown that increased circulatory levels of the ligand insulin-like growth factor 1 (IGF-1) and decreased levels of the predominant IGF-1 binding protein 3 (IGFBP-3) are associated with an increased incidence of breast cancer and poor outcome. Some studies suggest that, in addition to the influence of environmental factors on the levels of IGF-1 and IGFBP-3, alterations in their gene polymorphisms may play a significant role in the risk of cancer. In this study, we investigated the association between gene polymorphisms along the IGF axis and breast cancer, including the IGF-1 (CA) dinucleotide repeat, IGFBP-3 A-202C single nucleotide polymorphism, and the 2-bp deletion and (AGG)n repeat polymorphisms in the IGF type 1 receptor (IGF-IR). A total of 654 subjects, including both African-American and Hispanic/Latino subjects, were screened for various gene polymorphisms. IGF gene polymorphism genotyping was performed by PCR-GeneScan and PCR-RFLP methods. Our results demonstrated a significant association between the non-19/non-19 IGF-1 (CA)n polymorphism and breast cancer (OR = 1.75; 95% CI = 1.07-2.88; P = 0.027). Furthermore, absence of the wild-type-19 allele and alleles <(CA)19 were strongly associated with breast cancer (OR = 1.82; 95% CI = 1.20-2.77; P = 0.005 and OR = 1.70; 95% CI = 1.19-2.43; P = 0.003, respectively). The association of the non-19/non-19 polymorphism with breast cancer was also more significant in premenopausal women (P = 0.04). We did not find any significant association of the IGFBP-3 polymorphism with breast cancer. In the case of IGF-1R polymorphisms, the only significant trend was in the (AGG)5 allele; however, the frequency of this allele was very rare. In summary, our study demonstrated a significant association of IGF-1 polymorphisms and breast cancer. Future studies are necessary to understand the mechanistic value of these polymorphisms in breast cancer risk.
authors: Division of Cancer Research and Training, Center to Eliminate Cancer Health Disparities, Department of Internal Medicine, Charles Drew University of Medicine and Science, Los Angeles, CA 90059, USA.
authors: Marianna
authors: M
authors: Sarkissyan
authors: Dhruva Kumar
authors: DK
authors: Mishra
authors: Yanyuan
authors: Y
authors: Wu
authors: Xiying
authors: X
authors: Shang
authors: Suren
authors: S
authors: Sarkissyan
authors: Jaydutt V
authors: JV
authors: Vadgama
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics*; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D017526:Receptor, IGF Type 1 / Q000235:genetics; D014481:United States / Q000208:ethnology
chemical_list: D018972:Insulin-Like Growth Factor Binding Protein 3; D007334:Insulin-Like Growth Factor I; D017526:Receptor, IGF Type 1