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

Background: Genes that confer mild or moderate susceptibility to breast cancer may be involved in the pathogenesis of sporadic breast cancer, modifying the phenotypic expression of mutant BRCA1/BRCA2 alleles. An attractive candidate is the insulin-like growth factor I, a known mitogen to mammary ductal cells in vivo and in vitro, whose serum levels were reportedly elevated in breast cancer patients. Objective: To evaluate the contribution of the IGF-1 gene polymorphism to breast cancer risk by genotyping for a polymorphic allele size in breast cancer patients and controls. Methods: We analyzed allele size distribution of the polymorphic CA repeat upstream of the IGF-I gene in 412 Israeli Jewish women: 268 women with breast cancer (212 sporadic and 56 carriers of either a BRCA1 or BRCA2 mutation), and 144 controls. Genotyping was accomplished by radioactive polymerase chain reaction of the relevant genomic region and size fractionation on polyacrylamide gels with subsequent autoradiography. Results: Among women with breast cancer, with or without BRCA germline mutations, 196 and 198 basepair alleles were present in 4.7% (25/536 alleles), compared with 9% (26/288) controls (P = 0.02). This difference was more pronounced and significant in the non-Ashkenazi population. Conversely, the smaller size allele (176 bp) was present in the breast cancer group only (3/536, 0.6%). Conclusions: The IGF-I polymorphism may serve as a marker for breast cancer risk in the general Jewish population, in particular non-Ashkenazi Jews, but extension and confirmation of these preliminary data are needed.