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.
The IGF1 19 CA repeat polymorphism interacted with hormone replacement therapy (HRT) among NHW post-menopausal women; women who had the 19/19 IGF1 genotype were at reduced risk of breast cancer (OR 0.64, 95% CI 0.47-0.88) if they did not use HRT.
Genetic variants in the insulin-like growth factor-I (IGF-I)/insulin resistance axis may interact with lifestyle factors, influencing postmenopausal breast cancer risk, but these interrelated pathways are not fully understood.
We found no significant overall associations between breast cancer and common germline variation in 61 genes involved in steroid hormone and IGF-I metabolism in this large, comprehensive study.
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).
In the current study, IGF-1 gene polymorphism of SNP variants rs6220 and rs7136446 had no statistically significant association with breast cancer, both in premenopausal and postmenopausal women.
These data are compatible with the hypothesis that premenopausal women with a relatively high circulating concentration of IGF-I and low IGFBP-3 are at an increased risk of developing breast cancer.
We found a weak but significant association of polymorphisms at the 5' end of the IGF1 gene with breast cancer risk, particularly among women younger than 55 years, and a strong association of polymorphisms located in the 5' end of IGFBP3 with circulating levels of IGFBP-3, which confirms previous findings.
Since the IGF1-19/-19 genotype in combination with OC use or multiparity confers an increased risk for early onset breast cancer in high-risk women and in women from the general population, future studies are needed to elucidate the importance of the IGF1-19/-19 genotype concerning the variability in breast cancer risk among BRCA1 mutation carriers.
Our conclusion is that common genetic variation in the GH synthesis pathway, as measured by single nucleotide polymorphisms selected in the present study, is not a major determinant of IGF-I and IGFBP-3 circulating levels, and it does not play a major role in altering breast cancer risk.
As IGF1-19/-19, multiparity and early-onset breast cancer are more common in black than in white women, we aimed to study whether multiparity combined with IGF1-19/-19 increases the risk of early-onset breast cancer.
Breast cancer risk and circulating IGF-I concentration appear to be partly heritable, thus genetic variation at IGF1 could influence IGF-I levels and breast cancer risk.
Although a modest association cannot be excluded, our data do not support an important relation between this IGF-1 gene polymorphism and breast cancer risk.