| Insulin-like growth factor I (IGF-I) is an important regulator of growth and differentiation and is a potent mitogen for human breast cancer cells. Previous studies have suggested that there is an association between IGF1 genotype and phenotype and reports have shown an association for IGF1 genotype with breast cancer. The relation between a highly polymorphic region of variable cytosine-adenine dinucleotide (CA) repeats one kilobase upstream from the transcription start site and breast cancer association was assessed, and interaction of IGF1 genotype with hormonal birth control (HBC), body mass index (BMI) and cigarette smoking was evaluated, in a population-based case-control study. Cases were 1,028 women with a first primary in situ or invasive breast cancer between August 1, 1996 and July 31, 1997. Controls were 1,086 women frequency matched to the cases by 5-year age group. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the association between IGF1 genotype and breast cancer. An increased association with breast cancer was observed in genotypes with at least one repeat shorter than 19 CA compared to genotypes without a repeat shorter than 19 CA (OR = 1.67; 95% CI = 1.14, 2.44), an association that was stronger among premenopausal women (OR = 3.12; 95% CI = 1.47, 6.61). Additionally, cigarette smokers who carried a shorter repeat experienced a reduced breast cancer association (OR = 0.28; 95% CI = 0.11, 0.74). Little association was observed for main effects of IGF1 genotypes that do not include a 19 CA repeat compared to genotypes that do include a 19 CA repeat (OR = 1.17; 95% CI = 0.91, 1.51). However, there was evidence of heterogeneity of the OR with HBC use and BMI for genotypes that did not include the 19 CA repeat allele, where increased associations among premenopausal women for HBC use and reduced associations among postmenopausal women for high BMI were observed. Our results suggest a possible role of shorter CA repeat alleles as a risk factor for breast cancer and support the hypothesis that particular genotypes may have increased susceptibility for breast cancer for certain exposures. |
