A sequence repeat in the insulin-like growth factor-1 gene and risk of breast cancer

Insulin-like growth factor-1 (IGF-I), a potent mitogen, is hypothesized to influence breast cancer risk. In 3 previous studies, a polymorphism in the IGF-1 gene (sequence repeat length) was associated with plasma IGF-I level. We evaluated prospectively the relationships among a (CA)(n) repeat polymorphism in the IGF-1 gene, IGF-I level and breast cancer risk in a nested case-control study conducted within the Nurses' Health Study. Blood samples were collected in 1989-1990; up to June 1994, we identified 463 cases of breast cancer. One to 2 controls were selected per case, matched by age, menopausal status, postmenopausal hormone use, month and time of day of blood collection and fasting status, for a total of 622 controls. Although no significant trend was observed, plasma IGF-I levels were significantly lower among controls, with no copy of the 19 allele, compared with those homozygous for the 19 (CA)(n) repeat length (146 and 173 ng/ml, respectively; p-value for pairwise mean comparison = 0.005). In conditional logistic regression, controlling for established breast cancer risk factors, we observed no significant association between (CA)(n) repeat length genotype and risk of breast cancer [compared with repeat genotype 19/19-18/19 genotype relative risk (RR) = 0.96, 95% confidence interval (CI) = 0.56-1.64; 18/20 genotype RR = 0.92, 95% CI = 0.39-2.19; 19/20 genotype RR = 1.16, 95% CI = 0.82-1.64; 19/21 genotype RR = 0.69, 95% CI = 0.42-1.14; 20/20 genotype RR = 0.55, 95% CI = 0.28-1.10; 20/21 genotype RR = 0.72, 95% CI = 0.29-1.79]. Results did not vary substantially when evaluated according to menopausal status, tumor receptor status or category of other breast cancer risk factors. 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.