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

Abstract

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.