Cyclin D polymorphisms and breast cancer risk in a US population-based study

B82

The Cyclin D protein controls the transition from the G1 to S-phase during mitosis. Because of its checkpoint role in the cell cycle, genetic variation in Cyclin D may affect cancer risk. In a population based case-control study of mainly White women conducted in three U.S. states, including 1649 in situ and invasive breast cancer cases and 1273 population controls, we examined two single nucleotide polymorphisms in CCND1 including the exon 4 splice variant G870A (rs603965) and a common variant in the 3’UTR (rs678653) for associations with breast cancer. Information on breast cancer risk factors and demographic characteristics was collected in telephone interviews. Oral epithelial DNA samples were collected through the mail and genotyping was conducted using whole genome amplified DNA. Odds ratios and 95% confidence intervals adjusted for age and state of residence were obtained using logistic regression. Frequencies of both polymorphisms were in Hardy-Weinberg equilibrium among the controls (rs678653, p=0.49; rs603965, p=0.13). No association with breast cancer risk was observed among heterozygotes (OR=1.07, 95%CI 0.91-1.26) or homozygotes with the less common allele (OR=1.06, 95%CI 0.83-1.35) in rs678653. Similarly, no association with breast cancer was demonstrated among heterozygotes (OR=1.11, 95%CI 0.93-1.21) or homozygotes for the minor allele (OR=0.98, 95%CI 0.79-1.21) in rs603965. No associations emerged for either variant after stratifying by menopausal status, postmenopausal hormone use or stage of disease. Further adjustment for breast cancer risk factors did not materially change the results. We conclude that two common polymorphisms in CCND1 are not associated with breast cancer risk in this population.