Cyclin D1 Genotype and Breast Cancer Metastasis1

Abstract

To the Editors: We have reported previously that the 870G > A polymorphism in the Cyclin D1 gene (CCND1) is not associated with breast cancer risk (1). This has been confirmed in a recent larger study work by Shu et al. (2). Interestingly, the authors described a favorable outcome for carriers of the 870_A allele, particularly, in patients with stage III to IV cancer. Encouraged by that report, we have retrieved data on metastasis of the 500 breast cancer patients from our study and did a retrospective analysis of the association between metastases and CCND1 genotype. The study was done according to the Austrian Gene Technology Act and has been approved by the Ethical Committee of the Medical University Graz. Written informed consent was obtained from all participating subjects. All subjects were Caucasian.At the time of diagnoses, patients were between 28 and 84 years of age, with a mean age of 57 ± 11 years. In the subgroup of 302 patients with stage III to IV breast cancer, 250 (82.8%) patients developed metastases in the time between diagnosis and study entry, whereas 52 (17.2%) patients remained free of metastases. The CCND1 870_AA genotype was found more frequently among subjects without metastases (44.2%) than among those with metastases (24.8%; χ2 test, P = 0.005). In a logistic regression model including age at diagnosis and estrogen and/or progesterone receptor negativity in the primary tumor as potential confounders, the 870_AA genotype was still significantly associated with metastasis risk (odds ratio, 0.43; 95% confidence interval, 0.23-0.83; P = 0.010). In the subgroup of 198 patients with stage I to II breast cancer, none of patients developed metastases in the time between diagnosis and study entry. The association of the CCND1 polymorphism with metastases was restricted to homozygous carriers of the 870A variant, suggesting a recessive effect.We are aware that the retrospective design of our study limits its usefulness for the analysis of metastasis risk. Nevertheless, although our study was smaller than that of Shu et al., our data provide additional support for a protective effect of the CCND1 870A allele against breast cancer metastasis.