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Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms SNPs in eight vitamin D pathway genes and breast cancer disease-free survival DFS using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS; RXRA SNPs:rs881658, rs11185659, rs10881583, rs881657, and rs7864987 and PLAUR SNP:rs4251864. Treatment received no systemic therapy, hormone therapy alone or chemotherapy was an effect modifier of the RXRA SNPs association with DFS P 0.05, therefore we stratified further analysis by treatment group. Among patients who did not receive systemic therapy RXRA SNP:rs10881583 P0.02 was associated with poorer DFS and among patients who received chemotherapy, RXRA SNPs: rs881658, rs11185659, rs10881583, rs881657, rs7864987 were associated with poorer DFS P.001 for all SNPs. However, RXRA SNPs: rs10881583 P.001, rs881657 P0.02 were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated these markers could be used for risk stratification of breast cancer patients.
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