The relevance of vitamin D receptor (VDR) gene polymorphisms for cancer: a review of the literature.

BACKGROUND In recent years, the relevance of vitamin D receptor (VDR) gene restriction fragment length polymorphisms for various types of cancer has been investigated by a great number of studies. It has been hypothesized that VDR polymorphisms may influence both the risk of cancer occurrence and prognosis. However, studies investigating the associations between specific VDR polymorphisms and cancer often show controversial results. We have now performed a systematic review of the literature to analyse the relevance of VDR polymorphisms for individual malignancies, including cancer of the skin, prostate, breast, colon, ovary, kidney and bladder. MATERIALS AND METHODS An analysis of studies evaluating the association between vitamin D receptor gene polymorphisms Fok1, Bsm1, Taq1, Apa1, and Cdx2, poly (A) and Bgl1 as well as some haplotype combinations and cancer risk has been performed. Data were extracted from PubMed using the key words VDR polymorphism in combination with breast cancer, prostate cancer, skin cancer, colorectal cancer, ovarian cancer, renal cell carcinoma or bladder cancer. RESULTS This analysis was performed with the intent of giving an up-to-date overview of all data concerning the relevance of VDR polymorphisms for cancer. Obviously, at present it is still not possible to make any definitive statements about the importance of the VDR genotype for cancer occurrence. It seems probable that interactions with other factors such as calcium and vitamin D intake, 25(OH)D plasma levels and UV radiation exposure play a decisive role in cancer occurrence and should not be underestimated. Other risk factors such as obesity, smoking status, parity status, energy intake and others are also frequently mentioned as being more or less important for carcinogenesis depending on the VDR genotype. Moreover, it is often noticed that the same VDR polymorphism has a different effect depending on the type of cancer, or may be only decisive for more or less aggressive staging of the tumour. CONCLUSION Significant associations with VDR polymorphisms have been reported in cancer of the breast (Fok1, Bsm1, Taq1, Apa1, poly (A)), prostate (Fok1, Bsm1, Taq1, poly (A)), skin (Fok1, Bsm1, A-1210), colorectum (Fok1, Bsm1), ovary (Fok1, Apa1) and bladder (Fok1), and in renal cell carcinoma (Taq1, Apa1). However, conflicting data have been reported for most malignancies. After careful evaluation of the actual literature, it can be summarized that data indicating an association of VDR polymorphisms and cancer risk are strongest for breast cancer (Bsm1, Fok1), prostate cancer (Fok1) and malignant melanoma (MM) (Fok1). Data indicating an association of VDR polymorphisms and cancer prognosis are strongest for prostate cancer (Fok1), breast cancer (Bsm1, Taq1), MM (Bsm1) and renal cell carcinoma (Taq1).