Breast cancer is the most common malignancy among the Australian female population with women having a 1 in 11 chance of developing the disease before the age of 75. Currently, breast cancer accounts for 18.6% of annual cancer deaths with the incidence increasing by 4% from 1995 to 1996 (Coates and Armstrong, 1997). Breast cancer, like other cancers, exists in both sporadic and inherited forms with the latter accounting for up to 10% of all breast cancer cases (Jones et al., 1995). Familial breast cancer is commonly due to inheritance of germ line mutations, however sporadic breast cancer is often the result of a multifactorial etiology that includes a genetic component (Kelsey, 1993). A correlation between family history and increased risk of breast cancer development supports the hypothesis that genetic factors are involved in the etiology of sporadic breast cancer (Jones et al., 1995). Complex hormonal influences are also important in the development of breast cancer as the incidence rises steeply in post-menopausal women (Devilee and Cornelisse, 1994). It is possible that the impact of particular genes in sporadic cancer may be modulated by the hormonal milieu.Numerous studies have found that vitamin D and its analogues reduce cell proliferation in breast cancer cell lines and tumor samples and may hence play a protective role against breast cancer development (Jenkins et al., 1997). In addition to the traditional role of vitamin D in controlling calcium balance, the active form of vitamin D [1,25(OH) 2 D3] has potent anti-proliferative effects on breast, prostate and colon cancer cells in culture. This may be derived from stimulation of cellular differentiation or direct regulation of cell cycle genes such as p53 and p21 (James et al., 1996). Polymorphisms in the receptor generate restriction sites within the gene that may potentially influence the stability of mRNA and vitamin D expression (Jenkins et al., 1997; Ingles et al., 1997a,b). Low serum levels of 1,25(OH) 2 D3 have been reported to correlate with breast cancer disease progression and the development of bone metastases , hence polymorphisms in the vitamin D receptor (VDR) gene could be associated with breast cancer development.VDR gene polymorphisms located at the 3ЈUTR have been found to be associated with prostate cancer, bone mineral density and osteoporosis (Ingles et al., 1997a,b;Sainz et al., 1997) while the 5Ј polymorphism is involved in peak bone density (Harris et al., 1997). In this study, 3 sequence polymorphisms, 1 from the 5Ј region and 2 from the 3Ј region of the VDR gene, were analyzed for involvement in sporadic breast cancer development in an Australian breast cancer affected population.
MATERIAL AND METHODS
SubjectsThe affected tested population comprised 135 females previously diagnosed with breast cancer. Each was without a known family history of breast cancer, although there may have been unidentified familial cases (not expected to exceed 5%). The control population comprised 110 females with no history (either familial or ...
