To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5′ ′ ′ ′ promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5-50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58-1.64) for TC-genotype and 0.81 (0.39-1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother/sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5′ ′ ′ ′ promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.Key words: Breast cancer -CYP17 -Polymorphism -Case-control study CYP17 gene located on chromosome 10q24.3 encodes an enzyme, cytochrome p450c17, which has two different roles in steroid hormone metabolism; 17α-hydroxylase and 17,20-lyase activities. The former converts pregnenolone to 17-hydroxypregnenolone and progesterone to 17-hydroxyprogesterone, and the latter further converts the metabolites to dehydroepiandrosterone and androstenedione, respectively. 1) Since this enzyme is essential for estrogens synthesis, increased or decreased activities are speculated to modify the risk of breast cancer. A single nucleotide polymorphism (T-to-C transition) of CYP17 at 34 bp upstream of the translation initiation site in the 5′ untranslated region was reported to create an additional Sp1-type (CCACC box) promoter site, 2) which suggested an increased rate of transcription and possibly a consequent increase in activity of estrogens. To date, several studies have examined the association of the polymorphism with breast cancer risk, but the results were inconsistent. [3][4][5][6][7][8][9][10][11] Although the incidence of breast cancer in Japan is only one-fifth of that in the United States, it has been increasing since 1960s.12) Second-generation Japanese Americans in Hawaii and Los Angeles have the same level of breast cancer incidence as other Americans, indicating that lifestyle plays an important role in breast cancer carcinogenesis. However, similarly important are genetic factors which modify the effects of lifestyle factors. In Japan, there have been few studies on the association between genetic polymorphisms and breast cancer risk. This is a case-control study to examine the association of the 5′ promoter re...