CYP17 gene polymorphisms: prevalence and associations with hormone levels and related factors. A HuGE Review

The cytochrome P-450c17alpha (CYP17 ) gene, located on chromosome 10q24.3, encodes the enzyme cytochrome P-450c17alpha, which functions at key branch points in steroid hormone biosynthesis. Three polymorphisms have been described, but only the single base-pair change in the 5'-untranslated region (5'-UTR) has been investigated to any great extent. In single studies, the variant was associated with reduced messenger RNA level in ovarian cells but not with messenger RNA level in breast tissue. Homozygosity for the 5'-UTR variant is most common in East Asian (32%) and Japanese (22%) populations and is less common among White (mainly European and North American (14%)) and Black (mainly African-American (13%)) populations, but selection biases are likely to have affected these frequency estimates. Genotype appears to influence circulating estrogen levels in premenopausal women, while studies of relations with hormone levels in men have produced inconclusive results. However, relatively few studies have been conducted. Seven of 11 retrospective studies suggested a modest association between genotype and age at menarche. Random error in recall of age at menarche is likely to have attenuated this relation. Associations between genotype and postmenopausal estrogen use and bone mass have been observed in single studies. Further investigation of relations between genotype and hormone levels, exogenous hormone use, and markers of hormonal status may advance understanding of hormonally mediated diseases.