Asian Paciic Journal of Cancer Prevention, Vol 11, 2010 1653 Association of a CYP17 Gene Polymorphism with Development of Breast Cancer in India Asian Paciic J Cancer Prev, 11, 1653-1657 Introduction CPY17 plays key role in sex steroid synthesis and codes for enzyme which has bifunctional catalytic activity. One catalytic center performs the 17α-hydroxylation of pregnenolone and progesterone and another the 17, 20-lyase activity, is responsible for the conversions of 17 α-hydroxypregnenolone to dihydroepiandrosterone and 17α-hydroxyprogesterone to androstenedione, precursors of testosterone and estrogens (Weston et al., 1998). Recent studies had shown that estrogen metabolites could bind to DNA and trigger damage (Zhu and Conney., 1998). It was suggested that estrogen might be a complete carcinogen capable of causing genetic alterations and tumor initiation (Service, 1998). Since cytochrome P450c17 α is important in estrogen biosynthesis, increased or decreased activities might inluence susceptibility to breast cancer. The human CYP17 gene is located on chromosome 10q24.3 (Fan et al., 1992). Carey et al., (1994) irst identified the MspA1 polymorphism of the CYP17 gene and revealed a significant association with polycystic ovarian disease and male pattern baldness in which androgen play major role. Single nucleotide polymorphism (T to C substitution) in 5’-promotor region creates an additional (CCACT-CCACC) Sp1 promoter site at 34 base pair upstream of the initiation of translation but downstream from the transcription start site. The T allele and C allele were reported as A1 and A2 alleles in the 1 Department of Genetics, Osmania University, 2 Department of Medical Oncology, Nizams Insttute of Medical Sciences, Hyderabad, India *For correspondence : sattivishnupriya@gmail.com Abstract The human CYP17 gene, located on chromosome 10q24.3, plays a key role in sex steroid synthesis, mainly related to estrogen. A 5’ UTR polymorphism involving a single base pair change in the promoter region results in increased transcriptional activity. In the present study of 250 breast cancer cases and 250 ma tched controls, the A1 genotype frequency was elevated in the disease group, while the A2 genotype frequency demonstrated no association. When data were stratiied by risk conferring group, however, the A2 genotype frequency was increased in postmenopausal breast cancer cases (4.2%), patients positive for a family history of breast cancer (5.5%), high BMI, estrogen receptor (6.2%) and progesterone receptor negative (5.0%) status, HER2/neu positive (7.7%) status, positive node status (5.0%) as well as advanced stage of the disease. The A1A1 genotype linked with increased production of androgens might impact on onset of breast cancer while the A2 allele showed associations with respect to important risk conferring parameters. Keywords: CYP17 - breast cancer - PCR-RFLP - receptor status - India RESEARCH COMMUNICATION Association of a CYP17 Gene Polymorphism with Development of Breast Cancer in India D Surekha 1 , K Sailaja 1 , D Nageswara Rao 1 , T Padma 1 , Raghunadharao D 2 , S Vishnupriya 1* literature respectively. The A2 allele corresponds to an additional Sp-1 type promoter site in the 5’ untranslated region of CYP17. Since it was thought that the number of 5’ promoter elements correlates with promoter activity, it might be expected that an additional CCACC site might inluence promoter activity, thereby up-regulating transcription. Inter-individuals differences in susceptibility to breast cancer are partially mediated through the levels of endogenous and exogenous steroid hormones (Feigelson et al., 1996). Recent invitro data suggested that the 5’ Sp1-type site resulting from the T to C substitution does not actually bind transcription factor Sp-1 (Haung et al., 1999), but there was still some evidence to indicate that this polymorphism might inluence endogenous steroid hormone levels (Bergman-Jungestrome et al., 1999). Feigelson et al., (1998) found that the A2 allele was associated with higher serum estrogen and progesterone levels compared with the A1 allele. Another study reported that the women with A2 allele had elevated levels of steroid and dehydroepiandrosterone (Haiman et al., 1999). In the present study, we have examined a series of breast cancer cases as well as controls to determine whether CYP17 polymorphism inluence the risk for the development of breast cancer. Materials and Methods A group of 250 breast cancer patients were selected