title: Association of single nucleotide polymorphisms in CYP1B1 and COMT genes with breast cancer susceptibility in Indian women.
abstract: Cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes play critical roles in estrogen metabolism. Alterations in the catalytic activity of CYP1B1 and COMT enzymes have been found associated with altered breast cancer risk in postmenopausal women in many populations. The substitution of leucine (Leu) to valine (Val) at codon 432 increases the catalytic activity of CYP1B1, however, substitution of Val to methionine (Met) at codon 158 decreases the catalytic activity of COMT. The present study was performed to evaluate the associations of CYP1B1 Leu(432)Val and/or COMT Val(158)Met polymorphisms with total, premenopausal and postmenopausal breast cancer risks in Indian women. COMT and CYP1B1 polymorphisms in controls and breast cancer patients were analyzed employing polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) followed by gel electrophoresis. Although CYP1B1 and COMT genotypes did not exhibit statistically significant association with breast cancer risks when analyzed individually, COMT wild type (Val(158)Val) in combination with CYP1B1 heterozygous variant (Leu(432)Val) [OR: 0.21; 95% CI (0.05-0.82), p value; 0.021] and COMT heterozygous variant (Val(158)Met) in combination with CYP1B1 wild type (Leu(432)Leu) [OR: 0.29; 95% CI (0.08-0.96), p value; 0.042] showed significant protective association with premenopausal breast cancer risk. The results demonstrate that CYP1B1 wild type in combination with COMT heterozygous or their inverse combination offer protection against breast cancer in premenopausal Indian women.
authors.affiliation: Indian Institute of Toxicology Research, Council of Scientific and Industrial Research, Lucknow, India.
authors.forename: Sharawan
authors.initials: S
authors.lastname: Yadav
authors.forename: Naveen Kumar
authors.initials: NK
authors.lastname: Singhal
authors.forename: Virendra
authors.initials: V
authors.lastname: Singh
authors.forename: Neeraj
authors.initials: N
authors.lastname: Rastogi
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Srivastava
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002394:Catechol O-Methyltransferase