title: Polymorphism of xenobiotic-metabolizing genes and breast cancer susceptibility in North Indian women.
abstract: NAD(P)H:quinone oxidoreductase 1 (NQO1) and cytochrome P450 1A2 (CYP1A2) are involved in the metabolism of estrogens. Genetic polymorphisms in these genes may lead to interindividual variation in breast cancer susceptibility. This study was undertaken to investigate the association of NQO1 exon 6 proline187serine (C609T) and CYP1A2 exon 2 phenylalanine21leucine (C63G) polymorphisms with breast cancer susceptibility in North Indian women. Polymorphisms were analyzed by polymerase chain reaction amplification of the desired segment of NQO1 and CYP1A2 genes followed by restriction fragment length polymorphism. NQO1 mRNA expression was analyzed by semiquantitative reverse transcription-polymerase chain reaction and its enzyme activity was estimated spectrofluorophotometrically. Odds ratios for NQO1 C609T heterozygous and homozygous variants were 0.66 (95% confidence interval: 0.39-1.13; p-value: 0.141) and 1.07 (95% confidence interval: 0.46-2.46; p-value: 0.976). All cases and controls were monomorphic for the CYP1A2 exon 2 phenylalanine21leucine (C63G) genotype. NQO1 mRNA expression and its catalytic activity among wild-type genotype, homozygous variant, and heterozygous variant were not significantly altered, except for catalytic activity of the NQO1 homozygous variant, which was observed extremely low. The results of the study suggest that NQO1 exon 6 proline187serine (C609T) and CYP1A2 exon 2 phenylalanine21leucine (C63G) polymorphisms do not play a significant role in breast cancer susceptibility in North Indian women.
authors.affiliation: Indian Institute of Toxicology Research (Council of Scientific and Industrial Research), Lucknow, India.
authors.forename: Virendra
authors.initials: V
authors.lastname: Singh
authors.forename: Ghanshyam
authors.initials: G
authors.lastname: Upadhyay
authors.forename: Neeraj
authors.initials: N
authors.lastname: Rastogi
authors.forename: Kalpana
authors.initials: K
authors.lastname: Singh
authors.forename: Mahendra Pratap
authors.initials: MP
authors.lastname: Singh
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic; D007194:India; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*; D015262:Xenobiotics / Q000378:metabolism
chemical_list: D015262:Xenobiotics; D019388:Cytochrome P-450 CYP1A2; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human