title: MYH rs3219476 and rs3219472 polymorphisms and risk of cholangiocarcinoma.
abstract: Cholangiocarcinoma (CCA) is a rare but devastating malignancy. Up to 90% of patients presenting with CCA have no identifiable risk factors. The base excision repair (BER) pathway has a principal role in the repair of mutations caused by oxidized or reduced bases. The MutY homolog (MUTYH, MYH) is one of the key proteins in the BER pathway, but the role of MYH in the tumorigenesis of CCA is largely unknown. In this study, we investigated the influence of MYH rs3219476 and rs3219472 polymorphisms on CCA incidence. MYH genotypes were detected using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. We found that for rs3219472, compared with subjects carrying the MYH G/G genotype, those with the A/A genotype had a 2.816-fold higher risk of CCA [odds ratio (OR)=2.816, 95% confidence interval (CI)=0.992-7.999, P=0.047). For rs3219476, compared with subjects carrying the MYH T/T genotype, those with the T/G genotype had a reduced risk of CCA (OR=0.359, 95% CI=0.17-0.758, P=0.006). Our findings suggest that since significantly increased CCA risk was found in individuals with a homozygous variant genotype for rs3219472, it may be a biomarker for screening individuals at high risk of developing the disease.
authors.affiliation: Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, PR China.
authors.forename: Si-Hong
authors.initials: SH
authors.lastname: You
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Shu
authors.initials: S
authors.lastname: Huang
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.forename: Guo-Zhong
authors.initials: GZ
authors.lastname: Ji
authors.forename: Jin-Rong
authors.initials: JR
authors.lastname: Xia
authors.forename: Zhi-Ning
authors.initials: ZN
authors.lastname: Fan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001650:Bile Duct Neoplasms / Q000235:genetics*; D001653:Bile Ducts, Intrahepatic; D016022:Case-Control Studies; D018281:Cholangiocarcinoma / Q000235:genetics*; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase