Variants of DNA repair genes and the risk of biliary tract cancers and stones: a population-based study in China.
Biliary tract cancers, which encompass tumors of the gallbladder, extrahepatic ducts, and ampulla of Vater, are relatively rare tumors with a high fatality rate. Other than a close link with gallstones, the etiology of biliary tract cancers is poorly understood. We conducted a population-based case-control study in Shanghai, China, to examine whether genetic variants in several DNA repair genes are associated with biliary tract cancers or biliary stones. Genomic DNA from 410 patients with biliary tract cancers (236 gallbladder, 127 bile duct, and 47 ampulla of Vater), 891 patients with biliary stones, and 786 healthy subjects randomly selected from the Shanghai population were genotyped for putative functional single nucleotide polymorphisms in four DNA repair genes (MGMT, RAD23B, CCNH, and XRCC3). Of the five single nucleotide polymorphisms examined, only one (MGMT EX5-25C>T, rs12917) was associated with biliary tract cancer. Independent of gallstones, subjects carrying the CT genotype of the MGMT EX5-25C>T marker had a significantly reduced risk of gallbladder cancer [odds ratio (OR), 0.63; 95% confidence interval (95% CI), 0.41-0.97; P = 0.02] and nonsignificant reduced risks of bile duct (OR, 0.61; 95% CI, 0.35-1.06) and ampulla of Vater (OR, 0.85; 95% CI, 0.39-1.87) cancers. However, this marker was not associated with biliary stones, and the other markers examined were not significantly associated with either biliary tract cancers or stones. Findings from this population-based study in Shanghai suggest that MGMT gene variants may alter susceptibility to biliary tract cancer, particularly gallbladder cancer. Confirmation in future studies, however, is required.
Zhang
Mingdong
M
Food and Drug Administration, Rockville, Maryland, USA.
Huang
Wen-Yi
WY
Andreotti
Gabriella
G
Gao
Yu-Tang
YT
Rashid
Asif
A
Chen
Jinbo
J
Sakoda
Lori C
LC
Shen
Ming-Chang
MC
Wang
Bing-Sheng
BS
Chanock
Stephen
S
Hsing
Ann W
AW
D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D001661:Biliary Tract Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002681:China / Q000453:epidemiology; D056748:Cyclin H; D016213:Cyclins / Q000235:genetics; D015254:DNA Modification Methylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D025521:Tumor Suppressor Proteins / Q000235:genetics*
C534751:CCNH protein, human; D056748:Cyclin H; D016213:Cyclins; D004268:DNA-Binding Proteins; C513287:RAD23B protein, human; D025521:Tumor Suppressor Proteins; C110901:X-ray repair cross complementing protein 3; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes