Effects of metallothionein-1 genetic polymorphism and cigarette smoking on the development of hepatocellular carcinoma.
BACKGROUND
A low expression of metallothionein (MT) has been observed in liver cancer. Such a phenomenon might be influenced by oxidative stress, thus resulting in the cells being more susceptible to DNA damage and apoptotic death. In particular, oxidative stress induced by cigarette smoking might affect MT-1 expression. We designed a hospital-based case-control study to evaluate the effects of MT-1 genotypes and smoking on hepatocellular carcinoma (HCC) occurrence.


METHODS
A total of 102 HCC patients and 191 matched healthy control subjects were recruited, and epidemiological information was collected. Six genotypes of MT-1 were determined with TaqMan single-nucleotide polymorphism genotyping assays.


RESULTS
Individuals possessing MT-1 rs8052394 A, rs964372 G, and rs8052334 T alleles as well as engaging in cigarette smoking had increased risks of HCC; these alleles also had higher linkage disequilibrium. Carriers with MT-1 rs8052394, rs964372, and rs8052334 A-G-T haplotype had a 2.25-fold (95 % confidence interval [CI] 1.46-3.26) risk for HCC development than the control group (A-C-T, the most common haplotype). Compared to nonsmokers with other haplotypes (A-C-T, G-G-C, A-G-C, G-G-T, G-C-T, and G-C-C), nonsmokers with A-G-T haplotype had a 1.93-fold (95 % CI 1.01-3.71) increased risk, and smokers with other haplotypes had a 3.66-fold (95 % CI 1.78-7.54) increased risk, whereas smokers carrying the A-G-T haplotype had the highest risk (matched relative risk 6.72; 95 % CI 2.86-15.79) of developing HCC.


CONCLUSIONS
The MT-1 A-G-T haplotypes are associated with increased risk of HCC, especially in those who smoke.
Department of Public Health, Chung Shan Medical University, Taichung, Taiwan.
Ruey-Hong
RH
Wong
Chun-Huang
CH
Huang
Chao-Bin
CB
Yeh
Hong-Shen
HS
Lee
Ming-Hsien
MH
Chien
Shun-Fa
SF
Yang
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000235:genetics*; D008297:Male; D008668:Metallothionein / Q000235:genetics*; D008875:Middle Aged; D018384:Oxidative Stress; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D008668:Metallothionein