TY - JOUR
T1 - Effects of metallothionein-1 genetic polymorphism and cigarette smoking on the development of hepatocellular carcinoma
AU - Wong, Ruey Hong
AU - Huang, Chun Huang
AU - Yeh, Chao Bin
AU - Lee, Hong Shen
AU - Chien, Ming Hsien
AU - Yang, Shun Fa
N1 - Funding Information:
ACKNOWLEDGMENT Supported in part by a grant from the National Science Council, Taiwan (NSC-100-2632-B-040-001-MY3).
PY - 2013/6
Y1 - 2013/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878229475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878229475&partnerID=8YFLogxK
U2 - 10.1245/s10434-012-2456-6
DO - 10.1245/s10434-012-2456-6
M3 - Article
C2 - 22805858
AN - SCOPUS:84878229475
SN - 1068-9265
VL - 20
SP - 2088
EP - 2095
JO - Annals of Surgical Oncology
JF - Annals of Surgical Oncology
IS - 6
ER -