染色體1p32.2-36.1區域肝癌易感受基因連鎖高峰之定位：候選基因策略

Identification of Hepatocellular Carcinoma Susceptibility Gene by Peakwide Mapping on Chromosome 1p32.2-36.1: Application of Positional Candidate Gene Approach

王雅蕙(Ya-Hui Wang)

指導教授 ： 于明暉

國立臺灣大學/公共衛生學院/流行病學研究所/碩士(2008年)

https://doi.org/10.6342/NTU.2008.01182

摘要

無資料

關鍵字

候選基因策略 ； 家族研究 ； 病例對照 ； 關連性分析 ； 肝癌易感受基因

並列摘要

Background: In hepatocellular carcinomas (HCCs), frequent allelic loss on chromosome 1p has been reported. Using linkage analysis on multiplex families, a HCC-susceptibility locus has been mapped to a broad region of chromosome 1p32.2-36.1.
Materials and Methods: Here we have used a positional candidate gene strategy, based on association mapping with single nucleotide polymorphisms (SNPs) on 19 candidate genes within the linked region among 240 families with HCC, followed by a case-control analysis involving an independent set of 855 cases and 875 controls. Significance of the association was assessed by the false-discovery rate q value, which accounts for multiple testing.
Results: In the family sample, we observed a significant association between HCC and five single-nucleotide polymorphisms (SNPs) in a haplotype block by using the pedigree disequilibrium test. SNP 13, located in the 3’ untranslated region (UTR) of the retinoblastoma binding protein 4 (RBBP4) gene, showed the strongest evidence (nominal P=0.0047; empirical P=0.0025; q=0.0188). Further case-control analysis confirmed the genetic association between SNP13 and HCC, and identified additional two SNPs in the same haplotype block. The C allele (minor allele) of SNP13 conferred an increased risk for HCC (odds ratio [95% confidence interval]: 1.36 [1.11-1.65] for heterozygotes; 1.29 [0.90-1.84] for homozygotes ). SNP13 and two neighboring SNPs fell on a common haplotype (‘C-A-C’ at SNP13-SNP14-SNP15), which was also associated with an increase risk of HCC.
Conclusion:
SNP13 was consistently associated with HCC in both family and case-control sample.

並列關鍵字

Positional candidate gene approach ； family study ； case-control study ； association study ； HCC susceptibility gene

參考文獻

1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005;55:74-108.

2. Lu SN, Su WW, Yang SS, Chang TT, Cheng KS, Wu JC, et al. Secular trends and geographic variations of hepatitis B virus and hepatitis C virus-associated hepatocellular carcinoma in Taiwan. Int J Cancer 2006;119:1946-52.

4. Yu MW, You SL, Chang AS, Lu SN, Liaw YF, Chen CJ. Association between hepatitis C virus antibodies and hepatocellular carcinoma in Taiwan. Cancer Res 1991;51:5621-5.

5. Yu MC, Yuan JM. Environmental factors and risk for hepatocellular carcinoma. Gastroenterology 2004;127:S72-8.

6. Ross RK, Yuan JM, Yu MC, Wogan GN, Qian GS, Tu JT, et al. Urinary aflatoxin biomarkers and risk of hepatocellular carcinoma. Lancet 1992;339:943-6.