- 作者: Shi-Yi Yang, Chia-Ni Hsiung, Yao-Jen Li, Gee-Chen Chang, Ying-Huang Tsai, Kuan-Yu Chen, Ming-Shyan Huang, Wu-Chou Su, Yuh-Min Chen, Chao A. Hsiung, Pan-Chyr Yang, Chien-Jen Chen, Pei-Ei Wu, Jyh-Cherng Yu, Chen-Yang Shen and Huan-Ming Hsu
- 作者服務機構: Genomics Research Center, Academia Sinica, Taipei, Taiwan
- 中文摘要: --
- 英文摘要:
Background
Carcinogens in cigarette smoke can induce the formation of DNA-DNA cross-links, which are repaired by the Fanconi anemia (FA) pathway, and it is tempting to speculate that this pathway is involved in lung tumorigenesis. This study is to determine whether genetic polymorphism of the FA genes is associated with an elevated risk of lung adenocarcinoma, and whether the association between genotypes and risk is modified by exposure to cigarette smoke.
Methods
This case–control study genotyped 53 single-nucleotide polymorphisms (SNPs) in FA genes in 709 patients (354 males and 355 females) with lung adenocarcinoma and in 726 cancer-free individuals (339 males and 387 females). Genotypic frequencies of SNPs were compared between cases and controls to identify important FA genes associated with cancer susceptibility. Joint effects in determining cancer risk contributed by genes and smoking-related risk factors and by multiple genes involved in different FA subpathways were evaluated by multivariate regression analysis and stratified analysis. All analyses were performed on males and females separately, and the comparison of results was considered a way of examining the validity of study findings.
Results
Lung adenocarcinomas in both male and female patients were associated with (a) genotypic polymorphisms of FANCC and FANCD1; (b) a combined effect of harboring a higher number of high-risk genotypes and smoking/passive smoking; (c) specific interactions of multiple genes, proteins encoded by which have been known to work jointly within the FA pathway.
Conclusions
Genetic polymorphism of the FA genes is associated with inter-individual susceptibility to lung adenocarcinoma. - 中文關鍵字: --
- 英文關鍵字: Lung adenocarcinoma, DNA repair, Fanconi anemia, Genetic susceptibility, Polymorphism