Yang Shi-Yi, Hsiung Chia-Ni, Li Yao-Jen, Chang Gee-Chen, Tsai Ying-Huang, Chen Kuan-Yu, Huang Ming-Shyan, Su Wu-Chou, Chen Yuh-Min, Hsiung Chao A, Yang Pan-Chyr, Chen Chien-Jen, Wu Pei-Ei, Yu Jyh-Cherng, Shen Chen-Yang, Hsu Huan-Ming
Genomics Research Center, Taipei, Taiwan.
Graduate Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan.
J Biomed Sci. 2016 Feb 3;23:23. doi: 10.1186/s12929-016-0240-9.
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.
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.
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.
Genetic polymorphism of the FA genes is associated with inter-individual susceptibility to lung adenocarcinoma.
香烟烟雾中的致癌物可诱导DNA - DNA交联的形成，这种交联由范可尼贫血（FA）途径修复，因此很容易推测该途径参与了肺癌的发生。本研究旨在确定FA基因的遗传多态性是否与肺腺癌风险升高相关，以及基因型与风险之间的关联是否会因接触香烟烟雾而改变。
这项病例对照研究对709例肺腺癌患者（354例男性和355例女性）和726例无癌个体（339例男性和387例女性）的FA基因中的53个单核苷酸多态性（SNP）进行了基因分型。比较病例组和对照组中SNP的基因型频率，以确定与癌症易感性相关的重要FA基因。通过多因素回归分析和分层分析评估基因和吸烟相关风险因素以及参与不同FA亚途径的多个基因对确定癌症风险的联合作用。所有分析均分别在男性和女性中进行，结果的比较被视为检验研究结果有效性的一种方式。
男性和女性患者的肺腺癌均与以下因素相关：（a）FANCC和FANCD1的基因型多态性；（b）携带较多高危基因型与吸烟/被动吸烟的联合作用；（c）多个基因的特定相互作用，已知这些基因编码的蛋白质在FA途径内共同发挥作用。
FA基因的遗传多态性与个体对肺腺癌的易感性相关。
