Chen Dan, Jin Guangfu, Wang Ying, Wang Haifeng, Liu Hongliang, Liu Yanhong, Fan Weiwei, Ma Hongxia, Miao Ruifeng, Hu Zhibin, Sun Weiwei, Qian Ji, Jin Li, Wei Qingyi, Shen Hongbing, Huang Wei, Lu Daru
The State Key Laboratory of Genetic Engineering and The MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai 200433, China.
Carcinogenesis. 2008 Feb;29(2):342-50. doi: 10.1093/carcin/bgm285. Epub 2008 Jan 10.
Accumulating evidence indicates that activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) dampens the inflammation cascade and inhibits tumor growth of the lung, suggesting that it has tumor suppressor functions. We performed a case-control study of 500 incident lung cancer cases and 517 age- and sex frequency-matched cancer-free controls in a Chinese population to investigate the role of 11 selected single nucleotide polymorphisms (SNPs) of PPAR-gamma in the etiology of lung cancer. We found that decreased lung cancer risk was statistically significantly associated with seven SNPs (P = 0.0004 for rs13073869 and 0.0130 for rs1899951 in a dominant model; P = 0.0310 for rs4135247 in a log-additive model; and P = 0.0468 for rs2972162, 0.0175 for rs709151, 0.0172 for rs11715541 and 0.0386 for rs1175543 in an overdominant model). Consistent with these results of single-locus analysis, both the haplotype and the diplotype analyses revealed a protective effect of the haplotype 'AGA' and 'AAA' of rs13073869, rs1899951 and rs4135247. Furthermore, we observed a statistically significant interaction between the rs1899951 and cigarette smoking. Our results indicate that PPAR-gamma polymorphisms and their interaction with smoking may contribute to the etiology of lung cancer. These findings need to be validated in larger, preferably population-based, studies including different ethnic groups.
越来越多的证据表明,过氧化物酶体增殖物激活受体γ(PPAR-γ)的激活可抑制炎症级联反应并抑制肺癌的肿瘤生长,这表明它具有肿瘤抑制功能。我们在中国人群中对500例新发肺癌病例和517例年龄及性别频率匹配的无癌对照进行了病例对照研究,以调查PPAR-γ的11个选定单核苷酸多态性(SNP)在肺癌病因学中的作用。我们发现,在显性模型中,7个SNP与肺癌风险降低具有统计学显著相关性(rs13073869的P = 0.0004,rs1899951的P = 0.0130;在对数加性模型中,rs4135247的P = 0.0310;在超显性模型中,rs2972162的P = 0.0468,rs709151的P = 0.0175,rs11715541的P = 0.0172,rs1175543的P = 0.0386)。与这些单基因座分析结果一致,单倍型和双倍型分析均显示rs13073869、rs1899951和rs4135247的单倍型“AGA”和“AAA”具有保护作用。此外,我们观察到rs1899951与吸烟之间存在统计学显著的相互作用。我们的结果表明,PPAR-γ多态性及其与吸烟的相互作用可能在肺癌病因学中起作用。这些发现需要在包括不同种族群体的更大规模、最好是基于人群的研究中进行验证。