Carcinogenesis Advance Access published online on January 23, 2009
Carcinogenesis, doi:10.1093/carcin/bgp016
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FAS promoter polymorphisms and cancer risk: a meta-analysis based on 34 case-control studies
1 Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China
2 Department of Molecular & Genetic Toxicology, Cancer Center of Nanjing Medical University, Nanjing 210029, China
3 Institute of Cancer Research, Yangzhong People's Hospital, Yangzhong 212200, China
4 Department of Surgery, Yixing People's Hospital, Yixing 214200, China
5 Department of Obstetrics & Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
* Correspondence to: Zhengdong Zhang, Department of Molecular & Genetic Toxicology, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing 210029, China. Tel: +86 25 86862937; Fax: +86 25 86527613; Email: zdzhang{at}njmu.edu.cn
FAS is a cell surface receptor involved in apoptotic signal transmission and plays important roles in the etiology of cancer. The –1377G>A and –670A>G polymorphisms of the FAS gene influence the FAS transcription and have been implicated in cancer risk. However, the results from the published studies on the association between these two FAS polymorphisms and cancer risk are conflicting. To derive a more precise estimation of association between the FAS polymorphisms and risk of cancer, we performed a meta-analysis of 11,461 cancer cases and 12,708 controls from 34 published case-control studies for these two polymorphisms. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, individuals with the –1377AA genotype were associated with higher cancer risk than those with the –1377GG (OR = 1.21, 95% CI: 1.08-1.36, Pheterogeneity = 0.062) or GA/GG (OR = 1.23, 95% CI: 1.10-1.36, Pheterogeneity = 0.060) genotypes while the –670GG genotype had no effects on overall cancer risk. In the stratified analyses for the –1377G>A polymorphism, there was a significantly increased risk of breast cancer but a significantly decreased risk of melanoma in a dominant model. Moreover, a significantly increased risk was observed among smokers in a recessive model (OR = 1.96, 95% CI: 1.55-2.49; Pheterogeneity = 0.528). Although some modest bias could not be eliminated, this meta-analysis suggested that the FAS –1377A allele is a low-penetrant risk factor for cancer development, particularly among smokers.
Key Words: apoptosis • genetic variation • molecular epidemiology
These authors contributed equally to this work. Received November 6, 2008; revised December 30, 2008; accepted January 6, 2009.