FASL rs763110 polymorphism contributes to cancer risk: an updated meta-analysis involving 43,295 subjects

Lei Xu; Xin Zhou; Feng Jiang; Man-Tang Qiu; Zhi Zhang; Rong Yin; Lin Xu

doi:10.1371/journal.pone.0074543

FASL rs763110 polymorphism contributes to cancer risk: an updated meta-analysis involving 43,295 subjects

PLoS One. 2013 Sep 23;8(9):e74543. doi: 10.1371/journal.pone.0074543. eCollection 2013.

Authors

Lei Xu¹, Xin Zhou, Feng Jiang, Man-Tang Qiu, Zhi Zhang, Rong Yin, Lin Xu

Affiliation

¹ The Fourth Clinical College of Nanjing Medical University, Nanjing, China ; Department of Thoracic Surgery, Nanjing Medical University Affiliated Cancer Hospital Cancer Institute of Jiangsu Province, Nanjing, China.

Abstract

Background: Published studies investigating the association between genetic polymorphism -884C/T (rs763110) of the FAS ligand (FASL) promoter and cancer risk reported inconclusive results. To derive a more precise estimation of the relationship, we performed an updated meta-analysis of all eligible studies.

Methodology/principal findings: We carried out a meta-analysis, including 47 studies with 19,810 cases and 23,485 controls, to confirm a more conclusive association between the FASL rs763110 polymorphism and cancer susceptibility. Overall, significantly reduced cancer risk was associated with the variant -884T when all studies were pooled (TC vs. CC: OR = 0.83, 95%CI = 0.75-0.92; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.85, 95%CI = 0.77-0.94; P(heterogeneity)<0.001). Stratified analysis revealed that there was a statistically reduced cancer risk in Asians (TC vs. CC: OR = 0.76, 95%CI = 0.67-0.87; P(heterogeneity)<0.001; TT+TC vs. CC: OR = 0.79, 95%CI = 0.70-0.90; P(heterogeneity)<0.001) and in patients with cancers of head and neck (TC vs. CC: OR = 0.87, 95%CI = 0.77-0.99; P(heterogeneity) = 0.118; TT+TC vs. CC: OR = 0.88, 95%CI = 0.78-0.99; P(heterogeneity) = 0.168) and ovarian cancer (TC vs. CC: OR = 0.67, 95%CI = 0.49-0.90; P(heterogeneity) = 0.187; TT+TC vs. CC: OR = 0.64, 95%CI = 0.48-0.86; P(heterogeneity) = 0.199). Meta-regression showed that ethnicity (p = 0.029) and genotyping method (p = 0.043) but not cancer types (p = 0.772), sample size (p = 0.518), or source of controls (p = 0.826) were the source of heterogeneity in heterozygote comparison.

Conclusion: Our results suggest that the FASL polymorphism rs763110 is associated with a significantly reduced risk of cancer, especially in Asian populations.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Fas Ligand Protein / genetics*
Genetic Association Studies
Genetic Heterogeneity
Genetic Predisposition to Disease*
Heterozygote
Humans
Neoplasms / genetics*
Odds Ratio
Polymorphism, Single Nucleotide / genetics*
Publication Bias
Risk Factors

Substances

FASLG protein, human
Fas Ligand Protein

Grants and funding

This work was supported by the National Natural Science Foundation of China (81201830) and Natural Science Key Research Fundation of Jiangsu Province (BK2011036). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.