Association of the Polymorphisms in the <i>Fas/FasL</i> Promoter Regions with Cancer Susceptibility: A Systematic Review and Meta-Analysis of 52 Studies

<div><p>Fas and its ligand (FasL) play an important role in apoptosis and carcinogenesis. Therefore, the potential association of polymorphisms in the <i>Fas</i> (-670A>G, rs1800682; -1377G>A, rs2234767) and <i>FasL</i> (-844C>T, rs763110) with cancer risk has been widely investigated. However, all the currently available results are not always consistent. In this work, we performed a meta-analysis to further determine whether carriers of the polymorphisms in <i>Fas</i> and <i>FasL</i> of interest could confer an altered susceptibility to cancer. All relevant data were retrieved by PubMed and Web of Science, and 52 eligible studies were chosen for this meta-analysis. There was no association of the <i>Fas</i> -670A>G polymorphism with cancer risk in the pooled data. For the <i>Fas</i> -1377G>A and <i>FasL</i> -844C>T polymorphisms, results revealed that the homozygotes of -1377A and -844C were associated with elevated risk of cancer as a whole. Further stratified analysis indicated markedly increased risk for developing breast cancer, gastric cancer, and esophageal cancer, in particular in Asian population. We conclude that carriers of the <i>Fas</i>-1377A and the <i>FasL</i> -844C are more susceptible to the majority of cancers than non-carriers.</p></div

Flow chart of studies identified according to inclusion and exclusion criteria.

<p>Flow chart of studies identified according to inclusion and exclusion criteria.</p

Additional file 1: Table S1. of Genetic analysis of phytoene synthase 1 (Psy1) gene function and regulation in common wheat

Primers used for the RNAi vector construction and positive transgenic line detection. (DOCX 16.7 kb

Additional file 3: Table S3. of Genetic analysis of phytoene synthase 1 (Psy1) gene function and regulation in common wheat

Primers developed for qRT-PCR analysis. (DOCX 17.5 kb

Begg's funnel plot of Egger's test for publication bias for three polymorphisms.

<p>Each circle represents as an independent study for the indicated association. Log[OR], natural logarithm of OR. Horizontal lines mean effect size. A: Begg's funnel plot of publication bias test for <i>Fas</i> -670A>G polymorphism. B: Begg's funnel plot of publication bias test for <i>Fas</i> -1377G>A polymorphism. C: Begg's funnel plot of publication bias test for <i>FasL</i> -844C>T polymorphism.</p

<i>Fas</i> and <i>FasL</i> mRNA expression by the ethnicity, using data from the HapMap¹.

<p>CEU: 90 Utah residents with ancestry from northern and western Europe; YRI: 90 Yoruba in Ibadan, Nigeria; Asian: 45 unrelated Han Chinese in Beijing and 45 unrelated Japanese in Tokyo.</p>1<p>Genotyping data and mRNA expression levels for <i>Fas</i> and <i>FasL</i> by genotypes were obtained from the HapMap phase II release 23 data from EBV-transformed lymphoblastoid cell lines from 270 individuals.</p>2<p>Two-side Student's <i>t</i> test within the stratum was used.</p>3<p>There were missing data for unavailable genotyping data.</p><p>Statistically significant results were in bold.</p

Stratified analyses of the <i>Fas</i> -1377G>A (rs2234767) polymorphism and cancer.

a<p>Number of comparisons.</p>b<p><i>P</i> value of <i>Q</i>-test for heterogeneity test.</p>c<p>Random-effect model was applied when P value for heterogeneity <0.05; otherwise, fixed-effect model was applied.</p><p>Statistically significant results were in bold.</p

Forest plots of effect estimates for <i>Fas</i> -1377G>A polymorphism (AA vs GG).

<p>For each of the studies, the estimation of OR and its 95% CI is plotted with a <i>box</i> and a <i>horizontal line</i>. <i>Filled diamond</i> pooled OR and its 95% CI.</p

Stratified analyses of the <i>FasL</i>-844C>T (rs763110) polymorphism and cancer.

<p>PCR-RFLP: restriction fragment length polymorphism.</p>a<p>Number of comparisons.</p>b<p><i>P</i> value of <i>Q</i>-test for heterogeneity test.</p>c<p>Random-effect model was applied when P value for heterogeneity <0.05; otherwise, fixed-effect model was applied.</p><p>Statistically significant results were in bold.</p

Forest plots of effect estimates for rs11614913 stratified by country (TT vs CC+CT).

<p>For each studies, the estimate of OR and its 95% CI is plotted with a <i>box</i> and a <i>horizontal line</i>. <i>Filled diamond</i> pooled OR and its 95% CI.</p