Association between RASSF1A Ala133Ser Polymorphism and Cancer Susceptibility: A Meta-Analysis Involving 8,892 Subjects


Background: Published studies on the association between the Ras Association Domain Family 1 isoform A(RASSF1A) Ala133Ser polymorphism and cancer susceptibility have yielded conflicting results. Thus, a metaanalysiswas here performed to assess the possible association. Materials and
Methods: All eligible case-controlstudies published up to November 2013 on the association between RASSF1A Ala133Ser polymorphism and cancersusceptibility were identified by searching PubMed, Web of Science, Science Direct and hand search. Bothfixedeffectand random-effect models were used to calculate pooled odds ratios (ORs) with 95% confidence intervals(CIs) by using the Comprehensive Meta-Analysis software version 2.2.
Results: A total of 10 studies including4,572 cancer cases and 4,320 controls were included in the meta-analysis. Overall, significantly increased cancerrisk was associated with the variant Ser133 when all studies were pooled (Ser vs Ala: OR=1.51, 95% CI=1.08-2.12, Pheterogeneity≤0.001; Ser/Ser+Ala/Ser vs Ala/Ala: OR=1.55, 95% CI=1.08-2.22, Pheterogeneity≤0.001). Moreover,in subgroup analyses by cancer types, a significant association between RASSF1A Ala133Ser polymorphismand lung cancer risk was found (Ser vs Ala: OR=2.27, 95% CI=1.29-4.02, Pheterogeneity=0.61; Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.42, 95% CI=1.33-4.42, Pheterogeneity=0.75). In addition, in subgroup analyses by ethnicity, itwas found that the RASSF1A Ala133Ser polymorphism was associated with overall cancer risk in Asians (Servs Ala: OR=1.37, 95% CI=1.06-1.77, Pheterogeneity=0.06) and Caucasians (Ser/Ser+Ala/Ser vs Ala/Ala: OR=2.21,95% CI=1.01-4.82, Pheterogeneity≤0.001).
Conclusions: This meta-analysis suggests, for the first time, that RASSF1AAla133Ser polymorphism may contribute to cancer susceptibility, especially for lung cancer. Besides, additionalwell-designed studies with larger sample size focusing on different ethnicities and cancer types are needed toconfirm these findings.