Abstract
Background Evasion of apoptosis is a hallmark of cancer. Genetic polymorphisms in apoptosis-related genes can potentially alter apoptotic efficacy, which in turn influence risk of cancer. In this study, we investigated the association of three apoptosis-related genetic polymorphisms, namely FAS −670A>G, p53 codon 72, and MDM2 309T>G polymorphisms with HPV-mediated cervical cancer risk in the multiethnic Malaysian population. Methods 95 patients with histopathologically confirmed cervical cancer and 95 cancer-free healthy females were recruited into this case-control study. HPV types were determined by use of flow-through hybridisation technique. The polymorphisms were genotyped with the PCR-RFLP method. Logistic regression analysis was performed to measure the risk association present. Findings Variant genotypes of FAS and MDM2 polymorphisms were associated with increased cervical cancer risk (odds ratio (OR) 3.360, 95% confidence interval (CI) 1.494–7.556, p = 0.003 and OR 3.381, 95% CI 1.521–7.512, p = 0.003, respectively). The association of the FAS variant genotype was only significant among participants of Malay ethnicity (OR 5.377, 95% CI 2.085–13.865, p = 0.001), whereas significance of the MDM2 polymorphism was not observed in all ethnic groups. When stratified by patient HPV type, the association of the FAS polymorphism remained significant only in cervical cancers mediated by HPV16 (OR 3.333, 95% CI 1.127–9.863, p = 0.030) and ‘other’ HPV types (OR 6.00, 95% CI 1.565–23.007, p = 0.009), whereas MDM2 polymorphism remained significant only in HPV16-mediated cancer (OR 4.740, 95% CI 1.525–14.729, p = 0.007). Significant associations were also observed for various FAS -p53 and FAS - MDM2 , but not p53- MDM2 , combination genotypes. Interpretation FAS −670A>G and MDM2 309T>G polymorphisms could play a role in modulating cervical cancer risk among Malaysian women. This study is being continued with a larger sample size.
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