p21 protein is a cell cycle regulator that induces G1 arrest, leading to DNA repair or apoptosis. Previous studies have shown that p21 polymorphism in codon 31 (Ser 31 Arg) may play a role in susceptibility to cancer. However, the results from the published studies are conflicting. To derive a more precise estimation of association between the p21 Ser31Arg polymorphism and risk of cancer, we performed a meta-analysis of 33 120 cancer cases and 44 954 controls from 49 publications with 66 individual case-control studies for the polymorphism. We used odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Overall, no significant association was found between p21 Ser31Arg polymorphism and cancer risk. However, in the subgroup analysis by ethnicity, a significantly elevated risk was found among whites (for Arg/Arg versus Ser/Ser: OR = 1.48, 95% CI = 1.20-1.83; for Arg/Arg versus Ser/Arg + Ser/Ser: OR = 1.49, 95% CI = 1.20-1.83). Interestingly, when stratifying by cancer types, significantly increased risks were observed for breast cancer and 'other cancers' among whites and significantly decreased risks were found for oesophageal cancer and gastric cancer among Asians. When stratifying by sample size of studies, a significantly elevated risk was found among large sample studies (>500 subjects) but not among small sample studies (<= 500 subjects). Moreover, a significantly increased risk was observed among smokers in all models except for homozygotes comparison. This meta-analysis suggests that the p21 31Arg allele is a low-penetrant risk factor for cancer development, especially among whites.
