P21 (CDKN1A), a key cell cycle regulatory
protein that governs cell cycle progression from G1 to S phase, can regulate cell proliferation, growth arrest, and apoptosis. The Ser31Arg polymorphism is located in the highly conserved region of p21 and may encode functionally distinct
proteins. Although many epidemiological studies have been conducted to evaluate the association between the p21 Ser31Arg polymorphism and
cancer risk, the findings remain conflicting. This meta-analysis with 33 077 cases and 45 013 controls from 44 published case-control studies showed that the variant homozygous 31Arg/Arg genotype was associated with an increased risk of numerous types of
cancers in a random-effect model (homozygote comparison: OR = 1.17, 95% CI = 0.99 to 1.37, P = 0.0002 for the heterogeneity test; recessive model comparison: OR = 1.16, 95% CI = 1.01 to 1.33, P = 0.0001 for the heterogeneity test). Stratified analysis revealed that increased
cancer risk associated with the 31Arg/Arg genotype remained significant in subgroups of
colorectal cancer,
estrogen-related
cancer, Caucasians, population-based studies, studies with matching information or a larger sample size. Heterogeneity analysis showed that
tumor type contributed to substantial between-study heterogeneity (recessive model comparison: Χ(2) = 21.83, df = 7, P = 0.003). The results from this large-sample sized meta-analysis suggest that the p21 31Arg/Arg genotype may serve as a potential marker for increased
cancer risk.