Association between p21 Ser31Arg polymorphism and cancer risk: a meta-analysis

Abstract

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: χ2 = 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.

Genetic risk association of CDKN1A and RET gene SNPs with medullary thyroid carcinoma: Results from the largest MTC cohort and meta‐analysis

“…CDKN1A activity is regulated by p53 which binds to its promoter and induces cell cycle arrest in response to various stimuli . This gene is often deregulated in human cancers with altered expression reported in several cancers including cervical, breast, ovarian, liver, uterine, and head and neck cancers . The CDKN1A SNP (rs1801270) at codon 31 (Ser31Arg) reported in the present study falls in a highly conserved N‐terminal region of the protein, which is demonstrated to contain tumor suppressor function .…”

The Multifaceted p21 (Cip1/Waf1/CDKN1A) in Cell Differentiation, Migration and Cancer Therapy

“…Epigenetically silencing through long non-coding RNAs happens frequently [149] and was recently detected in cholangiocarcinoma [150]. Additionally, diverse single nucleotide polymorphisms of p21 are reported to influence the risk of developing cancers including esophageal [151], colorectal and estrogen-related cancer [152], associated with a higher risk of second primary malignancies in head and neck carcinoma [153].…”

Identification of key proteins in the signaling crossroads between wound healing and cancer hallmark phenotypes

“…The CDKN1A gene was initially considered as a potential tumor suppressor. However, studies have reported that this gene could act as an oncogene due to its anti-apoptotic activities 100 , 101 . It is involved in p53-mediated inhibition of cell proliferation in response to DNA damage leading to cell cycle arrest at the G1/S checkpoint 102 , 103 .…”