The cell cycle regulatory gene polymorphisms TP53 (rs1042522) and MDM2 (rs2279744) in lung cancer: a meta-analysis

Abstract

Lung cancer is one of the most common types of cancer in the world. Although the mechanism of lung cancer is still unknown, a large number of studies have found a link between gene polymorphisms and the risk of lung cancer. The tumor suppressor p53 plays a crucial role in maintaining genomic stability and tumor prevention. MDM2 is a critical regulator of the p53 protein. Despite the importance of p53 pathway in cancer, data on the contribution of SNPs of TP53 (rs1042522) and MDM2 (rs2279744) to the development of lung cancer are very contradictory. A metaanalysis that collects quantitative data from individual studies and combines their results has the advantage of improving accuracy, providing reliable estimates, and resolving those issues in which studies on individual associations are not effective enough. The aim of this study was to determine whether the TP53 (rs1042522) and MDM2 (rs2279744) polymorphisms confer susceptibility to lung cancer. A meta-analysis was conducted on the associations between the TP53 (rs1042522) and MDM2 (rs2279744) polymorphisms and lung cancer. A total of 51 comparison studies including 25,366 patients and 25,239 controls were considered in this meta-analysis. The meta-analysis showed no association between lung cancer and MDM2 (rs2279744) under any model. A noteworthy association of TP53 (rs1042522) with susceptibility to lung cancer in overall pooled subjects was observed under three different models (allele contrast, homozygote contrast (additive) and dominant). Stratification by ethnicity indicated an association between the TP53 (rs1042522) and lung cancer in Asians and Caucasians. This meta-analysis demonstrates that the TP53 (rs1042522), but not MDM2 (rs2279744) polymorphism may confer susceptibility to lung cancer.

Association between a polymorphic variant in the CDKN2B‐AS1/ANRIL gene and pancreatic cancer risk

“…It has been observed that common, low‐penetrance genetic polymorphisms in or near genes harbouring high‐penetrance germline mutations are associated with the genetic susceptibility to develop cancer. For example, the CHEK2 and BRCA1 genes for breast cancer, 11 the TERT gene for melanoma, 12 the CDKN2A/2B genes for PDAC and pancreatic neuroendocrine tumours 13,14 and the p53 gene for multiple cancers have both high‐penetrance and low‐penetrance variants that contribute to the disease risk 15‐18 . Even though this phenomenon is not widespread, at least according to the current literature, exploring common variants in genes known to harbour high‐penetrance variants in PDAC could still be valuable for understanding the risk of developing PDAC.…”

The Association between Single Nucleotide Polymorphisms rs1042522 and rs1642785 in the TP53 gene and Acute Myeloid leukemia in a sample of the Baghdad/ Iraq population

“…The substitution of this amino acid affects the structure and function of the p53 protein by causing structural modifications 10 . The rs1042522 SNP was investigated for its role in disease risk for the vast majority of common types of cancer, including prostate, breast, and lung cancers [11][12][13] . Another SNP, rs1642785, is found on intron 2 of the TP53 gene and is associated with an increased cancer risk 14 .…”