Abstract
Cell cycle deregulation is a major component of carcinogenesis. The p53 tumor suppressor gene plays an important role in regulating cell cycle arrest, and mouse double minute 2 (MDM2) is a key regulator of p53 activity and degradation. Abnormal expression of p53 and MDM2 occurs in various cancers including lung cancer. We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female non- smokers. Genotypes of 764 patients and 983 healthy controls were determined using the TaqMan SNP genotyping assay. The p53 Pro/Pro genotype (adjusted OR = 1.55, 95% CI = 1.17-2.06) significantly correlated with an increased risk of lung adenocarcinoma, compared with the Arg/Arg genotype. An increased risk was also noted for MDM2 GG genotype (adjusted OR = 1.68, 95% CI = 1.27-2.21) compared with the TT genotype. Combined p53 Pro/Pro and MDM2 GG genotypes (adjusted OR = 2.66, 95% CI = 1.54-4.60) had a supermultiplicative interaction with respect to lung adenocarcinoma risk. We also found that cooking oil fumes, fuel smoke, and passive smoking may increase the risk of lung adenocarcinomas in Chinese female non-smokers who carry p53 or MDM2 mutant alleles. P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers.
Highlights
Lung cancer is one of the leading causes of cancerrelated deaths in the world (Jemal et al.,2011)
We investigated the distribution of the p53 Arg72Pro and mouse double minute 2 (MDM2) SNP309 genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female nonsmokers
An increased risk was noted for MDM2 GG genotype compared with the TT genotype
Summary
Lung cancer is one of the leading causes of cancerrelated deaths in the world (Jemal et al.,2011). Unlike smokers, who commonly develop squamous cell carcinomas, nonsmokers (especially females) are more likely to develop adenocarcinomas (Zang et al, 1996), suggesting that genetic susceptibility and environmental factors may differentially affect lung cancer development. Single nucleotide polymorphisms (SNPs) in several genes involved in carcinogen metabolism, DNA damage repair, cell cycle control, and apoptosis are reported to be associated with lung cancer (Wu et al, 2002; Li et al, 2008; Yin et al, 2009). Methods: We investigated the distribution of the p53 Arg72Pro (rs1042522) and MDM2 SNP309 (rs2279744) genotypes in patients and healthy control subjects to assess whether these single nucleotide polymorphisms (SNPs) are associated with an increased risk of lung adenocarcinomas in Chinese female nonsmokers. Conclusions: P53 Arg72Pro and MDM2 SNP309 polymorphisms, either alone or in combination, are associated with an increased lung adenocarcinoma risk in Chinese female non-smokers
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
