Early onset lung cancer, cigarette smoking and the SNP309 of the murine double minute-2 (MDM2) gene

Abstract

The polymorphism SNP309 (rs2279744) in the promoter region of the MDM2 gene has been shown to alter protein expression and may play a role in the susceptibility to lung cancer. The MDM2 protein is a key inhibitor of p53 and several mechanisms of MDM2/p53 interactions are presently known: modulating DNA-repair, cell-cycle control, cell growth and apoptosis. We used 635 Caucasian patients diagnosed with lung cancer before 51 years of age and 1300 healthy gender and age frequency matched population Caucasian controls to investigate the association between the MDM2 SNP309 and the risk of developing early onset lung cancer. Conditional logistic models were applied to assess the genotype-phenotype association, adjusted for smoking.Compared to the GG genotype, the adjusted ORs for the TG and TT genotype were 0.9 (95% CI: 0.7-1.5) and 1.0 (95% CI: 0.7-1.5), respectively. Also no association was found for histological subtypes of lung cancer. The strength of this study is that within young cases the genetic component to develop lung cancer may be greater. Our results indicate that the MDM2 SNP309 is not significantly associated with lung carcinogenesis but point towards gender-specific differences.

The expression of COX-2, hTERT, MDM2, LATS2 and S100A2 in different types of non-small cell lung cancer (NSCLC)

“…However, the group of non-smokers was too small for any meaningful statistical estimation (less than 10%). We did not confirm the previously published relationship between MDM2 expression and the gender of the patients [54], although we did discover higher expression levels of COX-2 and hTERT for female patients. The higher expression of those two genes may be a consequence of the different pathways of tumourigenesis and different triggers for the expression of COX-2 and hTERT, or due to potential gender-specific differences.…”

Single-nucleotide polymorphism (c.309T>G) in the MDM2 gene and lung cancer risk

“…Conversely, only one study linked the 309T allele with the risk in Caucasians, notably in SQ patients and in males (12). The data of the present study suggests that c.309T>G is not associated with the lung cancer risk among the total population, which is in line with numerous epidemiological studies conducted in Caucasians (13,17,18), African-Americans (13) and Asians (14,16,20). A previous meta-analysis study (39) concluded that the association between c.309T>G and lung cancer was statistically significant in Asians, females and never-smokers, but not in Caucasians, males, ever-smokers or among any of the individual histological types.…”

“…In the study, the frequency of the MDM2 309G alleles among the controls was 0.544, which is almost identical to the frequency observed in the Japanese (0.525) (20), Han Chinese of southeast China (0.499) (14) and Korean (0.534) (16) populations; but is significantly higher compared to the Han Chinese of northeast China (0.455) (15), Caucasian (0.346-0.393) (11)(12)(13)18,38) and African-American (0.109-0.112) (13,38) populations (Fig. 1).…”

“…1). There are conflicting studies regarding the contribution of c.309T>G to the lung cancer risk (11)(12)(13)(14)(15)(16)(17)(18)(19)21). The differences in the allele frequencies among ethnic groups may have contributed to the disparities among the previous studies.…”

“…A previous meta-analysis reported that the G/G genotype of c.309T>G was associated with a significantly increased risk for lung, colorectal, gastric and bladder cancers and a significantly decreased risk for prostate cancer (10). Molecular epidemiological studies of c.309T>G and lung cancer susceptibility (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and survival rate (22)(23)(24) have reported disparate findings. It is noteworthy that there is a large difference among African-American, Caucasian and Asian populations with respect to the 309G allele frequency in lung cancer cases (25).…”