MDM2 SNP309 and SNP354 Are Not Associated with Lung Cancer Risk

Abstract

A single nucleotide polymorphism (SNP) in the MDM2 promoter (a T to G exchange at nucleotide 309) has been found to be associated with tumor formation. Publication of this null report is important because an association between MDM2 SNP309 and lung cancer was previously reported in two independent studies. Our findings suggest that MDM2 SNP309 is not a strong factor in lung carcinogenesis. In addition, this is the first MDM2 SNP309 report on a population consisting of Caucasians in the United States and African-Americans. A strength of the study design is that the controls consist of both population and hospital controls. (Cancer Epidemiol Biomarkers Prev 2006;15(8):1559 -61)

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).…”

The role of genetic and other biomarkers in NSCLC prognosis

“…There are controversial reports on MDM2 T309G polymorphism and its association with lung cancer. Pine et al [5] in their study showed that MDM2 T309G is not a major factor in lung carcinogenesis, whereas Zhuo et al [6] in their study confirmed that the same polymorphism might be a risk factor for lung cancer among never-smokers. Nonetheless, MDM2 inhibitors seem to have some promising effect in treatment of NSCLC.…”