MDM2 and TP53 Polymorphisms as Predictive Markers for Head and Neck Cancer in Northeast Indian Population: Effect of Gene-Gene and Gene-Environment Interactions

Abstract

Background: Polymorphisms in the MDM2 309 (T>G) and TP53 72 (G>C) genes are reported to increase the susceptibility to head and neck cancer (HNC) in various populations. The risk for HNC is also strongly associated with etiologic habits such as smoking, alcohol consumption and/or chewing of betel quid (BQ). In a case-control study, we investigated the significance of the above polymorphisms alone, and upon interaction with one another as well as with various etiologic habits in determining HNC risk in a Northeast Indian population. Materials and Methods: Genotyping at 309 MDM2 and 72 TP53 in 122 HNC patients and 86 cancer free healthy controls was performed by PCR using allele specific primers, and the results were confirmed by DNA sequencing. Results: Individuals with the GG mutant allele of MDM2 showed a higher risk for HNC in comparison to those with the TT wild type allele (OR=1.9, 95%CI: 1.1-3.3) (p=0.022). The risk was further increased in females by ~4-fold (OR=4.6, 95% CI: 1.1-19.4) (P=0.04). TP53 polymorphism did not contribute to HNC risk alone; however, interaction between the TP53 GC and MDM2 GG genotypes resulted in significant risk (OR=4.9, 95% CI: 0.2-105.1) (p=0.04). Smokers, BQ-chewers and alcohol consumers showed statistically significant and dosedependent increase in HNC risk, irrespective of the MDM2 genotype. Conclusions: MDM2 genotype could serve as an important predictive biomarker for HNC risk in the population of Northeast India.

Association of the rs2279744 Promoter Polymorphism in the MDM2 Gene with Breast Cancer in a Mexican Population

“…Furthermore, the data obtained in the present study also showed that the genotype distribution of the rs2279744 MDM2 polymorphism followed Hardy-Weinberg equilibrium (P > 0.05). The genotype G/G frequencies (25%) of the rs2279744 polymorphism in the control group were similar to those previously reported in Indian (28%) [12], Chinese (25.8%) [31], and Turkish populations (29.6%) [32]. Several authors have studied the MDM2 309 T > G polymorphism, although these studies did not analyze the same markers, and the studied groups have had different compositions (e.g., regarding female, male, menopause, tumor stages, ethnic backgrounds, and ages).…”

“…Thus, polymorphisms in the MDM2 gene might impair the function of the p53-mediated stress response. Some studies have demonstrated the overexpression of MDM2 in human tumors, associated with poor prognosis [11,12]; however, other studies have not shown evidence of these associations [13][14][15][16][17][18]. Because the evidence is contradictory, the aim of the present study was to determine whether there is an association between the rs2279744 polymorphism in the MDM2 gene and BC in Mexican women.…”

Association between OGG1 Ser326Cys polymorphism and risk of upper aero-digestive tract and gastrointestinal cancers: a meta-analysis

“…Gastrointestinal tract (GI) cancers which encompasses the cancers in the digestive system including gastric cancer, colorectal cancer, esophageal cancer and pancreatic cancer present an interesting pattern in distribution over the world with major occurrences in Asia (Pourhoseingholi et al 2015 ). Both genetic and environmental factors contribute to the onset of cancer (Bhowmik et al 2015 ). Most cancers primarily involve the dysregulation of three classes of genes viz., (proto) oncogenes, tumor suppressor genes and DNA repair genes.…”

Is MDM2 SNP309 Variation a Risk Factor for Head and Neck Carcinoma?

“…The necessary information is listed in Table 1 , which contains the first author and the number and characteristics of cases and controls for each study as well as other necessary data. The selected studies included 6 groups of Caucasians, 34 , 42 – 44 , 46 , 49 8 groups of Asians, 35 – 41 , 48 and 2 groups of mixed populations. 45 , 47 …”