Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk

• Published in: Environmental science and pollution research international 2018-11, Vol.25 (31), p.31691-31704
• Main Authors: Yadav, Ravi Prakash, Ghatak, Souvik, Chakraborty, Payel, Lalrohlui, Freda, Kannan, Ravi, Kumar, Rajeev, Pautu, Jeremy L., Zomingthanga, John, Chenkual, Saia, Muthukumaran, Rajendra, Senthil Kumar, Nachimuthu
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; Aneuploidy; Aquatic Pollution; Atmospheric Protection/Air Quality Control/Air Pollution; Cancer; Carcinogens; Cell cycle; Correlation analysis; Curing; Cyclin-dependent kinase inhibitor p21; Demographics; Deoxyribonucleic acid; Diploidy; DNA; DNA damage; DNA repair; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Environmental science; Flow cytometry; Gastric cancer; Genes; Health risks; Mathematical models; MDM2 protein; Meat; Mismatch repair; MLH1 protein; Mutation; Organic chemistry; Repair; Research Article; Risk analysis; Tumors; Waste Water Technology; Water Management; Water Pollution Control
• ISSN: 0944-1344; 1614-7499
• DOI: 10.1007/s11356-018-3080-1

In the present study, we correlated the various lifestyle habits and their associated mutations in cell cycle ( P21 and MDM2 ) and DNA damage repair ( MLH1 ) genes to investigate their role in gastric cancer (GC). Multifactor dimensionality reduction (MDR) analysis revealed the two-factor model of oral snuff and smoked meat as the significant model for GC risk. The interaction analysis between identified mutations and the significant demographic factors predicted that oral snuff is significantly associated with P21 3′UTR mutations. A total of five mutations in P21 gene, including three novel mutations in intron 2 (36651738G > A, 36651804A > T, 36651825G > T), were identified. In MLH1 gene, two variants were identified viz. one in exon 8 (37053568A > G; 219I > V) and a novel 37088831C > G in intron 16. Flow cytometric analysis predicted DNA aneuploidy in 07 (17.5%) and diploidy in 33 (82.5%) tumor samples. The G2/M phase was significantly arrested in aneuploid gastric tumor samples whereas high S-phase fraction was observed in all the gastric tumor samples. This study demonstrated that environmental chemical carcinogens along with alteration in cell cycle regulatory ( P21 ) and mismatch repair ( MLH1 ) genes may be stimulating the susceptibility of GC by altering the DNA content level abnormally in tumors in the Mizo ethic population.