Lifestyle chemical carcinogens associated with mutations in cell cycle regulatory genes increases the susceptibility to gastric cancer risk
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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.
KeywordsChemical carcinogens Gastric cancer Flow cytometer Cell cycle Mutation Mizo population
This work was supported by DBT—Advanced Level State Biotech Hub (BT/04/NE/2009 dt. 29.08.2014), Bioinformatics Infrastructure Facility (No. BT/BI/12/060/2012 (BTISNeT), and DBT eLibrary Consortium (DeLCON) sponsored by the Department of Biotechnology (DBT), New Delhi, Govt. of India, Mizoram University which provided all the essential facilities to carry out the work.
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Conflict of interest
The authors declare that they have no conflicts of interest to report.
Ethics, consent, and permissions
All participants gave written informed consent to the study protocol which was approved by the Ethical Committee of the Civil Hospital, Mizoram and Mizoram University, India (B.12018/1/13-CH(A)/IEC), to conduct and publish the research work. The study protocol was also approved by the Institutional Review Board of all institutes involved in the study.
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