We investigated the role of mtDNA mutations in stomach cancer and performed a case–control study to evaluate the relevance of GSTM1, GSTT and GSTP1 gene polymorphisms to GC susceptibility and phenotype and to assess their interaction with other environmental and lifestyle factors, namely H. pylori and smoking habits. We sequenced the whole mitochondrial genome in an effort to characterise genome variation in this Mizo population for genetic makeup association studies.
The COXI sequences containing the mutation were evaluated for their potential pathogenicity using the PolyPhen-2, SIFT, Mutation Assessor, Condel. The sample was genotyped for GSTM1, GSTT1 and GSTP1 by PCR. The presence of H. pylori infection was determined in GC patients by multiplex PCR amplification of 16SrRNA and CagA genes. Logistic regression modelling and Multifactor dimensionality reduction (MDR) analysis estimated odds ratios (ORs) with 95%confidence intervals (CIs) were estimated between GST gene polymorphisms and clinical-demographical factor associated with gastric cancer. Complete genome assembled sequences were used for the mitochondrial haplotypes estimation by using Haplogrep server.
In the case of COI gene, 12 non-synonymous point mutations were found out of 18, including. Six missense mutations are damaging mutation with 1.00 polyphen2 and SIFT score. We also found a novel 316C > CC microsatellite instability in the conserved position of control region. The simultaneous presence of both the GSTM1 and the GSTT1 null genotypes associated with gastric cancer. rs1695 polymorphism showed a significant relation to Gastric cancer susceptibility or phenotype in the presence of H. pylori CagA genotyping. Consumption of smoked-meat/ vegetables were also significantly associated with increase in the incidence of GC. We identified several novel variants that collectively form new and unique Mizo motifs – F1d2 (T152C, G5460A, A5894G, A7445G, T16311C).
These data reveals novel mitochondrial genome signatures in this Indian population and enhance the phylogenetic picture of maternal ancestry. The analysis of D-loop, COXI and GSTs alterations might help to identify patients at high risk for Stomach cancer diagnosis.
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All authors have declared no conflicts of interest.