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Sequence and expression variations in 23 genes involved in mitochondrial and non-mitochondrial apoptotic pathways and risk of oral leukoplakia and cancer

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Sequence and expression variations in 23 genes involved in mitochondrial and non-mitochondrial apoptotic pathways and risk of oral leukoplakia and cancer
 
Creator Datta, Sayantan
Ray, Anindita
Singh, Richa
Mondal, Pinaki
Basu, Analabha
De Sarkar, Navonil
Majumder, Mousumi
Maiti, Guruparasad
Baral, Aradhita
Jha, Ganga Nath
Mukhopadhyay, Indranil
Panda, Chinmay
Chowdhury, Shantanu
Ghosh, Saurabh
Roychoudhury, Susanta
Roy, Bidyut
 
Subject Molecular & Human Genetics
 
Description Oral cancer is usually preceded by pre-cancerous lesion and related to tobacco abuse. Tobacco carcinogens damage DNA and cells harboring such damaged DNA normally undergo apoptotic death, but cancer cells are exceptionally resistant to apoptosis. Here we studied association between sequence and expression variations in apoptotic pathway genes and risk of oral cancer and precancer. Ninety nine tag SNPs in 23 genes, involved in mitochondrial and non-mitochondrial apoptotic pathways,were genotyped in 525 cancer and 253 leukoplakia patients and 538 healthy controls using Illumina Golden Gate assay. Six SNPs (rs1473418 at BCL2; rs1950252 at BCL2L2; rs8190315 at BID; rs511044 at CASP1; rs2227310 at CASP7 and rs13010627 at CASP10) significantlymodified risk of oral cancer but SNPs only at BCL2, CASP1and CASP10 modulated risk of leukoplakia. Combination of SNPs showed a steep increase in risk of cancerwith increase in “effective” number of risk alleles. In silico analysis of published data set and our unpublished RNAseq data suggest that change in expression of BID and CASP7 may have affected risk of cancer. In conclusion, three SNPs, rs1473418 in BCL2, rs1950252 in BCL2L2 and rs511044 in CASP1, are being implicated for the first time in oral cancer. Since SNPs at BCL2, CASP1 and CASP10modulated risk of both leukoplakia and cancer, so, they should be studied inmore details for possible biomarkers in transition of leukoplakia to cancer. This study also implies importance of mitochondrial apoptotic pathway gene (such as BCL2) in progression of leukoplakia to oral cancer.
 
Publisher Elsevier
 
Date 2015
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/2454/1/MITOCHONDRION__Vol._25_%2C_28%2D33;_2015.pdf
Datta, Sayantan and Ray, Anindita and Singh, Richa and Mondal, Pinaki and Basu, Analabha and De Sarkar, Navonil and Majumder, Mousumi and Maiti, Guruparasad and Baral, Aradhita and Jha, Ganga Nath and Mukhopadhyay, Indranil and Panda, Chinmay and Chowdhury, Shantanu and Ghosh, Saurabh and Roychoudhury, Susanta and Roy, Bidyut (2015) Sequence and expression variations in 23 genes involved in mitochondrial and non-mitochondrial apoptotic pathways and risk of oral leukoplakia and cancer. Mitochondrion, 25. pp. 28-33.
 
Relation http://dx.doi.org/10.1016/j.mito.2015.09.001
http://www.eprints.iicb.res.in/2454/