Increased risk of oral cancer in relation to common Indian mitochondrial polymorphisms and Autosomal GSTP1 locus.
BACKGROUND
Polymorphisms at mitochondrial (mt) loci could modulate the risk of diseases including cancers. Here the mtDNA polymorphisms at 12,308 nucleotide pairs (np), 11,467 np, 10,400 np, and 10,398 np were studied to examine the association with the risk of oral cancer and leukoplakia, alone and in combination with polymorphisms at the GST loci.


METHODS
Polymorphisms at mt loci were screened in 310 cancer, 224 leukoplakia, and 389 control individuals by polymerase chain reaction (PCR) restriction length polymorphism (RFLP) and most of the GST genotype data were taken from previously published reports. Data were analyzed to determine the risk of the diseases.


RESULTS
The major allele, A, at 12,308 np on tRNA(Leu) (CUN), increased the risk of cancer (odd ratio [OR] of 1.7; 95% confidence interval [95% CI], 1.1-2.6) but not that of leukoplakia. The same allele also appeared to increase the risk of cancer in smokers (OR of 4.0; 95% CI, 1.1-14.4), who are mostly males (OR of 1.8; 95% CI, 1.1-3-2), but not in smokeless tobacco users, who are mostly females. The major allele A at 11467 np demonstrated identical results as the major allele, A, at 12,308 np. The major alleles G at 10,398 np and T at 10,400 np (ie, M-haplogroup) increased the risk of cancer significantly in smokers (OR of 2.6; 95% CI, 1.2-5.7 and OR of 2.4; 95% CI, 1.1-5.1, respectively). The risk-risk genotype-allele combination at GSTP1 and mt12308 np loci increased the risk of cancer (OR of 2.6; 95% CI, 1.4-4.9) when compared with the nonrisk-nonrisk combination in leukoplakia patients.


CONCLUSIONS
Polymorphisms at the mt loci alone and in combination with the risk genotype at GSTP1 increased the risk of oral cancer. Thus, risk genotypes from 2 different organelles may work in combination to increase the risk of oral cancer.
Datta
Sayantan
S
Human Genetics Unit, Indian Statistical Institute, Kolkata, India.
Majumder
Mousumi
M
Biswas
Nidhan K
NK
Sikdar
Nilabja
N
Roy
Bidyut
B
D005260:Female; D050259:Genes, Mitochondrial / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D051549:Glutathione S-Transferase pi / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D007972:Leukoplakia, Oral / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000235:genetics*; D009062:Mouth Neoplasms / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D014030:Tobacco, Smokeless / Q000009:adverse effects
C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi