Impacts of TNF-LTA SNPs/Haplotypes and Lifestyle Factors on Oral Carcinoma in an Indian Population.
To investigate a potential association between single-nucleotide polymorphisms (SNPs) and  haplotypes at the TNFA-LTA locus and the development of oral cancer in an Indian population.



In this study, 150 oral precancer/cancer samples (50 precancer and 100 cancer), along with an equal number of control samples, were genotyped. Six SNPs at the TNF-LTA locus (i.e., -238G/A, -308G/A, -857C/T, -863C/A, -1031T/C, and +252A/G) were analyzed by use of a polymerase chain reaction-restriction fragment length polymorphism method, the assay was validated by sequencing 10 % of samples.



The allelic frequencies of TNFA and LTA SNPs were found to be significantly associated with the risk of oral cancer and precancerous lesions in comparison with controls (P < 0.0003). Further haplotypic analysis showed that two haplotypes (ATCTGG and ACACGG) served as risk haplotypes for oral cancer. These haplotypes were also found to be significantly and positively associated with lifestyle habits (tobacco chewing P = 0.04, odds ratio [OR] 3.4) and socioeconomic status (P = 0.01, OR 3.4). We noticed an increased percentage of risk haplotypes correlating with the aggressiveness of oral cancer. The percentages of risk haplotypes were found to be threefold higher in precancer and fourfold higher in advanced stages of oral cancer in comparison with controls.



Five SNPs at the TNF-LTA locus (i.e., -308G>A, -857C>T, -863C>A, -1031T>C, and +252A>G) were found to be associated with the development of oral cancer. Two haplotypes (ATCTGG and ACACGG) emerged as major risk haplotypes for oral carcinoma progression and were also found to be associated with lifestyle factors and clinical aggressiveness. These findings make the TNF-LTA locus a suitable candidate for a future biomarker, which may be used either for early detection or for helping to improve treatment efficacy and effectiveness.
Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India.
Kapil
K
Bandil
Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India.
Pallavi
P
Singhal
Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India.
Upma
U
Sharma
Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India.
Showket
S
Hussain
Barasat Cancer Hospital, Kolkata, India.
Surojit
S
Basu
Division of Molecular Immunology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India.
Aditya
A
Parashari
Division of Clinical Oncology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India.
Veena
V
Singh
Division of Epidemiology and Biostatistics, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India.
Ashok
A
Sehgal
Department of Oral Pathology, Institute of Technology and Science, Greater Noida, India.
Animesh
A
Shivam
Department of Oral Pathology, Institute of Technology and Science, Greater Noida, India.
Puneet
P
Ahuja
Division of Molecular Genetics and Biochemistry, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, 20130, India. bharadwajm@icmr.org.in.
Mausumi
M
Bharadwaj
Department of Biochemistry, University College of Medical Sciences, University of Delhi Dilshad Graden, Delhi-65, India.
Basu Dev
BD
Banerjee
Division of Cytopathology, Institute of Cytology and Preventive Oncology (ICMR), I-7, Sector-39, Noida, India.
Ravi
R
Mehrotra
D000328:Adult; D000483:Alleles; D002277:Carcinoma / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008019:Life Style; D008233:Lymphotoxin-alpha / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012923:Social Class; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha