TNFalpha-308G/A polymorphism as a risk factor for HPV associated cervical cancer in Indian population.
BACKGROUND
Investigation of the potential association of single nucleotide polymorphisms (SNPs) at -308 G/A and -238 G/A of Tumor necrosis factor alpha (TNFalpha) with susceptibility to HPV-16 associated cervical cancer in Indian women.


METHODS
The study included 165 histologically confirmed cases with 45 precancer and 120 cancer patients and an equal number (165) of healthy controls with normal cervical cytology. PCR-RFLP was employed to analyze TNFalpha promoter polymorphisms, which were confirmed by direct sequencing. Both patients and controls were screened for Human Papillomavirus (HPV) infection.


RESULTS
The frequency of -308 A allele in TNFalpha was significantly higher in cases compared with control subjects (21% in cases vs. 9% in controls; p<0.01), with an odds ratio of 2.7 (95% CI = 1.41-5.15). Also, women carrying A allele for this locus presented 3 times increased susceptibility to HPV 16 infection as evident from carrier genotype distribution between HPV positive cases and control subjects (24% in HPV positive cases vs. 9% in controls; p<0.01; OR = 3.1; 95% CI = 1.60-6.03). No such association was found for TNFalpha-238 (G/A) polymorphism with the risk of development of cervical cancer.


CONCLUSIONS
It suggests that SNP at -308 (G/A) of TNFalpha promoter may represent an increased risk for HPV infection and development of cervical cancer in Indian women.
Kohaar
Indu
I
Division of Molecular Genetics & Biochemistry, Institute of Cytology & Preventive Oncology (ICMR), I-7, Sector 39, Noida, India.
Thakur
Nisha
N
Salhan
Sudha
S
Batra
Swaraj
S
Singh
Veena
V
Sharma
Anita
A
Sodhani
Pushpa
P
Das
B C
BC
Sarkar
Debi P
DP
Bharadwaj
Mausumi
M
D000225:Adenine; D001483:Base Sequence; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006147:Guanine; D052162:Human papillomavirus 16 / Q000502:physiology*; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011230:Precancerous Conditions / Q000235:genetics; D015995:Prevalence; D011401:Promoter Regions, Genetic / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000821:virology*; D044465:White People / Q000235:genetics
D014409:Tumor Necrosis Factor-alpha; D006147:Guanine; D000225:Adenine