ANALYSIS OF THE ASSOCIATION OF POLYMORPHISM OF THE TLR4 896 A>G GENES
(rs4986790) AND iNOS -1173 C>T (rs9282799) WITH CANCER SUSCEPTIBILITY
CERVICAL IN WOMEN INFECTED BY HPV IN A SAMPLE OF
POPULATION OF ALAGOAS, BRAZIL
Polymorphism. Cervical cancer. HPV.
Cervical cancer is one of the leading causes of death among women worldwide, representing
the fourth most frequent and fourth leading cause of cancer death in the female population
worldwide. In addition, immunological and genetic factors such as Single Nucleotide
Polymorphisms (SNPs) present in host genes may play an important role in virus clearance or
cervical cancer susceptibility, such as SNPs in Toll-like 4 receptor genes (TLR4) and
Inducible Nitric Oxide Synthase (iNOS). In view of the above, the present study aims to
evaluate the influence of TRL4 896A>G (rs4986790) and iNOS -1173C>T (rs9282799)
polymorphisms on cervical cancer susceptibility in HPV-infected women in a sample of the
population of Alagoas. This is a case-control study, where 99 samples were genotyped for the
TLR4 gene (72 healthy controls, 27 cases of HPV+ cervical cancer) and 120 samples for
iNOS (82 healthy controls, 38 cases of HPV+ cervical cancer). using the Polymerase Chain
Reaction (PCR) technique in real time. The results referring to SNP 896A>G in the TLR4
gene showed a statistically significant difference in the comparison of allele and genotypic
frequencies, where the G allele (p=0.015; OR with 95% CI=5.875 [1.414-24.405]) and the
A/G genotype were associated with increased risk of cervical cancer (p=0.012; OR with 95%
CI=6.571 [1.512-28.565]). This demonstrates that when comparing the ancestral A/A
genotype with the A/G heterozygote, the presence of a G allele was sufficient to increase the
risk. The sampling power was 100%. The results of the meta-analysis of the TLR4 896A>G
polymorphism performed in this work did not show significant associations, differing from
the results found in the population of the agreste of Alagoas. This fact can be explained by the
scarcity of association studies between the SNP TLR4 896 A>G (rs4986790) and cervical
cancer, as well as the low sample number of studies included in the meta-analysis. In the
overall analysis of the correlation between iNOS gene polymorphism and cervical cancer, no
association was found. The rare genotype -1173T/T was not identified in any group and the
heterozygote -1173T/C had a low frequency in this population. It can be concluded that the G
allele in the SNP TLR4 896A>G represents a risk factor for cervical cancer in the population
of the agreste of Alagoas. In the meta-analysis of other populations, no associations were
found. The iNOS -1173C>T SNP was not associated with cervical cancer in this population.
However, the results regarding the polymorphism of the iNOS -1173 C>T gene are
inconclusive due to the limited sample size, which presented a low sampling power. Thus,
further studies with a larger sample number are needed in order to elucidate the influence of
this polymorphism on the cervical carcinogenesis process, since the number of current studies
is limited.