Cancer Genetics and Epigenetics 2019, Vol.7, No.1, 1-10
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and nasopharyngeal carcinoma risk (Zhuo et al., 2009). The systematic review was conducted to further study
whether the TP53 codon 72 polymorphism plays an important effect in the form of nasopharyngeal carcinoma,
given that NPC has a high incidence in the people. So, the TP53 codon 72 polymorphism is a critical predictive
and prognostic marker for the researchers.
Our meta-analysis included a total of 1,588 nasopharyngeal carcinoma patients and 1,925 controls. The
meta-analysis indicated the persons who carry homozygote Arg/Arg genotype and heterozygote Arg/Pro have a
decreased susceptibility of NPC compared with those who carry Pro/Pro genotype
[OR 0.59, 95% CI 0.48-0.72;
OR 0.66, 95% CI 0.46-0.93]. For Arg allele, the persons who carry an integrated Arg genotype (Arg/Pro +
Arg/Arg) have an obviously decreased risk to NPC relative to the ones who with homozygote Pro/Pro genotype
[OR 0.62, 95% CI 0.45-0.68]. For Pro allele, the meta-analysis showed that the persons who with an integrated
Pro genotype (Arg/Pro + Pro/Pro) have a marked decreased susceptibility of NPC compared with the ones who
with Arg/Arg genotype [OR 0.75, 95% CI 0.64-0.87]. A positive relation of the TP53 codon 72 polymorphism and
nasopharyngeal carcinoma was demonstrated by results of the overall population. In the systematic reviews, the
current study indicated that the persons who have the homozygote Pro/Pro genotype could have increased NPC
susceptibility. In contrast, Arg carriers, particularly the persons who have homozygote Arg/Arg genotype, may
have an obvious relation in decreased risk to NPC.
Koushik et al. (2004) indicated susceptibility of both squamous cell carcinoma and adenocarcinoma were
increased by homozygote Arg/Arg genotype in cervical cancer. A non-association of TP53 codon 72
polymorphisms was showed by previous publication in lung cancer (Matakidou et al., 2003) and gastric
carcinoma (Zhou et al., 2007). And Jee et al. (2004) suggested increased susceptibility of cervical adenocarcinoma,
but it did not increase squamous cell carcinoma only associates with Arg/Arg genotype. In the present study, TP53
Arg/Arg genotype seemed unlikely to increase NPC risk, but Pro/Pro genotype may act as a risk factor.
The most often studied gene, which is often mutated in some tumors is TP53. This is unclear that the reason
underlying TP53 polymorphism increasing NPC risk. However, TP53 gene has reported a few single-nucleotide
polymorphisms (Pietsch et al., 2006). TP53 protein is thought to play an important role in apoptotic functions and
growth suppression and a proline-rich region was occurred by the polymorphism of TP53 codon 72 (Dumont et al.,
2003). Their ability of combining the transcriptional protein, suppressing the transformation and activating
transcription of some primary cells were differed by the two polymorphic variants (Chang et al., 2002). Pro
variants may induce apoptosis worse than Arg variants do, which may be attributed to the capability of the Arg
variant to locate to mitochondria and it controls the release of cytochrome C into cytosol. Thus, at least partly Pro
variant seemed to interrelate to apoptosis suppression of cells, which is an important convincing mechanism of
tumor form. The distinctive could be the reason that why the Pro allele could increase susceptibility to NPC. In
addition, TP53 gene may interact with other genes such as P73 and melanocortin 1 receptor (Nan et al., 2008).
Also, it may have a combined effect with some epidemiological factors such as smoking and alcohol consumption,
leading to NPC tumorigenesis and progression.
However, there was a number of limitations in the meta-analysis. First, various factors limit the publication,
because the publication is a secondary retrospective study, which include the used measurement tools, the original
studies quality, and study population differences, like all other meta-analyses. Second, although the publication is
very common in systematic reviews of genetic studies, statistical heterogeneity is critical. Therefore,
random-effects model analyses were performed by us to think over the factors which could have led to the high
level of heterogeneity. Third, this is the reason that the comprehensive genotype information was lacked in our
included studies, which induced using unadjusted data analyzed the results of our systematic review. And because
the strict inclusion criteria, the studies which been included is small and it is not sufficient to estimate the two
relationship. So, based on other adjusted factors, we could not form a more precise analysis. Finally, the number
of the systematic review is relatively small and we did not consider the publications for inclusion in languages
only including Chinese and English. So, in order to get more precise conclusions between the two, further
research should be studied.
