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Journal of Genomics in PubMed Central. International Journal of Biological Sciences. International Journal of Medical Sciences. Global reach, higher impact. J Cancer ; 6 4: However, the conclusions are inconsistent. Oral cancer is one of the most commonly occurred cancers worldwide and causes leei considerable problem to human health being a high mortality rates and disfigurement [ 12 ].
Despite advances in treatment for OSCC, the 5-year survival rate remains undesirable [ 4 – 6 ]. Hence, investigating the risk factors and developing the early diagnosis for treatment and prevention of OSCC are urgently needed. Epidemiological studies showed that OSCC have been associated with high tobacco abuse and alcohol consumption [ 7 – 11 ]. However, not all individuals who have smoking and alcohol habits develop this fatal disease, suggesting that individual genetic factor may also be involved in disease etiology.
The research results of human genome project HGP have demonstrated that different individuals are all Therefore, inter-individual kei in expression of SNPs might contribute to variability in risk towards various types of cancers including OSCC. Currently, the published evidences showed that there were significant associations of gene polymorphisms with the susceptibility of many cancers, such as Glutathione S-transferase GSTs and Cytochrome P A1 CYP1A1 gene polymorphisms with lung of squamous cell carcinoma, polymorphism of 8q24 rsl with risk of breast cancer, CYP1A1 and GSTs gene polymorphisms with head and neck cancer [ 12 – 19 ].
CYP1A1 is a member of the CYP family that participates in the metabolism of xenobiotics and endogenous compounds, encoding for the aryl hydrocarbon hydrolase AHHwhich is involved in activation of polycyclic aromatic hydrocarbon PAHs and aromatic amines and is expressed in oral tissue [ 25 ]. According to the published studies, the CYP1A1 have several single nucleotide polymorphisms, which may alter the activities of their enzymes and increase carcinogen activation and yield to carcinogenicity.
We searched the following databases: Pubmed, Web of Science, Ovid and Embase 1136 without language limitations, and the last research was updated on August 8, The search process was designed to find primarily all relevant articles and the search strategies were listed as follows: Searched results were in dependently screened by two authors according to the titles, abstracts and types of articles, and irrelevant papers were dropped out.
Manual review of the references cited in the selected articles was undertaken to obtain articles that might have been missed in the search process. Then we downloaded the relevant papers and further screened to identify 11063 eligible studies. If essential data were not provided in the original articles, every effort was made to contact the authors. All relevant case-control studies were screened, irrespective of languages. In the meta-analysis, the following criteria were set and reviewed by two independent authors Xiao-Lei Yang and Shang Xie: For conflicting evaluation, an agreement was pei following a discussion.
If a consensus could not be attained, another author was invited to solve the dispute and then a final result was made by the majority of the votes.
After rigorous searching, we viewed all papers in accordance with the criteria defined above for further lej. All data was independently reviewed and extracted from the included papers by pei investigators. Differences between reviewers were solved by discussion, or through consultation if necessary. The following characteristic were collected from each study, ethnicity, country, sample size, control source, matching contents, the Hardy-Weinberg Equilibrium HWEand genetic distribution of cases and controls.
When the data were not clear nor presented by the author in the publication, contacting them for further details were attempted. The NOS system categorizes into three dimensions including selection, comparability, and ascertainment of outcome.
A star system is leo to assess the quality of all selected studies. The scores of NOS ranges from zero the lowest to nine the highest stars, with more stars indicating a better methodological quality. The assessment was performed independently by two investigators and the inconformity was solved by a discussion, or consultation if necessary.
In order to calculate heterogeneity of studies, the Chi-Square test li used and significance was set at P value less than 0. The inconsistency index I 2 was calculated to assess the variation caused by heterogeneity.
The funnel plot was used to test the underlying publication bias, and the funnel plot asymmetry was estimated by Egger’s linear regression [ 31 ]. Sensitivity analyses were performed to identify the influence of the individual studies on the combined OR.
In the analysis, we excluded each study to assess if stability between the remaining studies was reached. According to the Cochrane Handbook, meta-analyses and systematic reviews are considered to be the best available evidence if all eligible trials are included.
However, ‘the best available evidence’ ,ei not be always equal to ‘sufficient evidence’. Based on this issue, we applied the TSA to estimate the power of the current conclusions [ 32 – 34 ]. As shown in Figure 1a total of studies were retrieved by the literature search. And one potential eligible article was obtained by screening the references of reviews. After more detailed assessment for the left 43 potential eligible articles, one article was excluded for animal study; two papers were reviews.
Besides, six papers were excluded because 110366 failing to provide sufficient data. In addition, seven studies were excluded because the cases just were diagnosed oral cancer, were not confirmed the identification of OSCC. And two studies were excluded as they were concerned of prognosis and only contained the cases, lacking of controls.
11063 Finally, 13 papers [ 20 – 2435 – 42 ] were conformed to the inclusion criteria and they were eligible for the meta-analysis of CYP1A1 IleVal polymorphism. We established a database concerning of the information extracted from each included paper. Summaries of these studies were presented in Table 1 which included the first author, ethnicity, country, number and characteristics of cases and controls, and other relevant information.
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Of the 13 studies included in this meta-analysis, eight studies were performed in Asians, four in Caucasians, and one in kei race. The number of cases and controls in the papers included in this lri for varied from 31 to60 torespectively. According to NOS system, of all observational studies are awarded a maximum of four stars in selection, two stars in comparability, and three stars in exposure. In this meta-analysis, the assessment results for the selected studies ranges from six to eight stars Table 1indicating all of the selected studies are moderate-high qualities in methodology.
In order to further explore the observed heterogeneity in dominant model ldi additive model, subgroup analyses were performed by ethnicity, source of control, and HWE and the details were shown in Table 2.
The details of allele comparing model were also shown in the Table 2. The Begg’s funnel plot was used to evaluate the possible publication bias. Besides, the Begg’s test and Egger’s linear regression were used to the quantitative evaluation of the symmetry of the meta-analysis funnel plots and the results were as follows: The data of all four models indicated that there were not significant publication biases for all them.
In order to evaluate the stability of the results and reveal the influence of each study on lel pooled ORs, sensitivity analysis were performed by excluding each case-control study respectively. When all of the four models were performed sensitivity analysis, the estimates in these four models changed between lower CI limits and upper CI limits, suggesting the results in this meta-analysis were stable.
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Using the recessive model including 10 trials with subjects as an example, we performed the TSA and found that the required information size to demonstrate clear conclusions was subjects Figure 3. The cumulative z-curve does not cross the trial monitoring boundary before reaching the required power, which indicates that the cumulative evidence is insufficient and further trials are necessary Figure 3.
The results of other models were not shown as the study methods were similar. Oral cancer is the cancer of mouth, including squamous cell carcinoma, adenocarcinoma, verrucous carcinoma, and so on. Different histopathologic types of cancers might have different genetic susceptibilities, for example, CYP1A1 IleVal polymorphism is a risk factor of squamous cell carcinoma of lung, but the associations vary in different histological types of lung cancer [ 1743 ].
Therefore, it is more reasonable to assess the association of gene polymorphisms with risks of OSCC, oral adenocarcinoma and other types, separately. The solid line represents the cumulative Z-curve. The dashed curve represents the trial sequential monitoring boundary. Although there were two previous meta-analyses [ 4445 ] concerning of CYP1A1 IleVal polymorphism and risks of oral cancer, the results did not involve in single histopathologic type and therefore they failed to be on behalf of the association of CYP1A1 IleVal polymorphism with OSCC risk.
For instance, Singh, et al. However, the cases included in this research are OSCC and verrucous carcinoma.
Based on what mentioned above and for obtaining a powerful conclusion concerning about risks of OSCC and CYP1A1 IleVal polymorphism, we performed this systematical meta-analysis to evaluate it. As for the other three models homozygous model, dominant model and allele comparing modelthey failed to show obvious association between CYP1A1 IleVal polymorphism and OSCC risk, and the heterogeneities among studies were observed in them, respectively.
In order to explore the source of heterogeneity, we performed the subgroup analyses. After the subgroup analyses by ethnicity, source of control, HWE, the heterogeneities were not removed, indicating that other factors, such as age, gender, country, lifestyle, social status, smoking and alcohol habits might also yield to heterogeneities.
The confused results may be resulted from few studies, few subjects, or other potential factors, and the more credible conclusions need the future studies containing large sample sizes and well-designed criteria to confirm.
Inevitably, several disadvantages should be noticed. First, the selected papers only involved in data of Asia, America, Europe, but without the lel data about Africa and Australia.
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People come from different places may share different genotypes, thus, applicability of the results are limited. Second, in the current meta-analysis, only 13 articles with cases and controls were included. Therefore, the study might only have limited statistical power. Third, we performed a subgroup analysis by ethnicity, source of control, HWE, but the other factors, such as gender, age, were not performed for data limitations.
Finally, heterogeneity was existed, which might weaken the reliability of conclusions. Based on the limitations mentioned above, the results should be considered with caution. Overall, in spite of these limitations, the results of this analysis suggest that the homozygous variant might be a risk factor of OSCC. And future studies focusing on CYP1A1 IleVal polymorphism containing large sample sizes and well-designed criteria are necessary to make the conclusions more credible.
Oral cancer prevention and control–the approach of the World Health Organization. Pathology and genetics of head and neck tumours: Kaohsiung J Med Sci. Surgery alone for squamous cell carcinoma of the oral cavity: P-cadherin expression and survival rate in oral squamous cell carcinoma: Prevalence and correlation of oral lesions among tobacco smokers, tobacco chewers, areca nut and alcohol users.
Asian Pac J Cancer Prev. Epidemiology of oral cancer in Asia in the past decade–an update Smoking lsi drinking in relation to oral and pharyngeal cancer.