Correlation between hypoxia-inducible factor-1α C1772T/G1790A polymorphisms and head and neck cancer risk: a meta-analysis

Objective This meta-analysis was implemented to evaluate the association between hypoxia-inducible factor-1α (HIF-1α) C1772T/G1790A polymorphisms and susceptibility to head and neck cancer (HNC). Material and methods This meta-analysis has been registered on PROSPERO platform (CRD42021257309). The PubMed, Embase and Web of Science databases were searched to retrieve eligible published papers. STATA software was used to calculate the pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) to assess the correlation strength. Results Our results demonstrated that the HIF-1α C1772T polymorphism was significantly related to an increased HNC risk (OR = 2.27, 95% CI = 1.17–4.42 for the homozygous model; OR = 11.53, 95% CI = 1.11–120.4 for the recessive model), especially in Caucasians (OR = 2.16, 95% CI = 1.09–4.27 for the homozygous model; OR = 2.28, 95% CI = 1.15–5.51 for the recessive model). Similarly, a remarkable correlation was discovered between the G1790A polymorphism and HNC risk (OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 58.05, 95% CI = 1.70–1985.77 for the recessive model). Moreover, in the subgroup analysis by source of controls, a statistically significant correlation was discovered in the population-based (PB) subgroup (OR = 9.43, 95% CI = 1.20–73.9 for allelic model; OR = 72.11, 95% CI = 2.08–2502.4 for the homozygous model; OR = 3.22, 95% CI = 1.28–8.08 for the heterozygous model; OR = 7.83, 95% CI = 1.48–41.37 for the dominant model; OR = 58.05, 95% CI = 1.70–1985.8 for the recessive model) but not in the hospital-based (HB) subgroup. Conclusion Our study found that both HIF-1α C1772T and G1790A polymorphisms might be a higher risk of HNC, especially in the Caucasian group with the C1772T polymorphism. Supplementary Information The online version contains supplementary material available at 10.1186/s12957-021-02324-0.


INTRODUCTION
Rationale 3 Our study demonstrated that both HIF-1α C1772T and G1790A polymorphisms might be strongly related to the higher risk of HNC, especially among Caucasion group for C1772T polymorphism.  A computerized literature search was conducted by the databases of PubMed, Embase and Web of Science for identifying the qualified studies with the following terms: 'hif-1α' or 'hypoxia-inducible factor-1α' or 'hif-1' or 'hypoxia-inducible factor-1' And 'mutation' or 'mutations' or 'variants' or 'variant' or 'polymorphism' or 'polymorphisms' And 'carcinoma' or 'neoplasm' or 'tumor' or 'cancer' or 'carcinogenesis' And 'head and neck' or 'HNC' or 'oral' or 'oral cavity' or 'pharyngeal' or 'laryngeal' or 'laryngopharyngeal' or 'hypopharyngeal' or 'nasopharyngeal' or 'oropharyngeal'. Finally, we scanned references cited by all the included studies to identify eligible studies.

Study selection 9
Data collection process 10 Three authors are responsible for extracting data and two authors are responsible for verifying the correctness of the data.
Data items 11 Data have already been shown in the article.

Risk of bias in individual studies
12 OHAT risk of bias rating tool was applied to evaluate the bias risk of the included articles.
Publication bias analysis and sensitivity analysis have been performed in our study.

Summary measures
13 State the principal summary measures (e.g., risk ratio, difference in means).

Synthesis of results
14 Results have already been shown in the article.
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Section/topic # Checklist item
Risk of bias across studies 15 No publication bias was found.

Additional analyses
16 Sensitivity and subgroup analyses were performed in our study.

Study selection 17
Study characteristics 18  Results of individual studies 20 Forest plots were shown in the article. In the sensitivity analysis, no remarkable change was observed in the pooled ORs after omitting one article at a time.

21
In the subgroup analyses of C1772T polymorphism, we found C1772T polymorphism could increase the HNC risk significantly in the poly chain reaction-restriction fragment length polymorphism (PCR-RFLP) genotyping method subgroup (

Summary of evidence 24
The study discovered that HIF-1α C1772T and G1790A polymorphisms were significantly related to the susceptibility to HNC. Moreover, found that C1772T polymorphism could statistically increase the HNC risk among Caucasions at the first time. In addition, HIF-1α G1790A polymorphism was remarkably related to a higher risk of HNC, especially with OC.
Limitations 25 Some inevitable limitations existed in the meta-analysis. Firstly, the sample size in some subgroup was small, so the results from certain s analysis could not have sufficient power to confirm the relationship. Secondly, publication bias might exist because several eligible arti have not published were not enrolled in our study. Thirdly, the subgroup analyses by age, gender, alcohol, smoking, or other variables w performed because of information limitation. Therefore, it is necessary to study the role of HIF-1α C1772T and G1790A polymorphisms risk with more data and larger sample size.

Conclusions 26
In conclusion, the study discovered that HIF-1α C1772T and G1790A polymorphisms were significantly related to the susceptibility t Moreover, we found that C1772T polymorphism could statistically increase the HNC risk among Caucasions at the first time. In addition G1790A polymorphism was remarkably related to a higher risk of HNC, especially with OC. However, further well-designed papers w sample size are required to confirm our results. For more information, visit: www.prisma-statement.org.