Risk genes in head and neck cancer: A systematic review and meta-analysis of last 5 years

TL;DR: The aim of this work was to identify risk genes related to the development and progression of squamous cell carcinoma head and neck (SCCHN) and do a meta-analysis of available estimates, showing no significant association between different allelic variants of Arg72Pro rs1042522 and SCCHN risk.

About: This article is published in Oral Oncology.The article was published on 2014-03-01 and is currently open access. It has received 48 citations till now. The article focuses on the topics: Odds ratio.

Summary

INTRODUCTION

• Head and Neck Carcinoma (HNC), of which the majority are squamous cell carcinomas of the head and neck , is the sixth most prevalent cancers in mankind and, presents high morbidity and low rates of survival.
• It is known that the apoptotic and proliferation genes are involved in cancer development and these could be useful as a biomarker of this pathology.
• Systematic reviews and meta-analysis allow stronger and more generalized conclusions for identifying some models of risk markers.
• This has led to the production of an enormous number of epidemiologic papers about the relationship between genetic polymorphism and disease.
• Focused on the microenvironment (focal proliferative lesions precede cancer) or morphostasis theory (morphostatic fields maintain the normal behavior of the cell and its tissue micro-architecture), also known as There are two subtypes.

METHODS

• This study was made according to the PRISMA reporting items for systematic reviews and metaanalysis guidelines.
• The search strategy included the following keywords (variably combined): “oral cancer”, “oral cancer polymorphism”, “oncogene”, “tumor suppressor gene”, “squamous cell carcinoma”, “head and neck cancer”.
• Abstracts and titles of all the identified papers obtained by the electronic search were evaluated.
• All studies which met the inclusion criteria (presence/absence of mutation and/or polymorphism by PCR, Odd Ratios (OR) adjusted for alcohol and tobacco, 95% Confidence Intervals (CIs) were assessed in order to establish their validity and subsequent data extraction.

RESULTS

• Nineteen original reports were retrieved from 2285 potential reports that addressed the issue of DNA gene / polymorphisms and risk of SCCHN.
• Twelve of the studies were of unpaired casecontrol design, 6 studies were matched case-control, and 1 nested case-control (Table 1).
• TP53, GSTM1, and CYPA1were described in four, three, and two studies respectively, which were considered for meta-analysis.
• No study reported a significant association between this polymorphism and SCCHN risk.

DISCUSSION

• There are still numerous points that are unclear or unknown.
• 57 The ADH7A92G 23 polymorphism has been described as associated with diminished SCCHN risk.
• As well as smoking, alcohol consumption is another known cancer risk factor.
• This gene is related to an increase of tumor survival because it promotes angiogenesis and inhibits apoptosis.
• The model proposed in this work shows the genetic composition of individuals that could be at risk or protected against malignancy transformation.

Contributors

• MB conceived and coordinated the project, made all the analyses, and wrote the report.
• All authors contributed individual patient data from trials and commented on the initial surrogate-end point protocol and on drafts of the report.

Figures

Table 2. Polymorphisms studied.(*)OR adjusted by habits, age, and gender. a Reference category. NA: not calculated. SCCHN: squamous cell carcinoma head and neck; OSCC: oral squamous cell carcinoma. Bold: OR-CI95% significant association.

Figure 1.Meta-analysis of TP53 R72P polymorphism.

Table 1. Characteristics of Studies. SCCHN: squamous cell carcinoma head and neck; OSCC: oral squamous cell carcinma; CC: case-control study.AF: absolute frequency; RF: relative frequency. M: male; F: female.

Figure 2. Meta-analysis of CYP1A1 polymorphism. Study 1: Cordero et al., 2010; study 2: Amtha et al., 2009

Frequently asked questions

Q1. What are the contributions mentioned in the paper "Risk genes in head and neck cancer: a systematic review and meta-analysis of last 5 years" ?

The case-control studies guidelines of the Scottish Intercollegiate Guidelines Network and MOOSE are followed. Two members of the team ( AB, AMZ ) evaluated complete articles independently and double-blinded, to establish their quality. The papers were encoded and delivered independently to each reviewer. 

Q2. What is the role of p53 suppressor tumor gene in cancer?

It is known that the p53 suppressor tumor gene has a key role in stress cellular response, to preserve genome stability, and it is universally recognized as a human cancer marker when it is mutated. 

Q3. What is the role of the DEC1 protein in causing squamous cell?

Overexpression of the DEC1 Protein InducesSenescence In Vitro and Is Related to Better Survival in Esophageal Squamous Cell Carcinoma. 

Q4. What is the AA genotype of the ADH1B R48H gene?

59 The AA genotype of the ADH1B R48H gene encodes an enzyme that is about 40 times more active than the enzyme encoded by AG and GG genotypes. 

Q5. What is the significance of the evaluation of diagnostic markers?

The evaluation of diagnostic markers such as symptoms and genetic tests helps to increase the sensitivity or specificity of the determination of the presence/absence of malignancy. 

Q6. Who have observed inflammatory infiltrate in epithelial dysplasia?

Authors such as Piva et al. 48 have observed inflammatory infiltrate in epithelial dysplasia with overexpression of NFKB and TNF-α, establishing a connection between the cancer and inflammation. 

Q7. What is the significance of the allele G of CRYAB C-802G?

61,62 Research by Su et al. 62 showed that allele G of CRYAB C-802G is correlated to breast cancer risk, and could be useful as a clinical marker for its early detection. 

Q8. What are the main features of the model proposed in this paper?

the model proposed in this paper could fit models 1, 2, and 3 because it considers such epigenetic events as inflammation, mutational compounds such as tobacco and alcohol, and genomic stability and the cell cycle regulation process. 

Q9. What databases were used for the systematic review and meta-analysis?

The authors conducted a systematic review and meta-analysis of case-control studies from the MEDLINE, Scopus, Cochrane, and CancerLit databases between January 2007 and January 2013. 

Q10. What are the main factors that affect the incidence of cancer?

3,29 Cancer is a complex pathology, and its incidence and survival index are closely related to social, cultural and socio-economic determinants of health. 

Q11. What is the role of alanine in the squamous cell carcinoma?

Pradhan S, Nagashri MN, Gopinath KS, Kumar A.Expression profiling of CYP1B1 in oral squamous cell carcinoma: counter intuitive down regulation in tumors. 

Q12. What is the gene that encodes glutathioneStransferase Mu 1?

This gene encodes glutathioneStransferase Mu 1, which is critical to detoxification and the removal of electrophilic carcinogens. 

Q13. What is the definition of a risk polymorphism?

The identification of a predictive model of risk polymorphisms could help in early diagnosis, and in understanding disease recurrence and/or progression in the subset of patients. 

Q14. What was the search strategy used to identify grey literature?

A search was made of combined electronic databases, and the bibliographies of all selected papers were searched to identify grey literature.