Abstract

Caspase-8 (CASP8) is one key regulator of apoptosis of T lymphocytes and is encoded by the CASP8 gene. It has been reported that the six-nucleotide deletion polymorphism (-652 6N del) of the CASP8 gene had effect on some cancer risk. Few studies explored the association between CASP8 gene polymorphism and digestive tract cancer risk. To evaluate the association between the CASP8 -652 6N del polymorphism and the risk of digestive tract cancer, we conducted this meta-analysis. We found that CASP8-652 6N del polymorphism was associated with a significantly reduced risk of digestive tract cancer in the co-dominant model (del/del vs. ins/ins: OR= 0.82, 95%CI= 0.72–0.95; del/ins vs. ins/ins: OR= 0.92, 95%CI= 0.87–0.97; dominant model (del/ins+ del/del vs. ins/ins: OR= 0.91, 95%CI= 0.87–0.96, recessive model: del/del vs. del/ins+ ins/ins: OR= 0.85, 95%CI= 0.75–0.97). In the stratified analysis by cancer types, we found that all genetic models had protective effect on gastric cancer. Similar results were observed for colorectal cancer under heterozygote comparison and dominant model, but not under homozygote comparison or recessive model. In addition, a significantly decreased risk was found on esophageal cancer for most genetic models, except heterozygote comparison. When stratified by ethnicity and source of control, an evidently decreased risk was identified in the Asian populations and population-based studies. In conclusion, there exists an association between the CASP8 -652 6N del polymorphism and reduced digestive cancer risk, especially among Asians and population-based studies.

Highlights

  • There are 353 single-nucleotide polymorphisms (SNP) of the CASP8 reported in the dbSNP database[12]

  • We carried out a search in PubMed and Embase databases with the following keywords:

  • A significant reduced risk of digestive tract cancer was associated with the CASP8-652 6N del polymorphism for the co-dominant model; dominant model, recessive model

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Summary

Introduction

The activity of many genes influences a cell's likelihood of activating its apoptotic program[1], which is mainly regulated by caspases, a family of cysteine proteases, that play a crucial role in the development and progression of cancer[2]. Received February 2016, Revised 7 August 2017, Accepted October 2017, Epub November 2017 CLC number: R735.1–3, Document code: A The authors reported no conflict of interests. It has been reported that polymorphic variation in CASP8 influences cancer risk, such as the variant D302H (rs1045485), the 652 6N insertion/deletion (ins/del) promoter variant (rs3834129), and the IVS12-19G/A (rs3769818). Previous meta-analysis suggested CASP8 -652 6N promoter polymorphism is associated with reduced renal cell carcinoma risk[5] and breast cancer risk[10]. Given the amount of data available on the association between CASP8 -652 6N promoter polymorphism and digestive tract cancer susceptibility, we performed the meta-analysis based on published casecontrol studies

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