Abstract
Purpose: Multiple genome-wide and candidate-gene association studies have been conducted to search for common risk variants of breast cancer. Recent large meta-analyses and consolidating evidence have highlighted the role of the caspase-8 gene in breast cancer pathogenesis. Therefore, this study aimed to identify common variations and haplotypes associated with risk and overall survival of breast cancer with respect to underlying susceptibility variants in the CASP8 gene region in a group of the Iranian population. Methods: In a case-control study with a total of 1008 samples (455 cases and 553 controls), genotyping of 12 candidate polymorphisms, consisting of rs3834129, rs2037815, rs7608692, rs12990906, rs3769821, rs6435074, rs3754934, rs3817578, rs10931936, rs1045485, rs1045487, and rs13113, were performed using PCR-based methods, including ARMS-PCR, AS-PCR, RFLP-PCR, HRM-PCR, and TaqMan-PCR. Results: rs3834129, rs3754934, rs12990906, and rs10931936 were associated with the risk and overall survival of breast cancer. Several haplotypes were also identified an associated with a higher risk of breast cancer, including a three-SNP haplotype rs3817578-rs10931936-rs1045485 [p < 0.001, OR = 1.78(1.32–2.41)]. rs3754934-C allele showed an association with a lower risk of death in all patients [p = 0.022; HR = 0.46(0.23–0.89)] and in the hormone-receptor-positive group [p = 0.038; HR = 0.37(0.14–0.95)], as well as CC genotype in the hormone-receptor-positive group [p = 0.002; HR = 0.09(0.02–0.43)]. Conclusion: The present study suggests a diagnostic and prognostic role of CASP8 gene variations in breast cancer. The risky haplotypes are likely to have one or more underlying breast cancer susceptibility alleles. Understanding the mode of action of these alleles will aid individual-level risk prediction. It also may help identify at-risk patients to provide them with better surveillance.
| Original language | English |
|---|---|
| Article number | 72 |
| Journal | BMC Medical Genomics |
| Volume | 16 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 4 Apr 2023 |
Bibliographical note
AcknowledgementsThe authors thank all participants in this research. We would also like to thank Mashhad University of Medical Sciences, Omid, Ghaem and Imam Reza hospitals, Reza Radiotherapy & Oncology Center and Dr. Ejtehadi laboratory for supporting the project.
Funding
This work was based on the PhD thesis of Dr. Fahimeh Afzaljavan and was financially supported by Mashhad University of Medical Sciences under grant 931185.
Data Availability Statement
The datasets generated and/or analyzed during the current study are not publicly available due Mashhad University of Medical Sciences research council rules, but are available from the corresponding author on reasonable request.Keywords
- Biomarker
- Breast neoplasm
- Caspase 8
- Diplotype
- Overall survival
- Prognosis
Access to Document
- Afzaljavan_BMCMG_Genetic_Contribution_Of_VOR
Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.