Additional prognostic value of polymorphisms within the 3'-untranslated region of programmed cell death pathway genes in early-stage breast cancer

Hanxi Chen; Minyan Chen; Bangwei Zeng; Lili Tang; Qian Nie; Xuan Jin; Wenhui Guo; Lili Chen; Yuxiang Lin; Chuan Wang; Fangmeng Fu

doi:10.3389/fimmu.2024.1284579

Additional prognostic value of polymorphisms within the 3'-untranslated region of programmed cell death pathway genes in early-stage breast cancer

Front Immunol. 2024 Apr 16:15:1284579. doi: 10.3389/fimmu.2024.1284579. eCollection 2024.

Authors

Hanxi Chen^#^{1

2

3}, Minyan Chen^#^{1

2

3}, Bangwei Zeng^#⁴, Lili Tang^#⁵, Qian Nie^{1

2

3}, Xuan Jin^{1

2

3}, Wenhui Guo^{1

2

3}, Lili Chen^{1

2

3}, Yuxiang Lin^{1

2

3}, Chuan Wang^{1

2

3}, Fangmeng Fu^{1

2

3}

Affiliations

¹ Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
² Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
³ Breast Cancer Institute, Fujian Medical University, Fuzhou, Fujian, China.
⁴ Administration Department of Nosocomial Infection, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
⁵ Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.

^# Contributed equally.

Abstract

Introduction: The programmed cell death (PCD) pathway plays an important role in restricting cancer cell survival and proliferation. However, limited studies have investigated the association between genetic variants in the 3'-untranslated region of the PCD pathway genes and breast cancer outcomes.

Methods: In this study, we genotyped 28 potentially functional single nucleotide polymorphisms (SNPs) in 23 PCD pathway genes in 1,177 patients with early-stage breast cancer (EBC) from a Han Chinese population. The median follow-up period was 174 months.

Results: Among all the candidate SNPs, four independent SNPs (rs4900321 and rs7150025 in ATG2B, rs6753785 in BCL2L11, and rs2213181 in c-Kit) were associated with invasive disease-free survival (iDFS), distant disease-free survival (DDFS), breast cancer-specific survival (BCSS) and overall survival (OS), respectively. Further combined genotypes of these four SNPs revealed that the survival decreased as the number of unfavorable genotypes increased (Ptrend = 1.0 × 10-6, 8.5 × 10-8, 3.6 × 10-4, and 1.3 × 10-4 for iDFS, DDFS, BCSS, and OS, respectively). Receiver operating characteristic curve analysis demonstrated that incorporating unfavorable genotypes and clinicopathological variables improved the ability to predict EBC survival (P = 0.006, 0.004, 0.029, and 0.019 for iDFS, DDFS, BCSS, and OS, respectively). Additionally, rs6753785 and rs2213181 were associated with BCL2L11 and c-Kit mRNA expression, respectively.

Conclusions: Our results suggest that these four SNPs may act as novel biomarkers for EBC survival, possibly by modulating the expression of the corresponding genes.

Keywords: breast cancer; prognosis; programmed cell death; single nucleotide polymorphism; survival.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

3' Untranslated Regions* / genetics
Adult
Aged
Apoptosis / genetics
Biomarkers, Tumor / genetics
Breast Neoplasms* / genetics
Breast Neoplasms* / mortality
Breast Neoplasms* / pathology
Female
Genetic Predisposition to Disease
Genotype
Humans
Middle Aged
Neoplasm Staging
Polymorphism, Single Nucleotide*
Prognosis

Substances

3' Untranslated Regions
Biomarkers, Tumor

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was supported by grants from the Joint Funds for the Innovation of Science and Technology, Fujian Province (2018Y9055 and 2019Y9103), Natural Science Foundation of Fujian Province (2020J01995), and Fujian Provincial Health Technology Project (2020QNA039).