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Association of SOD2 rs2758339, rs5746136 and rs2842980 polymorphisms with increased risk of breast cancer: a haplotype-based case–control study

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Abstract

Background

A growing body of evidence indicates that oxidative stress, high levels of reactive oxygen species (ROS), is implicated in the pathogenesis of breast cancer (BC). Superoxide dismutase (SOD2), a mitochondria-resident antioxidant enzyme, protects cells from ROS by catalytically converting the superoxide radicals into less reactive species.

Objective

We aimed to investigate whether SOD2 rs2758339, rs5746136 and rs2842980 polymorphisms are associated with increased risk of BC.

Methods

A total of 100 patients with BC and 100 healthy controls were enrolled in the study. We used polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) assay for genotyping the SOD2 single-nucleotide polymorphisms (SNPs). Under co-dominant, dominant and recessive inheritance models, the genotypic and allelic associations of SOD2 SNPs with susceptibility to BC were evaluated using logistic regression analysis. The haplotype analysis was performed on the SOD2 SNPs to determine their combined effect on the BC risk.

Results

We found that SOD2 rs5746136 was significantly associated with decreased risk of developing BC in co-dominant and dominant inheritance models (P < 0.05). The SOD2 rs5746136 T allele confers an apparent protective effect against breast carcinogenesis (OR: 1.956; 95% CI 1.312–2.916; P < 0.0001). The SOD2 rs5746136/rs2842980 combined genotypes (CT/AA, CT/AT and TT/AA) were significantly more frequent in healthy subjects compared to BC patients (P < 0.05). The CTA and ACA haplotypes (rs2758339, rs5746136, rs2842980) were found to be a protective and a risk factor for BC, respectively.

Conclusion

These data strongly suggest that SOD2 rs5746136 was significantly associated with reduced risk of BC, indicating its protective role in BC development.

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Data availability

The author confirm that the data supporting the findings of this study are available within the article.

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Acknowledgements

Authors would like to express their sincerest appreciation to all subjects for participating in this study.

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Authors and Affiliations

  1. Department of Biotechnology, Faculty of Biological Sciences and Technology, Shahid Ashrafi Esfahani University, Isfahan, Iran

    Sara Asadi, Morteza Abkar, Zahra Zamanzadeh, Setareh Taghipour Kamalabad, Maryam Sedghi & Saghar Yousefnia

  2. Medical Genetics Laboratory, Alzahra University Hospital, Isfahan University of Medical Sciences, Isfahan, Iran

    Maryam Sedghi

  3. Department of Cell and Molecular Biology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran

    Saghar Yousefnia

Authors
  1. Sara Asadi
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  2. Morteza Abkar
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  3. Zahra Zamanzadeh
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  5. Maryam Sedghi
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  6. Saghar Yousefnia
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Correspondence to Saghar Yousefnia.

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Conflict of interest

Sara Asadi, Morteza Abkar, Zahra Zamanzadeh, Setareh Taghipour Kamalabad, Maryam Sedghi, and Saghar Yousefnia declare that they have no conflict of interest.

Ethical approval

The study protocol was approved the Institutional Review Board /Independent Ethics Committee (IRB/IEC) of the Shahid Ashrafi Esfahani University, Isfahan, Iran.

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Written informed consent was obtained from all participants after receiving an explanation of the study.

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Asadi, S., Abkar, M., Zamanzadeh, Z. et al. Association of SOD2 rs2758339, rs5746136 and rs2842980 polymorphisms with increased risk of breast cancer: a haplotype-based case–control study. Genes Genom 45, 1165–1178 (2023). https://doi.org/10.1007/s13258-023-01399-1

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