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

• Published in: Genes & genomics Vol. 45; no. 9; pp. 1165 - 1178
• Main Authors: Asadi, Sara, Abkar, Morteza, Zamanzadeh, Zahra, Taghipour Kamalabad, Setareh, Sedghi, Maryam, Yousefnia, Saghar
• Format: Journal Article
• Language: English
• Published: Singapore Springer Nature Singapore 01.09.2023; Springer; Springer Nature B.V; 한국유전학회
• Subjects: Animal Genetics and Genomics; Antioxidants; Biomedical and Life Sciences; Breast cancer; Cancer; Carcinogenesis; Enzymes; Ethylenediaminetetraacetic acid; Gene polymorphism; Genetic aspects; Genotyping; Haplotypes; Heredity; Human Genetics; Inheritances; Life Sciences; Microbial Genetics and Genomics; Oncology, Experimental; Oxidative stress; Plant Genetics and Genomics; Polymerase chain reaction; Reactive oxygen species; Research Article; Restriction fragment length polymorphism; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Superoxide; Superoxide dismutase; 생물학; Breast cancer; rs5746136; rs2758339; rs2842980; Polymorphism; SOD2
• ISSN: 1976-9571; 2092-9293
• DOI: 10.1007/s13258-023-01399-1

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.