Interferon Gamma Gene Polymorphisms in Greek Primary Breast Cancer Patients

Abstract

Background: Breast cancer is a heterogeneous disease with distinct clinical subtypes, categorized by hormone receptor status, which exhibits different prognoses and requires personalized treatment approaches. These subtypes included luminal A and luminal B, which have different prognoses. Breast cancer development and progression involve many factors, including interferon-gamma (IFNG). Moreover, single nucleotide polymorphisms (SNPs) in IFNG have been associated with cancer risk. However, the functional role of IFNG polymorphisms in primary breast cancer subtypes, luminal A and luminal B, is unclear.

Methods: A total of 138 breast cancer tissues were acquired: 81 had luminal A, 42 had luminal B, 10 had triple-negative, and 3 had human epidermal growth factor receptor 2 (HER2) subtypes, while 2 had missing data. The tissues were evaluated in relation to luminal A and luminal B primary breast cancer subtypes. DNA was extracted from freshly frozen samples, and three SNPs (rs1861493 (chr12:68157416 (GRCh38.p13)), rs1861494 (chr12:68157629 (GRCh38.p13)) and rs2430561 (chr12:68158742 (GRCh38.p13))) in the IFNG gene were selected and evaluated based on previously published associations with cancer or other diseases.

Results: The data showed that IFNG polymorphisms rs1861493 and rs1861494 were associated with breast cancer risk, with the A allele of rs1861493 and T allele of rs1861494 being noted as the risk alleles. Furthermore, the IFNG polymorphism rs2430561 was associated with breast cancer risk, with the A allele being the risk allele. In addition, the risk alleles were more prevalent in the more aggressive subtype, luminal B breast cancer, compared to luminal A. Similarly, the rs2430561 AA genotype was associated with the breast cancer severity.

Conclusion: IFNG polymorphisms rs1861493, rs1861494, and rs2430561, with their respective risk alleles, are associated with increased breast cancer risk and severity. These risk alleles are more prevalent in the aggressive luminal B subtype compared to luminal A, indicating their role in both the prevalence and prognosis of breast cancer in a Greek population.

Keywords: SNPs; breast cancer; interferon-gamma; luminal A; luminal B; single nucleotide polymorphisms; subtypes.