Single nucleotide polymorphisms in ATM, TNF-α and IL6 genes and risk of radiotoxicity in breast cancer patients

Abstract

Although oncological therapies have improved in the last decades, breast cancer (BC) remains a serious health problem worldwide. Radiotherapy (RT) is one of the most frequently used treatments for cancer aimed at eliminating tumor cells. However, it can also alter the surrounding normal tissue, especially the skin, and patient reactions may vary as a result of extrinsic and intrinsic factors. We evaluated the association of gene polymorphisms ATM Asp1853Asn, IL-6 G-174C and TNF-α G-308A involved in central phenotype pathways and development of individual radiosensitivity in BC patients with an exacerbated response to RT. Although univariate analysis results did not show a significant association with this trait, the interaction analysis between polymorphisms showed an increased risk of patients presenting wild-type TNFα G-308A genotype and mutant IL-6 G-174C genotype, and heterozygous TNF-α G-308A genotype and heterozygous IL-6G-174C genotype. On the other hand, our results showed that breast size and patient age influenced the determination of RT-associated effects. Considering that the trait is multifactorial, other significant elements for the determination of individual radiosensitivity should be considered, together with the establishment of specific polymorphic variants.

A Competing Endogenous RNA Network Reveals Novel lncRNA, miRNA and mRNA Biomarkers With Diagnostic and Prognostic Value for Early Breast Cancer

“…IL-6 is one of the most widely studied immune factors on multiple cancers. 26 Ahmad et al have reported that IL-6 is associated with good prognosis in early stage invasive BC patients. 27 Here, IL-6 was not only a diagnostic biomarkers, but also related to survival time.…”

Genetic Factors in the Locoregional Management of Breast Cancer

“…Single-nucleotide polymorphisms in a number of candidate genes, including XRCC1, MSH2, PARP1, RAD50, TGF-B, TNF-a, and others, have been reported to be associated with increased radiation sensitivity in a variety of studies with no significant clinical implications to date. 53 A recent prospective evaluation of the C-509 T TGF-b in patients with BC demonstrated grade $ 2 fibrosis in 13.8% of patients with the C509-T variant as opposed to only 3.8% fibrosis in those without the variant. 69 This is one of the first prospective trials to address the value of a specific variant in predicting RT fibrosis in patients with BC.…”

“…Like BRCA1/ 2, many of these genes are involved in DNA repair and have potential implications regarding RT. 53 However, despite their critical role in DNA repair, heterozygous carriers appear to have normal, intact, DNA-repair mechanisms with respect to acute and long-term effects of RT. 53,54 Although pathogenic mutations are relatively rare in some of these genes, given the increased utility of multigene-panel testing, any given practice is likely to be faced with localregional decision-making in affected patients with BC.…”