Presentation Individual Sensitivity to Clinical Radiotherapy: Assessing Interactions among SNPs of Genes of the Radiation-response Pathways

Imai, Takashi

The prediction of sensitivities of both tumor and the surrounding healthy tissue is important for effective radiotherapy. A cancer patient might have intrinsic radiosensitivity, which is inherited through germline cells, while a tumor accumulates many other mutations during its progression in addition to the inherited variations. Therefore, separate types of prediction assays need to be developed for the tumor and for the surrounding tissue. In this symposium, however, I will focus mainly on an individual’s inherited radiosensitivity. Many research groups in the worldwide, including ours, have attempted to identify genetic variants, especially single nucleotide polymorphisms (SNPs), which might be associated with the risks of adverse effects after radiotherapy. Some of these SNPs include those in DNA repair genes and signal transduction genes. Several powerful analytical approaches to identify the association between genetic variants and complex traits have been proposed recently. On the basis of pathway approaches and SNP–SNP interaction analyses, we investigated the genetic risk of skin reaction after radiotherapy in breast cancer patients as a model. The candidate genes selected from our previous studies were re-classified into 8 pathways, including apoptosis, DNA repair, and cell cycle pathways. Then, SNPs of the genes in each pathway were assessed for possible interactions. The possible associations were tested by logistic regression analysis. Our results highlight the advantages of the pathway and SNP–SNP interaction approaches for determining genetic interactions associated with complex radiosensitivity.
15th International Congress of Radiation Research (ICRR 2015)

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