Multigene p-value integration based on SNPs investigation for seeking radiosensitivity signatures

Abstract

Dysregulation of apoptosis is a key attribute of cancer, especially the one induced by p53 expression disruption. Radiotherapy, sometimes supported by chemotherapy and/or pre-surgery, is recommended in majority of cases, but despite of the very well defined treatment protocols and high quality irradiation procedure, the huge dispersion in response to the radiotherapy is observed among cancer patients. Patient radiosensitivity, according to up-to-date knowledge, is at least partially responsible for different reactions to ionising radiation. Here we concentrate on investigation of single nucleotide polymorphisms (SNP) which can possibly explain the radiation response phenomena. To reach this goal dependent and independent methods of p-value integrations are presented and compared. Both statistical and molecular function domains are used in comparison study. We propose a novel method of p-value integration which includes the control of gene expression trend and introduces the adaptive significance level. What is more the multigene approach is proposed in contrary to classical single gene investigation. As a result, set of statistically significant polymorphisms was obtained, among which some were identified as possible deleterious for KRAS signalling pathway.