RETRACTED ARTICLE: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

Abstract

BackgroundBiomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.MethodsA cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).ResultsUnivariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.ConclusionsUnivariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy.

Association of XRCC1 and XRCC3 gene haplotypes with the development of radiation-induced fibrosis in patients with nasopharyngeal carcinoma

“…Our results were in line with findings reported by other studies with relatively large sample sizes (16,17). However, our results were in contrast to those reported by 3 studies performed in Saudi Arabian NPC patients by Alsbeih et al (4,5,18). Our results indicated a trend of possible association between rs861539 of XRCC3 and radiation-induced fibrosis in Chinese NPC patients, but not rs25487 of XRCC1.…”

“…The discrepancies between studies may be due to variations in the study design, length of follow-up period and allele frequencies in different ethnic groups. The MAFs of rs25487 obtained by Alsbeih et al (18) and the present study were 0.232 and 0.258, respectively. The MAFs of rs861539 obtained by Alsbeih et al (18) and the present study were 0.394 and 0.075, respectively.…”

“…The MAFs of rs25487 obtained by Alsbeih et al (18) and the present study were 0.232 and 0.258, respectively. The MAFs of rs861539 obtained by Alsbeih et al (18) and the present study were 0.394 and 0.075, respectively. While the deviation of allele frequencies between the two studies was small for rs25487, an increased risk of developing fibrosis was not identified by the present study.…”

“…Our results indicated a trend of possible association between rs861539 of XRCC3 and radiation-induced fibrosis in Chinese NPC patients, but not rs25487 of XRCC1. In order to investigate the heterogeneity between studies with a similar study design, forest plots of rs25487 and rs861539 were constructed based on genotyped data from our study and the most recent study by Alsbeih et al (18).…”

“…Since different patients may present with different degrees of skin fibrosis despite receiving identical treatment, it was hypothesized that the severity of such complications may be genetically determined. Previous studies investigated the association of single-nucleotide polymorphisms (SNPs) in genes involved in DNA repair, such as X-ray repair cross-complementing protein 1 (XRCC1) rs25487 (c.1196A>G, p.Gln399Arg) and X-ray repair cross-complementing protein 3 (XRCC3) rs861539 (c.722C>T, p.Thr241Met) with late complications in various types of cancer (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18).…”