Association of Single Nucleotide Polymorphisms inSOD2, XRCC1andXRCC3with Susceptibility for the Development of Adverse Effects Resulting from Radiotherapy for Prostate Cancer

Abstract

The objective of this study was to determine whether an association exists between certain single nucleotide polymorphisms (SNPs), which have previously been linked with adverse normal tissue effects resulting from radiotherapy, and the development of radiation injury resulting from radiotherapy for prostate cancer. A total of 135 consecutive patients with clinically localized prostate cancer and a minimum of 1 year of follow-up who had been treated with radiation therapy, either brachytherapy alone or in combination with external-beam radiotherapy, with or without hormone therapy, were genotyped for SNPs in SOD2, XRCC1 and XRCC3. Three common late tissue toxicities were investigated: late rectal bleeding, urinary morbidity, and erectile dysfunction. Patients with the XRCC1 rs25489 G/A (Arg280His) genotype were more likely to develop erectile dysfunction after irradiation than patients who had the G/G genotype (67% compared to 24%; P=0.048). In addition, patients who had the SOD2 rs4880 T/C (Val16Ala) genotype exhibited a significant increase in grade 2 late rectal bleeding compared to patients who had either the C/C or T/T genotype for this SNP (8% compared to 0%; P=0.02). Finally, patients with the combination of the SOD2 rs4880 C/T genotype and XRCC3 rs861539 T/C (Thr241Met) genotype experienced a significant increase in grade 2 late rectal bleeding compared to patients without this particular genotypic arrangement (14% compared to 1%; P=0.002). These results suggest that SNPs in the SOD2, XRCC1 and XRCC3 genes are associated with the development of late radiation injury in patients treated with radiation therapy for prostate adenocarcinoma.

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

“…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).…”

Predictive Value of Xrcc1 Gene Polymorphisms for Side Effects in Patients undergoing Whole Breast Radiotherapy: a Meta-analysis

“…However, these authors could not find a significant association between the investigated SNPs in XRCC1 and grade >2 late toxicity. Furthermore, in an investigation by Burri et al (2008), a significant association between the XRCC1 194, 280, and 399 polymorphisms and late rectal and urinary morbidity was not detected.…”

The association of XRCC3 Thr241Met genetic variant with risk of prostate cancer: a meta-analysis

“…The etiology of prostate cancer is largely unknown, although genetic and environmental factors might increase risk of prostate cancer [2][3][4][5][6] . The X-ray repair cross-complementing group 3 (XRCC3) is one of the DNA repair genes, and is an important candidate gene for mediating the genetic influence on prostate cancer [7][8][9][10][11][12][13] . The C18067T genetic variant in XRCC3 gene at exon 7(C>T, rs861539), one of the most studied functional genetic variants, results from a C to T mutation and causes the substitution of Threonine (Thr) to Methionine (Met) at codons 241 (p.Thr241Met), has been potentially associated with the risk of prostate cancer [7][8][9][10] .…”