Predictive value of single nucleotide polymorphisms in &lt;em&gt;XRCC1&lt;/em&gt; for radiation-induced normal tissue toxicity

Zhao, Jing; Zheng, Zhi; Zhang, Ming; Li, Qingxia; Li, Jing; Wang, Xiao; Ma, Chunling

doi:10.2147/ott.s156175

Cited by 13 publications

(10 citation statements)

References 66 publications

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“…Polymorphisms of XRCC1 were the most widely investigated. The results contradicted each other [29]. For NPC, little is known about the genetic variants that correlate with skin toxicities.…”

Section: Discussionmentioning

confidence: 86%

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma

et al. 2022

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Background Genetic variants associated with acute side effects of radiotherapy in nasopharyngeal carcinoma (NPC) remain largely unknown. Methods We performed a two-stage genome-wide association analysis including a total of 1084 patients, where 319 individuals in the discovery stage were genotyped for 688,783 SNPs using whole genome-wide screening microarray. Significant variants were then validated in an independent cohort of 765 patients using the MassARRAY system. Gene mapping, linkage disequilibrium, genome-wide association analysis, and polygenic risk score were conducted or calculated using FUMA, LDBlockShow, PLINK, and PRSice software programs, respectively. Results Five SNPs (rs6711678, rs4848597, rs4848598, rs2091255, and rs584547) showed statistical significance after validation. Radiotherapy toxicity was more serious in mutant minor allele carriers of all five SNPs. Stratified analysis further indicated that rs6711678, rs4848597, rs4848598, and rs2091255 correlated with skin toxicity in patients of EBV positive, late stage (III and IV), receiving both concurrent chemoradiotherapy and induction/adjuvant chemotherapy, and with OR values ranging from 1.92 to 2.66. For rs584547, high occurrence of dysphagia was found in A allele carriers in both the discovery (P = 1.27 × 10− 6, OR = 1.55) and validation (P = 0.002, OR = 4.20) cohorts. Furthermore, prediction models integrating both genetic and clinical factors for skin reaction and dysphagia were established. The area under curve (AUC) value of receiver operating characteristic (ROC) curves were 0.657 (skin reaction) and 0.788 (dysphagia). Conclusions Rs6711678, rs4848597, rs4848598, and rs2091255 on chromosome 2q14.2 and rs584547 were found to be novel risk loci for skin toxicity and dysphagia in NPC patients receiving radiotherapy. Trial registration Chinese Clinical Trial Register (registration number: ChiCTR-OPC-14005257 and CTXY-140007-2).

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Section: Discussionmentioning

confidence: 86%

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma

et al. 2022

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“…This variant was associated by multiple studies with an increased risk of severe oral mucositis in patients with oropharyngeal carcinoma treated with radiotherapy 25 and the risk of radiation-induced side effects on normal tissues including acute mucositis. 26 A missense variant (rs861539) in a gene of the same pathway, XRCC3, was also identified. This variant was similarly found to increase the risk of early adverse effects, with a statistically significant relationship identified in HNC irradiation.…”

Section: Discussionmentioning

confidence: 99%

Extreme acute radiation‐induced toxicity in a patient with polymorphous low‐grade adenocarcinoma of the nasopharynx and rare variants in DNA repair genes

Nowicka,

Kuna,

Stawiski

et al. 2023

Head & Neck

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BackgroundPolymorphous low‐grade adenocarcinoma (PLGA) is an extremely rare finding in the nasopharynx. There are no guidelines for the treatment of PLGA in this localization. Radiotherapy may be administered to treat this malignancy; however, in radiosensitive individuals, it is associated with a risk of severe radiotherapy‐induced toxicity.MethodsWe present a case of a 73‐year‐old woman with locally advanced polymorphous low‐grade adenocarcinoma of the nasopharynx who developed a severe adverse acute reaction to radiotherapy leading to treatment discontinuation. Despite intensive treatment, the patient died 40 days after RT initiation. Whole genome sequencing was performed using DNA from peripheral blood mononuclear cells in the search for variants that could explain such extreme toxicity.ResultsWe identified a combination of pathogenic variants that may have contributed to the patient's reaction to radiation therapy, including predisposing variants in XRCC1, XRCC3, and LIG4. We also identified candidate variants, not previously described in this context, which could be associated with radiation toxicity based on plausible mechanisms. We discuss previous reports of this rare tumor from the literature and known contributors to radiation‐induced toxicity.ConclusionsGenetic causes should be considered in cases of extreme radiosensitivity, especially when is not explained by clinical factors.

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“…The ERCC1 rs3212986 AA genotype was associated with a greater risk of late-onset GI-M in women with cervical cancer undergoing chemoradiotherapy [67]. Systematic review showed XRCC1 rs25487 was strongly predictive of OM and GI-M risk in HSCT recipients [68], however this was not upheld in a smaller cohort of HNC patients [69]. XRCC1 polymorphic variants were also associated with OM risk in HNC patients treated with chemoradiation [70].…”

Section: Cell Signalling Variantsmentioning

confidence: 99%

“…Similarly, two large studies (N=322, N=113) failed to identify any significant association between MTX transporter mutations and TYMS SNPs for OM risk in children with ALL [19,97] despite strong evidence supporting its role in adult cohorts [57]. While a systematic review of over 6500 patients supported a strong association between XRCC1 (rs25487) and OM and GI-M risk in HSCT recipients [68], another reported no significant association in XRCC1 mutations and OM risk in HNC patients [69]. Similarly, Lunberg et al, (2010) and Goutham et al, (2017) reported no significant effect of TGFB on OM despite a positive association identified for GI-M. Several studies, including a large prospective trial in 381 participants [98], also failed to identify any demographic influence on mucositis risk, including age, sex, BMI and race [99][100][101]24,48].…”

Section: Areas Requiring Further Investigationmentioning

confidence: 99%

Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action

Wardill

Sonis

Blijlevens

et al. 2020

Support Care Cancer

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peer review but prior to copyediting and typesetting that can be made available under the following conditions:(i) Author(s) retain the right to make an AAM of their Article available on their own personal, selfmaintained website immediately on acceptance, (ii) Author(s) retain the right to make an AAM of their Article available for public release on any of the following 12 months after first publication ("Embargo Period"): their employer's internal website; their institutional and/or funder repositories. AAMs may also be deposited in such repositories immediately on acceptance, provided that they are not made publicly available until after the Embargo Period.

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Predictive value of single nucleotide polymorphisms in <em>XRCC1</em> for radiation-induced normal tissue toxicity

Cited by 13 publications

References 66 publications

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma

A two-stage genome-wide association study to identify novel genetic loci associated with acute radiotherapy toxicity in nasopharyngeal carcinoma

Extreme acute radiation‐induced toxicity in a patient with polymorphous low‐grade adenocarcinoma of the nasopharynx and rare variants in DNA repair genes

Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action

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