Prospective evaluation of XRCC‐1 Arg194Trp polymorphism as bio‐predictor for clinical outcome in locally advanced laryngeal cancer undergoing cisplatin‐based chemoradiation

Raturi, Vijay Parshuram; Hojo, Hidehiro; Bhatt, Madan Lal Brahma; Mohammad, Suhel; Wu, Chen‐Ta; Bei, Yanping; Nakamura, Masaki; Okumura, Masayuki; Zhang, Haiqin; Parmar, Devendra; Badajena, Avinash; Singh, Rahul; Kumar, Saurabh; Katiyar, Tridev; Gaur, Jalaj

doi:10.1002/hed.26083

Cited by 10 publications

(10 citation statements)

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“…Several studies reported the correlation of genetic variants and skin reaction. However, these studies mainly investigated breast cancer patients using candidate gene association study strategies [24][25][26][27][28]. Polymorphisms of XRCC1 were the most widely investigated.…”

Section: Discussionmentioning

confidence: 99%

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: 99%

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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“…Variants detected in genes involved in DNA damage response or DNA repair are associated with acute toxicities (mucositis and dermatitis) related to RT. 18 published studies evaluated the association of variants in DNA damage and DNA repair with RT-induced acute toxicities, 6 out of the 18 studies focused on variants in X-Ray Repair Cross Complementing 1 gene (XRCC1) as a DNA repair gene highly associated with radiotherapy toxicity 61, 63, 74, 75, 98 . Other variants in DNA damage and repair genes; XRCC2, XPD, ERCC1, ZNF24, NBN, Ku70, ATM, CHEK1, RAD51C, ERCC2, PMS1, MLH1 were associated with RT-acute toxicities, these results matched our study of the potential mechanisms of inflammatory pain induced by RT 22 .…”

Section: Discussionmentioning

confidence: 99%

“…(Figure 3, Table 5). 61,63,74,75,98 . Other variants in DNA damage and repair genes; XRCC2, XPD, ERCC1, ZNF24, NBN, Ku70, ATM, CHEK1, RAD51C, ERCC2, PMS1, MLH1 were associated with RTacute toxicities, these results matched our study of the potential mechanisms of inflammatory pain induced by RT 22 .…”

Section: -Variants Associated With Mixed Types Of Radiotherapy Induce...mentioning

confidence: 99%

Systematic Review of Genetic Polymorphisms Associated with Acute Pain and Relevant Acute Toxicities Induced by Radiotherapy for Head and Neck Cancer

Salama

Geng

Rigert

et al. 2022

Preprint

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Background/objectivePain is the most common acute toxicity following radiation therapy (RT) for head and neck cancer (HNC). The multifactorial origin of radiotherapy-induced pain makes it highly challenging to manage in HNC patients. Multiple studies have been conducted to identify different germline genetic variants associated with cancer pain, however few of them focused on RT-induced acute pain. In this systematic review, we summarize potential mechanisms of acute pain after radiotherapy in HNC focusing on oral cavity/oropharyngeal cancer and identify genetic variants associated with radiotherapy-induced acute pain and other relevant acute toxicities.MethodsA comprehensive search of Ovid Medline, EMBASE and Web of Science databases using concepts and terms including “Variants”, “Polymorphisms”, “Radiotherapy”, “Acute pain”, “Acute toxicity” published up to February 28, 2022 was performed by two reviewers. Review articles and citations were reviewed manually. The reported SNPs associated with RT-induced acute pain and toxicities were reported, and the molecular function of the associated genes and pathways were described based on genetic annotation using The Human Gene Database; GeneCards.ResultsA total of 386 articles were identified electronically and an additional 8 articles were included after manual search. 39 articles were finally included. 51 variants were associated with 40 genes, of which 30 % had function in DNA damage response and repair, 25% in inflammatory and immune response, 17.5 % in cell death or cell cycle, and were associated with RT-inflammatory pain and acute mucositis or dermatitis. 4 variants in 4 genes were associated with neuropathy and neuropathic pain. 13 variants in 10 genes and were associated with RT-induced mixed types of post-RT-pain.ConclusionDifferent types of pain develop after RT, including inflammatory pain (acute mucositis and acute skin reaction); neuropathic pain; nociceptive pain; and mixed oral pain. Genetic variants involved in DNA damage response and repair, cell death, inflammation and neuropathic pathways may affect pain presentation post-RT. These variants could be used for acute pain prediction and personalized pain management in HNC patients receiving RT.

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“…Studies have investigated the association between XRCC1 Arg399Gln/XRCC1 Arg194Trp polymorphisms and HNSCC risk [17][18][19][20][21][22][23]. However, these results were contradictory.…”

Section: Discussionmentioning

confidence: 99%

Prospective Evaluation of XRCC-1 as a Biopredictor for Survival Outcomes in Patients of Head and Neck Squamous Cell Carcinoma (HNSCC): A Meta-analysis

Yang¹,

Zhou²,

Wang³

2021

Preprint

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Background: Epidemiologic studies have demonstrated that X-ray repair cross-complementary group 1 (XRCC1) is one of the susceptibility factors in head and neck squamous cell carcinoma(HNSCC) patients. However, its clinical prognostic impact remains controversial. Thus, a meta-analysis was performed to clarify the survival value of XRCC1 in HNSCC patients.Methods: Following the Preferred Reporting Items or Systematic Reviews Meta Analyses (PRISMA) 2020 guidelines, literature searches were systematically performed by PubMed, EMBASE and Web of Science with a manual retreive to evaluate the prognostic consequence of XRCC1 in HNSCC patients. Hazard ratios (HRs) and 95% confidence intervals (CIs) were collected to estimate the correlation between XRCC1 and the survival outcomes of HNSCC patients.Results: Ten studies including 2086 HNSCC patients who satisfied the inclusion and exclusion criteria were included in this meta-analysis. The meta-analysis showed that high XRCC1 expression and Arg399Gln and Arg194Trp were significantly correlated with poorer overall survival (OS), with HRs of 1.97 (95% CI, 1.36–2.84, P<0.001), 1.30 (95% CI, 1.12–1.51, P<0.001), and 1.65 (95% CI, 1.18–2.32 P<0.05), respectively.Conclusion: XRCC1 was associated with poorer survival outcomes in HNSCC patients. Hence, XRCC1 is a potential therapeutic target for HNSCC.

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Prospective evaluation of XRCC‐1 Arg194Trp polymorphism as bio‐predictor for clinical outcome in locally advanced laryngeal cancer undergoing cisplatin‐based chemoradiation

Cited by 10 publications

References 47 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

Systematic Review of Genetic Polymorphisms Associated with Acute Pain and Relevant Acute Toxicities Induced by Radiotherapy for Head and Neck Cancer

Prospective Evaluation of XRCC-1 as a Biopredictor for Survival Outcomes in Patients of Head and Neck Squamous Cell Carcinoma (HNSCC): A Meta-analysis

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