An ERCC4 regulatory variant predicts grade‐3 or ‐4 toxicities in patients with advanced non‐small cell lung cancer treated by platinum‐based therapy

Zhang, Ruoxin; Jia, Ming; Xu, Yuan; Qian, Danwen; Wang, Mengyun; Zhu, Meiling; Sun, Menghong; Chang, Jianhua; Wei, Qingyi

doi:10.1002/ijc.31153

Cited by 6 publications

(4 citation statements)

References 31 publications

(55 reference statements)

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“…XPF, located on chromosome 16p13.12, is also another important protein in the NER pathway, which plays a key role in DNA repair and maintenance of chromosome stability [27]. XPF polymorphisms can alter the function of XPF , leading to tumorigenesis and affecting the outcome of cisplatin-based chemotherapy [28]. Previously, XPF variants were reported to be associated with various tumors, including colorectal, ovarian, and lung cancer [29-31].…”

Section: Discussionmentioning

confidence: 99%

Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas

Chen

et al. 2021

Public Health Genomics

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Background: We aimed to explore the relation of XPD and XPF variants with non-small cell lung cancer (NSCLC) risk and the effect of these variants on the sensitivity to cisplatin-based chemotherapy among the Chinese Han population in high-altitude areas. Methods: Eight single-nucleotide polymorphisms (SNPs) in XPD and XPF were genotyped by Agena MassARRAY platform among 506 NSCLC cases and 510 healthy controls. Correlation of XPD and XPF gene polymorphisms with NSCLC susceptibility and the response of cisplatin-based chemotherapy were analyzed with logistic regression by calculating odds ratios (ORs) and 95% confidence intervals (CIs). Results: XPD rs13181 (OR = 1.53, 95% CI: 1.04–2.24, p = 0.029) and rs1052555 (OR = 1.63, 95% CI: 1.05–2.53, p = 0.029) possibly contributed to the increased risk of lung adenocarcinoma, while XPD rs238406 (OR = 0.63, 95% CI: 0.43–0.94, p = 0.024) was a protective factor for lung squamous cell carcinoma. Age, gender, BMI, smoking, and drinking might affect the correlation of XPD and XPF polymorphisms with NSCLC risk. More importantly, XPD rs13181 (OR = 2.91, p = 0.015), XPD rs1052555 (OR = 2.67, p = 0.022), and XPF rs231127 (OR = 4.15, p = 0.008) were associated with treatment response in NSCLC patients underwent cisplatin-based chemotherapy. Conclusion: This study found that XPD and XPF variants might contribute to NSCLC risk and the response of cisplatin-based chemotherapy among the Chinese Han population in high-altitude areas.

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Section: Discussionmentioning

confidence: 99%

Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas

Chen

et al. 2021

Public Health Genomics

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“…And there were missense mutations located in 6 tumor susceptibility genes, including PTCH1, BRCA2, BLM, ERCC4, BRCA1, and SETBP1 (Table S7), whose function loss have been closely associated with several hereditary tumor susceptibility syndromes (Acuna-Hidalgo et al, 2017;Qian et al, 2017;Romagnolo, Romagnolo & Selmin, 2015;Zhang et al, 2018). Interestingly, BRCA1 and BRCA2 are key members participating in homologous recombination (HR) repair upon DNA damage and the missense mutations were likely to affect the HR repair potential.…”

Section: Pcb153 Poisoning Induced Missense Mutations Of 6 Tumor Suppressor Genesmentioning

confidence: 99%

Large chromosomal deletions and impaired homologous recombination repairing in HEK293T cells exposed to polychlorinated biphenyl 153

Jing

Liu

et al. 2021

PeerJ

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Background Polychlorinated biphenyls (PCBs) are persistent pollutants with carcinogenesis and mutagenesis effects which have been closely associated with PCBs-induced DNA damage. However, the detailed DNA damage events and corresponding pathway alterations under PCBs poisoning is still not well understood. Methods Whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) were used to explore genome wide variations and related pathway changes in HEK293T cells that challenged by 15 µM PCB153 for 96 h in vitro. Double strand breaks (DSBs) were measured by 53BP1 foci detection, altered pathways were confirmed by quantitative real-time PCR (qPCR). Results The results indicated that abundant copy number variations (CNVs), including four duplications and 30 deletions, occurred in PCB153-exposed HEK293T cells. Multiple large fragment deletions (>1 Mb) involving up to 245 Mb regions on many chromosomes. Missense mutations were found in six tumor susceptibility genes, two of which are key members participating in homologous recombination (HR) repair response, BRCA1 and BRCA2. RNA-seq data showed that PCB153 poisoning apparently suppressedHR repairing genes. Besides, 15 µM PCB153 exposure significantly increased 53BP1 foci formation and effectively reduced BRCA1, RAD51B and RAD51C expression, indicating an elevated DSBs and impaired HR repairing. Conclusion This study firstly reported multiple large chromosomal deletions and impaired HR repairing in PCB153-exposed HEK293T cells, which provided a new insight into the understanding of early response and the mechanism underlying PCB153 genotoxicity. The chromosomal instabilities might be related to the impaired HR repairing that induced by PCB153; however, further investigations, especially on actual toxic effects of human body, are needed to confirm such speculation.

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“…Driver mutations in codons 12,13,59,61,117,and 146 of KRAS and NRAS genes,and the mutation in codon 600 of BRAF gene (Sepulveda et al, 2017) in patient samples were analyzed by FastTarget next-generation sequencing (Zhang et al, 2018).…”

Section: Screening For Tumor Microsatellite Instability and Kras Nras And Braf Oncogene Mutationsmentioning

confidence: 99%

MICA ∗012:01 Allele Facilitates the Metastasis of KRAS-Mutant Colorectal Cancer

Ding

Zhu

et al. 2020

Front. Genet.

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Major histocompatibility complex (HLA) class I chain-related protein A (MICA) regulates immune surveillance through activation of NKG2D (natural killer group 2D) receptor. However, the genetic association, potential function, and predictive ability of MICA alleles with colorectal cancer (CRC) prognosis remain undefined. In this study, we characterized MICA alleles in tissue samples from 104 patients with CRC and 536 healthy controls and carried out genetic association studies by molecular and clinical CRC phenotypes. Preliminary sequence analysis revealed that MICA * 009:01 or * 049 alleles were significantly decreased in patients with CRC (p = 0.0049), and further stratification analysis indicated that MICA * 012:01 allele was associated with patients with CRC and carrying KRAS codon 12 mutation (p = 0.027). The functional consequences of MICA alleles were examined via transfected CRC cell lines which showed that overexpression of MICA * 012:01 enhanced the proliferation, invasion, and metastatic phenotype of CRC. Preliminary analysis of disease-free survival time in patients with and without MICA * 012:01 suggest this allele may be predictive for poor prognosis of patients with KRAS codon 12 mutated CRC, as no somatic mutation of MICA gene was detected in CRC tumors compared to paracancerous tissues. Our study indicates that MICA * 012:01 allele is associated with KRAS-mutated CRC, facilitates CRC invasion and metastasis, and possibly reduces the survival of patients with KRAS-mutated CRC.

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An ERCC4 regulatory variant predicts grade‐3 or ‐4 toxicities in patients with advanced non‐small cell lung cancer treated by platinum‐based therapy

Cited by 6 publications

References 31 publications

Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas

Contribution of XPD and XPF Polymorphisms to Susceptibility of Non-Small Cell Lung Cancer in High-Altitude Areas

Large chromosomal deletions and impaired homologous recombination repairing in HEK293T cells exposed to polychlorinated biphenyl 153

MICA ∗012:01 Allele Facilitates the Metastasis of KRAS-Mutant Colorectal Cancer

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