scholarly journals Use a survival model to correlate single-nucleotide polymorphisms of DNA repair genes with radiation dose–response in patients with non-small cell lung cancer

2015 ◽  
Vol 117 (1) ◽  
pp. 77-82 ◽  
Author(s):  
Jian-Yue Jin ◽  
Weili Wang ◽  
Randall K. Ten Haken ◽  
Jie Chen ◽  
Nan Bi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Radiation Dose ◽  
Dose Response ◽  
Small Cell ◽  
Dna Repair Genes ◽  
Nucleotide Polymorphisms ◽  
Small Cell Lung ◽  
Single Nucleotide ◽  
Repair Genes

Associations between polymorphisms in DNA repair genes and TP53 mutations in non-small cell lung cancer

Lung Cancer ◽  
2011 ◽  
Vol 73 (1) ◽  
pp. 25-31 ◽  
Author(s):  
Sukki Cho ◽  
Min Jung Kim ◽  
Yi Young Choi ◽  
Seung Soo Yoo ◽  
Won Kee Lee ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Dna Repair Genes ◽  
Small Cell Lung ◽  
Tp53 Mutations ◽  
Repair Genes

Association of DNA Repair Gene Polymorphisms With Response to Platinum-Based Doublet Chemotherapy in Patients With Non–Small-Cell Lung Cancer

2010 ◽  
Vol 28 (33) ◽  
pp. 4945-4952 ◽  
Author(s):  
Kouya Shiraishi ◽  
Takashi Kohno ◽  
Chiharu Tanai ◽  
Yasushi Goto ◽  
Aya Kuchiba ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Response Rate ◽  
Small Cell ◽  
Minor Allele ◽  
Dna Repair Genes ◽  
Small Cell Lung ◽  
Major Allele ◽  
Repair Genes ◽  
Doublet Chemotherapy

Purpose To identify polymorphisms in DNA repair genes that affect responses to platinum-based doublet chemotherapy in patients with non–small-cell lung cancer (NSCLC). Patients and Methods In total, 640 patients with NSCLC who received platinum-based doublet chemotherapy in the National Cancer Center Hospital in Japan from 2000 to 2008 and whose responses were evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) participated in a study of the association between response and genotypes for 30 single nucleotide polymorphisms (SNPs) in 27 DNA repair genes. Candidate SNPs were selected in a discovery set of 201 patients, and their associations were validated in an independent set of 439 patients by prespecified P value criteria. Results Homozygotes for the minor allele TP53-72Pro of the Arg72Pro SNP in the TP53 gene showed a better response rate (54.3%) than those for the major allele TP53-72Arg (29.1%; P = 4.4 × 10−5) irrespective of therapeutic regimens, and minor allele homozygotes had significantly longer progression-free and overall survivals than major allele homozygotes (hazard ratio [HR], 0.85; 95% CI, 0.74 to 0.98; P = .020; and HR, 0.86; 95% CI, 0.74 to 0.99; P = .039). Minor allele carriers for SNP Lys940Arg in the poly (ADP-ribose) polymerase 1 (PARP1) gene showed a better response rate to the paclitaxel regimen (45.8%) than to the gemcitabine regimen (10.5%; P for interaction = .019). Conclusion Polymorphisms in the TP53 and PARP1 genes are involved in inter-individual differences in the response to platinum-based doublet chemotherapy in patients with NSCLC.

scholarly journals Potential Functional Variants in DNA Repair Genes Are Associated with Efficacy and Toxicity of Radiotherapy in Patients with Non-Small-Cell Lung Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Zhiguang Yang ◽  
Zhaoyu Liu
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Dna Repair Genes ◽  
Small Cell Lung ◽  
Repair Gene ◽  
Repair Genes ◽  
Toxic Reactions

Background. Lung cancer is one of the leading causes of cancer-related deaths. Radiotherapy, either alone or with chemotherapy, is still the primary treatment for patients with non-small-cell lung cancer (NSCLC). There are variations in how patients with NSCLC respond to radiotherapy and how toxic the therapy is. DNA repair gene polymorphisms are related to cancer development; however, their association with radiotherapy outcomes remains unknown. We hypothesized that gDNA repair gene variation could affect the efficacy and toxicity of radiotherapy in patients with NSCLC. Methods. A total of 486 histologically confirmed patients with NSCLC were recruited from the Shengjing Hospital of China Medical University from July 2015 to September 2019. Eleven potentially functional single nucleotide polymorphisms (SNPs) in four DNA repair genes (XRCC1, XRCC2, XPD, and MSH2) were genotyped in these patients. A multiple factor logistic regression analysis was used to assess the association between these SNPs and the efficacy and toxicity of radiotherapy. Results. Three SNPs, rs25487 (XRCC1), rs3218556 (XRCC2), and rs13181 (XPD), were all significantly associated with the efficacy of radiotherapy. The allele frequencies of the rs25487 CC genotype (OR = 0.457, 95% CI = 0.259–0.804, p=0.006) and the rs3218556 AG or AA genotypes (AG genotype: OR = 0.664, 95% CI = 0.442–0.999, p=0.049; AA genotype: OR = 0.380, 95% CI = 0.181–0.795, p=0.008) were both significantly higher in the response group than in the nonresponse group. For rs13181, the radiotherapy efficacy was associated with the heterozygous genotype GT (OR = 1.663, 95% CI = 1.057–2.614,p=0.027). Statistically significant associations between radiation-induced toxic reactions and rs25487 (XRCC1), rs3218556 (XRCC2), and rs13181 (XPD) were also observed. The rs13181GT genotype was associated with lower toxic reactions than the TT genotype (OR = 1.680, 95% CI = 1.035–2.728,p=0.035). Conclusions. The variants rs25487 (XRCC1), rs3218556 (XRCC2), and rs13181 (XPD) all contribute to the efficacy and toxicity of radiotherapy in patients with NSCLC. Our findings may clarify the predictive value of DNA repair genes for prognosis in patients with NSCLC after radiotherapy. Further investigation of more genes and samples should be performed to confirm our findings.

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