scholarly journals DNA Repair Gene Polymorphisms in Relation to Non-Small Cell Lung Cancer Survival

2015 ◽  
Vol 36 (4) ◽  
pp. 1419-1429 ◽  
Author(s):  
Yuliang Su ◽  
Huan Zhang ◽  
Fangxiu Xu ◽  
Jinyu Kong ◽  
Herbert Yu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Cancer Survival ◽  
Disease Stage ◽  
Repair Gene ◽  
Lung Cancer Patients ◽  
Homozygous Variant ◽  
Dna Repair Gene ◽  
Nsclc Patients ◽  
Repair Genes

Background: Single nucleotide polymorphisms (SNPs) in the DNA repair genes are suspected to be related to the survival of lung cancer patients due to their possible influence on DNA repair capacity (DRC). However, the study results are inconsistent. Methods: A follow-up study of 610 non-small cell lung cancer (NSCLC) patients was conducted to investigate genetic polymorphisms associated with the DNA repair genes in relation to NSCLC survival; 6 SNPs were genotyped, including XRCC1 (rs25487 G>A), hOGG1 (rs1052133 C>G), MUTYH (rs3219489 G>C), XPA (rs1800975 G>A), ERCC2 (rs1799793 G>A) and XRCC3 (rs861539 C>T). Kaplan-Meier survival curve and Cox proportional hazards regression analyses were performed. SNP-SNP interaction was also examined using the survival tree analysis. Results: Advanced disease stage and older age at diagnosis were associated with poor prognosis of NSCLC. Patients with the variant ‘G' allele of hOGG1 rs1052133 had poor overall survival compared with those with the homozygous wild ‘CC' genotype, especially in female patients, adenocarcinoma histology, early stage, light smokers and without family history of cancer. For never smoking female lung cancer patients, individuals carrying homozygous variant ‘AA' genotype of XPA had shorter survival time compared to those with wild ‘G' alleles. Furthermore, females carrying homozygous variant XPA and hOGG1 genotypes simultaneously had 2.78-fold increased risk for death. Among all 6 polymorphisms, the homozygous variant ‘AA' of XPA carriers had poor prognosis compared to the carriers of wild ‘G' alleles of XPA together with other base excision repair (BER) polymorphisms. Conclusions: Besides disease stage and age, the study found DNA repair gene polymorphisms were associated with lung cancer survival.

DNA Repair Gene Polymorphisms in Non-Small-Cell Lung Cancer Patients Treated with First-Line Platinum-Containing Chemotherapy

2016 ◽  
Vol 102 (4) ◽  
pp. 367-375 ◽  
Author(s):  
Eliana Rulli ◽  
Mirko Marabese ◽  
Sheila Piva ◽  
Lucia Bonomi ◽  
Elisa Caiola ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Repair Gene ◽  
Lung Cancer Patients ◽  
Dna Repair Gene

Links between DNA-repair gene polymorphisms and chromosomal aberrations in lung-cancer patients

2013 ◽  
Vol 28 (4) ◽  
pp. 133-136 ◽  
Author(s):  
M. L. Bakanova ◽  
V. I. Minina ◽  
Ya. A. Savchenko ◽  
A. A. Timofeeva ◽  
O. A. Dudkina ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Cancer Patients ◽  
Chromosomal Aberrations ◽  
Gene Polymorphisms ◽  
Repair Gene ◽  
Lung Cancer Patients ◽  
Dna Repair Gene

scholarly journals Association of DNA repair gene polymorphisms with the risk of radiation pneumonitis in lung cancer patients

Oncotarget ◽  
2017 ◽  
Vol 9 (1) ◽  
pp. 958-968 ◽  
Author(s):  
Lehui Du ◽  
Wei Yu ◽  
Xiangkun Dai ◽  
Nana Zhao ◽  
Xiang Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Radiation Pneumonitis ◽  
Repair Gene ◽  
Lung Cancer Patients ◽  
Dna Repair Gene

scholarly journals DNA Repair Gene Expression Adjusted by the PCNA Metagene Predicts Survival in Multiple Cancers

2018 ◽  
Author(s):  
Leif E. Peterson ◽  
Tatiana Kovyrshina
Keyword(s):  
Gene Expression ◽  
Dna Repair ◽  
Cancer Survival ◽  
P Value ◽  
Survival Prediction ◽  
Dna Repair Genes ◽  
Driver Genes ◽  
Repair Gene ◽  
Dna Repair Gene ◽  
Repair Genes

AbstractOne of the hallmarks of cancer is the existence of a high mutational load in driver genes, which is balanced by upregulation (downregulation) of DNA repair pathways, since almost complete DNA repair is required for mitosis. The prediction of cancer survival with gene expression has been investigated by many groups, however, results of a comprehensive re-evaluation of the original data adjusted by the PCNA metagene indicate that only a small proportion of genes are truly predictive of survival. However, little is known regarding the effect of the PCNA metagene on survival prediction specifically by DNA repair genes. We investigated prediction of overall survival (OS) in 18 cancers by using normalized RNA-Seq data for 126 DNA repair genes with expression available in TCGA. Transformations for normality and adjustments for age at diagnosis, stage, and PCNA metagene were performed for all DNA repair genes. We also analyzed genomic event rates (GER) for somatic mutations, deletions, and amplification in driver genes and DNA repair genes. After performing empirical p-value testing with use of randomly selected gene sets, it was observed that OS could be predicted significantly by sets of DNA repair genes for 61% (11/18) of the cancers. Pathway activation analysis indicates that in the presence of dysfunctional driver genes, the initial damage signaling and minor single-gene repair mechanisms may be abrogated, but with later pathway genes fully activated and intact. Neither PARP1 or PARP2 were significant predictors of survival for any of the 11 cancers. Results from cluster analysis of GERs indicates that the most opportunistic set of cancers warranting further study are AML, colorectal, and renal papillary, because of their lower GERs for mutations, deletions, and amplifications in DNA repair genes. However, the most opportunistic cancer to study is likely to be AML, since it showed the lowest GERs for mutations, deletions, and amplifications, suggesting that DNA repair pathway activation in AML is intact and unaltered genomically. In conclusion, our hypothesis-driven focus to target DNA repair gene expression adjusted for the PCNA metagene as a means of predicting OS in various cancers resulted in statistically significant sets of genes.Author summaryThe proliferating cell nuclear antigen (PCNA) protein is a homotrimer and activator of polymerase δ, which encircles DNA during transcription to recruit other proteins involved in replication and repair. In tumor cells, expression of PCNA is highly upregulated; however, PCNA-related activity is a normal process for DNA transcription in eukaryotes and therefore is not considered to play a central role in the selective genetic pressure associated with tumor development. Since PCNA is widely co-regulated with other genes in normal tissues, we developed workflow involving several functional transforms and regression models to “remove” the co-regulatory effect of PCNA on expression of DNA repair genes, and predicted overall cancer survival using DNA repair gene expression with and without removal of the PCNA effect. Other adjustments to survival prediction were employed, such as subject age at diagnosis and tumor stage. Random selection of gene sets was also employed for empirical p-value testing to determine the strength of the PCNA effect on DNA repair and overall survival adjustments. Since TCGA RNA-Seq data were used, we also characterized the frequency of deletions, amplifications, and somatic mutations in the DNA repair genes considered in order to observe which genomic events are the most frequent for the cancers evaluated.

Prognostic importance of DNA repair gene polymorphisms of XRCC1 Arg399Gln and XPD Lys751Gln in lung cancer patients from India

2007 ◽  
Vol 134 (6) ◽  
pp. 645-652 ◽  
Author(s):  
Leelakumari Sreeja ◽  
Volga S. Syamala ◽  
Vani Syamala ◽  
Sreedharan Hariharan ◽  
Praveenkumar B. Raveendran ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dna Repair ◽  
Cancer Patients ◽  
Gene Polymorphisms ◽  
Repair Gene ◽  
Xrcc1 Arg399gln ◽  
Lung Cancer Patients ◽  
Dna Repair Gene ◽  
Prognostic Importance
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