Polymorphisms of DNA repair genes and risk of non-small cell lung cancer

Zienolddiny, Shanbeh; Campa, Daniele; Lind, Helge; Ryberg, David; Skaug, Vidar; Stangeland, Lodve; Phillips, David H.; Canzian, Federico; Haugen, Aage

doi:10.1093/carcin/bgi232

Cited by 363 publications

(324 citation statements)

References 51 publications

Supporting

Mentioning

280

Contrasting

Unclassified

Order By: Relevance

“…The results of studies on XPF and ERCC1 variants and the risk of cancer are also contradictory. [29][30][31]. The XPG gene encodes the 3' endonuclease of the NER pathway.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

et al. 2011

View full text Add to dashboard Cite

Abstract:Background: Epidemiological data show that colorectal cancer (CRC) is the second most frequent malignancy worldwide. The involvement of "minor impact genes" such as XME and DNA-repair genes in the etiology of sporadic cancer has been postulated by other authors.Aim: we focused on analyzing polymorphisms in DNA-repair genes in CRC. We considered the following genes involved in DNA-repair pathways: base excision repair (OGG1 Ser326Cys, XRCC1 Trp194Arg and Arg399Gln); nucleotide excision repair [XPA (-4)G/A, XPC C/A (i11) and A33512C (Lys939Gln), XPD Asp312Asn and A18911CMaterial and methods: The study group consisted of 133 patients diagnosed with sporadic CRC, while the control group was composed of 100 age-matched non-cancer volunteers. Genotyping was performed by PCR and PCR-RFLP. Fisher's exact test with a Bonferroni correction for multiple testing was used.Results: We found that: i) XPC C/A (i11) heterozygous variant is associated with increased risk of CRC [OR is 2.07 (95% CI 1.1391,3.7782) p=0.038], ii) XPD A18911C (Lys751Gln) is associated with decreased risk of CRC [OR=0.4497, (95% CI 0.2215,0,9131) p=0.031] for an individual with at least one A allele at this locus. Conclusions:1. the XPC C/A (i11) genotype is associated with an increased risk of sporadic colorectal cancer.2. the NER pathway has been highlighted in our study, as a most important in modulation of individual susceptibility to sCRC.

show abstract

“…The results of studies on XPF and ERCC1 variants and the risk of cancer are also contradictory. [29][30][31]. The XPG gene encodes the 3' endonuclease of the NER pathway.…”

Section: Introductionmentioning

confidence: 99%

“…The NBS1 (Nibrin) protein is a component of the MRN-complex, which recognizes DSBs [31]. Most studies investigating the NBS1 Glu185Gln polymorphism have focused on assessing the risk of breast cancer [32].…”

Section: Introductionmentioning

confidence: 99%

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

et al. 2011

View full text Add to dashboard Cite

show abstract

“…5 To date, a number of molecular epidemiological studies have been done to evaluate the association between XPA À4G>A polymorphism and different types of cancer risk in diverse populations. The tumor types included lung cancer, 6,13,22,24,[29][30][31][32][33][34] gastric cancer, 7,17 colorectal cancer, 8,12,23 squamous cell carcinoma of the head and neck, 8,10 basal and squamous cell carcinomas of the skin (BCC and SCC), 20,27 breast cancer, 8,18,26 esophageal cancer, 11,14,15 and so on. However, the results were inconsistent or even contradictory.…”

mentioning

confidence: 99%

Genetic variation of XPA gene and risk of cancer: A systematic review and pooled analysis

Ding

Zhang

et al. 2011

Intl Journal of Cancer

View full text Add to dashboard Cite

XPA, a zinc-finger DNA-binding protein, play an important role in both global genome and transcription-coupled repair pathways. XPA 24G>A polymorphism was identified in the 5 0 noncoding region, located four nucleotides upstream of the ATG start codon. Previous studies have shown that this polymorphism may affect mRNA tertiary structure and stability and play a role in susceptibility to cancer. However, the results remained controversial. To derive a more precise estimation of association between this polymorphism and risk of different types of cancer, we performed a meta-analysis based on 36 case-control or case-cohort studies, including a total of 11,700 cases and 15,033 controls. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, no significantly elevated cancer risk was found in all genetic models when eligible studies were pooled into the meta-analysis. In the stratified analyses, we found that individuals with A-allele had a higher risk of lung cancer (AA versus GG: OR 5 1.25, 95% CI 5 1.09-1.43; recessive model: OR 5 1.31, 95% CI 5 1.16-1.48). When stratified by ethnicity, significantly elevated risks were observed among Asian populations (AA versus GG: OR 5 1.31, 95% CI 5 1.01-1.70; dominant model: OR 5 1.14, 95% CI 5 1.00-1.30). This meta-analysis suggests that XPA 24G>A polymorphism is associated with increased lung cancer risk and may be a low-penetrant risk factor in Asian ethnicity for cancer development.

show abstract

“…PCNA is reported to be overexpressed in cancer cells and it is also very often used as a marker of proliferation [12]. In the base excision repair pathway, PCNA (A1876G) polymorphisms were found to be associated with increased risk of non-small cell lung cancer [13]. It is reported that two mutant forms of PCNA formed due to amino acid substitutions cause defects in mismatch repair system.…”

Section: Introductionmentioning

confidence: 99%

Untitled

2017

RJLBPCS

View full text Add to dashboard Cite

Aim: Proliferating cell nuclear antigen (PCNA) is an ancillary protein that assists in DNA replication and DNA repair process. Detection of mutations in PCNA gene or protein could be helpful to analyze many disorders relating to DNA replication and repair. In the present study, non-synonymous single nucleotide polymorphisms (nsSNPs) generated by missense mutation were studied using different computational methods to evaluate the nsSNPs that may be deleterious to PCNA function.Method: The missense nsSNPs were retrieved from the database of NCBI and subjected to functional prediction by the computational algorithms. The evolutionary conservation data of the PCNA protein was obtained from the ConSurf web server. The protein structural analysis for the variants was performed using I-Mutant, SPDB viewer and YASARA to check their structural variations and energy minimizations. Results: Out of the 42 nsSNPs, 5 nsSNPs namely rs780735449 (Q38R), rs1050525 (S39R), rs781573975 (E104G), rs772308650 (L182W) and rs753494859 (K248N) were identified as deleterious by using different computational algorithms. The evolutionary conservation data revealed that all the high risk nsSNPs positions were highly conserved and were either functional or structural residues in the protein. The I-Mutant tool had showed a decrease in the protein stability for the five high risk nsSNPs. A deviance in the energy minimization was observed for the variants with respect to the native protein. The RMSD (root mean square deviation) and TM (template modeling) values predicted that the mutants were structurally similar to the wild type protein. The PTM (post translational modifications) analysis using various in silico tools showed that S39R and K248N were putative PTM sites and through FTSite it was observed that these two variants were also involved in the ligand binding sites.Conclusion: Through the robust use of various in silico tools, five nsSNPs of PCNA protein were found to deleterious. Out of them two mutations at 39th and 248th positions (S39R & K248N) are to be further validated for their effect on the PCNA protein function.

show abstract

Polymorphisms of DNA repair genes and risk of non-small cell lung cancer

Cited by 363 publications

References 51 publications

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

The C/A polymorphism in intron 11 of the XPC gene plays a crucial role in the modulation of an individual’s susceptibility to sporadic colorectal cancer

Genetic variation of XPA gene and risk of cancer: A systematic review and pooled analysis

Untitled

Contact Info

Product

Resources

About