Dataset Information

A case-control study on association of nucleotide excision repair polymorphisms and its interaction with environment factors with the susceptibility to non-melanoma skin cancer.

ABSTRACT: To investigate the association of several single nucleotide polymorphisms (SNPs) within nucleotide excision repair (NER) gene and additional gene- gene and gene- smoking interaction with non-melanoma skin cancer (NMSC) risk in a Chinese population.A total of 1322 participants (939 males, 383 females) were selected, including 660 NMSC patients and 662 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among SNPs and smoking. Logistic regression was performed to investigate association between 4 SNPs within NER gene, additional gene- gene and gene- smoking interaction on NMSC risk.NMSC risk was significantly higher in carriers with G allele of rs2228527 than those with AA genotype (AG + GG versus AA), adjusted OR (95%CI) =1.76 (1.24-2.37), and higher in carriers with the G allele of rs2228529 than those with AA genotype (AG + GG versus AA), adjusted OR (95%CI) = 1.66 (1.24-2.13). However, we did not find any direct association of the rs4134822 and rs1799793 with NMSC risk after covariates adjustment. GMDR model indicated a significant interaction combination (p=0.0010), including rs2228529 and current smoking. Overall, the cross-validation consistency of this model was 9/ 10, and the testing accuracy was 60.72%. Current smokers with rs2228529- GA or GG genotype have the highest NMSC risk, compared to never- smokers with rs2228529- AA genotype, OR (95%CI) = 2.92 (1.61-4.29).We found that the G allele of rs2228527 and the G allele of rs2228529 within NER gene, interaction between rs2228529 and current smoking were all associated with increased NMSC risk.

SUBMITTER: Li YL

PROVIDER: S-EPMC5655256 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A case-control study on association of nucleotide excision repair polymorphisms and its interaction with environment factors with the susceptibility to non-melanoma skin cancer.

Li Yan-Ling YL Wei Feng F Li Yu-Ping YP Zhang Li-Hua LH Bai Yan-Zhi YZ

Oncotarget 20170915 46

<h4>Aims</h4>To investigate the association of several single nucleotide polymorphisms (SNPs) within nucleotide excision repair (<i>NER</i>) gene and additional gene- gene and gene- smoking interaction with non-melanoma skin cancer (NMSC) risk in a Chinese population.<h4>Methods</h4>A total of 1322 participants (939 males, 383 females) were selected, including 660 NMSC patients and 662 control participants. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best inter ...[more]

PMID: 29113361

Similar Datasets

Project description:BACKGROUND:The causative link between UV exposure and melanoma development is well known, however the mechanistic relationship remains incompletely characterised. UVA and UVB components of sunlight are implicated in melanomagenesis; however the majority of studies have focused on the effects of UVB and UVC light. Interestingly, melanoma tumour sequencing has revealed an overrepresentation of mutations signature of unrepaired UV-induced DNA damage. Repair of UVA-induced DNA damage is thought to occur primarily through the Nucleotide Excision Repair (NER) pathway, which recognises and repairs damage either coupled to transcription (Transcription Coupled Repair; TCR), or through global genome scanning (Global Genome Repair; GGR). Current literature suggests NER is deficient in melanoma, however the cause of this remains unknown; and whether reduced NER activity in response to UVA may be involved in melanoma development remains uncharacterised. In this study we aimed to determine if melanoma cells exhibit reduced levels of NER activity in response to UVA. METHODS:Melanocyte and melanoma cell lines were UVA-irradiated, and DNA damage levels assessed by immunodetection of Cyclobutane Pyrimidine Dimer (CPD) and (6-4) Photoproduct [(6-4)PP] lesions. Expression of NER pathway components and p53 following UVA treatment was quantified by qPCR and western blot. RESULTS:UVA did not induce detectable induction of (6-4)PP lesions, consistent with previous studies. Repair of CPDs induced by UVA was initiated at 4 h and complete within 48 h in normal melanocytes, whereas repair initiation was delayed to 24 h and >40 % of lesions remained in melanoma cell lines at 48 h. This was coupled with a delayed and reduced induction of GGR component XPC in melanoma cells, independent of p53. CONCLUSION:These findings support that NER activity is reduced in melanoma cells due to deficient GGR. Further investigation into the role of NER in UVA-induced melanomagenesis is warranted and may have implications for melanoma treatment.

Dataset Information

A case-control study on association of nucleotide excision repair polymorphisms and its interaction with environment factors with the susceptibility to non-melanoma skin cancer.

Publications

A case-control study on association of nucleotide excision repair polymorphisms and its interaction with environment factors with the susceptibility to non-melanoma skin cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets