Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer

Abstract Background Gene-gene and gene-environment interactions play an important role in cancer susceptibility. In this work, we studied the association of XRCC1 rs25487, ERCC1 rs735482, and CHRNA3 rs1051730 variants with lung cancer and assessed the modulatory effect of potential interaction betwe...

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Main Authors: Nada Ezzeldin, Dalia El-Lebedy, Asmaa Mohammed
Format: Article
Language:English
Published: SpringerOpen 2019-11-01
Series:Egyptian Journal of Medical Human Genetics
Subjects:
Online Access:http://link.springer.com/article/10.1186/s43042-019-0034-1
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author Nada Ezzeldin
Dalia El-Lebedy
Asmaa Mohammed
author_facet Nada Ezzeldin
Dalia El-Lebedy
Asmaa Mohammed
author_sort Nada Ezzeldin
collection DOAJ
description Abstract Background Gene-gene and gene-environment interactions play an important role in cancer susceptibility. In this work, we studied the association of XRCC1 rs25487, ERCC1 rs735482, and CHRNA3 rs1051730 variants with lung cancer and assessed the modulatory effect of potential interaction between these variants on disease risk. Results In this study, 86 primary lung cancer patients and 64 control subjects were genotyped for CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 by real-time PCR. The frequency of the three studied variants was higher among lung cancer patients than in control subjects, but with no statistical significance. ERCC1 rs735482 variant was associated with 6.9-fold increased risk to develop lung cancer among smokers (p = 0.03). Concomitant presence of CHRNA3 and ERCC1 wild alleles was associated with 2.7-fold elevated risk of lung cancer (p < 0.0001), while concomitant presence of CHRNA3 rs1051730 variant allele with ERCC1 wild allele was associated with 20-fold elevated risk (p < 0.000). Concomitant presence of both variants, ERCC1 rs735482 and CHRNA3 rs1051730, was associated with 9.9-fold elevated risk (p < 0.0001). Meanwhile, the concomitant presence of XRCC1 rs25487 with either ERCC1 rs735482 or CHRNA3 rs1051730 or both was not associated with increased risk of the disease. Conclusion Our results emphasize the role of gene-gene interaction in the pathogenesis of lung cancer. Large-scale further studies to clarify the underlying mechanisms are needed.
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spelling doaj.art-24faac3ba56d4abb98cb022253f9f0d32022-12-22T00:56:36ZengSpringerOpenEgyptian Journal of Medical Human Genetics2090-24412019-11-012011710.1186/s43042-019-0034-1Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancerNada Ezzeldin0Dalia El-Lebedy1Asmaa Mohammed2Chest Diseases, Department of Internal Medicine, Medical Division, National Research CenterDepartment of Clinical and Chemical Pathology, Medical Research Division, National Research CenterDepartment of Environmental and Occupational Medicine, National Research CenterAbstract Background Gene-gene and gene-environment interactions play an important role in cancer susceptibility. In this work, we studied the association of XRCC1 rs25487, ERCC1 rs735482, and CHRNA3 rs1051730 variants with lung cancer and assessed the modulatory effect of potential interaction between these variants on disease risk. Results In this study, 86 primary lung cancer patients and 64 control subjects were genotyped for CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 by real-time PCR. The frequency of the three studied variants was higher among lung cancer patients than in control subjects, but with no statistical significance. ERCC1 rs735482 variant was associated with 6.9-fold increased risk to develop lung cancer among smokers (p = 0.03). Concomitant presence of CHRNA3 and ERCC1 wild alleles was associated with 2.7-fold elevated risk of lung cancer (p < 0.0001), while concomitant presence of CHRNA3 rs1051730 variant allele with ERCC1 wild allele was associated with 20-fold elevated risk (p < 0.000). Concomitant presence of both variants, ERCC1 rs735482 and CHRNA3 rs1051730, was associated with 9.9-fold elevated risk (p < 0.0001). Meanwhile, the concomitant presence of XRCC1 rs25487 with either ERCC1 rs735482 or CHRNA3 rs1051730 or both was not associated with increased risk of the disease. Conclusion Our results emphasize the role of gene-gene interaction in the pathogenesis of lung cancer. Large-scale further studies to clarify the underlying mechanisms are needed.http://link.springer.com/article/10.1186/s43042-019-0034-1Lung cancerSmokingXRCC1ERCC1CHRNA3Polymorphism
spellingShingle Nada Ezzeldin
Dalia El-Lebedy
Asmaa Mohammed
Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
Egyptian Journal of Medical Human Genetics
Lung cancer
Smoking
XRCC1
ERCC1
CHRNA3
Polymorphism
title Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
title_full Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
title_fullStr Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
title_full_unstemmed Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
title_short Gene-environment and gene-gene interactions between CHRNA3 rs1051730, XRCC1 rs25487, and ERCC1 rs735482 variants highly elevate the risk of lung cancer
title_sort gene environment and gene gene interactions between chrna3 rs1051730 xrcc1 rs25487 and ercc1 rs735482 variants highly elevate the risk of lung cancer
topic Lung cancer
Smoking
XRCC1
ERCC1
CHRNA3
Polymorphism
url http://link.springer.com/article/10.1186/s43042-019-0034-1
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AT asmaamohammed geneenvironmentandgenegeneinteractionsbetweenchrna3rs1051730xrcc1rs25487andercc1rs735482variantshighlyelevatetheriskoflungcancer