Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes: A multiple genotype-phenotype study

Ruo Chia Tseng, Feng Jen Hsieh, Chuen Ming Shih, Han Shui Hsu, Chih Yi Chen, Yi-Ching Wang

研究成果: Article

48 引文 (Scopus)

摘要

BACKGROUND: Nonsmall cell lung cancer (NSCLC) frequently exhibits genomic instability, such as high fractional allelic loss (FAL). Genomic instability may result from unrepaired or misrepaired double-strand breaks (DSBs). The authors of this report postulated that polymorphisms in genes of the nonhomologous end-joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells, may modulate lung cancer susceptibility and prognosis. METHODS: Patients with NSCLC (n = 152) and a group of appropriate age-matched and sex-matched controls (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x-ray repair complementing defective repair in Chinese hamster cells 6 (Ku70) (reference single nucleotide polymorphism number [rs] 2267437), x-ray repair complementing defective repair in Chinese hamster cells 5 (Ku80) (rs3835), x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) (rs1805377), and DNA ligase IV (LIG4) (rs1805388). The gene-gene interaction (joint effect), genotype-environmental (ie, smoking) correlation, and genotype-phenotype (ie, FAL) correlation were examined. The Kaplan-Meier method and log-rank tests were used to assess the prognostic effect. RESULTS: There was a significant association between the XRCC4 and LIG4 genotypes with NSCLC risk in an analysis of individual polymorphism associations, and the risk of NSCLC increased further in a combined analysis of multiple polymorphisms (adjusted odds ratio [OR], 8.74). The patients who had a homozygous variant guanine/ guanine genotype of the XRCC4 gene had a poorer prognosis compared with other patients (P = .015). There was a significant difference between the patient smokers and controls for XRCC4 (adjusted OR, 2.67) and LIG4 (adjusted OR, 2.04). In addition, polymorphisms in XRCC4 and LIG4 were linked significantly with patients who had high FAL (adjusted OR, 2.03-3.84). CONCLUSIONS: To the authors' knowledge, this is the first nested case-control study to demonstrate a significant association between the polymorphisms of genes in the NHEJ pathway and lung cancer susceptibility and prognosis. The results may be useful for risk assessment and disease monitoring of patients with NSCLC.

原文English
頁(從 - 到)2939-2948
頁數10
期刊Cancer
115
發行號13
DOIs
出版狀態Published - 2009 七月 1

指紋

Lung Neoplasms
Non-Small Cell Lung Carcinoma
Genotype
Phenotype
Loss of Heterozygosity
Cricetulus
Odds Ratio
Genes
Genomic Instability
X-Rays
Guanine
Genetic Association Studies
Physiologic Monitoring
Single Nucleotide Polymorphism
Case-Control Studies
Age Groups
Smoking

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

引用此文

Tseng, Ruo Chia ; Hsieh, Feng Jen ; Shih, Chuen Ming ; Hsu, Han Shui ; Chen, Chih Yi ; Wang, Yi-Ching. / Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes : A multiple genotype-phenotype study. 於: Cancer. 2009 ; 卷 115, 編號 13. 頁 2939-2948.
@article{6ea8cad16ae8473bba8ef4522c884f1d,
title = "Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes: A multiple genotype-phenotype study",
abstract = "BACKGROUND: Nonsmall cell lung cancer (NSCLC) frequently exhibits genomic instability, such as high fractional allelic loss (FAL). Genomic instability may result from unrepaired or misrepaired double-strand breaks (DSBs). The authors of this report postulated that polymorphisms in genes of the nonhomologous end-joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells, may modulate lung cancer susceptibility and prognosis. METHODS: Patients with NSCLC (n = 152) and a group of appropriate age-matched and sex-matched controls (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x-ray repair complementing defective repair in Chinese hamster cells 6 (Ku70) (reference single nucleotide polymorphism number [rs] 2267437), x-ray repair complementing defective repair in Chinese hamster cells 5 (Ku80) (rs3835), x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) (rs1805377), and DNA ligase IV (LIG4) (rs1805388). The gene-gene interaction (joint effect), genotype-environmental (ie, smoking) correlation, and genotype-phenotype (ie, FAL) correlation were examined. The Kaplan-Meier method and log-rank tests were used to assess the prognostic effect. RESULTS: There was a significant association between the XRCC4 and LIG4 genotypes with NSCLC risk in an analysis of individual polymorphism associations, and the risk of NSCLC increased further in a combined analysis of multiple polymorphisms (adjusted odds ratio [OR], 8.74). The patients who had a homozygous variant guanine/ guanine genotype of the XRCC4 gene had a poorer prognosis compared with other patients (P = .015). There was a significant difference between the patient smokers and controls for XRCC4 (adjusted OR, 2.67) and LIG4 (adjusted OR, 2.04). In addition, polymorphisms in XRCC4 and LIG4 were linked significantly with patients who had high FAL (adjusted OR, 2.03-3.84). CONCLUSIONS: To the authors' knowledge, this is the first nested case-control study to demonstrate a significant association between the polymorphisms of genes in the NHEJ pathway and lung cancer susceptibility and prognosis. The results may be useful for risk assessment and disease monitoring of patients with NSCLC.",
author = "Tseng, {Ruo Chia} and Hsieh, {Feng Jen} and Shih, {Chuen Ming} and Hsu, {Han Shui} and Chen, {Chih Yi} and Yi-Ching Wang",
year = "2009",
month = "7",
day = "1",
doi = "10.1002/cncr.24327",
language = "English",
volume = "115",
pages = "2939--2948",
journal = "Cancer",
issn = "0008-543X",
publisher = "John Wiley and Sons Inc.",
number = "13",

}

Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes : A multiple genotype-phenotype study. / Tseng, Ruo Chia; Hsieh, Feng Jen; Shih, Chuen Ming; Hsu, Han Shui; Chen, Chih Yi; Wang, Yi-Ching.

於: Cancer, 卷 115, 編號 13, 01.07.2009, p. 2939-2948.

研究成果: Article

TY - JOUR

T1 - Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end-joining pathway genes

T2 - A multiple genotype-phenotype study

AU - Tseng, Ruo Chia

AU - Hsieh, Feng Jen

AU - Shih, Chuen Ming

AU - Hsu, Han Shui

AU - Chen, Chih Yi

AU - Wang, Yi-Ching

PY - 2009/7/1

Y1 - 2009/7/1

N2 - BACKGROUND: Nonsmall cell lung cancer (NSCLC) frequently exhibits genomic instability, such as high fractional allelic loss (FAL). Genomic instability may result from unrepaired or misrepaired double-strand breaks (DSBs). The authors of this report postulated that polymorphisms in genes of the nonhomologous end-joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells, may modulate lung cancer susceptibility and prognosis. METHODS: Patients with NSCLC (n = 152) and a group of appropriate age-matched and sex-matched controls (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x-ray repair complementing defective repair in Chinese hamster cells 6 (Ku70) (reference single nucleotide polymorphism number [rs] 2267437), x-ray repair complementing defective repair in Chinese hamster cells 5 (Ku80) (rs3835), x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) (rs1805377), and DNA ligase IV (LIG4) (rs1805388). The gene-gene interaction (joint effect), genotype-environmental (ie, smoking) correlation, and genotype-phenotype (ie, FAL) correlation were examined. The Kaplan-Meier method and log-rank tests were used to assess the prognostic effect. RESULTS: There was a significant association between the XRCC4 and LIG4 genotypes with NSCLC risk in an analysis of individual polymorphism associations, and the risk of NSCLC increased further in a combined analysis of multiple polymorphisms (adjusted odds ratio [OR], 8.74). The patients who had a homozygous variant guanine/ guanine genotype of the XRCC4 gene had a poorer prognosis compared with other patients (P = .015). There was a significant difference between the patient smokers and controls for XRCC4 (adjusted OR, 2.67) and LIG4 (adjusted OR, 2.04). In addition, polymorphisms in XRCC4 and LIG4 were linked significantly with patients who had high FAL (adjusted OR, 2.03-3.84). CONCLUSIONS: To the authors' knowledge, this is the first nested case-control study to demonstrate a significant association between the polymorphisms of genes in the NHEJ pathway and lung cancer susceptibility and prognosis. The results may be useful for risk assessment and disease monitoring of patients with NSCLC.

AB - BACKGROUND: Nonsmall cell lung cancer (NSCLC) frequently exhibits genomic instability, such as high fractional allelic loss (FAL). Genomic instability may result from unrepaired or misrepaired double-strand breaks (DSBs). The authors of this report postulated that polymorphisms in genes of the nonhomologous end-joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells, may modulate lung cancer susceptibility and prognosis. METHODS: Patients with NSCLC (n = 152) and a group of appropriate age-matched and sex-matched controls (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x-ray repair complementing defective repair in Chinese hamster cells 6 (Ku70) (reference single nucleotide polymorphism number [rs] 2267437), x-ray repair complementing defective repair in Chinese hamster cells 5 (Ku80) (rs3835), x-ray repair complementing defective repair in Chinese hamster cells 4 (XRCC4) (rs1805377), and DNA ligase IV (LIG4) (rs1805388). The gene-gene interaction (joint effect), genotype-environmental (ie, smoking) correlation, and genotype-phenotype (ie, FAL) correlation were examined. The Kaplan-Meier method and log-rank tests were used to assess the prognostic effect. RESULTS: There was a significant association between the XRCC4 and LIG4 genotypes with NSCLC risk in an analysis of individual polymorphism associations, and the risk of NSCLC increased further in a combined analysis of multiple polymorphisms (adjusted odds ratio [OR], 8.74). The patients who had a homozygous variant guanine/ guanine genotype of the XRCC4 gene had a poorer prognosis compared with other patients (P = .015). There was a significant difference between the patient smokers and controls for XRCC4 (adjusted OR, 2.67) and LIG4 (adjusted OR, 2.04). In addition, polymorphisms in XRCC4 and LIG4 were linked significantly with patients who had high FAL (adjusted OR, 2.03-3.84). CONCLUSIONS: To the authors' knowledge, this is the first nested case-control study to demonstrate a significant association between the polymorphisms of genes in the NHEJ pathway and lung cancer susceptibility and prognosis. The results may be useful for risk assessment and disease monitoring of patients with NSCLC.

UR - http://www.scopus.com/inward/record.url?scp=67649618877&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67649618877&partnerID=8YFLogxK

U2 - 10.1002/cncr.24327

DO - 10.1002/cncr.24327

M3 - Article

C2 - 19408343

AN - SCOPUS:67649618877

VL - 115

SP - 2939

EP - 2948

JO - Cancer

JF - Cancer

SN - 0008-543X

IS - 13

ER -