{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:50:46Z","timestamp":1791010246069,"version":"4.1.0"},"reference-count":35,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2009,4,30]],"date-time":"2009-04-30T00:00:00Z","timestamp":1241049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2009,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>BACKGROUND:<\/jats:title><jats:p>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\u2010strand breaks (DSBs). The authors of this report postulated that polymorphisms in genes of the nonhomologous end\u2010joining (NHEJ) pathway, which is the major DSB repair pathway in mammalian cells, may modulate lung cancer susceptibility and prognosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS:<\/jats:title><jats:p>Patients with NSCLC (n = 152) and a group of appropriate age\u2010matched and sex\u2010matched controls (n = 162) were subjected to genotype analysis of the NHEJ pathway genes x\u2010ray repair complementing defective repair in Chinese hamster cells 6 (<jats:italic>Ku70<\/jats:italic>) (reference single nucleotide polymorphism number [rs] 2267437), x\u2010ray repair complementing defective repair in Chinese hamster cells 5 (<jats:italic>Ku80<\/jats:italic>) (rs3835), x\u2010ray repair complementing defective repair in Chinese hamster cells 4 (<jats:italic>XRCC4<\/jats:italic>) (rs1805377), and DNA ligase IV (<jats:italic>LIG4<\/jats:italic>) (rs1805388). The gene\u2010gene interaction (joint effect), genotype\u2010environmental (ie, smoking) correlation, and genotype\u2010phenotype (ie, FAL) correlation were examined. The Kaplan\u2010Meier method and log\u2010rank tests were used to assess the prognostic effect.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS:<\/jats:title><jats:p>There was a significant association between the <jats:italic>XRCC4<\/jats:italic> and <jats:italic>LIG4<\/jats:italic> 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 <jats:italic>XRCC4<\/jats:italic> gene had a poorer prognosis compared with other patients (<jats:italic>P<\/jats:italic> = .015). There was a significant difference between the patient smokers and controls for <jats:italic>XRCC4<\/jats:italic> (adjusted OR, 2.67) and <jats:italic>LIG4<\/jats:italic> (adjusted OR, 2.04). In addition, polymorphisms in <jats:italic>XRCC4<\/jats:italic> and <jats:italic>LIG4<\/jats:italic> were linked significantly with patients who had high FAL (adjusted OR, 2.03\u20103.84).<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSIONS:<\/jats:title><jats:p>To the authors' knowledge, this is the first nested case\u2010control 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. Cancer 2009. \u00a9 2009 American Cancer Society.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncr.24327","type":"journal-article","created":{"date-parts":[[2009,4,30]],"date-time":"2009-04-30T16:26:38Z","timestamp":1241108798000},"page":"2939-2948","source":"Crossref","is-referenced-by-count":55,"title":["Lung cancer susceptibility and prognosis associated with polymorphisms in the nonhomologous end\u2010joining pathway 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