Smoking is by far the leading risk factor for<unk>  cancer. Cigarette smoke contains more than 6,000 components, many of which lead to DNA damage (see table of tobacco-related DNA damages in Tobacco smoking). Other causes include radon, exposure to secondhand smoke, exposure to substances such as asbestos, chromium, nickel, beryllium, soot, or tar, family history of<unk>  cancer, and air pollution. In general, DNA damage appears to be the primary underlying cause of cancer. Though most DNA damages are repairable, leftover unrepaired DNA damages from cigarette smoke are the likely cause of NSCLC. DNA replication past an unrepaired damage can give rise to a mutation because of inaccurate translesion synthesis. In addition, during repair of DNA double-strand breaks, or repair of other DNA damages, incompletely cleared sites of repair can lead to epigenetic gene silencing. DNA repair deficiency in NSCLC Deficiencies in DNA repair underlie many forms of cancer. If DNA repair is deficient, the frequency of unrepaired DNA damages increases, and these tend to cause inaccurate translesion synthesis leading to mutation. Furthermore, increased damages can elevate incomplete repair, leading to epigenetic alterations. As indicated as in the article Carcinogenesis, mutations in DNA repair genes occasionally occur in cancer, but deficiencies of DNA repair due to epigenetic alterations that reduce or silence DNA repair-gene expression occur much more frequently in cancer. Epigenetic gene silencing of DNA repair genes occurs frequently in NSCLC. At least nine DNA repair genes that normally function in relatively accurate DNA repair pathways are often repressed by promoter hypermethylation in NSCLC. One DNA repair gene, FEN1, that functions in an inaccurate DNA repair pathway, is expressed at an increased level due to hypo-, rather than hyper-, methylation of its promoter region (deficiency of promoter methylation) in NSCLC. +Epigenetic promoter methylation in DNA repair genes in NSCLC Gene Frequency of hyper- (or hypo-) methylation DNA repair pathway Ref. NEIL1 42% base excision repair WRN 38% homologous recombinational repair, nonhomologous end joining, base excision repair MGMT 13% - 64% direct reversal ATM 47% homologous recombinational repair MLH1 48% - 73% mismatch repair MSH2 42% - 63% mismatch repair BRCA2 42% homologous recombinational repair BRCA1 30% homologous recombinational repair XRCC5 (Ku80) 20% nonhomologous end joining FEN1 100% hypomethylated (increased expression) microhomology-mediated end joining The frequent deficiencies in accurate DNA repair, and the increase in inaccurate repair, likely cause the high level of mutation in<unk>  cancer cells of more than 100,000 mutations per genome (see Whole genome sequencing).
types of Lung cancer
medical cause of Hemoptysis
symptom of Lung cancer
medical cause of Bronchiolitis
medical cause of Bronchiectasis
types of Kidney cancer
symptom of Mesothelioma
medical cause of Neoplasm