2012 Volume 34 Issue 2 Pages 94-100
Recent advances in genome analysis technologies have provided a detailed genome-wide view of cancerous and non-cancerous cells. Lung cancer is largely caused by tobacco smoking, but several studies have implicated inherited genetic factors in disease etiology. Genome-wide association studies (GWASs) using DNA chips have identified loci/genes with polymorphisms that underlie inter-individual differences in cancer susceptibility, including single nucleotide polymorphisms (SNPs). CHRNA (cholinergic receptor, nicotinic, alpha), TERT (telomerase reverse transcriptase) and TP63 (tumor protein p63) loci have been linked to lung cancer susceptibility by GWASs. SNPs in TERT and TP63 are preferentially associated with the risk of adenocarcinoma, the commonest histological type of lung cancer affecting both smokers and non-smokers, whereas those in CHRNA are associated with lung cancer risk irrespective of histological type. An association of functional polymorphisms in DNA repair/metabolic genes with the risk of squamous cell carcinoma, a major histological type developed in smokers, has been suggested, but it remains inconclusive. It was also suggested that an SNP in the TP53 tumor suppressor gene influences the response to platinum-doublet chemotherapy in lung cancer patients. However, analyses have shown that only a subset of SNPs is involved in lung carcinogenesis/therapy. Further GWASs are needed to translate the information on genetic variations into cancer prevention and clinical practice by focusing on specific subtypes of lung cancers or therapeutic responses.
