Identification of low penetrance alleles for lung cancer: The GEnetic Lung CAncer Predisposition Study (GELCAPS)

GELCAPS was one of the first genetic epidemiological trials in the UK to be adopted by the National Cancer Research Network (NCRN) onto its portfolio with the participation of over 100 oncology departments specialising in the management of lung cancer.Samples from over 5,000 independent lung cancer cases and 2,000 controls have so far been assembled through GELCAPS.GELCAPS represents one of the largest datasets of its type in the world capable of informing on the contribution of low penetrance alleles to the development of lung cancer and the influence of genetic variation on outcome. In addition our experience in developing the GELCAPS serves to illustrate how large DNA biobanks for genetic analyses can be rapidly generated within the UK using the NCRN.Lung cancer is a major cause of cancer mortality worldwide [1]. In the United Kingdom, it accounts for more than 33,000 cancer deaths each year (Cancer Research UK). The disease is frequently cited as a malignancy solely attributable to environmental exposure, principally tobacco smoking. It has, however, long been postulated that individuals may differ in their susceptibility and there is strong evidence from epidemiological studies for a familial risk [reviewed in [2]]. Direct evidence for a genetic predisposition is provided by the increased risk of lung cancer associated with a number of rare Mendelian cancer syndromes, such as in carriers of germline TP53 [3]and RB [4,5] mutations, as well as in patients with Bloom's [6] and Werner's [7] syndromes.The two major types of lung cancer, non-small cell lung cancer (NSCLC), and small cell lung cancer (SCLC) account for 75% and 25% of cases respectively. Although the histological features are different between these (reflected in differences in patterns of gene expression), there are similarities in the spectrum of underlying somatic genetic alterations suggesting commonality in pathogenesis. Moreover, the observation that the familial risks are not subtype dependent [