The IARC study of lung cancer in central Europe was conducted with cancer institutes in 6 countries including Czech Republic (Prague, Olomouc, Brno), Hungary (Borsod, Heves, Szabolcs, Szolnok, Budapest), Poland (Warsaw, Lodz), Romania (Bucharest), Russia (Moscow) and Slovakia (Banska Bystrica, Bratislava, Nitra) between 1998 and 2002.A little random deviation from the (1,0,0) (Europe, Africa, Asia) point in the triangle plot is expected, and this is visible along the Europe->Africa axis where the presence of any level of Sub-Saharan African ancestry seems improbable. A stronger degree of deviation along the Europe->Asia axis is consistent with a small degree of East Eurasian admixture in these mainly Eastern European populations.
A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
Rayjean J. Hung et al.
Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually1. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 times 10-10). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 times 10-20 overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines2, 3, and they bind to N'-nitrosonornicotine and potential lung carcinogens4. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets5.