News
Find related articles on
Latest News
Recent comments
- keith grimaldi on Genetic factors and cardiovascular risk prediction in women (02/03/2010)
- Andro Hsu on Australian private insurer offers half-price genome scan (26/02/2010)
- Andro Hsu on Pre-conceptual genetic testing for multiple conditions (09/02/2010)
- PHG Foundation on Involvement of rare variants in common disease (05/02/2010)
- peter on Inquiry into synthetic biology, stem cells and genetic engineering (28/11/2009)
Common genetic variation influences risk of lung cancer
Lung cancer is the most common cancer in the world, with 1.3 million new cases diagnosed every year, and is the second most common cancer diagnosed in the UK according to Cancer Research UK. Recently, it has been estimated that the lifetime risk of developing lung cancer is 1 in 14 for men and 1 in 21 for women in the UK, and it has one of the lowest survival outcomes of any cancer. Around 90% of lung cancers in men and 83% in women can be attributed to cigarette smoking, but there is recent evidence which indicates that inherited genetic factors may influence the development and progression of this disease.
In order to explore the impact of common genetic variation on the risk of lung cancer, a two phase genome-wide association (GWA) study followed by a meta-analysis was carried out by British and American scientists [Broderick P et al. (2009) Cancer Res 69(16):6633-41]. Nearly 5000 cases and 5000 controls were genotyped, and the strongest associations (p<10-7) were identified in single nucleotide polymorphisms (SNPs) mapping to a region of chromosome 15 (15q25.1), chromosome 5 (5p15.33) and chromosome 6 (6p21.33). The odds ratio associated with each of these variants was around 1.3, 0.9 and 1.2 respectively. These associations point towards four genes, all of which represent strong candidates for combined lung cancer susceptibility and predilection to smoking a priori: the acetylcholine receptor alpha-subunit (CHRNA; 15q), cisplatin resistance related protein (CLPTM1L; 5p), telomerase reverse transcriptase (TERT; 5p), and HLA-B-associated transcript 3 (BAT3; 6p). The relationship between these variants and both tumour histology and smoking behaviour was also examined; the variation at 5p15.33 was shown to influence lung cancer histology, while a strong relationship between all 15q25.1 variants and smoking was observed, which is consistent with earlier studies (see previous news).
These findings were further strengthened through meta-analysis by pooling the UK-GWA Phase 1 and 2 with two other studies from France (IARC-GWA) and USA (Texas-GWA). This process conferred enough power to detect major common loci exerting risk at or above an odds ratio of around 1.2; however, a much larger class of low frequency or penetrance variants may be potentially identified in the future with the evolution of better technology combined with larger studies and meta-analyses.
Keywords: Disease Susceptibility (Genetic)