Changes in BRCA2 and CHEK2 genes may increase the risk of lung cancer, according to a study -
Genetic causes of lung cancer explored in the overall project of the genome
new research confirms vulnerability to lung cancer can be hereditary and involves the BRCA2 gene as harboring genetic mutations involved. An international consortium of scientists, including researchers from the Institute for Research on Cancer in London, the International Agency for Research on Cancer in Lyon, the National Cancer Institute in Bethesda, Harvard and Dartmouth used the integrated results project 1000 Genomes with the genetics of lung cancer studies to complete the survey published June 1, 2014 Nature genetics .
study scanned the genomes of more than 11,000 people of European descent to look for common variations associated with non small cell carcinoma, a common form of lung cancer. The analysis showed that variations in the gene BRCA2 and CHEK2 can significantly increase the risk of an individual for lung cancer. The chances of a smoker developing lung cancer may be doubled if he or she carries the BRCA2 variation. In addition, the TP63 gene, which was previously only associated with a risk of lung cancer in Asian populations, has been associated with a risk for adenocarcinoma, a form of non-small cell cancer, in those of European origin .
The study four associations (GWA) studies genome-wide opportunity for the UT MD Anderson Cancer Center, the Institute for Research on Cancer, the National Cancer Institute, and the International Agency for Research cancer. The scientists used imputation, a statistical form of inference, in which data from a group of individuals who were sequenced reference is used to fill in missing values on the genome for participants to 'study. The study validated the use of this approach in the search for common genetic variations between different data sets and genotyping many other Harvard participants, the International Agency for Cancer Research, University of Toronto , the Institute for research on cancer and the German cancer research Institute.
Chris Amos, PhD, lead author of the paper and director of the Center for Genomic Medicine at Dartmouth said: "This variant confers the strongest associations found to date for cancer among those identified by genome - wide association studies, and identifies a subset of people who are particularly vulnerable to the adverse effects of smoking. "
The BRCA2 gene for a large protein that functions primarily to coordinate the activities of many different genes involved in DNA repair. DNA cells accumulate damage due to environmental toxins such as those in tobacco smoke. Mutations in BRCA2 can affect the ability of cells to respond to DNA damage, which increases the chance that a cell becomes a cancer.
Previous studies did not detect a link between BRCA2 and lung cancer. All four GWA all data analysis in this study showed a significant association of the BRCA2 gene (of rs11571833) with non-small cell carcinoma, especially squamous cell carcinoma. In addition, the results of previous studies linking validated CHEK2 (rs17879961) with squamous cell carcinoma. The results of the variation TP63 (rs13314271) in individuals in the European ancestry provides strong evidence for its connection to adenocarcinoma.
"Our study showed that mutations in two genes, BRCA2 and CHEK2, have a very important effect on lung cancer risk in the context of smoking. Mutated BRCA2 in particular, appears to increase the risk about 1.8 times, "said study leader Richard Houlston, professor of molecular and population genetics at the Institute for research on cancer (ICR). "Smokers generally have nearly a 15 per cent chance of developing lung cancer, much higher than among nonsmokers Our results indicate that some smokers with BRCA2 mutations are at a huge risk of cancer lung -.. Somewhere in the region of 25 percent in their life lung cancer claims more than a million lives a year worldwide and is by far the biggest cancer killer in the UK. We know that the main thing we can do to reduce mortality is to persuade people not to smoke, and our new results clearly indicate that this is even more critical in people with a genetic risk underlying. "
the results of this study may influence how individuals are examined and treated for lung cancer. Those with genetic mutations who smoke may be candidates for lung cancer screening with low dose CT. Given that individuals with mutations in the germline BRCA1 or BRCA2 respond to a specific chemotherapy PARP inhibition, it is possible that individuals with this mutation BRCA2 and lung cancer may well respond more favorably to inhibition of PARP as other cases of lung cancer.
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