The BRCA2 gene has been associated with breast cancer in the past. Now a new study has linked a gene mutation in the BRCA2 gene to an increased risk of developing lung cancer.
Approximately a quarter of smokers who carry a defect in the BRCA2 gene will develop lung cancer at some point in their lifetime, a large-scale, international study reveals.
The research published in the journal Nature Genetics suggests that smokers who possess the gene have a one in four chance to develop lung cancer compared to the average risk of 16 % for men and 9.5 % for women.
The population group studied consisted of 11, 348 Europeans with lung cancer and 15, 861 without the disease where researchers investigated the differences at specific points in their DNA.
The findings of the study reflected that the association between lung cancer and the BRCA2 gene variant was particularly strong in patients with the most common lung cancer sub-type, called squamous cell lung cancer. The researchers also detected a link between squamous cell lung cancer and a defect in a second gene, CHEK2, which normally prevents cells from dividing when they have suffered damage to their DNA.
Study leader Professor Richard Houlston, Professor of Molecular and Population Genetics at The Institute of Cancer Research (ICR), said: “Our study showed that mutations to two genes, BRCA2 and CHEK2, have a very large effect on lung cancer risk in the context of smoking. Mutated BRCA2 in particular seems to increase risk by around 1.8 times.
“Smokers in general have nearly a 15 per cent chance of developing lung cancer, far higher than in non-smokers. Our results show that some smokers with BRCA2 mutations are at an enormous risk of lung cancer — somewhere in the region of 25 per cent over their lifetime.
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 single biggest thing we can do to reduce death rates is to persuade people not to smoke, and our new findings make plain that this is even more critical in people with an underlying genetic risk.”
Yufei Wang, James D McKay, Thorunn Rafnar, Zhaoming Wang, Maria N Timofeeva, Peter Broderick, Xuchen Zong, Marina Laplana, Yongyue Wei, Younghun Han, Amy Lloyd, Manon Delahaye-Sourdeix, Daniel Chubb, Valerie Gaborieau, William Wheeler, Nilanjan Chatterjee, Gudmar Thorleifsson, Patrick Sulem, Geoffrey Liu, Rudolf Kaaks, Marc Henrion, Ben Kinnersley, Maxime Vallée, Florence LeCalvez-Kelm, Victoria L Stevens, Susan M Gapstur, Wei V Chen, David Zaridze, Neonilia Szeszenia-Dabrowska, Jolanta Lissowska, Peter Rudnai, Eleonora Fabianova, Dana Mates, Vladimir Bencko, Lenka Foretova, Vladimir Janout, Hans E Krokan, Maiken Elvestad Gabrielsen, Frank Skorpen, Lars Vatten, Inger Njølstad, Chu Chen, Gary Goodman, Simone Benhamou, Tonu Vooder, Kristjan Välk, Mari Nelis, Andres Metspalu, Marcin Lener, Jan Lubiński, Mattias Johansson, Paolo Vineis, Antonio Agudo, Francoise Clavel-Chapelon, H Bas Bueno-de-Mesquita, Dimitrios Trichopoulos, Kay-Tee Khaw, Mikael Johansson, Elisabete Weiderpass, Anne Tjønneland, Elio Riboli, Mark Lathrop, Ghislaine Scelo, Demetrius Albanes, Neil E Caporaso, Yuanqing Ye, Jian Gu, Xifeng Wu, Margaret R Spitz, Hendrik Dienemann, Albert Rosenberger, Li Su, Athena Matakidou, Timothy Eisen, Kari Stefansson, Angela Risch, Stephen J Chanock, David C Christiani, Rayjean J Hung, Paul Brennan, Maria Teresa Landi, Richard S Houlston, Christopher I Amos. Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. Nature Genetics, 2014; DOI: 10.1038/ng.3002