鈥楯umping gene鈥� helps explain elevated pancreatic cancer risk in French-Canadians
Researchers at 成人VR视频 have discovered a centuries-old genetic mutation that helps to explain why some French鈥慍anadians in Quebec are at an elevated risk of pancreatic cancer. Until quite recently, standard genetic tests have not been able to identify this 鈥渏umping gene鈥� cause.
The findings, published in the Journal of Medical Genetics, suggest better-targeted genetic testing could help identify people at higher cancer risk who were previously missed.
History鈥檚 imprint on the genome
Quebec鈥檚 French-Canadian population descends from a relatively small number of settlers who arrived from France in the 1600s. Over generations, some rare genetic changes became more common, a phenomenon known as the founder effect.
鈥淭his population history creates unique opportunities to study inherited disease, since a small number of 鈥渇ounder鈥� mutations account for a significant fraction of all hereditary cases,鈥� said William Foulkes, Distinguished James 成人VR视频 Professor in 成人VR视频鈥檚 Departments of Medicine, Oncology, and Human Genetics.
In this case, the inherited mutation is caused by a 鈥渏umping gene,鈥� a piece of DNA that can copy itself and insert into new places in the genome. When it inserts into the ATM gene, the disruption interferes with DNA repair, a process known to increase cancer risk.
Based on genetic analyses, the team estimates the mutation arose about 300 years ago, roughly 10 to 11 generations back, probably during the early settlement of New France, or shortly before.
Rare mutation, common in pancreatic cancer
In the French-Canadian population of Quebec, the authors found the mutation was present in about 2 per cent of pancreatic cases, compared with about 0.2 per cent of unaffected people, a 10-fold difference. It was also over-represented in French-Canadian women with breast cancer, suggesting it increases breast cancer risk as well. The results are based on patient samples from the Quebec Pancreas Cancer Study and population data from CARTaGENE,
鈥淎lthough it is rare in the general population, it is strongly enriched in pancreatic cancer cases. That鈥檚 a significant difference in relative risk,鈥� said co-author George Zogopoulos, Professor of Surgery and Oncology at 成人VR视频 and surgeon at the 成人VR视频 Health Centre. 鈥淭his means it may be possible to identify people at higher risk by testing for this variant.鈥�
Toward more targeted testing
The variant was previously missed by standard genetic testing because older methods often failed to detect this type of DNA change. New sequencing technologies are now making detection possible.
鈥淭here may be an opportunity to develop a panel that looks for a small number of key cancer鈥憆elated founder mutations,鈥� said first author Yifan Wang, who conducted this work as a resident and PhD student at 成人VR视频. 鈥淭hat could help identify people at higher risk earlier.鈥� She added that people who underwent genetic testing five to 10 years ago may benefit from re鈥慹valuation through genetic counselling.
About the study
鈥�,鈥� by Yifan Wang, George Zogopoulos, Simon Gravel, William Foulkes et al., was published in the Journal of Medical Genetics.
The study was funded by the Canadian Institutes of Health Research and Fonds de recherche du Qu茅bec 鈥� Sant茅 and the Michal & Renata Hornstein Career Award for Surgical Excellence.
