Mutation found to multiply nearly by four the risk of suffering breast cancer

The study concludes that specific rare mutations in the FANCM gene predisposes the body to develop ER-negative and triple negative breast cancers, considered to be the most aggressive and with the worst prognosis.

22/07/2020

Geneticists from the Institute of Research at the Hospital de Sant Pau – IIB Sant Pau and the cancer research institute IFOM in Milan, Italy, led by Dr Jordi Surrallés – director of the Sant Pau Research Institute and professor at the UAB Department of Genetics and Microbiology - and Dr Paolo Peterlongo, have discovered that rare mutations in the FANCM gene are a factor that influences the development of ER-positive and triple negative breast cancers, considered to be the most aggressive and with a worst outcome from among the different types of breast cancers.

The study was conducted evaluating the association of three recurring variants of the FANCM gene with risk of developing breast cancer in 67,112 cases, 53,766 control cases and 26,662 carriers of the pathogenic variants in BRCA1 or BRCA2. The research involved more than 200 laboratories and hospitals from around the world under the OncoArray Consortium framework, a multinational collaboration set up to discover variants that influence the appearance of several different cancers in humans, such as breast, colom, lung, ovary, endometic and prostate cancers.

Dr Massimo Bogliolo, member of the team and first author of the article, explains that “genetic data indicates that one of the FANCM's genetic variants analysed is associated with a 3.8 higher risk of developing triple negative cancer and 2.44 times higher risk of developing ER-negative breast cancer”.

Researchers also studied the function of mutations in cell models with the aim of analysing their role in the response to olaparib, a drug used to treat ovarian cancer, or breast cancer in patients with BRCA1 or BRCA2 mutations in advanced stages of the disease and resistant to other treatments. The functional data showed that the genetic variants did actually alter the functioning of the FANCM gene by producing greater sensitivity to the antitumoral effect of olaparib, suggesting that this drug could be a possible treatment alternativefor patients with breast tumours associated with the pathogenic variants of FANCM.

The study has been published in Nature Partner Journals Breast Cancer (NPJ Breast Cancer)
https://www.nature.com/articles/s41523-019-0127-5

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