Faulty BRCA genes linked to prostate and pancreatic cancers

Date:
January 25, 2022
Source:
University of Cambridge
Summary:
Faulty versions of the BRCA1 and BRCA2 genes are well known
to increase the risk of breast cancer in men and women, and in
ovarian cancer. Now BRCA1 and BRCA2 have been linked to several
other cancers, including those that affect men.



FULL STORY ========================================================================== Faulty versions of the BRCA1 and BRCA2 genes are well known to increase
the risk of breast cancer in men and women, and in ovarian cancer. Now
BRCA1 and BRCA2 have been linked to several other cancers, including
those that affect men.


==========================================================================
A study published today in the Journal of Clinical Oncology has provided
the strongest evidence to date of these links and helped researchers
estimate more accurately the associated risk.

Since these genes were discovered in the mid 90s, numerous studies
have explored possible links between BRCA1 and BRCA2 mutations and
other cancers.

However, these studies had small sample sizes, resulting in imprecise
estimates of cancer risk. Being able to estimate the risks accurately is important for informing cancer prevention and screening strategies and providing genetic counselling to those at greatest risk. BRCA mutations
are uncommon, affecting around 1 in 300-400 people in the population.

To further investigate these risk estimates, a team led by researchers
at the University of Cambridge, funded by Cancer Research UK, analysed
data from almost 3,200 families with one or more members with the
BRCA1 mutation and almost 2,200 families with members carrying the
BRCA2 mutation. The families had all been recruited to the Consortium
of Investigators of Modi?ers of BRCA1/ 2. The researchers examined the associations with 22 primary cancers.

From the data, the researchers estimated that men who carry a
BRCA2 mutation have a 27% risk of developing prostate cancer by the
time they are 80 years old, more than double the rate compared to
non-carriers. BRCA1 mutations were not associated with an increase in
prostate cancer risk.

Carrying a defective copy of either BRCA1 or BRCA2 more than doubled an individual's risk of pancreatic cancer to 2.5-3% by age 80.



==========================================================================
The mutations were also found to increase the risk of stomach cancer,
though the researchers caution that because of the rarity of this form
of cancer, the number of patients in their datasets was small.

Mutations in both genes significantly increased the risk of breast cancer
in men, though the disease is still very rare, accounting for less than
1% of all male cancer cases in the UK. While a BRCA1 mutation increased
a man's risk of developing breast cancer more than four-fold to 0.4%
by age 80, a BRCA2 mutation increased this risk by 44 times to 3.8%
by age 80. It is estimated that 38 out of 1,000 male carriers of the
BRCA2 mutation will develop breast cancer by age 80.

The researchers were unable to find compelling evidence that mutations
were linked to increased risk of some other cancers which were previously thought to be linked to faulty BRCA genes, such as melanoma.

Cancer Research UK says that people who are worried about their risk of
cancer should talk to their GP. GPs can refer patients to a genetics
clinic if they think someone has a strong family history and might be
at an increased risk.

Professor Antonis Antoniou from the Department of Public Health and
Primary Care at the University of Cambridge, who led the research, said:
"These large datasets of patients have allowed us to estimate with much
greater accuracy the extent to which faulty BRCA1 and BRCA2 genes increase
the risk of several cancers. We've known for some time that they're
linked to breast and ovarian cancer, but there's been uncertainty about
other cancers." Professor Marc Tischkowitz from the Department of Medical Genetics at the University of Cambridge added: "The link between BRCA2
and prostate cancer and pancreatic cancer is now much clearer, thanks to
the data we've analysed. We have also identified a potential link with
stomach cancer, but this is based on small numbers and needs further
study. Our data suggests that there is no strong link between BRCA2 and melanoma, which may provide greater clarity to BRCA2 gene carriers.



========================================================================== "Overall, the results will add to our knowledge on optimising cancer
screening and early detection strategies for people who are known
to carry these faulty genes." Michelle Mitchell, Chief Executive of
Cancer Research UK, said: "Our scientists helped to discover BRCA over
25 years ago and established that faults in these genes increase breast
cancer risk. This study has built on that vital knowledge, giving us
some important new insights into BRCA genes and the likely risks of
developing prostate and pancreatic cancer.

"Cancers caused by inherited faulty BRCA genes are relatively rare,
and other factors like age, smoking, diet and other preventable factors contribute to a person's risk.

"Improving our understanding of how faults in our genes
are associated with certain cancers puts us in a much better
position to pinpoint those at a higher risk of developing cancer." ========================================================================== Story Source: Materials provided by University_of_Cambridge. The original
text of this story is licensed under a Creative_Commons_License. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Shuai Li, Valentina Silvestri, Goska Leslie, Timothy R. Rebbeck,
Susan L.

Neuhausen, John L. Hopper, Henriette Roed Nielsen, Andrew Lee,
Xin Yang, Lesley McGuffog, Michael T. Parsons, Irene L. Andrulis,
Norbert Arnold, Muriel Belotti, AAke Borg, Bruno Buecher, Saundra
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Caputo, Wendy K. Chung, Chrystelle Colas, Sarah V. Colonna,
Jackie Cook, Mary B. Daly, Miguel de la Hoya, Antoine de Pauw,
He'le`ne Delhomelle, Jacqueline Eason, Christoph Engel, D. Gareth
Evans, Ulrike Faust, Tanja N. Fehm, Florentia Fostira, George
Fountzilas, Megan Frone, Vanesa Garcia-Barberan, Pilar Garre,
Marion Gauthier-Villars, Andrea Gehrig, Gord Glendon, David
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Helen Hanson, Tiara Hassan, Julia Hentschel, Judit Horvath, Louise
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Sung-Won Kim, Irene Konstantopoulou, Ava Kwong, Anthony Lauge',
Jong Won Lee, Fabienne Lesueur, Noura Mebirouk, Alfons Meindl,
Emmanuelle Mouret-Fourme, Hannah Musgrave, Joanne Ngeow Yuen Yie,
Dieter Niederacher, Sue K. Park, Inge Sokilde Pedersen, Juliane
Ramser, Susan J.

Ramus, Johanna Rantala, Muhammad U. Rashid, Florian Reichl,
Julia Ritter, Andreas Rump, Marta Santamarin~a, Claire Saule,
Gunnar Schmidt, Rita K.

Schmutzler, Leigha Senter, Saba Shariff, Christian F. Singer,
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Southey, Dominique Stoppa-Lyonnet, Christian Sutter, Yen Tan,
Soo Hwang Teo, Mary Beth Terry, Mads Thomassen, Marc Tischkowitz,
Amanda E. Toland, Diana Torres, Ana Vega, Sebastian A. Wagner,
Shan Wang-Gohrke, Barbara Wappenschmidt, Bernhard H. F. Weber,
Drakoulis Yannoukakos, Amanda B.

Spurdle, Douglas F. Easton, Georgia Chenevix-Trench, Laura Ottini,
Antonis C. Antoniou. Cancer Risks Associated With BRCA1 and BRCA2
Pathogenic Variants. Journal of Clinical Oncology, 2022; DOI:
10.1200/ JCO.21.02112 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/01/220125162420.htm

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