A damaged version of the BRCA1 gene, which gives women a high risk of developing breast and ovarian cancer, is also involved in a number of other cancers, according to research1 published today.
In the largest study of its kind Cancer Research UK scientists found that women with a damaged BRCA1 gene also have an increased risk of cancer of the uterus, cervix, pancreas and colon.
Researchers believe the findings could help doctors to monitor women with the faulty gene more carefully for the signs of cancer.
The BRCA1 gene plays an important role in cells; regulating growth and repairing the DNA that is the instruction manual for all living things.
Scientists already knew that when one copy of BRCA1 is inherited in a defective form, a woman has a much higher risk of developing breast or ovarian cancer. But the risk of cancer in other parts of the body was less clear.
Researchers looked at the incidence of cancer in around 12,000 women and men, from 700 families with a history of breast or ovarian cancer living in Europe and North America. Using statistical techniques they calculated the cancer risk among people with a mutated BRCA1 gene compared with the general population.
The lead researcher, Dr Doug Easton from the Cancer Research UK Genetic Epidemiology Unit at the University of Cambridge, says: “We analysed a large amount of data to get an accurate picture of the specific cancers linked to the mutation. Previous studies looked at information from a small number of families and had mixed results.
“We found that the main implication of the study was for female carriers of the damaged BRCA1 gene. Women with the altered version had a two-fold increased risk of developing cancer at sites other than the breast or ovary.”
Women were twice as likely than average to develop colon or pancreatic cancer, three times more likely to develop cancer in the uterus and four times more likely to develop cervical cancer. Researchers also found that there was a substantially increased risk of cancer developing in the fallopian tubes.
Dr Easton says: “It is important to realise that not every woman with an altered BRCA1 gene will develop breast or ovarian cancer and the same applies to the other cancers linked to the mutation in this study. Though there is a big increase in the relative risk to women with the faulty gene the absolute risk for these other cancers is still quite low.
“For example women with the mutation were twice as likely to develop pancreatic cancer than women with a normal BRCA1 gene but the absolute risk for the cancer in women with the faulty gene is as low as one per cent.”
In contrast the overall cancer risk for male BRCA1 mutation carriers was generally very close to that expected for men in the general population. Although men with the altered gene were found to have a slightly increased risk of prostate and a two-fold increase risk in pancreatic cancer.
Currently women found to have the BRCA1 mutation can be monitored more carefully by their doctors for breast and ovarian cancer. They may have more frequent scans – mammograms to pick up breast cancer and ultrasound to help detect ovarian cancer.
Researchers think the new information can help doctors increase surveillance for other cancers. Cervical screening may be especially important for women with the BRCAI mutation.
As well as regular checks for cancer there may be medical or lifestyle choices women with the damaged gene can make to bring down their risk of certain cancers.
Dr Easton explains: “Women with the faulty version of the BRCA1 gene who have a high risk of breast or ovarian cancer may have surgery to remove healthy tissue as a preventative measure.
“This research provides women and their doctors with further information that can help them discuss their medical options.”
Sir Paul Nurse, Chief Executive of Cancer Research UK, says: “Understanding the genetic basis of cancer provides vital information for scientists to develop new treatments and doctors to identify and monitor susceptible people.
“The advances in genetic research will reveal further genes that pre-dispose people to cancer. Cancer Research UK is not only concerned with finding these genes but also educating and counselling people about genetic information and cancer risk.”
- Journal of the National Cancer Institute94 No 18
The BRCA1 and BRCA2 gene mutations are responsible for 2-5 per cent of all breast cancer cases. But the faulty genes account for most cases of breast cancer where there are four or more cases of breast cancer in a family.
Carriers of the faulty version of the BRCA2 gene have a five-fold increased risk of prostate cancer, three and a half fold increase of pancreatic cancer and also an increased risk of skin and stomach cancer. The risk of ovarian cancer and other abdominal cancers are less for carriers of a damaged BRCA2 gene than for carriers of the damaged BRCA1.