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Sunday September 8, 2013 MYT 12:00:00 AM
Sunday September 8, 2013 MYT 8:44:34 AM
by tan shiow chin
To date, the study has identified an additional 42 gene mutations that directly affect the development of breast cancer, bringing the total number of known gene mutations causing the cancer up to 76. – Filepic
Several new genetic mutations have been uncovered after a three-year international study looking at breast, ovarian and prostrate cancer patients.
IT’S probably just a coincidence, but actress Angelina Jolie’s revelation of undergoing a preventative double mastectomy to reduce her risk of developing breast cancer due to having a BRCA1 gene mutation, came just a few weeks after several papers were published in the journal Nature Genetics on the discovery of several new genetic contributors to breast, ovarian and prostate cancer.
The Collaborative Oncological Gene-Environment Study (COGS) is an international study involving around 100,000 patients worldwide with one of the three cancers mentioned above, as well as an equal number of healthy controls from the general population.
In Malaysia, the Cancer Research Initiatives Foundation (Carif) and Universiti Malaya (UM) participated in the study under the aegis of the University of Cambridge, United Kingdom – one of the 16 consortia working together for COGS.
Although the four-year study began in 2009, the work in Malaysia had actually started before that.
Carif chief executive officer and UM adjunct professor Dr Teo Soo Hwang shares that the collaboration between the two bodies for the Malaysian Breast Cancer Genetic Study (MyBRCA) began in 2003.
“We started the study to understand why breast cancer occurs, who is at risk, and what are the genes that cause risk in breast cancer,” she says.
She adds that so far, around 1,500 breast cancer patients have taken part in the ongoing study.
In addition, Carif later worked with UM’s Prof Dr Woo Yin Ling, who specialises in gynaecological oncology, to conduct a separate study on ovarian cancer.
Prof Teo explains: “Ovarian cancer, although it is rare, is important because most people succumb to it.”
They did not, however, participate in the prostate cancer part of the COGS study.
Both genetic and environmental factors are known to contribute to the occurrence of breast cancer.
Says Prof Teo: “Every female’s risk of getting breast cancer in Malaysia is 5%. By contrast, if you have the BRCA1 or 2 gene, the risk ranges from 50-87%.”
According to UM consultant breast surgeon Prof Dr Nur Aishah Mohd Taib, only about 15% of breast cancer cases are inherited.
However, as Prof Teo points out, you cannot change your genetic make-up, unlike environmental factors.
Therefore, one of the objectives of the COGS study is to develop a risk model, which includes genetic and environmental or lifestyle factors, that will allow educated prediction of the three cancers under study among the population at large.
To date, the study has identified an additional 42 gene mutations that directly affect the development of breast cancer, bringing the total number of known gene mutations causing the cancer up to 76.
However, the risk of developing breast cancer from each of these individual mutations differs widely, depending on which genes are involved.
The known mutations that cause breast cancer can be broadly divided into two categories: rare mutations, which include the two BRCA genes, and single-nucleotide polymorphisms (SNPs).
While those with the rare mutations have a much higher risk of developing breast cancer, these genes are also – as their classification states – rarely found among the general population.
For example, according to Prof Teo, the BRCA genes are only found in 0.6% of the general population.
However, the story is different for those who have a family history of breast cancer – around one-fifth of those whose relatives have breast cancer are at risk of having these rare mutations.
SNPs in contrast, are much more commonly found among the general population.
“Individuals with one SNP only have a very low increase in risk; so, for example, from 5% to 5.05%.
“But each SNP adds multiplicatively, so the risk among individuals who inherit many SNPs together can be three times higher than the general population, or 15% relative risk compared to the general population,” says Prof Teo.
Most importantly, Prof Nur Aishah points out that despite the numerous genes that have been discovered to be implicated in breast cancer development, the only two genes that can be detected in a clinical setting are the BRCA1 and 2.
“Sometimes, it is the interpretation of the results that is very important. (Patients) get back a negative BRCA result and get told that their risk is normalised, but their family history is very indicative of it – for example, several relatives have breast cancer – so, it is likely they have one of the other rare genes.”
Therefore, Prof Teo advises that anyone who has relatives with breast cancer should be extra diligent about getting regular breast check-ups to enable them to catch the disease at the earliest possible stage.
Ideally, Prof Nur Aishah says that such women should start going for regular screening around 10 years before the youngest age at which their relatives were diagnosed with breast cancer. (For example, if someone has a 60-year-old aunt who was diagnosed at 55, a 40-year-old sister who was diagnosed at 39, and a 45-year-old cousin who was diagnosed at 35, then they should start going for regular screening by the age of 25.)
Meanwhile, for ovarian cancer, Prof Teo shares that the COGS study only discovered eight new genes related to the disease, bringing the total number of genes associated to ovarian cancer up to 12.
The BRCA genes play a much bigger role in the development of this cancer, with up to 30% of cases involving these genes.
Although Prof Woo notes that the occurrence of ovarian cancer is rare compared to breast cancer, it is often diagnosed late, frequently resulting in the death of the patient.
“The five-year survival rate is less than 50%. Patients are usually diagnosed at stage 3 and 4,” she says. By stage 3 of ovarian cancer, the tumour has already spread to the abdominal lining and/or lymph nodes.
But if a woman is tested positive for the BRCA mutations, then she can ensure that she goes for regular screening to monitor for any development of ovarian cancer.
For women under the age of 40, this usually comprises an ultrasound scan and blood tests once every six months.
According to Prof Woo, the reason for this is that doctors will try to avoid removing the ovaries and Fallopian tubes of those under 40 in order to prevent them from experiencing premature menopause, and the attendant biological changes.
However, those above 40 with a high risk of ovarian cancer would be recommended to undergo this risk-reducing bilateral salphingo-oophorectomy, which is a minor operation, she says.
Both Prof Woo and Prof Nur Aishah run a monthly Risk Management Clinic at UM Medical Centre (UMMC) that offers counselling and advice for individuals and families with the risk of developing breast, ovarian or prostrate cancers, on how to manage their risk.
Carif supports the clinic by offering genetic counselling and testing.
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Health, Health, Breast cancer genetics, Carif, UM
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