One of the aims of Ovarian Cancer Awareness Month is to educate Australians on the diagnosis and treatment of ovarian cancer. Pathology plays a huge role in this, especially in some of the most recent breakthroughs improving outcomes for women diagnosed with the disease.

Last month it was announced that the Peter MacCallum Cancer Centre in Melbourne is launching the Traceback program. The program will test 11,000 tissue samples from women diagnosed with ovarian cancer between 2001 and 2016 to see if they carry the BRCA gene mutations.[2]

The BRCA 1 and BRCA 2 genes produce tumour suppressor proteins, which play an important role in repairing damaged DNA. But specific mutations in these genes can stop them from being able to perform this role effectively and therefore cells are more likely to develop additional mutations which can lead to cancer.

Previous research indicates that approximately 15% to 20% of ovarian cancer patients carry a BRCA mutation, and the program leaders at the Peter MacCallum estimate they could discover as many as 1,500 women who have the mutation and don’t yet know.

By arming them with this knowledge the program is helping women to take any necessary preventative measures or to have regular testing or screening, to avoid another cancer in the future.

The program is important not just for the women themselves but for their families too; having a relative with a BRCA mutation raises a person’s risk of also having a gene mutation that could increase the likelihood of developing several types of cancer.

Approximately 44% of women with a BRCA1 mutation, and 16% of women with a BRCA2 mutation, will develop ovarian cancer by the age of 80. This is compared to 1.3% of the general population. The risk of breast cancer also increases for women with a BRCA mutation – around 70% of women with either mutation will develop breast cancer by 80. The mutations are also linked to increased risks of pancreatic cancer for men and women and prostate cancer for men.

The recent announcement from the Peter MacCallum is just the latest in a growing list of improvements to the accessibility of genetic testing for Australian patients.

Last year, for example, it was announced that the Medicare Benefits Schedule (MBS) would offer a rebate to women with breast or ovarian cancer who have the test. And if a mutation is found, their family members will also be eligible to have the test.

Cancers are most treatable when they are detected early, but this is often long before symptoms develop. Knowing about a genetic risk factor can save many lives – and that’s why more access to appropriate pathology testing is such a powerful weapon.

[1] https://ovarian-cancer.canceraustralia.gov.au/statistics

[2] http://www.abc.net.au/news/2018-02-06/ovarian-cancer-patients-tissue-samples-brca-mutation-test/9397470

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Fortunately, genetic variations are not all bad news, there are ways in which they can have positive effects and scientists are constantly learning more about our genes that could help inform new tests and treatments.

Here are a few examples of some genetic discoveries that could have a future impact on our health.

Unbreakable bones – the LRP5 gene

Scientists have been aware for some time that a mutation in the LRP5 gene that regulates bone density could cause low bone density, making bones weaker.

However, a different mutation in the LRP5 gene can also cause an uncommon disorder in which bone density is greatly increased making the bones very strong and resistant to fractures. Scientists at Yale who were working on different patients discovered that they had the same unusual trait of dense bones; when comparing notes and looking at the patients’ family tree, they worked out these were different members of one extended family. Through blood samples provided by 20 family members and DNA mapping they discovered a gene mutation in LRP5 that was causing the ‘unbreakable’ bones.

Research is ongoing in this area but it is hoped that knowing more about this gene could help researchers find better treatment for conditions affecting the bones including osteoporosis.

HIV resistance inherited from plague survivors

A mutation in the CCR5 gene known as CCR5-delta32 is associated with resistance to HIV infection. The mutation is not common but is seen more often in people of European descent.

Researchers at the University of Liverpool in the UK found this resistance was likely to have been developed due to ancestors in northern Europe who survived the ‘plagues’ of the Middle Ages. Despite the name, these plagues were not the bubonic plague (an illness that was bacterial not viral) but were epidemics of a severe, viral haemorrhagic fever that swept across Europe for 300 years from the mid-1300s.

The virus is thought to have used the CCR5 gene as the entry point into the immune system, acting in a similar way to HIV, which is the reason the CCR5-delta32 mutation, that blocks entry of the virus, allowed some Europeans to survive the deadly fever and pass on their genes to subsequent generations.

This knowledge could contribute to a cure for HIV and researchers are investigating how the CCR5-delta32 mutation could be used along with stem cell transplant technology to treat people with HIV.

The malaria protection puzzle

Scientists have known for a while that some people are naturally resistant to malaria and that resistance has a genetic cause.

The latest research comes from a recent study that compared genomic data from over 700 hundred people in Africa to genomes from the 1000 Genomes project as well as 4500 people with severe malaria who had previously had their genomes sequenced.

They found that differences in the GYPA and GYPB genes were present in many of those from eastern African nations but were not present in West Africa. These variations lead to an increase in malaria resistance of around 40%.

Other genes also offer malaria resistance. The HbC gene that affects haemoglobin (a protein in the blood carrying oxygen) has also been found to give protection against malaria. A single copy of the gene offers around 29% protection, but 2 copies gives around 93% protection.

As with the GYPA and GYPB genetic mutations, there are questions over why this protective genetic trait is not more common in Africa, particularly in regions badly affected by malaria. It could be that these are relatively new mutations which only began to appear shortly before the research was conducted. It could also be that there is some sort of negative effect of these mutations that limits how readily they are passed on.

Another piece of the puzzle is the HbS mutation which is common in sub-Saharan Africa; a single copy of the gene offers significant malaria protection. However, 2 copies cause sickle cell anaemia, a disease that shortens life expectancy and has a host of complications including stroke and organ damage. The seriousness of the disease means that scientists would expect the gene mutation to be less common than the HbS mutation, because higher rates of illness and mortality would make it less likely to be passed on.

All of this information can help scientists to better understand the devastating effects of malaria and to fight it more effectively.

The post Magnificent mutations: when genetic variations are good news first appeared on Know Pathology Know Healthcare.