Expression of DNA repair genes in some Black women may be linked to higher breast cancer mortality rates JGI/Jamie Grill/Blend Images LLC
Black women in the US have a higher mortality rate from breast cancer than white women. This may be in part due to differences in how a person鈥檚 environment affects the expression of genes involved in DNA repair.
鈥淭hese differences aren鈥檛 about mutations that are in you from the moment you鈥檙e born, but are instead about how cells adapt to your environment,鈥 says at the Sanford Burnham Prebys Medical Discovery Institute in California. There is no genetic basis to race, she says, but our environments and our lifestyles affect our biology.
Haricharan and her colleagues analysed breast tissue data from 847 women, including 144 Black women. This shows the lack of tumour samples from Black women in general in US data sets, she says.
Advertisement
Most of the women had been diagnosed with a common type of breast cancer, while some samples used as a control were from healthy breast tissue in women without cancer.
鈥淥estrogen receptor positive cancer is the most common type of breast cancer diagnosed in the world,鈥 says Haricharan. 鈥淏ased on estimates, it accounts for about 60 to 80 per cent of breast cancer.鈥
Previous studies have found that Black women are more likely to die from this type of cancer than white women. Structural racism, socioeconomics and lifestyle all play a role in this disparity, says Haricharan, but it is also important to study differences in molecular biology. 鈥淏y better understanding this biology, we can tailor treatments for people from different demographics,鈥 she says.
The researchers focused their efforts on genes that drive DNA repair mechanisms, which have been shown in previous studies to affect how well a person with breast cancer responds to a treatment called endocrine therapy. This therapy slows tumour growth by stopping a person from producing growth-stimulating hormones.
Genes involved in the repair of DNA damage also affect how hormones alter cell growth as they play a role in how cells divide and multiply. The researchers found eight DNA damage repair genes that were expressed differently in a subset of Black women than in white women and other Black women.
The team found these differences in between 6 and 15 per cent of Black women in their sample. 鈥淚 don鈥檛 want to put a specific number on it because of the small sample size,鈥 says Haricharan. The team did not look at whether this altered gene expression explicitly made endocrine therapy less effective but speculate that such a gene expression would lead to treatment resistance.
鈥淲e saw these differences exclusively in Black women,鈥 says Haricharan. 鈥淸This altered gene expression is] almost undetectable in white women.鈥 This difference in gene expression is due to the differences in peoples鈥 environments. While the genes we possess are due to our ancestry, the way they are expressed is affected by circumstances, such as how much stress people face and the type of diet they eat.
Haricharan believes that overlooking these differences when treating people can have real consequences.聽鈥淧recision medicine today is based on white people,鈥 she says. 鈥淎nd I think people who come from other backgrounds, other races, other ethnicities 鈥 who might have different molecular signals 鈥 we鈥檙e not taking that into account.鈥
For example, the team found a link between an altered expression of the eight DNA repair genes and higher levels of cyclin-dependent kinases (CDKs) in a person鈥檚 cells. These molecules cause cancer cells to multiply faster and are targeted in cancer therapy by inhibitor drugs.
Haricharan says doctors only prescribe CDK inhibitors after seeing that endocrine therapy is having an effect, but giving CDK inhibitors earlier may work better for Black women who have this altered gene expression.
鈥淎lthough the findings are interesting, it certainly isn鈥檛 enough to explain the entirety of the difference we see,鈥 says at the Institute of Cancer Research in the UK. 鈥淭he patient numbers are too small, and it鈥檒l need larger data sets to validate the findings.鈥
鈥淗owever, along with other papers published on this topic, it highlights the need to consider molecular differences linked to ethnicity when developing future therapies,鈥 she says.
The lack of cancer tissue samples from Black people and those in other ethnic minority groups is holding back research into effective treatment, says Haricharan. 鈥淧eople of colour have a historical mistrust of the medical establishment and so are less likely to provide medical samples, but it鈥檚 important we try to rebuild this trust.鈥
Therapeutic Advances in Medical Oncology
Join us for a mind-blowing festival of ideas and experiences. 快猫短视频 Live is going hybrid, with a live in-person event in Manchester, UK, that you can also enjoy from the comfort of your own home, from 12 to 14 March 2022. .
Topics: