DNA damage repair genes behave differently in black and white women with breast cancer

Differences in the expression of DNA repair genes due to environmental impacts may help to explain why breast cancer mortality is higher in black women than white women, researchers report.

Women of African descent in the US are up to 42 percent more likely to die after developing breast cancer than women of European descent. Previous studies indicate that factors including socioeconomics, access to healthcare and lifestyle differences all contribute. But new research from the Sanford Burnham Prebys Medical Discovery Institute in California, which compared tumours from black women and white women, has identified gene expression changes more common in black women which may also play a role. Eight genes involved in DNA repair were found, with different expression levels in tumours from black and white women. The authors hypothesised that this difference could worsen treatment outcomes in some black women.

'What we're seeing here is a tangible molecular difference in how these cells repair damaged DNA – a critical factor in the development of cancer – which affects how cells grow and reproduce in tumours,' said Dr Svasti Haricharan, head of the research team behind the study.

Black women are underrepresented in cancer research cohorts, said the authors. As a result, they suggest that previous research using largely white cohorts only reflects what is true for white women.

The researchers focused on the expression of genes driving DNA repair, previously shown to affect responses to breast cancer therapy. They compared tumour samples from 144 black women and 703 white women, looking at the expression of 104 DNA repair genes. Eight genes were differently regulated in the black women. At an individual level, this meant that 45-60 percent of black women had dysregulation of at least one of these eight genes, compared to just 25-30 percent of white women. The authors speculate that this altered expression pattern could lead to cancer therapy resistance.

Differences in expression of DNA repair genes' activity between black and white women were also observed in non-cancer breast tissue, although the impact of this is unclear.

An association was also found between expression level of some DNA repair genes and increases in cyclin dependent kinases (CDKs). Cancer cells can be stimulated to multiply by CDKs, and CDKs are often targeted by anti-cancer drugs. Dr Haricharan suggested that earlier use of CDK inhibitors may be beneficial for some black women.

'Although the findings are interesting, it certainly isn't enough to explain the entirety of the difference we see... it'll need larger data sets to validate the findings,' said Dr Navita Somaiah from the Institute of Cancer Research, UK. '[However], it highlights the need to consider molecular differences linked to ethnicity when developing future therapies.'