Genetic variants alter breast cancer risk

Genetic variants of the DNA repair protein RAD51 are associated with differential risks of breast cancer in Saudi women.

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@2016 Maciej Frolow

Variations in a crucial DNA repair gene can alter the risk of breast cancer in Saudi women, according to new research. The findings add weight to studies of other populations and could help identify patients at high risk of the disease. 

Cumulative DNA damage can disrupt cell growth and division, leading to cancer. DNA repair mechanisms usually suppress cancer, but can be faulty. RAD51 is an essential component of a protein complex that repairs DNA. Its levels are low in some women with breast cancer. The same repair complex also includes other proteins associated with breast cancer, so RAD51 has been proposed as a significant protein in protecting against the disease. 

Genes can vary between individuals owing to changes in single letters of the DNA code, known as single nucleotide polymorphisms (SNPs). These SNPs in the gene that encodes RAD51 might be expected to alter the risk of developing breast cancer, given its proposed role in suppressing the disease. Several studies have assessed the effects of genetic alterations in RAD51 on this risk, but different results have been found in different populations.  

Biochemist Arjumand Warsy from King Saud University in Saudi Arabia and colleagues from other institutions in the kingdom investigated the effect of RAD51 variants on the risk of breast cancer in Saudi women, a population in which this association has not been previously studied. 

The researchers sequenced the gene that encodes RAD51 in healthy women and in women with breast cancer. They compared the variation in genotype at three specific sites. At each of these sites, women had either a ‘normal’ genotype or one of two variants. 

Genetic variation at one of the specific sites made no difference to the risk of breast cancer; a result in line with findings in US and Polish populations but contradicts analyses that showed SNPs at this site increase the overall risk of cancer. At the other two sites, the ‘normal’ sequence was associated with a higher risk of breast cancer and the variants protected against the disease.  

The results indicate a relationship between genetic variation in RAD51 and the risk of breast cancer in Saudi women. The variants associated with a lower risk of breast cancer are thought to facilitate the production of RAD51, thus promoting DNA repair. This mechanism could explain the protective effect of the variants, but needs to be confirmed in future studies.

References

  1. Tulbah, S., Alabdulkarim, H., Alanazi, M., Parine, N. R., Shaik, J. et al. Polymorphisms in RAD51 and their relation with breast cancer in Saudi females. Oncotargets and Therapy  (2016). | article

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