AsianScientist (Jul 30, 2014) – A genome-wide association study among East Asian women has allowed scientists to identify three new genetic loci (regions) linked to breast cancer susceptibility. The findings have been published in Nature Genetics.
Globally, breast cancer is one of the most common cancers seen in women. Many genetic variants have been identified in association with the disease; however, most of these studies have been conducted exclusively in European women. Given the differences in genetic composition between humans of various ethnicities and geographies, and the increasingly worldwide impact of breast cancer, there has been a need to expand the scope of genetic research into the disease.
Researchers, led by Professor Cai Qiuyin at the Vanderbilt University School of Medicine, USA, collected data from almost 23,000 cases and more than 24,000 controls from across China, Japan and South Korea.
In the first of three rigorous stages of analysis, the scientists used the genomes of almost 10,000 Chinese and Korean women to identify genetic variants, known as single nucleotide polymorphisms, which appeared to be most significantly associated with increased breast cancer risk. Those showing linkages to known breast cancer susceptibility genes were filtered out, and the ones making the cut—numbering almost 4,000—were then verified against an independent set of data collected from Shanghai, China. Of the successfully genotyped regions, the top 50 were checked against approximately 14,000 cases collected from studies participating in the Asian Breast Cancer Consortium.
The authors were then able to identify that three particular DNA sequence variants were consistently present in each stage, in addition to indicating significant cancer risk. Further investigation against data collected from European women showed weaker links of these variants to breast cancer susceptibility in that demographic, suggesting that these newly discovered loci have unique roles in the pathology of breast cancer in East Asians.
Interestingly, Prof. Cai and colleagues found one of the three variants to be located in close proximity to a suspected breast cancer gene, AARDC3. It has been previously observed that AARDC3 expression is significantly lower in breast cancer tissue than in normal tissue.
The study authors suggest that their identified variant could play a regulatory role in AARDC3 expression. Another variant was thought to lie in an enhancer region of DNA, acting as a promoter of gene expression. The third genetic region was inside a gene encoding a cell cycle regulator known as protein regulator of cytokinesis 1 (PRC1), but no further link to PRC1 was observed.
The study authors hope that their findings will provide new insights into the genetic mechanisms of the disease, particularly in East Asian women.
The article can be found at: Cai et al. (2014) Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1.
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