Study: No new high-risk breast cancer genes here

IN-DEPTH REVIEW OF RESEARCH

Study background:

Scientists sometimes try to identify common DNA variations called single nucleotide polymorphisms (SNPs) in the human genome that maybe associated with a particular disease.  These genome-wide association studies (GWAS) are conducted in two groups:  people with the disease being studied (e.g. breast cancer) and similar people without the disease. DNA from participants in each group is scanned on automated laboratory machines and the DNA from the two groups are compared for differences. If certain SNPs are found to be significantly more frequent in people with the disease compared to people without the disease, the SNPs are said to be "associated" with the disease. Newly identified SNPs can serve as pointers to a region of the human genome where disease-causing problems in the DNA may reside.

Much of our DNA does not actually get transcribed into proteins. Because these GWAS studies look at SNPs scattered throughout the human genome– most outside of the actual portion of the DNA that codes for proteins – the SNPS identified through GWAS studies rarely provide clear answers about how they contribute to disease development. Although GWAS studies have provided clues for several different diseases, they do not always lead to changes in how patients are managed.

Two recent GWAS studies, “Association analysis identifies 65 new breast cancer risk loci” published in Nature and “Identification of ten variants associated with risk of estrogen-receptor-negative breast cancer” published in Nature Genetics, together identified 72 SNPs in the human genome that are associated with breast cancer risk.

Researchers of this study wanted to know:

If they could identify common genetic changes that influence breast cancer risk.

Population(s) looked at in the study:

The study published in Nature compared genome SNP data from more than 100,000 breast cancer patients and a similar number of cancer-free controls.

The study published in Nature Genetics compared genome SNP data from 21,468 patients with ER-negative breast cancer and 100,594 controls, as well as 18,908 BRCA1 mutation carriers. (BRCA1 mutation carriers are more likely to develop estrogen receptor-negative disease).

Study findings: 

The Nature report identified 65 new genetic SNPs associated with increased breast cancer risk, while the Nature Genetics report identified 10 new SNPs (3 of which overlapped with the 65) associated with increased risk of ER-negative disease. These 72 new DNA SNPs were most commonly located in non-coding regions of the genome which are outside of or away from coding regions which contain genes.  Many of these SNPs likely regulate (turn on or off) genes, although how they do this is currently unknown. 

The amount of increased risk caused by each individual SNP is uncertain. However, because they are common and their impacts multiply together, the collective effect may be considerable. For instance, the researchers predicted that the breast cancer risk among women who carry many of these SNPs—1% of women studied—is more than 3 times greater than the rest of the population. 

Limitations:

These studies were conducted with women who were primarily of European ancestry and it is likely that SNPs associated with breast cancer that are common in non-European populations were missed. To find these, similar studies in Africans, African Americans, Latinas, Chinese and other populations are ongoing.

It is possible that patterns in the inheritance of these SNPs may help us to understand why some women are predisposed to breast cancer. Researchers hope that identifying these SNPs may lead to a better understanding of specific genes and mechanisms that are involved in the development of breast cancer. The biggest problem in taking advantage of GWAS information is our limited understanding of why and how these common variations in the human genome might increase breast cancer risk. These changes in DNA sequence are not mutations found in coding regions of genes. It will take time and effort to understand exactly how they contribute to disease risk as well as the best way to manage these increased risks.

Conclusions:

At the time of this review, this research does not change expert recommendations for risk assessment and risk management for breast cancer. Researchers will now work toward using these SNPs and other factors to better predict breast cancer risk. With additional research, it may be possible to use the SNPs identified in these studies to categorize more women into groups based on their breast cancer risk. If successful, these could be incorporated into tests that would allow women with increased risks to receive screening and prevention that is tailored to their personal risk.

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Posted 1/12/18