Genetic 'Spelling Mistakes' Increase The Risk Of Common Cancers

More than 80 genetic 'spelling mistakes' can increase the risk of breast, prostate and ovarian cancer, according to a large, international research study. The researchers say they also have a relatively clear picture of the total number of genetic alterations that can be linked to these cancers. Ultimately, they hope to be able to calculate the individual risk of cancer, to better understand how these cancers develop and to be able to generate new treatments.  In five Collaborative Oncological Gene-environment Study (COGS) studies 100,000 patients with breast, ovarian or prostate cancer and 100,000 healthy individuals from the general population were included.

More than 80 genetic 'spelling mistakes' can increase the risk of breast, prostate and ovarian cancer, according to a large, international research study.

The researchers say they also have a relatively clear picture of the total number of genetic alterations that can be linked to these cancers. Ultimately, they hope to be able to calculate the individual risk of cancer, to better understand how these cancers develop and to be able to generate new treatments. 

In five Collaborative Oncological Gene-environment Study (COGS) studies 100,000 patients with breast, ovarian or prostate cancer and 100,000 healthy individuals from the general population were included.

The scientists performed genetic analyses on all study participants. The composition of the nitrogen bases A, G, C and T was studied on 200,000 selected sections of the DNA strand. When cancer patients had significantly different compositions compared to healthy control subjects, the differences were considered to be relevant to risk of disease. The alterations can be described as a genetic 'spelling mistake', where A, G, C or T have been replaced with another letter. This 'spelling mistake' is called Single Nucleotide Polymorphism (SNP) – pronounced 'snip'.

For breast cancer the researchers found 49 genetic typos or SNPs, which is more than double the number previously found. In the case of prostate cancer, researchers have discovered another 26 deviations, which means that a total number of 78 SNPs may be linked to the disease. For ovarian cancer 8 new relevant SNPs were found.

"An equally important finding is that we identified how many additional SNPs that could influence the risk of breast cancer and prostate cancer, respectively. For breast cancer the number is 1,000 and for prostate cancer 2,000," says Per Hall, Professor at Karolinska Institutet in Sweden and the coordinator of the COGS consortium. "We also have a picture of where in the genome we should look in future studies."

SNPs are part of our natural heritage, we all have them. How it affects the individual depends on where on the DNA strand the genetic deviation is found. The researchers now hope to be able to evaluate the importance of the identified deviations, so that it will be possible to more clearly predict which individuals are at high risk of developing one of these cancers.

"We're now on the verge of being able to use our knowledge to develop tests that could complement breast cancer screening and take us a step closer to having an effective prostate cancer screening program,'' says Professor Doug Easton of the University of Cambridge, UK, who has led several of the presented studies. 

 Published in Nature Genetics.

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