Scientists have found that genetic variation in regions of DNA that do not code for proteins, previously characterised as 'junk DNA', may affect a person's risk to develop a form of inherited cancer.
The research, which was led by an international group of scientists, was published in the British Journal of Cancer and sheds new light on why some people develop cancer more than others.
The DNA that does not code for proteins plays a role in regulating the expression of the protein-coding DNA, or genes. A single variation, known scientifically as a SNP, is a particular position in the human genome where a single letter of the genetic code varies between people. The study links SNPs found in non-coding DNA with an increased risk of cancer.
Mutations in key cancer genes, such as BRCA1, make the risk of developing cancer significantly higher. SNPs, however, which are more common than genetic mutations, are linked to a smaller increase in risk.
The team of researchers looked at 846 SNPs within non-coding DNA regions that were previously identified as affecting cancer risk. Their method included correlation analysis for the presence of a particular SNP and how it affects expression of certain genes. Overall, they analysed 6 million such variations across 13 different tissues of the body.
They found that SNPs in regions that regulate the expression of key cancer genes, such as oncogenes and tumour suppressor genes, increase the risk of developing cancer. Interestingly, these cancer-risk SNPs were found to be mostly located in regions that regulate the immune system and genes that regulate tissue-specific functions.
The lead author of the study, Professor John Quackenbush, from Harvard T.H. Chan School of Public Health said, 'what we found surprised us as it had never been reported before - our results show that small genetic variations work collectively to subtly shift the activity of genes that drive cancer. We hope that this approach could one day save lives by helping to identify people at risk of cancer, as well as other complex diseases'.
Senior research information manager, Dr Emily Farthing, from Cancer Research UK said, 'while minor genetic changes only have a small impact on cancer risk, the variations analysed in this study are numerous and common in the population. This could begin to explain some of the variation in cancer incidence between individuals and families that cannot be explained through well-known cancer-risk genes or lifestyle factors alone.'
The next step for the team is to develop artificial intelligence models for better cancer risk prediction and to identify whether there are 'control centres' for the regulation of expression of many genes relevant to cancers, which could then be the target for novel therapies.