Previous studies have shown the connection between age, exposure to carcinogens and the risk of developing cancer due to the accumulation of mutations over time. Scientists from Yale University and Emmanuel College demonstrate a new scientific approach to determine the origins of different types of cancer.
The causes of mutations can be divided into two broad categories: exogenous carcinogens, environmental factors originating from outside the body, and endogenous causes associated with normal aging. An increase in the number of mutations, regardless of cause, leads to an increase in the occurrence of cancer.
Identification of cancer-causing mutations has been facilitated by rapid advances in the speed and cost of DNA sequencing. Researchers have become particularly interested in studying mutations caused by a preventable exogenous mutagenic process, such as exposure to chemicals that alter DNA.
The more researchers learn about the causes of preventable mutations, the better they can eliminate those causes from our environment and decrease cancer risk.
Cancer research scientists who have been studying cancer biology for the past 10 years discovered patterns in the genome sequencing data indicative of specific underlying mutational processes. The study provides quantification of the relative impact of endogenous and exogenous mutagenic processes on the generation of SNV mutations, SNVs are single base changes in the gene sequence.
Dr. Jeffery Townsend, a professor at Yale School of Public Health and a co-author of the study, said that the main objectives of the study were to quantify how many cancers are caused by exogenous mutagenesis versus endogenous mutagenesis in both individual tumors and cancer types. The research team also studied the impact of mutagenic processes on the development of various types of cancers.
In other words, this study differentiated between “bad luck cancers” resulting from the inevitable effects of aging and preventable cancers resulting from mutagens like ultraviolet light, tobacco and gene editing.
In the new biostatistics approach used, Dr. Townsend and his colleagues were able to calculate the proportional contributions of each mutational process to the cause of various cancers. The research team discovered that distinct mutagenic causes could be attributed to individual tumors.
Dr. Townsend shared that the study found that “different cancer types vary in their mutagenic causes ranging from melanoma (nearly all exogenous UV) and lung cancers (substantial exogenous tobacco-related processes) to prostate and glioma (largely endogenous aging processes).”
Dr. Townsend shared that mutagenic causes vary among cancer types. For example, almost all melanoma is caused by ultraviolet light. Majority of lung cancers are caused by exogenous tobacco-related processes. Endogenous again processes are more likely to cause prostate and glioma.
Understanding these mutagenesis patterns provide researchers with broad knowledge of the development of cancer and can guide lifestyle changes to prevent the development of cancers.
While this new method provides novel insight into the mutagenetic processes causing various cancers, the method does not yet address the cancer-causing effects of larger mutational events. Some of the important large-scale mutations that need to be addressed include loss of heterozygosity, copy-number changes and chromosomal number aberrations. Each of these is a large-scale mutational event.
Loss of heterozygosity refers to the loss of one parent’s genetic information; normally, each parent contributes half of the child’s genetic information. Copy-number variation occurs when regions of the genome containing one or more genes are duplicated or lost during cell division. Chromosomal number aberrations refer to changes in chromosome number. All of these changes are much larger in scale than the single-nucleotide variations addressed in this study, but all of them can contribute to the development of cancer.
Rather than exclusively implementing this new method in clinical settings addressing individual patients, it can be implemented in different fields.
“It is much more important to public health,” Dr. Townsend said.
“If we can propagate this knowledge to individuals who would like to know ‘why me?’ it will propagate a better understanding of the causation of cancer and risk factors from cancer survivors to their family and friends—trusted sources for communication—potentially saving many lives by enhancing informative preventive efforts against commonplace sources of a cancer-causing mutation” Dr. Townsend said.
To extend this method and better present an accurate quantification of endogenous and exogenous mutagenic causation contributing to cancer development, Dr. Townsend and his research team are undertaking a new project.
“We are working to develop approaches to characterize the cancer effects of loss of heterozygosity, copy-number and chromosomal number aberrations” Dr. Townsend said.
Dr. Townsend’s lab and the broader cancer research community continue to focus on methods that advance our understanding of the causes of cancer that will develop effective cancer interventions that will save more lives.
