UT researchers map genetic code to determine cancer risk, by Rose Zolondek, doctoral student in the Biomedical Science programApril 3rd, 2017
Lung cancer is the leading cause of cancer-related death in the United States and is the most common cancer worldwide. About 160,000 Americans were expected to die from lung cancer in 2016, accounting for 27 percent of all cancer-related deaths.
Identifying and then screening a person at high risk can reduce the likelihood of that person dying from lung cancer. Screening allows doctors to find tumors at an earlier stage when they are more responsive to treatment and potentially curable by surgical removal. About 9 million Americans are at high risk for lung cancer. Based on a large clinical trial, early screening of people at high risk reduced the risk of dying from lung cancer by 20 percent.
How do we identify who is at risk? The risk of lung cancer varies from person to person and depends on both a person’s inherited genetics and on environmental exposures such as smoking, radon, asbestos, and many other toxins that can get into your lungs.
At the University of Toledo college of medicine and life sciences, formerly the Medical College of Ohio, we are investigating the differences in our risk of lung cancer by studying differences in inherited genetic code. Most of the cells in the body, including lung cells, contain chromosomes you inherited from one’s parents. Each chromosome is composed of DNA building blocks in a sequence that defines an individual’s unique genetic code, just like sequences of letters define a word, sequences of musical notes define a song, or sequences of symbols define a computer program.
We now know specific DNA sequences of each human genome that produce different hair and eye color. We also see differences in DNA sequences at certain genetic locations that increase the risk for human diseases such as lung cancer. For example, certain inherited DNA sequence differences can change the way cells in the lung react to environmental exposures such as tobacco smoke.
Differences in DNA sequence are called single nucleotide polymorphisms, or SNPs. Each SNP is a change in a single DNA building block, also called a nucleotide. SNPs are found every 300 nucleotides on average. This means that one’s entire genome contains about 10 million SNPs total. Most SNPs do not have any effect on one’s health. However, some SNPs are within DNA sequences that code for proteins and therefore can affect one’s risk for a specific disease such as lung cancer.
Our research lab studies SNPs in genetic sequences that are responsible for the repair of damaged DNA. This is a very important function within one’s cells. Damaged DNA, if not repaired properly, can result in a population of cells with a DNA mutation that may lead to cancer.
We now know that if certain SNPs occur in specific genetic sequences, they can inhibit DNA from being repaired properly, which increases the chance of lung cancer, especially if you smoke.
We now have machines that can rapidly sequence the entire human genome, which is 3 billion nucleotides long. Our research lab uses these machines to identify the nucleotide sequence of SNPs that are associated with increased risk for lung cancer. My research focus is based on our recent results with genes that are responsible for protecting DNA in lung cells from damage and other genes that repair damage when it occurs.
For example, we are studying genes such as glutathione peroxidase, or GPX1, that protect lung cells from certain toxic effects of cigarette smoke. We are also studying genes called TTC38 and TRMU. Very little is known about the function of TTC38, which makes it exciting to study. We know that TRMU helps to modify letters in the DNA code and SNPs in this gene are associated with deafness, but also appear to have a role in lung cancer.
Identifying the function of SNPs in these genes help us better identify high risk individuals who may have the best benefit from regular screenings in the clinic. This would increase early detection of lung cancer and allow patients to be treated earlier. Earlier treatment often means better outcomes especially for lung cancer.
We continue to increase our understanding of lung cancer risk and to fight against this devastating disease by our ongoing collaborative work with other researchers and pulmonary doctors at the University of Toledo, the Toledo Hospital, the University of Michigan, and many other centers of excellence in lung cancer research. Our research is supported by the National Institutes of Health and the George Isaac Cancer Research Fund.
Rose Zolondek is a student pursuing her doctorate of philosophy in the University of Toledo college of medicine and life sciences biomedical science program. Ms. Zolondek is doing her research in the laboratory of Dr. James Willey. For information, contact firstname.lastname@example.org or go to utoledo.edu/med/grad/biomedical.