Why Smoking Causes Cancers In Some People

Researchers from the University of North Carolina School of Medicine have mapped DNA damage caused by smoking, a finding that could help scientists better understand how smoking-induced cancers originate, and how they can be prevented.

According to a study published online in the Proceedings of the National Academy of Sciences, a research team has succeeded in developing a useful technique for mapping sites on the genome that are undergoing repair due to damage caused by benzo[α]pyrene diol epoxide (BPDE). This particular carcinogen is a byproduct of burning organic material, such as smoking tobacco. The team believe that better understanding the exact damage caused by BPDE will help scientists better understand how smoking-related cancers begin, why some people are more vulnerable or resistant to certain cancers, and how these cancers can be prevented.

"This is a carcinogen that accounts for about 30 percent of the cancer deaths in the United States, and we now have a genome-wide map of the damage it causes," said study researcher and Nobel laureate Dr. Aziz Sancar in a recent statement. “It would be good if this helps raise awareness of how harmful smoking can be. It also would be helpful to drug developers if we knew exactly how DNA damage is repaired throughout the entire genome."

When we burn tobacco leaves, or any other organic matter, it releases a compound called Benzo[α]pyrene (BaP). When BaP enters our body, it is synthesized to create BPDE. This compound then binds to our genes, making it difficult for them to function effectively. Eventually, the damage caused by BPDE can cause genetic mutations that could lead to cancer.

"If a BPDE adduct occurs in a tumor suppressor gene and isn't repaired in a timely manner, it can lead to a permanent mutation that turns a cell cancerous," Wentao Li, PhD, lead author of the study, said in the statement.

The new mapping technique allows the researchers to look at the exact sites on the genome that are under repair due to BPDE damage. By doing this, the technique allows scientists to better understand the exact dose of the BPDE needed to bring about certain damage, which genes are involved in DNA repair, and areas of the genome where repair is less likely occur. What’s more, this technique is not limited to reading damage caused by BPDE, but can be used for any type of DNA damage that uses something called nucleotide excision repair.

"I'm certain that all this information will lead to a better understanding of why certain people are predisposed to cancer, and which smoking-related mutations lead to lung cancer specifically," added Sancar.

Lung cancer is the second most common type of cancer in men and women, exceeded only by prostate cancer and breast cancer. According to the American Cancer Society, lung cancer is also by far the leading cause of cancer death in both men and women, accounting for a quarter of all cancer deaths each year. Lung cancer survival depends heavily on the point in which the disease is diagnosed.

Source: Li W, Hu J, Sancar A, et al. Human genome-wide repair map of DNA damage caused by the cigarette smoke carcinogen benzo[a]pyrene. PNAS. 2017