More Bad News for Smokers

Oct. 24, 2014

By Medical Discovery News

Lung X-ray

Smoking isn’t the only thing that raises your risk of lung cancer. As it turns out, your DNA can have that effect too.

A scientific study scanned the genomes, the entire genetic code, of 11,000 people of European descent in an effort to identify if there was any correlation between gene sequences and a common form of lung cancer, non-small cell carcinoma. They discovered that variants of certain genes increase a person’s susceptibility to developing lung cancer, especially in smokers.

One of the three gene variants they identified, named BRCA2, can double a smoker’s chance for developing lung cancer. BRCA2 is a tumor suppressor gene. It encodes a protein involved in the repair of damaged DNA, which is critical to ensure the stability of cell’s genetic material. When cellular DNA is damaged, there are several ways for the body to detect and repair that damage. If the damage to DNA cannot be repaired, then the cell is programmed to die by a process called apoptosis in order to prevent the damage being passed on to its daughter cells.

Like other tumor suppressor genes, the BRCA2 protein helps to repair breaks in DNA. It also prevents damaged cells from growing and dividing too rapidly. Variants of BRCA2 associated with breast, ovarian, and now lung cancers produce proteins that do not repair DNA damage properly. This causes cells to accumulate additional mutations, which can lead to cells that grow and divide uncontrollably. Such mutations lead to an increased risk of developing cancer.

Scientists have discovered over 800 mutations of BRCA2 that cause disease, including breast, ovarian, lung, prostate, pancreatic, fallopian, and melanoma cancers. Most of the mutations result from the insertion or deletion of a few letters of genetic code into the part of the gene that code for a protein. This disrupts the production of the BRCA2 protein and results in a shortened and nonfunctional form of the BRCA2 protein.

Lung cancer is a leading killer of Americans. Nearly 160,000 Americans will die from lung cancer this year, representing 27 percent of all cancer deaths. Active smoking causes close to 90 percent of lung cancers.

The good news from this discovery is that since scientists first linked BRCA2 to an increased risk of breast cancer, new therapies have been developed. Current treatments for breast and ovarian cancers could be effective with BRCA2-associated lung cancers, such as PARP inhibition.  PARP1 is another protein involved in repairing DNA damage. When one of two strands of DNA are broken or nicked, PARP1 moves to the region and recruits other proteins to the site to repair the damage. Many chemotherapy agents kill cancer cells by inducing DNA damage in the tumor and inhibiting PARP1. This doesn’t allow cancer cells to repair damage and makes them more susceptible to chemotherapy and radiation therapy. Now that we know this gene is linked to lung cancer, such therapies may be more effective in treating lung cancer and saving lives.

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