Genetic fixer-uppers may predict bladder cancer prognosis

May 15, 2018 by Katie Bohn, Pennsylvania State University
Credit: CC0 Public Domain

Mutations in genes that help repair damage to DNA may aid in predicting the prognosis of patients with bladder and other related cancers, according to researchers.

The researchers found that bladder who had in their ATM or RB1 genes—proteins that help repair DNA damage when they're functioning normally—tended not to live as long as patients without the mutations.

Monika Joshi, assistant professor of medicine, Penn State Cancer Institute, said that as researchers try to design better treatments for cancer patients, it's important for them to find biomarkers that can help researchers understand the differences between patients and their prognoses.

"We're coming to realize that not every cancer patient is the same," Joshi said. "We see some patients responding to therapies, while others do not. Treatments like chemotherapy and immunotherapy, do not have a 100 percent response rate. So we're trying to delve deeper to better understand biological differences between patients."

According to the researchers, mutations or defects in DNA repair genes—like ATM and RB1—play a role in tumor growth and how the cancer responds to treatment, and are often found in patients with bladder cancer.

Previous research has also shown a connection between these mutated DNA repair genes and patients who respond better to certain types of chemotherapy. Joshi said this could be because the drug used in the treatment works better in cells when they're dividing.

"These genes help repair damage to the DNA, but when these genes are mutated, then they actually reduce the repair response allowing tumor cells with defective DNA to proliferate," Joshi said. "And when those tumor cells are proliferating, at that point they may be more susceptible to certain treatments like chemotherapy."

Joshi and the other researchers wanted to better examine how ATM and RB1 genes predicted the outcomes of patients with bladder cancer and analyzed information from two separate data sets.

The first dataset, or "discovery" dataset, included information about 130 bladder cancer patients from the Cancer Genome Atlas, a public database of cancer and genomic data. The second dataset, or "validation" dataset, included information about 81 patients with or other related cancers from three academic medical centers.

Mutations in the ATM or RB1 genes were found in 24 percent of patients in the discovery data set, and 22.2 percent of patients in the validation data set. Patients in both data sets with these mutations also tended not to live as long.

After two years, a significant difference was observed in the discovery data set in which about 15 percent of patients with mutations were still alive as compared to 45 percent of patients without mutations. A similar (although non-statistically significant) trend was noted in the validation data set, where about 50 percent of patients with mutations were still alive as opposed to 60 percent of patients without mutations.

Joshi said the results—recently published in the journal Oncotarget—bring up interesting questions when compared with the findings of previous studies.

"It would be interesting to further study these two specific and see what about them may make patients fare worse," Joshi said.

While it may be discouraging for patients to discover they have a gene that may predict a poor prognosis, Joshi added that the findings also have the potential for to help researchers decide where to focus their work in the future.

"If we know patients with this gene have a poorer prognosis, we can focus our efforts to learn more about why this might be happening so we can improve therapies for these patients," Joshi said. "We might not have all the answers after this study, but I think it helps pave the way for future development of targeted therapies in ."

Explore further: Simultaneous chemo and immunotherapy may be better for some with metastatic bladder cancer

More information: Ming Yin et al, ATM/RB1 mutations predict shorter overall survival in urothelial cancer, Oncotarget (2018). DOI: 10.18632/oncotarget.24738 , dx.doi.org/10.18632/oncotarget.24738

Related Stories

Simultaneous chemo and immunotherapy may be better for some with metastatic bladder cancer

April 11, 2018
Researchers from Mount Sinai and Sema4, a health information company and Mount Sinai venture, have discovered that giving metastatic bladder cancer patients simultaneous chemotherapy and immunotherapy is safe and that patients ...

Add broken DNA repair to the list of inherited colorectal cancer risk factors

February 23, 2018
An analysis of nearly 3,800 colorectal cancer patients—the largest germline risk study for this cancer to date—reveals opportunities for improved risk screening and, possibly, treatment.

Even DNA that doesn't encode genes can drive cancer

April 2, 2018
Most of the human genome—98 percent—is made up of DNA but doesn't actually encode genes, the recipes cells use to build proteins. The vast majority of genetic mutations associated with cancer occur in these non-coding ...

Genetic profile predicts which bladder cancer patients will benefit from early chemotherapy

May 30, 2014
Three genetic changes can predict whether a patient will benefit from chemotherapy before surgery to remove bladder cancer, according to new findings presented by Fox Chase Cancer Center researchers during the 50th Annual ...

Scientists identify gene mutations in smoking-related cancers

July 25, 2017
African-Americans typically have worse outcomes from smoking-related cancers than Caucasians, but the reasons for this remain elusive. However, scientists at Wake Forest Baptist Medical Center have taken a big step toward ...

Genes that hold the clues to bladder cancer and its treatment

November 13, 2017
Scientists have discovered the 'genetic signatures' of the most common form of bladder cancer - and it could open up the possibility of better-targeted treatment, according to research published today (13 November).

Recommended for you

Colon cancer is caused by bacteria and cell stress

September 19, 2018
Researchers at Technical University Munich have reported findings related to the development of colon cancer. "We originally wanted to study the role of bacteria in the intestines in the development of intestinal inflammation," ...

Researchers find adult stem cell characteristics in aggressive cancers from different tissues

September 19, 2018
UCLA researchers have discovered genetic similarities between the adult stem cells responsible for maintaining and repairing epithelial tissues—which line all of the organs and cavities inside the body—and the cells that ...

Ketogenic diet reduces body fat in women with ovarian or endometrial cancer

September 19, 2018
Women with ovarian or endometrial cancer who followed the ketogenic diet for 12 weeks lost more body fat and had lower insulin levels compared to those who followed the low-fat diet recommended by the American Cancer Society, ...

Eating foods with low nutritional quality ratings linked to cancer risk in large European cohort

September 18, 2018
The consumption of foods with higher scores on the British Food Standards Agency nutrient profiling system (FSAm-NPS), reflecting a lower nutritional quality, is associated with an increased risk of developing cancer, according ...

Could the zika virus fight the brain cancer that killed john McCain?

September 18, 2018
(HealthDay)—Preliminary research in mice suggests that the Zika virus might be turned from foe into friend—enlisted to curb deadly glioblastoma brain tumors.

CRISPR screen reveals new targets in more than half of all squamous cell carcinomas

September 18, 2018
A little p63 goes a long way in embryonic development—and flaws in p63 can result in birth defects like cleft palette, fused fingers or even missing limbs. But once this early work is done, p63 goes silent, sitting quietly ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.