People with type 1 diabetes (previously called juvenile diabetes) are 4.29 times more likely to develop bladder cancer, according to a systematic review and meta-analysis by researchers at the Keck School of Medicine of USC. The new analysis is the first to control for the effects of tobacco smoking, a factor that likely obscured the heightened risk in earlier studies. The results were just published in the journal Diabetes Research and Clinical Practice .
Bladder cancer is a relatively common disease, affecting about 2% of the U.S. population. Cigarette smoking accounts for about half of all bladder cancer in the United States and Europe, but causes of the remaining half are poorly understood. Recent data suggest that type 2 diabetes may play a role, but years of epidemiological studies found no link between type 1 diabetes and bladder cancer.
Now, a new analysis reveals why a possible link may have been missed. Because smoking is a strong contributor to bladder cancer, research designed to identify other risk factors must control for—or separate out—the influences of smoking from influences of other proposed causes. But no prior studies on type 1 diabetes and cancer had done so.
"Of nine original studies and one meta-analysis published before ours, none had adequately controlled for smoking. When we evaluated the vulnerabilities of these studies and addressed them, we found a very clear pattern indicating substantially elevated risk for bladder cancer in people with type 1 diabetes," said Victoria K. Cortessis, PhD , a clinical professor of population and public health sciences at the Keck School of Medicine and the study's senior author.
The new findings provide important clues about causes of bladder cancer and may help guide decision making by patients with type 1 diabetes and their providers. For example, avoiding or quitting smoking may be especially important for this group, Cortessis said.
A missing link
For years, studies that tracked people with type 1 diabetes found no increased risk of bladder cancer—and a closer look reveals why. Most datasets on type 1 diabetes began as studies that followed patients diagnosed with type 1 diabetes over time. The initial goal was to learn how the condition impacted patients by tracking events like hospitalizations and early complications. Data on smoking, however, were either not collected or asked about once and not updated.
Years later, researchers used those same datasets to ask a different question: Does type 1 diabetes raise the risk of other diseases, such as bladder cancer, in adulthood? To find out, they compared disease rates among people with type 1 diabetes to rates in the general population. Those analyses found no increased risk for bladder cancer.
The problem with this method: Smoking is a major contributor to bladder cancer. Without accurate data on smoking in the diabetes group or the general population, it was impossible to know how much risk of bladder cancer was linked to smoking versus type 1 diabetes itself.
The Keck School of Medicine team suspected that people with type 1 diabetes may smoke less than the general population. After managing a serious health condition starting early in life, these individuals may have been more health conscious as adolescents and adults. If true, lower smoking rates could skew the comparisons and mask any increased bladder cancer risk tied to diabetes itself.
To investigate that idea, first author Helena Oskoui Bennett, MPH, a student at the Keck School when the research was conducted, gathered data from authoritative sources such as the World Health Organization to estimate smoking prevalence in populations where the original studies were conducted. The patterns the team found using a technique called meta-regression supported the team's hypothesis, helping explain why earlier analyses failed to detect a connection. After accounting for patterns of smoking, they estimated that people with type 1 diabetes were 4.29 times more likely to get bladder cancer.
Controlling bladder cancer risk
The reason for the link between type 1 diabetes and bladder cancer is not yet clear, but researchers suspect the disease may trigger biological changes that contribute to the cancer's development. For that reason, careful management of diabetes—including maintaining healthy blood sugar levels—could be key for reducing bladder cancer risk. Those biological changes may also interact with the effects of smoking to further raise risk.
"More work is needed to understand the mechanisms at play, but it's possible that there is a biological synergy between diabetes and smoking that increases risk more than either factor alone," Cortessis said.
The study emerged from the team's larger analysis of type 2 diabetes, another condition linked to bladder cancer. They are now reviewing nearly 100 studies on type 2 diabetes and its treatments to pinpoint what drives the increased risk.
About this research
In addition to Cortessis and Bennett, the study's other authors are David Bogumil and Kimberly D. Siegmund from the Department of Population and Public Health Sciences, Keck School of Medicine of USC, University of Southern California; Richard M. Watanabe from the Department of Population and Public Health Sciences, the Department of Physiology & Neuroscience, and the Diabetes and Obesity Research Center, Keck School of Medicine of USC, University of Southern California; Lynn Kysh from the University of California at Davis; and Piet van den Brandt from Maastricht University Medical Center, Netherlands.
