1. Jong, Kelly

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Opioid use may be a risk factor for pancreatic cancer, research from Rush University Medical Center has found. The deadly disease is currently the third-leading cause of cancer-related mortality in the U.S., with a 5-year survival rate of only 10 percent.

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A majority of patients with pancreatic cancer have asymptomatic progression of the disease and 85 percent have non-surgically resectable disease at the time of diagnosis, lending to the cancer's high rate of mortality. The increasing incidence of pancreatic cancer will place the disease as the second cause of cancer mortality by the end of the decade, the research predicted. With such high rates of mortality, the identification of opioids as a risk factor could save patients from the dark fate of pancreatic cancer in the future.


Opioid Misuse: A Health Crisis

Established risk factors for pancreatic cancer include genetic predisposition syndromes and chronic pancreatitis, including both alcohol and non-alcohol causes. But these known risks account for only a small portion of incident cases, with the etiology of the majority of cases being unknown, according to the research.


Though several factors associated with lifestyle habits such as smoking and alcohol use have also been proposed to modulate the risk of pancreatic cancer, the study found exposure to those substances has been steady or decreasing at a national level, contrary to increasing rates of pancreatic cancer.


While increasing obesity rates may play a factor in incidence of pancreatic cancer, the research authors found a strong correlation with a novel factor that suggested a greater increased risk for developing the disease-opioid use.


"We wanted to correct for factors that are known to contribute to the risk of pancreatic cancer to assure the trend we see for opioid use is not dependent on those factors," explained Faraz Bishehsari, MD, PhD, study co-author and Associate Professor of Medicine at Rush University. "We looked at the trend of pancreatic cancer over the last 2 decades nationally and at the state level, as well as the opioid death rates as a surrogate for prescription and illicit opioid use over that period."


Although opium use is not a common recreational habit in the United States, opioid use has been rising remarkably over the past decade, Bishehsari said. "In fact, opioid misuse and overdose have evolved into a public health crisis with increasing opioid prescription use and abuse over the past decade."


Approximately 70,000 drug overdose deaths were reported in 2017, 68 percent of which involved an opioid, according to the research. The use of prescription opioids for the management of chronic pain had also markedly increased, with more than 191 million opioid prescriptions given to patients in the U.S. in 2017. Addiction rates among those patients prescribed opioids also predictably increased, with 29 percent of patients misusing the drug and 12 percent developing an opioid use disorder.


Pancreatic Cancer Incidence

Using data from the CDC's Vital Statistics Cooperative Program and a linear mixed-effects model to allow for state-specific slopes and intercepts, the study authors compared patient opioid death rate, obesity rate, and use of alcohol and cigarettes to pancreatic cancer trends. The model was used to examine the multivariate longitudinal association between the change of pancreatic cancer incidence rates and the aforementioned risk factors for a period between 1999 and 2016. During that time period, the study found there were 700,300 incident cases of pancreatic cancer in the U.S. and 351,630 concurrent opioid overdose deaths.


Though there were differences in the distribution of pancreatic cancer incidence and opioid death rates among the state, the research found that both factors increased in most states, with an average increase of 0.137 percentage points per year for the 7 years studied.


"We found that both pancreatic cancer and opioid death rates rose over time at the national and state levels," Bishehsari said. "Opioid death rates at a given time significantly predicted the change in the incidence of pancreatic cancer years after."


The mixed-effects regression model also revealed an increase in obesity prevalence, though the rate of obesity was not associated to the rate of pancreatic cancer, nor the degree of change of pancreatic cancer rates. The data did reveal, however, a significant interaction between opioid death rate and obesity prevalence. Indicating rates of pancreatic cancer were higher in states with elevated levels of both obesity and opioid usage, according to the study. The researchers noted that this may be explained by the observation that opioid usage is associated with a poorer lifestyle in general, and populations in those regions could be exposed to other conditions and comorbidities associated with a poor lifestyle that were not included in the study model.


Changing the Course

Moving forward, Bishehsari and the study co-authors hope to conduct further studies to support the data indicating a link between opioid use and pancreatic cancer.


"This was a data set-based study," Bishehsari said. "Our findings should be tested at the population-based level where individual-level data on opioid consumption and risk of pancreatic cancer are available."


Such tests would include a population-based study and an experimental study, he added. "Further research could find mechanisms that potentially link opioid use to the development and/or progression of pancreatic cancer."


Once confirmed, the implications of opioid use on pancreatic cancer development could pose significant changes in clinical recommendations, such as the widespread prescription and use of opioids throughout the country. Interestingly, the study noted that opioids are widely used for pain management in pancreatitis, which is an established precursor to pancreatic cancer.


In addition, Bishehsari noted that the research could facilitate a significant re-evaluation of pancreatic cancer treatment and pain management.


"These findings could have direct clinical relevance by considering the possible effect of anti-narcotic receptor medications for the treatment of pancreatic cancer," he said. "In addition, non-narcotic alternative pain control approaches in patients with pancreatic cancer could be explored."


Kelly Jong is a contributing writer.