UPDATED July 2, 2019 // OSLO, Norway — Compared with the general population, patients with multiple sclerosis (MS) have a higher risk of developing cancer, particularly of the respiratory and central nervous systems, a large and lengthy new Norwegian study suggests.
"We want to get the message out about clinical awareness," study author Nina Grytten Torkildsen, PhD, researcher at Norwegian Multiple Sclerosis Competence Centre, Haukeland University Hospital, Bergen, Norway, told Medscape Medical News.
"It's easy for clinicians treating MS patients not to have cancer symptoms in mind, but they shouldn't interpret every single symptom that these patients have as part of their MS," Grytten Torkildsen said.
She added that delays in cancer diagnosis in MS patients can affect treatment outcomes, including survival.
Interestingly, the study showed that patients with MS had a slightly lower risk of overall cancer compared with their siblings, due to these siblings having a higher rate of hematological cancers.
The findings were presented here at the Congress of the European Academy of Neurology (EAN) 2019.
14% Higher Risk
Using prevalence studies and the Norwegian MS Registry, the researchers gathered data on patients with MS born between 1930 and 1979. They obtained cancer information from the Norwegian Cancer Registry.
The study included 6883 patients, 8918 of their siblings, and 37,919 individuals from the general Norwegian population who acted as "healthy controls."
Over a 65-year follow-up period (from 1952 when the Cancer Registry was established, to 2017), the overall cancer risk among patients with MS was 14% higher than in non-MS population controls (hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.05 - 1.23).
This higher rate was particularly evident for cancers of the respiratory system, including lymphomas and leukemia (HR, 1.66; 95% CI, 1.26 - 2.19), urinary organs (HR, 1.51; 95% CI, 1.12 - 2.04), and the central nervous system (CNS) including the meninges (HR, 1.52; 95% CI, 1.11 - 2.09).
The association was significant in women, but not in men. However, Grytten Torkildsen said she believes this is because of the small number of male study subjects with MS.
The researchers note that smoking may help explain some of the increased cancer risk in MS patients.
"Previous studies from Norway have shown that MS patients are more excessive smokers compared to the Norwegian population, so maybe that can explain the respiratory and urinary cancers," said Grytten Torkildsen.
Some cancers of the CNS may also be due to survivor "bias" she added.
"MS patients undergo very frequent MRI scans, which might detect these cancers early, while members of the general population might wait until symptoms manifest before they go to the doctor," she said.
Inflammation, a hallmark of MS, possibly contributes to increased risk of cancer of the meninges, noted Grytten Torkildsen.
Although the researchers didn’t look at MS subtypes, they note that the cancer risk is likely equally distributed. "Whether it’s relapsing remitting or primary progressive, we believe it involves the same inflammatory processes," Grytten Torkildsen said.
Very few of the patients in the study had primary progressive MS.
The investigators are now "very much" interested in looking at the cancer risk in patients with other autoimmune disorders, including rheumatoid arthritis, said Grytten Torkildsen.
Another finding of the study was that MS patients did not have an overall increased cancer risk compared with their own siblings (HR, 0.92; 95% CI, 0.83 - 1.03). This finding can be linked to a much lower risk of hematologic cancer in these patients vs their siblings (HR, 0.55; 95% CI, 0.37 - 0.82).
While a previous study in Sweden showed that hematologic cancers were increased in fathers of MS patients, "this is the first time that we have seen this in same-generation relatives," Grytten Torkildsen said. "We are going to expand on this in follow-up studies to look further at hematological cancers."
The study is unique in a number of ways, including its prospective nature, the inclusion of two control groups, and a very lengthy follow-up period, she noted.
Following her presentation, a number of meeting attendees asked whether the research group looked at the impact of disease-modifying therapies and various combinations of such treatments on cancer risk. This "will be the next step" said Grytten Torkildsen.
One attendee pointed out that the study follow-up period was "very long," and during this time "there were a lot of changes" regarding medications. "Have you had an opportunity to look at the prevalence and the risk by time segment, because that could help you interpret some of the data?" the attendee asked.
Grytten Torkildsen said that this, too, is being taken into consideration.
Commenting for Medscape Medical News, Ludwig Kappos, MD, professor and chair in the Department of Neurology, University Hospital Basel, Switzerland, and cochair of the EAN Scientific Panel on MS, said the current study has some advantages over other related research.
For one thing, it included a large group of people who were assessed "in a more comprehensive way," so the results "may be closer to reality," said Kappos, who was not involved with the research.
The issue of the frequency of cancer among patients with MS is controversial and has been ongoing for at least the past 3 decades. Some studies have shown a higher cancer rate among patients with MS, but others have shown a lower rate, he noted.
"My overall view has been that it is very similar to what you find in the normal population," he said.
The frequency of cancer in MS patients "has to be checked in an independent group before we can make a firmer conclusion," Kappos added.
As for the higher rate of hematologic cancers in siblings of MS patients, he said this may have something to do with the close connection between immune cells and the hematologic system.
Other research has found that cancer rates are elevated in patients with autoimmune diseases other than MS, noted Kappos.
Grytten Torkildsen and Kappos have disclosed no relevant financial relationships.
Congress of the European Academy of Neurology (EAN) 2019: Abstract O1204. Presented June 29, 2019.
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Cite this: MS May Increase Cancer Risk - Medscape - Jul 01, 2019.