Immune-mediated diseases collectively were associated with an increased risk of cancer, with the risks not always isolated to the involved organ, a large cohort study demonstrated.
Overall, 48 common autoimmune and other immune-mediated conditions were linked with a modest total cancer risk (HR 1.08, 95% CI 1.04-1.12), reported Mingyang Song, MD, ScD, of Harvard T.H. Chan School of Public Health in Boston, and colleagues.
On multivariable analysis, three conditions specifically were associated with an increased total cancer risk: ulcerative colitis (HR 1.33, 95% CI 1.17-1.51), asthma (HR 1.06, 95% CI 1.01-1.12), and primary biliary cholangitis (HR 1.74, 95% CI 1.10-2.76), according to the findings in JAMA Oncology.
A number of immune-mediated diseases were significantly associated with an increased risk of cancer in the involved organs:
But the study also found 13 conditions linked with cancers in near organs and 12 associated with cancers in different systems, including:
- Crohn’s disease/hepatobiliary cancer: HR 4.01 (95% CI 1.65-9.72)
- Ulcerative colitis/hepatobiliary cancer: HR 2.59 (95% CI 1.15-5.81)
- Ulcerative colitis/tongue cancer: HR 3.49 (95% CI 1.29-9.43)
- Ulcerative colitis/prostate cancer: HR 1.45 (95% CI 1.13-1.85)
- Autoimmune hepatitis/tongue cancer: HR 27.65 (95% CI 3.82-199.91)
- Autoimmune hepatitis/esophageal cancer: HR 9.28 (95% CI 1.31-65.94)
- ITP/hepatobiliary cancer: HR 11.96 (95% CI 3.82-37.42)
- Bullous disorders/laryngeal cancer: HR 26.23 (95% CI 3.62-190.15)
- Graves disease or autoimmune thyroiditis/soft-tissue cancer: HR 9.19 (95% CI 2.93-28.81)
“The findings suggest that immune-mediated diseases are associated with risk of cancer at the local and systemic levels, supporting the role of local and systemic immunoregulation in carcinogenesis,” wrote Song and coauthors, and “may inform future research elucidating the role of immunoregulation and microbiota in cancer development.”
Writing in an accompanying commentary, Douglas Stewart, MD, of the NCI’s Clinical Genetics Branch, said the “most intriguing findings” were about the cancers that arose at sites distant to a specific organ and therefore may not have been previously suspected.
He explained that although it has long been known that immune-mediated diseases such as ulcerative colitis are associated with an increased risk of organ-specific cancers, and that there is also an association with cancer risk in more distant organs, the understanding of the relationships has been incomplete.
Large, longitudinal data sets derived from electronic health records as used in the new analysis are “powerful tools for discovery,” and the results of the study deserve attention, Stewart said, particularly the implications that increased surveillance may be warranted for the immune-mediated diseases with large hazard ratios for cancer risk, such as that of primary biliary cholangitis and hepatobiliary cancer.
For the study, Song’s group identified 48 immune-mediated diseases and compared cancer risk between individuals with and without any of the diseases. The study population consisted of 478,753 adults ages 37 to 73 from the U.K. Biobank cohort study who were recruited in the U.K. from 2006 to 2010, with follow-up through February 2019.
There were a total of 2,834 cancer cases in 61,496 patients with immune-mediated diseases, and 26,817 cancer cases in 417,257 individuals without any immune-mediated diseases.
Participants with any immune-mediated disease were at higher risk of developing lung cancer (multivariable-adjusted HR 1.36, 95% CI 1.20-1.53), lymphoma (multivariable-adjusted HR 1.49, 95% CI 1.26-1.75), and liver cancer (HR 1.75, 95% CI 1.30-2.36).
Study limitations, the team said, included a lack of detailed information on immune-mediated disease treatment; a small number of cancer cases for some of the rarer conditions; the possibility of chance findings in some cases and of missed diagnoses; and that the cohort was relatively young (which reduced the power to identify associations) and predominantly white.
The study was supported by grants from the American Cancer Society, the U.S. National Institutes of Health, and the German Research Foundation.
Song and co-authors noted no conflict-of-interest disclosures.
Stewart reported performing contract clinical telehealth services for Genome Medical Inc. in accordance with relevant National Cancer Institute ethics policies.