Immune-Mediated Diseases Tied to Risk of Cancer

By Marilynn Larkin

December 10, 2021

NEW YORK (Reuters Health) - Immune-mediated diseases were associated with an increased risk of local and systemic cancers, as well as total cancers, in a large cohort study, supporting the role of local and systemic immunoregulation in the development of cancer, researchers say.

"Most findings were expected," Dr. Mingyang Song of the Harvard HT Chan School of Public Health in Boston told Reuters Health by email. "However, I was surprised by the strong associations of some immune-mediated diseases with a higher risk of cancers in the near organs (e.g., Crohn disease with liver cancer). This highlights the 'spillover' effect of immune changes on the carcinogenic process in the neighboring organs, highlighting the need for further studies."

As reported in JAMA Oncology, the data are from close to 480,000 individuals in the UK Biobank cohort (mean age, 56.4; 54%, women).

During 4.6 million person-years of follow-up, 2,834 cancer cases were documented in 61,496 patients with immune-mediated diseases, as were 26,817 cancer cases in 417,257 patients without immune-mediated diseases (multivariable HR,1.08).

Five organ-specific immune-mediated diseases were significantly associated with a higher risk of local, but not extralocal, cancers: asthma (HR, 1.34), celiac disease (HR, 6.89), idiopathic thrombocytopenic purpura (HR, 6.94), primary biliary cholangitis (HR, 42.12), and autoimmune hepatitis (HR, 21.26).

Nine immune-mediated diseases were associated with an increased risk of cancers in the involved organs: for example, asthma with lung cancer (HR, 1.34) and celiac disease with small intestine cancer (HR, 6.89).

Thirteen immune-mediated diseases were associated with an increased risk of cancer either in near organs (e.g., Crohn disease with liver cancer; HR, 4.01), in distant organs (e.g., autoimmune hepatitis with tongue cancer; HR, 27.75), or in different systems (e.g., idiopathic thrombocytopenic purpura with liver cancer; HR, 11.96).

Twelve immune-mediated diseases were associated with cancers in different systems, such as idiopathic thrombocytopenic purpura with liver cancer (HR, 11.96), bullous disorders with laryngeal cancer (HR, 26.23), Graves disease or autoimmune thyroiditis with soft tissue cancer (HR, 9.19), and ulcerative colitis with prostate cancer (HR, 1.45).

Among all cancers, lymphoma showed an extensive association with immune-mediated diseases, with HRs ranging from 2.01 for rheumatoid arthritis to 7.72 for idiopathic thrombocytopenic purpura.

Dr. Song noted, "Clinicians caring for patients with immune-mediated diseases should be mindful of the increased cancer risk in these patients. The cancers with risk elevation may develop in the involved, near, or even distant organs of the immune-mediated diseases. Cancer prevention measures (e.g., lifestyle modification and adherence to cancer screening guidelines) should be discussed with these patients."

"We plan to conduct further biomarker studies to investigate the potential mechanisms underlying (these associations)," he added. "For example, given the intricate relationship between the immune system, the gut microbiome and cancer, we plan to study whether the gut microbiome may play a role in the immune disease-cancer link."

Dr. Douglas Stewart of the US National Cancer Institute in Rockville, author of a related editorial, noted that the researchers' "comprehensive, prospective approach, reassuringly, confirmed a number of known associations, like the link between primary biliary cholangitis and hepatobiliary cancer."

"They also uncovered novel and unsuspected cancer risks at more distant sites from the immune disease, such as a putative association between Graves' disease and soft tissue cancer," he said.

"Their findings need replication, ideally in cohorts of more diverse ancestry," he added. "We know that in studies of the genetics of complex traits (including immune-mediated disease), inclusion of diverse populations can improve discovery."

SOURCE: https://bit.ly/3pGxDsG and https://bit.ly/336ckJe JAMA Oncology, online December 2, 2021.

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