Cancer risk highest soon after IgG4-related disease diagnosis: Study
Researchers suggest careful cancer monitoring, especially in early years
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The risk of developing cancer is more than four times higher in people with immunoglobulin G4-related disease (IgG4-RD) compared with the general population, with the greatest risk seen during the first year after diagnosis.
That’s according to a large-scale nationwide study from South Korea. The researchers also found that two of the most commonly detected cancers in people with IgG4-RD were pancreatic cancer and non-Hodgkin’s lymphoma, a type of blood cancer.
“These findings highlight the need for tailored cancer surveillance strategies in IgG4-RD, ideally starting at diagnosis and continuing for several years,” the researchers wrote.
The study, “Increased cancer risk in patients with IgG4-related disease in a nationwide South Korean cohort, 2012–2021,” was published in Scientific Reports.
Understanding IgG4-related disease and its symptoms
IgG4-RD occurs when immune cells move into healthy tissues, causing inflammation and scarring. This can sometimes lead to the formation of masses that resemble tumors. Symptoms vary widely depending on which organs are affected. IgG4-RD can appear almost anywhere in the body, but it most often involves the pancreas, salivary glands and other head-and-neck tissues, the bile ducts, kidneys, and lungs.
Research indicates that people with IgG4-RD may have a higher likelihood of developing certain cancers, particularly pancreatic cancer and lymphoma, a type of blood cancer. A previous small study also suggested that IgG4-RD patients may be susceptible to developing multiple cancers, most commonly prostate cancer, lymphoma, and melanoma, a type of skin cancer.
In this study, researchers in South Korea looked at cancer risk in more than 1,200 people diagnosed with IgG4-RD between 2012 and 2020. None of the patients had a previous history of cancer.
“By comparing cancer incidence in this [group of patients] to that of the general population, we aimed to clarify the overall and site-specific cancer risks associated with IgG4-RD,” the team wrote.
Patients’ mean age at IgG4-RD diagnosis was 56.36, and 42.46% were women. They were followed for a mean of 3.22 years. Nearly all patients (92.34%) were receiving glucocorticoids — the standard first-line IgG4-RD treatment — while 22.49% received azathioprine and 16.81% received methotrexate.
After adjusting for age and sex, the overall risk of cancer in people with IgG4-RD was more than four times higher than in the general population. During follow-up, 147 patients developed cancer, including 110 solid tumors and 28 blood cancers.
These results emphasize that while younger patients face the highest relative risk, ongoing cancer monitoring is crucial for all age groups throughout the follow-up period.
Among solid cancers, pancreatic cancer was the most common and was more than 14 times more likely to occur in people with IgG4-RD. This was followed by cancers of the central nervous system (brain and spinal cord) and the biliary tract — the system that includes the liver, gallbladder, and bile ducts, which carry bile from the liver to the intestines.
Among blood cancers, non-Hodgkin’s lymphoma was the most common, followed by myelodysplastic syndrome (MDS) and multiple myeloma. Compared with the general population, people with IgG4-RD were about 49 times more likely to develop MDS and about 20 times more likely to develop non-Hodgkin’s lymphoma.
Women had a higher overall cancer risk than men — 5.51 times higher than the general population, compared with 3.45 times higher in men. However, certain cancers were significantly elevated only in men, including those of the liver, bladder, prostate, and central nervous system. In women, stomach, colon, and breast cancers showed significantly higher risk.
Cancer risk in people with IgG4-RD was higher than in the general population across all age groups, with the most significant relative risk seen in those ages 20-39. The risk was highest during the first year after diagnosis, but it remained elevated over the long term.
“These results emphasize that while younger patients face the highest relative risk, ongoing cancer monitoring is crucial for all age groups throughout the follow-up period,” the team wrote.
Cancer risk varied by type of immune-suppressing therapy
The use of some immunosuppressive medications — including azathioprine, methotrexate, hydroxychloroquine, and tacrolimus — was associated with higher overall cancer risk. However, no significant increase in cancer risk was seen with mycophenolic acid or cyclophosphamide.
“These findings underscore the importance of judicious immunosuppressive use and suggest that effective disease control — even with low-dose glucocorticoids — may help mitigate cancer risk,” the team wrote.
The researchers suggested that increased medical monitoring and imaging soon after an IgG4-RD diagnosis may lead to earlier cancer detection, potentially exaggerating the observed associations. In addition, they said it is possible that, in some cases, undiagnosed cancers might trigger IgG4-RD, a concept known as reverse causality.
“Patients with IgG4-RD have a significantly increased risk of both hematologic and solid malignancies, particularly within the first year and in those with high disease burden requiring immunosuppressive therapy,” the researchers wrote.
Future studies following patients over time and “incorporating clinical, immunologic, and treatment data are essential to better characterize cancer risk and its [mechanistic] underpinnings in this complex disease,” they concluded.
