Cancer Rates Raised in Patients With Primary Immunodeficiency Diseases

Patients with primary immunodeficiency diseases are at increased risk of certain cancers, according to a new study. The strongest association was with lymphoma.

Patients with primary immunodeficiency diseases (PIDD) are at increased risk of certain cancers, according to a new study. The strongest association was with lymphoma.

The results point to the important role the immune system plays in cancer prevention.

PIDD are a group of more than 300 disorders caused by single-gene defects that prevent the immune system from functioning properly and affect 1 in every 1,200 people. Previously, researchers have noted an association between these diseases and cancer. Researchers led by senior author Brahm Segal, MD, of the Department of Immunology at Roswell Park Cancer Institute in Buffalo, New York, evaluated the overall cancer incidence and site-specific cancer incidence in patients with PIDD in the United States Immune Deficiency Network (USIDNET) database.

“We found that patients with primary immunodeficiency have a modest but significant increase in the overall incidence of cancer. Although we did not observe an increased risk of the most common solid-tumor malignancies, we did find that patients with specific forms of PIDD are predisposed to certain types of cancers,” said Segal. “Cancers observed with higher frequency in patients with PIDD were generally associated with an infectious cause, such as Epstein–Barr virus (EBV)-associated lymphoma. Our results point to a restricted role of the immune system in protecting against specific cancers, and underscore the need for evidence-based approaches for early detection in high-risk PIDD patients.”

The researchers published their results online in the Journal of Allergy and Clinical Immunology.

The study compared rates of cancer in 3,658 PIDD patients with an age-adjusted general population from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database.

The researchers observed a 1.42-fold excess relative risk of cancer in subjects with PIDD compared with the age-adjusted SEER population. Men with PIDD had a 1.91-fold excess relative risk of cancer; women with PIDD had similar overall cancer rates. They found significant increases in lymphoma in both men (10-fold increase) and women (8.34-fold increase) with PIDD and concluded that this excessive lymphoma risk was largely driven by common variable immunodeficiency (CVID).

Of the four most common malignancies in men and women in SEER (lung, colon, breast, and prostate cancers), there was no significant increase in these diagnoses among those with PIDD.

Overall, there was a 42% increase in cancer incidence among patients with PIDD. The majority of cancers were noted in patients with CVID, which comprised 70% of those in the database, including an increased risk of non-Hodgkin lymphoma, gastric cancer, and skin cancer. Other types of PIDD included hypogammaglobulinemia, agammaglobulinemia, and Wiskott–Aldrich syndrome. The cancer types with the highest incidence rates among PIDD patients in the USIDNET registry were lymphoma, skin cancer, and thyroid cancer.

Two major factors appear to drive increased cancer risk among specific subjects with PIDD: defective DNA repair and failure to provide immune surveillance against chronic viral infections, such as EBV and human papillomavirus, which cause cancer, they stated.