Translational and clinical immunology
Cancer in primary immunodeficiency diseases: Cancer incidence in the United States Immune Deficiency Network Registry

https://doi.org/10.1016/j.jaci.2017.05.024Get rights and content

Background

We evaluated the overall and site-specific incidence of cancer in subjects with primary immunodeficiency diseases (PIDD) enrolled in the United States Immune Deficiency Network (USIDNET) registry compared with age-adjusted cancer incidence in the Surveillance, Epidemiology and End Results Program (SEER) database.

Objective

We hypothesized that subjects with PIDD would have an increased incidence of cancer due to impaired immune function.

Methods

Overall and site-specific cancer incidence rates were evaluated in subjects with PIDD (n = 3658) enrolled in the USIDNET registry from 2003 to 2015 and compared with age-adjusted incidence rates in the SEER database.

Results

We observed a 1.42-fold excess relative risk of cancer in subjects with PIDD compared with the age-adjusted SEER population (P < .001). Men with PIDD had a 1.91-fold excess relative risk of cancer compared with the age-adjusted male population (P < .001), while women with PIDD had similar overall cancer rates compared with the age-adjusted female population. Of the 4 most common malignancies in men and women in SEER (lung, colon, breast, and prostate cancers), we found no significant increase in these diagnoses in subjects with PIDD. Significant increases in lymphoma in both men (10-fold increase, P < .001) and women (8.34-fold increase, P < .001) with PIDD were observed.

Conclusions

Excess incidence of cancer occurred in subjects with PIDD. An excess of lymphoma in specific PIDD populations principally drove this increased incidence, while no increased risk of the most common solid tumor malignancies was observed. These data point to a restricted role of the immune system in protecting from specific cancers.

Section snippets

USIDNET registry

The USIDNET registry collects a number of variables on subjects with PIDD including clinical, laboratory, and outcome data, which together provide a health survey of this rare group of subjects. The registry data are based on entries from physicians or their designees from 39 academic institutions in the United States who have institutional review board (IRB)-approved protocols and 5 medical offices that use the USIDNET IRB consent protocol. In addition, patients may enroll themselves, also

Cancer incidence in subjects with PIDD

As of July 1, 2015, 3844 subjects with a PIDD diagnosis were included in the USIDNET registry. To be considered for analysis, subjects needed their PIDD diagnosis and age of last follow-up to be entered into the database by July 1, 2015. Because subjects in the database did not have the age of cancer diagnosis listed, age at last follow-up was used as a surrogate for age of cancer diagnosis. We excluded 186 subjects who did not have the age at last follow-up, which left 3658 subjects in the

Discussion

The USIDNET registry is supported by the National Institutes of Health to enhance the understanding and care of subjects with PIDD. For many years, attempts have been made to evaluate the excess number of malignancy in these subjects. As the USIDNET registry is populated with data on these rare diseases, we undertook an examination of the current registry to gain an up-to-date survey of cancers in PIDD. We observed a 1.42-fold excess relative risk of cancer in subjects with PIDD compared with

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    Supported by Roswell Park Cancer Institute National Cancer Institute Cancer Center support grants (P30CA016056, 5T32CA108456 [to P.C.M.], NLM K01LM012100 [to K.E.], T32CA085183 [to K.L.S.], R01CA140622 [to S.I.A.], P50 CA159981 [to K.O.], R01CA188900 [to B.H.S. and K.B.M.]), and the United States Immunodeficiency Network and Immune Deficiency Foundation (U24AI086037-06).

    This work was presented at the American Society of Clinical Oncology annual meeting in Chicago, IL June 3-7, 2016, as a poster discussion session.

    Disclosure of potential conflict of interest: B. Segal's and P. Mayor's institutions received a grant from the National Institutes of Health (NIH) for this work. K. Eng's institution received NIH grant K01LM012100 for this work. K. Singel's institution received a grant from NIH. R. Fuleihan's institution received consultancy fees from CSL Behring and Shire, and payment for lectures from Shire. H. Ochs' institution received a grant from Jeffrey Modell Foundation. F. Bonilla personally received consultancy fees from CSL Behring, Grand Rounds Health Immune Deficiency Foundation, Advance Medical Consultation, Charles River Associates International, Green Cross, American Research Group, Guidepoint Global Advisors, Sarepta, Inc., and Health Resources Services Administration; payment for lectures from Brigham Board Review in Allergy and Immunology (Distance Learning) Course; royalties from UpToDate; and travel expenses from Immune Deficiency Foundation. R. Buckley is employed by Duke University Medical Center. K. Sullivan's institution received USIDNET subcontract from NIH; and K. Sullivan personally received consultancy fees from UpToDate and Immune Deficiency Foundation. Z. Ballas's institution received consultancy fees from Checkmate Pharmaceutical and grants from Checkmate Pharmaceutical for other works, and has a pending patent application using EGF level as a biomarker for response to ipilimumab; Z. Ballas personally received royalties from UpToDate C. Cunningham-Rundles's institute received U24 grant to the Immune Deficiency Foundation for USIDNET. The rest of the authors declare that they have no relevant conflicts of interest.

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