Serum immunoglobulin levels and the risk of bladder cancer in the AMORIS Cohort
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1
King's College London, United Kingdom
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2
Karolinska Institute (KI), Sweden
Background: Cancer of the urinary bladder is the ninth most common type of cancer worldwide and is responsible for an estimated 165,000 deaths annually. Bladder cancer is characterized by a very high mutational burden, a substantial mutation-associated neoantigen load and a strong response to immunotherapy. The anti-tumour T-cell response in bladder cancer has been shown to correlate with response to treatment and prognosis. However, little is known about the role of humoral immunity in the pathogenesis of this highly immunogenic human cancer. In the present study, we interrogated the Swedish Apolipoprotein Mortality Risk Study (AMORIS) to explore the relationship between pre-diagnostic serum immunoglobulin levels and the risk of developing bladder cancer.
Methods: Analysis of the AMORIS cohort was performed by including all participants aged 20 years or older who had the three serum immunoglobulin levels (IgA, IgM, IgG) recorded at the same baseline measurement (n=29,876). All participants were free from bladder cancer at the time of blood sampling. Samples were obtained between 1985-1996, with follow-up information extended up to 2011. Multivariate Cox proportional hazards regression was used to investigate the association between bladder cancer risk and different levels of pre-diagnostic serum immunoglobulins.
Results: During a mean follow-up period of 15.31 years, 163 (0.5%) individuals were diagnosed with bladder cancer. Multivariate Cox proportional hazards models showed a lack of association between pre-diagnostic serum total IgA or IgG levels and bladder cancer risk. In contrast, we observed an inverse association between pre-diagnostic serum IgM levels and the risk of developing bladder cancer using the cut-off value of serum IgM of 1.40 g/L (HR 0.68, 95% CI 0.45-1.03).
Conclusion: Our findings implicate serum IgM levels in the pathogenesis of bladder cancer and suggest that the concept of “humoral immune surveillance” against cancer requires further mechanistic investigation.
Keywords:
bladder cancer;,
serum immunoglobulins,
IgA,
IgG,
IgM,
cohort study
Conference:
Bladder Cancer Translational Research Meeting, London, United Kingdom, 29 Mar - 29 Mar, 2019.
Presentation Type:
Poster
Topic:
Optimisation of diagnostic pathways
Citation:
Peppas
I,
Sollie
S,
Josephs
DH,
Hammar
N,
Walldius
G,
Karagiannis
SN and
Van Hemelrijck
M
(2019). Serum immunoglobulin levels and the risk of bladder cancer in the AMORIS Cohort.
Front. Oncol.
Conference Abstract:
Bladder Cancer Translational Research Meeting.
doi: 10.3389/conf.fonc.2019.01.00003
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Received:
27 Feb 2019;
Published Online:
27 Sep 2019.
*
Correspondence:
Dr. Ioannis Peppas, King's College London, London, United Kingdom, ioannis.peppas@nhs.net