Abstract
Background: Emerging evidence points to potential roles of the humoral immune responses in the development of pancreatic cancer. Epidemiological studies have suggested involvement of viral and bacterial infections in pancreatic carcinogenesis. Experimental studies have reported high expression levels of antigens in pancreatic cancer cells. Therefore, we aimed to investigate the role of different components of humoral immunity in the context of pancreatic cancer. We evaluated associations between pre-diagnostic serum markers of the overall humoral immune system [immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM)], and the risk of pancreatic cancer in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study.Methods: We selected all participants (≥20 years old) with baseline measurements of IgA, IgG or IgM (n = 41,900, 136,221, and 29,919, respectively). Participants were excluded if they had a history of chronic pancreatitis and individuals were free from pancreatic cancer at baseline. Multivariate Cox proportional hazards regression was used to estimate risk of pancreatic cancer for medical cut-offs of IgA, IgG, and IgM.Results: Compared to the reference level of 6.10–14.99 g/L, risk of pancreatic cancer was elevated among those with IgG levels <6.10 g/L [HR: 1.69 (95% CI 0.99–2.87)], and an inverse association was observed among those with IgG levels ≥15.00 g/L [0.82 (95% CI 0.64–1.05); Ptrend = 0.027]. The association appeared to be stronger for women than men [HR: 0.64 (95% CI 0.43–0.97) and 0.95 (95% CI 0.69–1.29), respectively]. No associations were observed with IgA or IgM.Conclusion: An inverse association was observed between pre-diagnostic serum levels of IgG and risk of pancreatic cancer. Our findings highlight the need to further investigate the role of immune response in pancreatic cancer etiology.
Highlights
Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2030 [1], and is frequently diagnosed at an advanced stage
Multivariate Cox regression for the association between immunoglobulin G and the risk of pancreatic cancer showed that, compared to the IgG reference level of 6.10–14.99 g/L, there was a positive association for those with IgG levels
We found an inverse association for those with IgG levels ≥15.00 g/L [0.82; Ptrend = 0.027] (Table 2)
Summary
Pancreatic cancer is predicted to be the second leading cause of cancer-related death by 2030 [1], and is frequently diagnosed at an advanced stage. There has been mounting evidence that the humoral immune system plays a role in the development of pancreatic cancer. Epidemiological studies have suggested that viral and bacterial infections contribute to pancreatic cancer pathogenesis [8,9,10,11,12,13]. Periodontal disease, caused by bacterial infections of pathogens such as Porphyromonas gingivalis and Fusobacterium species, has been suggested to play a role in the development and prognosis of pancreatic cancer [18,19,20,21,22,23,24]. Emerging evidence points to potential roles of the humoral immune responses in the development of pancreatic cancer. Epidemiological studies have suggested involvement of viral and bacterial infections in pancreatic carcinogenesis. We evaluated associations between pre-diagnostic serum markers of the overall humoral immune system [immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM)], and the risk of pancreatic cancer in the Swedish Apolipoprotein-related MORtality RISk (AMORIS) study
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