Serum Immunoglobulin G Is Associated With Decreased Risk of Pancreatic Cancer in the Swedish AMORIS Study

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.

Keywords: AMORIS; IgA; IgG; IgM; immune system and cancer; pancreatic cancer; serum immunoglobulin.

Figure 1

Adjusted dose-response association between serum levels of IgG (g/L) and risk of pancreatic cancer (HR) using restrictive cubic splines. The direction of the hazard ratios observed in Tables 2, 3 was consistent with the shape of the curve, which presents a positive association for IgG levels lower than 11.00 g/L with pancreatic cancer risk (HR > 1.00) and a protective effect for high levels of IgG (11.00–20.00 g/L) (HR <1.00). However, the inverse association was only statistically significant for concentrations of IgG between 11.00 and 16.00 g/L.