Incidence of Malignancies in Diagnosed Celiac Patients
Incidence of Malignancies in Diagnosed Celiac Patients
Objectives: The association between celiac disease and malignancies is well recognized. In Finland, the prevalence of clinically diagnosed adult celiac disease is 0.6%. In this large, population-based cohort, we aimed at a realistic projection of the cancer risk.
Methods: In the period 2002–2011, the register comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer Registry, which covers over 98% of diagnosed malignancies. The standardized incidence ratio (SIR) was calculated for the malignancies, on the basis of incidence figures for the whole population. A time-stratified analysis was made in celiac patients diagnosed after 2004 (n=11,991). Lifestyle factors, including smoking habits and obesity, were not obtainable.
Results: The overall incidence ratio of malignant diseases was not increased (SIR 0.94; 95% confidence intervals 0.89–0.98), but it was ≥5 years from the diagnosis of celiac disease (1.31, 1.04–1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62–2.29), small-intestinal cancer (4.29; 2.83–6.24), colon cancer (1.35; 1.13–1.58), and basal cell carcinoma of the skin (1.13; 1.03–1.22) were increased, whereas those for lung cancer (0.60; 0.48–0.74), pancreatic cancer (0.73; 0.53–0.97), bladder cancer (0.53; 0.35–0.77), renal cancer (0.72; 0.51–0.99), and breast cancer (0.70; 0.62–0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37–4.38).
Conclusions: There was no increased SIR of cancer in the whole series, but SIR was increased after 5 years from the diagnosis of celiac disease. The risk of breast and lung cancers was decreased. The risk of small-intestinal cancer and NHL was increased, but to a lesser extent than previously described.
Celiac disease is a chronic autoimmune disorder triggered by ingestion of gluten in genetically predisposed persons. An increased risk of small-bowel lymphoma (later referred to as enteropathy-associated T-cell lymphoma) in celiac patients has been acknowledged since the 1960s, and an increased risk of other malignancies of the gastrointestinal tract has also been documented in a number of studies. In contrast, the risk of breast and lung cancer in celiac patients has been argued to be decreased. However, the literature on the overall risk of malignancy in celiac disease is contradictory. In a recent meta-analysis, the risk was found to be equal to that in the normal population, which is in line with our previous observations in Finland. By contrast, in well-designed studies from the United States and United Kingdom, the standard incidence ratio (SIR) for overall malignancies in celiac disease patients has been found to be elevated up to 1.5-fold.
If only patients suffering from overt symptoms are included, the cancer risk is obviously higher than that in a cohort of patients with mild or even no symptoms. Although the serological prevalence of celiac disease is high, up to 1–2% of the population in most Western countries, the number of patients with an established diagnosis remains much lower. In Finland we have reached a high (0.6%) prevalence of clinically diagnosed celiac disease by active case-finding screening patients also with only mild symptoms such as flatulence and dyspepsia, and with extraintestinal manifestations such as osteoporosis. Compliance to a gluten-free diet is good, as about 90% of Finnish patients adhere strictly.
The problem with many previous studies on the cancer risk in celiac disease is that the identified study populations have been more or less selected. Our nationwide dietary reimbursement register made it possible to evaluate the risk of malignancies in an unselected, population-based cohort including virtually all clinically diagnosed celiac disease patients alive in 2002–2011.
Abstract and Introduction
Abstract
Objectives: The association between celiac disease and malignancies is well recognized. In Finland, the prevalence of clinically diagnosed adult celiac disease is 0.6%. In this large, population-based cohort, we aimed at a realistic projection of the cancer risk.
Methods: In the period 2002–2011, the register comprised 32,439 adult celiac patients. This was linked with the Finnish Cancer Registry, which covers over 98% of diagnosed malignancies. The standardized incidence ratio (SIR) was calculated for the malignancies, on the basis of incidence figures for the whole population. A time-stratified analysis was made in celiac patients diagnosed after 2004 (n=11,991). Lifestyle factors, including smoking habits and obesity, were not obtainable.
Results: The overall incidence ratio of malignant diseases was not increased (SIR 0.94; 95% confidence intervals 0.89–0.98), but it was ≥5 years from the diagnosis of celiac disease (1.31, 1.04–1.63). The SIRs for non-Hodgkin lymphoma (NHL; 1.94; 1.62–2.29), small-intestinal cancer (4.29; 2.83–6.24), colon cancer (1.35; 1.13–1.58), and basal cell carcinoma of the skin (1.13; 1.03–1.22) were increased, whereas those for lung cancer (0.60; 0.48–0.74), pancreatic cancer (0.73; 0.53–0.97), bladder cancer (0.53; 0.35–0.77), renal cancer (0.72; 0.51–0.99), and breast cancer (0.70; 0.62–0.79) were decreased. SIR for NHL immediately after the diagnosis of celiac disease was 2.56 (1.37–4.38).
Conclusions: There was no increased SIR of cancer in the whole series, but SIR was increased after 5 years from the diagnosis of celiac disease. The risk of breast and lung cancers was decreased. The risk of small-intestinal cancer and NHL was increased, but to a lesser extent than previously described.
Introduction
Celiac disease is a chronic autoimmune disorder triggered by ingestion of gluten in genetically predisposed persons. An increased risk of small-bowel lymphoma (later referred to as enteropathy-associated T-cell lymphoma) in celiac patients has been acknowledged since the 1960s, and an increased risk of other malignancies of the gastrointestinal tract has also been documented in a number of studies. In contrast, the risk of breast and lung cancer in celiac patients has been argued to be decreased. However, the literature on the overall risk of malignancy in celiac disease is contradictory. In a recent meta-analysis, the risk was found to be equal to that in the normal population, which is in line with our previous observations in Finland. By contrast, in well-designed studies from the United States and United Kingdom, the standard incidence ratio (SIR) for overall malignancies in celiac disease patients has been found to be elevated up to 1.5-fold.
If only patients suffering from overt symptoms are included, the cancer risk is obviously higher than that in a cohort of patients with mild or even no symptoms. Although the serological prevalence of celiac disease is high, up to 1–2% of the population in most Western countries, the number of patients with an established diagnosis remains much lower. In Finland we have reached a high (0.6%) prevalence of clinically diagnosed celiac disease by active case-finding screening patients also with only mild symptoms such as flatulence and dyspepsia, and with extraintestinal manifestations such as osteoporosis. Compliance to a gluten-free diet is good, as about 90% of Finnish patients adhere strictly.
The problem with many previous studies on the cancer risk in celiac disease is that the identified study populations have been more or less selected. Our nationwide dietary reimbursement register made it possible to evaluate the risk of malignancies in an unselected, population-based cohort including virtually all clinically diagnosed celiac disease patients alive in 2002–2011.
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