Gastric Cancer Is the Leading Cause of Death in Italian Adult Patients With Common Variable Immunodeficiency

Abstract

An increased prevalence of malignant lymphoma and of gastric cancer has been observed in large cohorts of patients with common variable immunodeficiency (CVID), the most frequently symptomatic primary immunodeficiency. Surveillance strategies for cancers in CVID should be defined based on epidemiological data. Risks and mortality for cancers among 455 Italian patients with CVID were compared to cancer incidence data from the Italian Cancer Registry database. CVID patients showed an increased cancer incidence for all sites combined (Obs = 133, SIR = 2.4; 95%CI = 1.7-3.5), due to an excess of non-Hodgkin lymphoma (Obs = 33, SIR = 14.3; 95%CI = 8.4-22.6) and of gastric cancer (Obs = 25; SIR = 6.4; 95%CI = 3.2-12.5). CVID patients with gastric cancer and lymphoma had a worse survival in comparison to cancer-free CVID (HR: 4.8, 95%CI: 4.2-44.4 and HR: 4.2, 95%CI: 2.8-44.4). Similar to what observed in other series, CVID-associated lymphomas were more likely to be of B cell origin and often occurred at extra-nodal sites. We collected the largest case-series of gastric cancers in CVID subjects. In contrast to other reports, gastric cancer was the leading cause of death in CVID. Standardized mortality ratio indicated a 10.1-fold excess mortality among CVID patients with gastric cancer. CVID developed gastric cancer 15 years earlier than the normative population, but they had a similar overall survival. Only CVID diagnosed at early stage gastric cancer survived >24 months. Stomach histology from upper endoscopy performed before cancer onset showed areas of atrophic gastritis, intestinal metaplasia or dysplasia. CVID patients might progress rapidly to an advanced cancer stage as shown by patients developing a III-IV stage gastric cancer within 1 year from an endoscopy without signs of dysplasia. Based on high rate of mortality due to gastric cancer in Italian CVID patients, we hereby suggest a strategy aimed at early diagnosis, based on regular upper endoscopy and on Helicobacter pylori infection treatment, recommending an implementation of national guidelines.

Keywords: IgA; common variable immunodeficiency: cancer; gastric cancer; guidelines; lymphoma; risk; upper endoscopy.

Figure 1

Cancers diagnosis and death for cancer in CVID and in the normative population. Data related to the proportion of the five most frequently diagnosed cancers in male and female CVID patients (dashed bars) are shown in comparison to the normative population (IT, white bars) (A). Proportion of deaths for cancer in male and female CVID patients (dashed bars) are shown in comparison to the normative population (IT, white bars) (B). In CVID, NHL and gastric cancer were the most commonly diagnosed cancers in both sexes, whereas breast cancer and prostate cancer were the most frequently recorded malignancies in Italian normative population. Gastric cancer was the first cause of death for cancer in CVID females and males, followed by NHL; breast and lung cancers were the most common cause of death for cancer in normative population. Data of normative population referred to 2017 AIRTUM report. NHL, non-Hodgkin lymphoma. ^*p < 0.01; ^***p < 0.0001.

Figure 2

CVID survival. Survival in female (A) and male (B) CVID participants: data were shown as overall survival (black dashed line), in CVID patients with gastric cancer (black bold line), in patients with lymphoma (black line) and in cancer-free CVID patients (gray dashed line). No survival differences were observed between females and males; CVID subjects with gastric cancer or lymphoma had a worse survival in comparison to cancer-free CVID population.

Figure 3

Gastric cancer survival by sex and staging. Survival in the cancer free CVID subjects (black bold line) and in CVID females (gray dashed line) and males (gray line) with gastric cancer was shown in (A). Survival in patients scored as stage I (gray line) and in patients scored as stage III-IV (dashed line) was shown in (B). No difference was observed between CVID females and males with gastric cancer; patients scored as stage I had a better survival in comparison to patients scored as stage III-IV.