Familial gastric conditions indicating helicobacter pylori infection and risk of childhood leukemia

Background : Helicobacter pylori ( H. pylori ) is a cause of gastric cancer and B-cell MALT lymphoma. Cancer may arise from bone-marrow derived hematopoietic stem cells. H. pylori antigens are linked to B-cell proliferation, secondary to T cell response and the release of cytokines. However, H. pylori may inhibit T-cell proliferation. H. pylori is genotoxic and promotes chronic inflammation and oxidative stress. Infection is typically acquired in childhood, resulting from close personal contact with infected family members. Infections are suspected to play a role in the etiology of childhood leukemia. However, an earlier study found mixed results for any association between maternal H. pylori IgG and IgM antibodies. The purpose of this study was to investigate parental and childhood H. pylori -related diagnoses of peptic ulcer and gastritis in relation to risk for childhood leukemia. H. pylori colonizes the stomach lining and is a major cause of gastritis and peptic ulcer disease. As the study was based on registry data, we used these diagnoses as proxy for H. pylori infection. Methods : The study was based upon Danish national registers (births 1968-2013). We extracted H. pylori -related diagnoses of peptic ulcer and gastritis (ICD8 codes: 531-534; ICD-10 codes: K25-K28) and gastritis (ICD-8 code: 535; ICD-10 code: K29) from the National Patient Register for the parents and children. We linked these to childhood leukemia diagnoses from the Cancer Registry. Controls were 20:1 matched and selected at random from the Central Person Register. Conditional logistic regression was used to estimate associations between H. pylori -related diagnoses and childhood acute lymphoblastic leukemia (ALL), with adjustment for covariates. Results : We observed 3.1% of mothers and 4.2% of fathers had ever been diagnosed with gastric conditions. Maternal lifetime diagnosis with gastric conditions was not notably related to offspring ALL (OR=1.21, 95% CI 0.89-1.65). When we examined maternal gastric conditions diagnosed prior to the child's cancer diagnosis, risks increased (OR=1.74, 95% CI 1.11-2.73). There was no association with paternal lifetime history of gastric conditions (OR=1.10, 95% CI 0.83-1.45). Children's lifetime diagnosis of gastric conditions was associated with ALL (OR=1.87, 95% CI 1.08-3.23). Conclusions : Maternal and childhood H pylori -related diagnoses of peptic ulcer and gastritis are related to increased risk of childhood leukemia, perhaps related to aberrant immune responses. The child's increased risk may reflect heightened medical surveillance in cancer survivors and should be taken with caution. The findings warrant replication using serologic data.