Background: In the Copenhagen Male Study men with the Lewis blood group phenotype Le(a+b-), non-secretors of ABH antigen, and men with the O or the A phenotype in the ABO blood group have been found to have a significantly higher lifetime prevalence of peptic ulcer than others. We investigated the importance of the association of these genetic markers, life-style factors, and social class with lifetime risk of peptic ulcer, testing specifically the hypothesis that the strength of the association of risk factors with peptic ulcer depends on genetic susceptibility.
Methods: Three thousand three hundred and forty-six white men 55-74 years old were included for study. From a questionnaire validated during an interview information was obtained about life-style factors and peptic ulcer history (gastric or duodenal). Potential non-genetic risk factors examined were smoking history, alcohol consumption, physical activity level, consumption of tea and coffee, and use of sugar in tea or coffee.
Results: Three hundred and eighty-four men (11.5%) had a history of peptic ulcer; 120 (3.6%) had had an operation due to peptic ulcer. Non-genetic peptic ulcer risk factors identified were ever having been a smoker, use of sugar in tea or coffee, abstention from tea consumption, and low social class. On the basis of these and the genetic factors, it was possible to identify a low-risk group (n = 142) with a lifetime prevalence of 4.2%, several intermediate-risk groups, and a high-risk group (n = 55) with a prevalence of 29%; the odds ratio with 95% confidence limits (OR) was 9.3 (3.4-25.3). Corresponding values with regard to operation were 1.4% and 20.0%; OR = 17.5 (3.7-82.0). Several significant interactions were found; for example, the use of sugar was associated with peptic ulcer risk only when interacting with genetic risk groups.
Conclusions: Considering the role of Helicobacter pylori, it is interesting that the factors identified in this study were able to identify groups with extremely different lifetime risks. This finding and also the finding of strong interactions between genetic and life-style factors and between genetic factors and social class for the risk of peptic ulcer may have both public-health and clinical implications.