Lifestyle, stress, and genes in peptic ulcer disease: a nationwide twin cohort study.
BACKGROUND
The familial accumulation of peptic ulcer disease observed in several studies may be attributable to genetic effects, aggregation of environmental exposure (shared environment), or both. The intrafamilial spread of Helicobacter pylori infection has raised the question whether shared environment could explain the familial aggregation of peptic ulcer disease rather than genetic similarity of family members.


OBJECTIVE
To examine the contribution of genetic and environmental factors to the pathogenesis of peptic ulcer disease in a nationwide population-based cohort of adult twins.


METHODS
The Finnish Twin Cohort consists of all same-sexed twin pairs born before 1958 with both twins alive in 1975. The total number of twin pairs is 13888, of whom 4307 are monozygotic (MZ) and 9581 are dizygotic (DZ) twins. Questionnaire surveys of twins were carried out in 1975, 1981, and 1990, including medical and psychosocial questions. One question asked whether a physician had ever made a diagnosis of gastric or duodenal ulcer. In addition, hospital discharge data from 1972 to 1991 were linked with the twin cohort to obtain those twin individuals who had been treated for gastric or duodenal ulcer. The prevalence of and concordance for peptic ulcer disease were examined in MZ and DZ twins. Model-fitting analysis was used to specify the relative roles of genetic and environmental factors. The contribution of lifestyle factors and stress was examined prospectively in an incidence study and by comparison of discordant pairs.


RESULTS
The prevalence of peptic ulcer disease was 6.2% in men and 2.8% in women in 1975. There were 63 MZ and 86 DZ pairs concordant for peptic ulcer disease. Concordance for disease was significantly higher in MZ than in DZ twin pairs; the probandwise concordance rate was 23.6% (95% confidence interval [CI], 20.9%-26.3%) in MZ twins and 14.8% (95% CI, 13.3%-16.3%) in DZ twins. In the model-fitting analysis, a model with both additive genetic and unshared environmental effects had the best goodness-of-fit. Thirty-nine percent (95% CI, 32%-47%) of the liability to peptic ulcer disease was explained by genetic factors and 61% (95% CI, 53%-68%) by individual environmental factors. In the incidence study (logistic regression analysis of the entire cohort initially free of peptic ulcer disease, with subjects diagnosed as having peptic ulcer after 1975 as cases), current smoking (relative risk, 2.2; 95% CI, 1.5-3.2) and high stress levels (relative risk, 3.2; 95% CI, 1.4-7.6) in men and regular use of analgesics (relative risk, 3.3; 95% CI, 1.3-8.1) in women predicted peptic ulcer disease during the follow-up from 1976 to 1991. In the analysis of discordant pairs, smoking in men and regular use of analgesics in both sexes were predictors of peptic ulcer disease.


CONCLUSIONS
The questionnaire and hospital usage data on peptic ulcer disease in the population-based twin cohort suggest that the familial aggregation of the disease is modest, and attributable almost solely to genetic factors. Environmental effects not shared by family members were significant predictors of disease, and they were attributable to smoking and stress in men and the use of analgesics in women. The minor effects of shared environment to disease liability do not support the concept that the clustering of risk factors, such as H pylori infection, would explain the familial accumulation of peptic ulcer disease.
Räihä
I
I
Department of Geriatrics, University of Turku, Finland.
Kemppainen
H
H
Kaprio
J
J
Koskenvuo
M
M
Sourander
L
L
D000203:Activities of Daily Living; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D000700:Analgesics / Q000009:adverse effects; D015331:Cohort Studies; D004200:Diseases in Twins / Q000209:etiology* / Q000235:genetics / Q000523:psychology; D005260:Female; D005387:Finland; D006801:Humans; D008019:Life Style; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010437:Peptic Ulcer / Q000209:etiology* / Q000235:genetics / Q000523:psychology; D011446:Prospective Studies; D017678:Sex Distribution; D012907:Smoking / Q000009:adverse effects; D013315:Stress, Psychological / Q000150:complications*; D011795:Surveys and Questionnaires
D000700:Analgesics