Institutionen för medicinsk epidemiologi och biostatistik / Department of Medical Epidemiology and Biostatistics
Abstract
Aims: The aims of this thesis were to study the association of overall
dietary habits, duodenal ulcer and gastric ulcer diseases, as two models
of Helicobacter pylori (H. pylori) infection and the development of
gastroesophageal cancers to further explore the etiology of these
malignancies. Moreover, the association between parity, a proxy for high
level of female hormones, and stomach cancer risk was studied to shed
light on the enigma of male predominance in this cancer.
Methods: In a nationwide population-based case-control study in Sweden
with 165 esophageal squamous cell carcinoma, 185 esophageal
adenocarcinoma and 258 cardia cancer cases and 815 randomly selected
controls we estimated relative risks associated with dietary patterns.
Furthermore, cohorts of 61,548 and 81,379 unoperated patients with
duodenal ulcer and gastric ulcer, respectively, recorded in the Swedish
Inpatient Register since 1965, were followed and standardized incidence
ratios were estimated for esophageal cancer by histology, compared with
the Swedish general population. We also followed cohorts of 59,550 and
79,412 unoperated patients with duodenal ulcer and gastric ulcer,
respectively, plus 12,840 patients with partial gastric resection and
8,105 with vagotomy, recorded since 1970. We estimated relative risks for
stomach cancer by anatomical subtype compared to the Swedish general
population for unoperated cohorts, whereas relative risks were estimated
among operated patients relative to unoperated ones with the same ulcer
type. Finally, in a case-control study, nested within a cohort of Swedish
women born in 1925 or later, with 286 cardia cancer and 2,498 non-cardia
stomach cancer as well as corresponding 1,430 and 12,490 controls, we
investigated the relationship between parity and risk of stomach cancer
by anatomic subsite.
Results: A healthy diet tended to moderately decrease the risk of
esophageal and cardia cancers, Western diet increased risks of cardia
cancer and esophageal adenocarcinoma, whereas a dietary pattern
characterized by high beer and liquor intake significantly increased the
risk of squamous-cell carcinoma of the esophagus. We observed that
patients with duodenal ulcer had a significant 70% excess risk of
esophageal adenocarcinoma, a nonsignificant small excess risk of
esophageal squamous cell carcinoma, a halved risk of noncardia cancer,
and a risk of cardia cancer slightly above expectation. Gastric ulcer was
unrelated to esophageal adenocarcinoma but linked to 80% increased risk
of esophageal squamous cell carcinoma, and doubled risks for both
anatomical types of stomach cancer. Duodenal ulcer patients who underwent
gastric resection had a 60% risk elevation for noncardia cancer compared
to unoperated ones. Vagotomy was associated with a greater risk in the
first 10 years, but this excess disappeared with further follow-up.
Resected gastric ulcer patients had a 40% risk reduction for non-cardia
cancer relative to their unoperated peers. We found no association
between parity and risk of non-cardia stomach cancer comparing everparous
women with nulliparous, whereas a statistically significant 30% risk
reduction for postmenopausal cardia cancer was noted among ever-parous
women relative to nulliparous.
Conclusions: Overall dietary habits seem to play an important role in the
carcinogenesis of esophageal and cardia cancer. The well-established
strong inverse association of H. pylori seropositivity and risk of
esophageal adenocarcinoma does not pertain to all infections. The
duodenal ulcer related protection against stomach cancer does not seem to
affect cardia cancer. It seems that the pattern of stomach colonization
and/or the clinical consequences in the stomach might play a pivotal role
in the long term outcome of H. pylori infection. With gastric resection,
risks are shifted toward normality, regardless of underlying ulcer type.
Exposure to female sex hormones is not associated with protection against
stomach cancer and does not seem to explain the male predominance for
such cancer. However the observed moderate inverse relationship between
parity and cardia cancer might be mediated by other factors than
hormonal