Gastroesophageal reflux : etiological factors

Gastroesophageal reflux disease (GERD) is one of the most common health problems in the Western world today, affecting up to 20% of the adult population weekly and 50% monthly, generating substantial suffering among patients as well as significant costs to both patients and also to society in general. GERD can result in serious complications such as esophageal strictures, Barrett’s esophagus, and esophageal adenocarcinoma. Several risk factors for developing GERD have been identified, but there are still large bits of information on the etiology of GERD and its consequences missing. The purpose of this thesis is therefore to bring to light more knowledge in the etiology of GERD.

In the first paper, the association between several respiratory symptoms and gastroesophageal reflux symptoms is evaluated based on data from a large population-based health survey from Norway, comprising more than 40,000 participants. In study participants with respiratory symptoms, a two- to threefold increased risk for reflux symptoms was seen.

The second paper uses a nested case-control study, also based on the large Norwegian population-based health survey, to investigate the relation between Helicobacter pylori infection, gastric atrophy, and gastroesophageal reflux symptoms. A total of 944 study participants were included. Infection with Helicobacter pylori did not influence the risk for reflux symptoms after adjustments for confounding.

The third paper employs a monozygotic co-twin control design, within the Swedish Twin Registry, to determine the effect of lifestyle factors on the risk of GERD. The study shows a dose-response association between increasing body mass and GERD in women, but not in men. When genetic and early environmental factors were taken into account an increased risk for reflux symptoms was seen among both women and men. Smoking, physical activity at work and a low educational level were also associated with an increased risk of reflux symptoms, while recreational physical activity seemed to decrease this risk. No association with reflux was seen for the potential risk factors alcohol consumption, or dietary items.

The fourth paper is also based on the Swedish Twin Registry. In monozygotic co-twin control analyses and in prospective nested case-control analyses, the potential effect of female sex hormones, in postmenopausal hormone therapy and oral contraceptives, on reflux symptoms was evaluated. In women who had ever used estrogen postmenopausal therapy there was a 60% increased risk of reflux symptoms. This association was seen in normal-weight women, and was slightly further increased in overweight and obese women. There were indications of an association between use of both progestin postmenopausal hormone therapy and oral contraceptives on the risk of reflux symptoms, but this did not remain in the prospective nested case-control analyses.

List of scientific papers

I. Nordenstedt H, Nilsson M, Johansson S, Wallander MA, Johnsen R, Hveem K, Lagergren J (2006). The relation between gastroesophageal reflux and respiratory symptoms in a population-based study: the Nord-Trondelag health survey. Chest. 129(4): 1051-6
https://pubmed.ncbi.nlm.nih.gov/16608957

II. Nordenstedt H, Nilsson M, Johnsen R, Lagergren J, Hveem K (2007). Helicobacter pylori infection and gastroesophageal reflux in a population-based study (The HUNT Study). Helicobacter. 12(1): 16-22
https://pubmed.ncbi.nlm.nih.gov/17241296

III. Zheng Z, Nordenstedt H, Pedersen NL, Lagergren J, Ye W (2007). Lifestyle factors and risk for symptomatic gastroesophageal reflux in monozygotic twins. Gastroenterology. 132(1): 87-95. Epub 2006 Nov 17
https://pubmed.ncbi.nlm.nih.gov/17241862

IV. Nordenstedt H, Zheng Z, Cameron AJ, Ye W, Pedersen NL, Lagergren J (2007). Use of postmenopausal hormone therapy and oral contraaceptives in relation to gastroesophageal reflux in a population-based twin study. [Submitted]