The condition most commonly affects people between the ages of 30 and 60. The prevalence in unknown, but estimated to be about 1 per 100,000 people.

The average age of onset is 40 to 60 years, and men are affected more often than women. Adults with Ménétrier disease have a higher risk of developing gastric adenocarcinoma.

The role of "Helicobacter pylori" in functional dyspepsia is controversial, and no clear causal relationship has been established. This is true for both the symptom profile and pathophysiology of functional dyspepsia. Although some epidemiologic studies have suggested an association between "H. pylori" infection and functional dyspepsia, others have not. The discrepancy may stem in part from differences in methodology and lack of adequate consideration of confounding factors such as past history of peptic ulcer disease and socioeconomic status. Controlled trials disagree about whether or not "H. pylori" eradication is beneficial in functional dyspepsia, with roughly half of the trials showing improvement and the other half no improvement. In a recent multicenter U.S. trial that randomized 240 patients to treatment or placebo, and followed patients for 12 months, 28% of treated patients versus 23% of those receiving placebo reported relief of symptoms at the 12-month follow-up. Similarly, recent European trials have not shown significant differences in symptoms after "H. pylori" eradication as compared with controls. Systematic reviews of eradication have been conducted, with varying results. A systematic review in the Annals of Internal Medicine suggested no statistically significant effect, with an odds ratio (OR) for treatment success versus control of 1.29 (95% CI, 0.89–1.89; P = 0.18). Still, no effect was seen after adjusting for heterogeneity and for cure of "H. pylori". In contrast, a Cochrane review found a small but statistically significant effect in curing symptoms ("H. pylori" cure vs placebo, 36% vs 30%, respectively).

There are a number of systemic diseases that may involve dyspepsia, including coronary disease, congestive heart failure, diabetes mellitus, hyperparathyroidism, thyroid disease, and chronic renal disease.

Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists (such as famotidine and ranitidine) are used to slow acid secretion. Once gastric acid is suppressed, symptoms normally improve.

A gastrinoma is a tumor in the pancreas or duodenum that secretes excess of gastrin leading to ulceration in the duodenum, stomach and the small intestine. There is hypersecretion of HCl acid into the duodenum, which causes the ulcers. Excessive HCl acid production also causes hyperperistalsis, and inhibits the activity of lipase, causing severe diarrhea.

It is frequently the source of the gastrin in Zollinger-Ellison syndrome.

It is usually found in the duodenum, although it may arise in the stomach or pancreas. Those occurring in the pancreas have a greater potential for malignancy. Most gastrinomas are found in the gastrinoma triangle; this is bound by the junction of cystic and common bile ducts, junction of the second and third parts of the duodenum, and the junction of the neck and body of the pancreas.

Dietary factors such as spice consumption, were hypothesized to cause ulcers until late in the 20th century, but have been shown to be of relatively minor importance. Caffeine and coffee, also commonly thought to cause or exacerbate ulcers, appear to have little effect. Similarly, while studies have found that alcohol consumption increases risk when associated with "H. pylori" infection, it does not seem to independently increase risk. Even when coupled with "H. pylori" infection, the increase is modest in comparison to the primary risk factor.

The cause of Ménétrier disease is unknown, but it has been associated with HCMV infection in children and "H. pylori "infections in adults. Additionally, increased TGF-α has been noted in the gastric mucosa of patients with the disease.

Gastrinoma causes the following symptoms:

- Hypergastrinemia

- Ulcers of the duodenum, stomach, and small intestine.

- Severe diarrhea.

- Generalized cancer symptoms.

Stress due to serious health problems such as those requiring treatment in an intensive care unit is well described as a cause of peptic ulcers, which are termed stress ulcers.

While chronic life stress was once believed to be the main cause of ulcers, this is no longer the case. It is, however, still occasionally believed to play a role. This may be by increasing the risk in those with other causes such as "H. pylori" or NSAID use.

GERD may lead to Barrett's esophagus, a type of intestinal metaplasia, which is in turn a precursor condition for esophageal cancer. The risk of progression from Barrett's to dysplasia is uncertain, but is estimated at about 20% of cases. Due to the risk of chronic heartburn progressing to Barrett's, EGD every five years is recommended for people with chronic heartburn, or who take drugs for chronic GERD.

GERD is caused by a failure of the lower esophageal sphincter. In healthy patients, the "Angle of His"—the angle at which the esophagus enters the stomach—creates a valve that prevents duodenal bile, enzymes, and stomach acid from traveling back into the esophagus where they can cause burning and inflammation of sensitive esophageal tissue.

Factors that can contribute to GERD:

- Hiatal hernia, which increases the likelihood of GERD due to mechanical and motility factors.

- Obesity: increasing body mass index is associated with more severe GERD. In a large series of 2,000 patients with symptomatic reflux disease, it has been shown that 13% of changes in esophageal acid exposure is attributable to changes in body mass index.

- Zollinger-Ellison syndrome, which can be present with increased gastric acidity due to gastrin production.

- A high blood calcium level, which can increase gastrin production, leading to increased acidity.

- Scleroderma and systemic sclerosis, which can feature esophageal dysmotility.

- The use of medicines such as prednisolone.

- Visceroptosis or Glénard syndrome, in which the stomach has sunk in the abdomen upsetting the motility and acid secretion of the stomach.

GERD has been linked to a variety of respiratory and laryngeal complaints such as laryngitis, chronic cough, pulmonary fibrosis, earache, and asthma, even when not clinically apparent. These atypical manifestations of GERD are commonly referred to as laryngopharyngeal reflux (LPR) or as extraesophageal reflux disease (EERD).

Factors that have been linked with GERD, but not conclusively:

- Obstructive sleep apnea

- Gallstones, which can impede the flow of bile into the duodenum, which can affect the ability to neutralize gastric acid

In 1999, a review of existing studies found that, on average, 40% of GERD patients also had "H. pylori" infection. The eradication of "H. pylori" can lead to an increase in acid secretion, leading to the question of whether "H. pylori"-infected GERD patients are any different than non-infected GERD patients. A double-blind study, reported in 2004, found no clinically significant difference between these two types of patients with regard to the subjective or objective measures of disease severity.

Fundic gland polyps are found in 0.8 to 1.9% of patients who undergo esophagogastroduodenoscopy, and are more common in middle aged women.

The most important consideration in evaluating patients with FGPs is distinguishing between sporadic form (patients without any other gastrointestinal condition, usually in middle age with female prevalence) and syndromic form. This is to ascertain the risk of development of gastric cancer, and to ascertain the risk of concomitant colon cancer.

FGPs can be found in association with the following genetic conditions:

- familial adenomatous polyposis

- attenuated familial adenomatous polyposis syndromes

- Zollinger-Ellison syndrome

- gastric adenocarcinoma associated with proxymal polyposis of the stomach (GAPPS): this condition, described in three families is characterized by development of antral adenomas and FGPs, with early development of severe dysplasia and gastric cancer, in absence of overt intestinal polyposis. This condition has been recently characterized by a point mutation in exon 1B of APC gene.

Sporadic FGPs have been associated with:

- chronic use of proton pump inhibitors (proposed by some authors, denied by others)

- "Helicobacter pylori" infection: there is a reverse relationship between infection and fundic gland polyps, and infection by "H pylori" causes polyps regression.

There is a risk of development of cancer with fundic gland polyposis, but it varies based on the underlying cause of the polyposis. The risk is highest with congenital polyposis syndromes, and is lowest in acquired causes. As a result, it is recommended that patients with multiple fundic polyps have a colonoscopy to evaluate the colon. If there are polyps seen on colonoscopy, genetic testing and testing of family members is recommended.

In the gastric adenocarcinoma associated with proximal polyposis of the stomach (GAPPS), there is a high risk of early development of proximal gastric adenocarcinoma.

It is still unclear which patients would benefit with surveillance gastroscopy, but most physicians recommend endoscopy every one to three years to survey polyps for dysplasia or cancer. In the event of high grade dysplasia, polypectomy, which is done through the endoscopy, or partial gastrectomy may be recommended. One study showed the benefit of NSAID therapy in regression of gastric polyps, but the efficacy of this strategy (given the side effects of NSAIDs) is still dubious.

There is considerable research into the causes, diagnosis and treatments for FGIDs. Diet, microbiome, genetics, neuromuscular function and immunological response all interact. Heightened mast cell activation has been proposed to be a common factor among FGIDs, contributing to visceral hypersensitivity as well as epithelial, neuromuscular, and motility dysfunction.

Exocrine pancreatic insufficiency (EPI) is the inability to properly digest food due to a lack of digestive enzymes made by the pancreas. EPI is found in humans afflicted with cystic fibrosis and Shwachman–Diamond syndrome. It is caused by a progressive loss of the pancreatic cells that make digestive enzymes. Chronic pancreatitis is the most common cause of EPI in humans. Loss of digestive enzymes leads to maldigestion and malabsorption of nutrients.

Functional gastrointestinal disorders (FGID) include a number of separate idiopathic disorders which affect different parts of the gastrointestinal tract and involve visceral hypersensitivity and impaired gastrointestinal motility.

Pancreatitis is inflammation of the pancreas. There are two forms of pancreatitis, which are different in causes and symptoms, and require different treatment:

- Acute pancreatitis is a rapid-onset inflammation of the pancreas, most frequently caused by alcoholism or gallstones.

- Chronic pancreatitis is a long-standing inflammation of the pancreas.

Risk factors for pancreatic adenocarcinoma include:

- Age, gender, and ethnicity; the risk of developing pancreatic cancer increases with age. Most cases occur after age 65, while cases before age 40 are uncommon. The disease is slightly more common in men than women, and in the United States is over 1.5 times more common in African Americans, though incidence in Africa is low.

- Cigarette smoking is the best-established avoidable risk factor for pancreatic cancer, approximately doubling risk among long-term smokers, the risk increasing with the number of cigarettes smoked and the years of smoking. The risk declines slowly after smoking cessation, taking some 20 years to return to almost that of non-smokers.

- Obesity; a BMI greater than 35 increases relative risk by about half.

- Family history; 5–10% of pancreatic cancer cases have an inherited component, where people have a family history of pancreatic cancer. The risk escalates greatly if more than one first-degree relative had the disease, and more modestly if they developed it before the age of 50. Most of the genes involved have not been identified. Hereditary pancreatitis gives a greatly increased lifetime risk of pancreatic cancer of 30–40% to the age of 70. Screening for early pancreatic cancer may be offered to individuals with hereditary pancreatitis on a research basis. Some people may choose to have their pancreas surgically removed to prevent cancer developing in the future.

- Chronic pancreatitis appears to almost triple risk, and as with diabetes, new-onset pancreatitis may be a symptom of a tumor. The risk of pancreatic cancer in individuals with familial pancreatitis is particularly high.

- Diabetes mellitus is a risk factor for pancreatic cancer and (as noted in the Signs and symptoms section) new-onset diabetes may also be an early sign of the disease. People who have been diagnosed with Type 2 diabetes for longer than ten years may have a 50% increased risk, as compared with non-diabetics.

- Specific types of food (as distinct from obesity) have not been clearly shown to increase the risk of pancreatic cancer. Dietary factors for which there is some evidence of slightly increased risk include processed meat, red meat, and meat cooked at very high temperatures (e.g. by frying, broiling or barbecuing).

If there is dysphagia to both solids and liquids, then it is most likely a motility problem. If there is dysphagia initially to solids but progresses to also involve liquids, then it is most likely a mechanical obstruction. Once a distinction has been made between a motility problem and a mechanical obstruction, it is important to note whether the dysphagia is intermittent or progressive. An intermittent motility dysphagia likely can be diffuse esophageal spasm (DES) or nonspecific esophageal motility disorder (NEMD). Progressive motility dysphagia disorders include scleroderma or achalasia with chronic heartburn, regurgitation, respiratory problems, or weight loss. Intermittent mechanical dysphagia is likely to be an esophageal ring. Progressive mechanical dysphagia is most likely due to peptic stricture or esophageal cancer.

Esophageal stricture, or narrowing of the esophagus, is usually a complication of acid reflux, most commonly due to gastroesophageal reflux (GERD). These patients are usually older and have had GERD for a long time. Esophageal stricture can also be due to other causes, such as acid reflux from Zollinger-Ellison syndrome, trauma from a nasogastric tube placement, and chronic acid exposure in patients with poor esophageal motility from scleroderma. Other non-acid related causes of peptic strictures include infectious esophagitis, ingestion of chemical irritant, pill irritation, and radiation. Peptic stricture is a progressive mechanical dysphagia, meaning patients will complain of initial intolerance to solids followed by inability to tolerate liquids. When the diameter of the stricture is less than 12 mm the patient will always have dysphagia, while dysphagia is not seen when the diameter of the stricture is above 30 mm. Symptoms relating to the underlying cause of the stricture usually will also be present.

Esophageal cancer also presents with progressive mechanical dysphagia. Patients usually come with

rapidly progressive dysphagia first with solids then with liquids, weight loss (> 10 kg), and anorexia (loss of appetite). Esophageal cancer usually affects the elderly. Esophageal cancers can be either squamous cell carcinoma or adenocarcinoma. Adenocarcinoma is the most prevalent in the US and is associated with patients with chronic GERD who have developed Barrett's esophagus (intestinal metaplasia of esophageal mucosa). Squamous cell carcinoma is more prevalent in Asia and is associated with tobacco smoking and alcohol use.

Esophageal rings and webs, are actual rings and webs of tissue that may occlude the esophageal lumen.

- "Rings" --- Also known as Schatzki rings from the discoverer, these rings are usually mucosal rings rather than muscular rings, and are located near the gastroesophageal junction at the squamo-columnar junction. Presence of multiple rings may suggest eosinophilic esophagitis. Rings cause intermittent mechanical dysphagia, meaning patients will usually present with transient discomfort and regurgitation while swallowing solids and then liquids, depending on the constriction of the ring.

- "Webs" --- Usually squamous mucosal protrusion into the esophageal lumen, especially anterior cervical esophagus behind the cricoid area. Patients are usually asymptomatic or have intermittent dysphagia. An important association of esophageal webs is to the Plummer-Vinson syndrome in iron deficiency, in which case patients will also have anemia, koilonychia, fatigue, and other symptoms of anemia.

Achalasia is an idiopathic motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation as well as loss of peristalsis in the distal esophagus, which is mostly smooth muscle. Both of these features impair the ability of the esophagus to empty contents into the stomach. Patients usually complain of dysphagia to both solids and liquids. Dysphagia to liquids, in particular, is a characteristic of achalasia. Other symptoms of achalasia include regurgitation, night coughing, chest pain, weight loss, and heartburn. The combination of achalasia, adrenal insufficiency, and alacrima (lack of tear production) in children is known as the triple A (Allgrove) syndrome. In most cases the cause is unknown (idiopathic), but in some regions of the world, achalasia can also be caused by Chagas disease due to infection by "Trypanosoma cruzi".

Scleroderma is a disease characterized by atrophy and sclerosis of the gut wall, most commonly of the distal esophagus (~90%). Consequently, the lower esophageal sphincter cannot close and this can lead to severe gastroesophageal reflux disease (GERD). Patients typically present with progressive dysphagia to both solids and liquids secondary to motility problems or peptic stricture from acid reflux.

Spastic motility disorders include diffuse esophageal spasm (DES), nutcracker esophagus, hypertensive lower esophageal sphincter, and nonspecific spastic esophageal motility disorders (NEMD).

- "DES" can be caused by many factors that affect muscular or neural functions, including acid reflux, stress, hot or cold food, or carbonated drinks. Patients present with intermittent dysphagia, chest pain, or heartburn.

Rare causes of esophageal dysphagia not mentioned above

- Diverticulum

- Aberrant subclavian artery, or (dysphagia lusoria)

- Cervical osteophytes

- Enlarged aorta

- Enlarged left atrium

- Mediastinal tumor

Causes can be:

- Mallory-Weiss syndrome: bleeding tears in the esophagal mucosa, usually caused by prolonged and vigorous retching.

- Irritation or erosion of the lining of the esophagus or stomach

- Vomiting of ingested blood after hemorrhage in the oral cavity, nose or throat

- Vascular malfunctions of the gastrointestinal tract, such as bleeding gastric varices or intestinal varices

- Tumors of the stomach or esophagus.

- Radiation poisoning

- Viral hemorrhagic fevers

- Gastroenteritis

- Gastritis

- Peptic ulcer

- Chronic viral hepatitis

- Intestinal schistosomiasis (caused by the parasite "Schistosoma mansoni")

- History of smoking

- Iatrogenic injury (invasive procedure such as endoscopy or transesophageal echocardiography)

- Zollinger–Ellison syndrome (severe peptic ulcer)

- Atrio-oesophageal fistula

- Yellow fever

Drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer. However, considerable research has failed to firmly establish alcohol consumption as a direct risk factor for pancreatic cancer. Overall, the association is consistently weak and the majority of studies have found no association, with smoking a strong confounding factor. The evidence is stronger for a link with heavy drinking, of at least six drinks per day.

Whilst the association between alcohol abuse and pancreatitis is well established the association between alcohol consumption and pancreatic cancer is less clear. Overall the evidence suggests a slightly increased risk of pancreatic cancer with chronic heavy alcohol consumption but the evidence remains conflicting with a number of studies finding no association., but no increased risk for people consuming up to 30g of alcohol a day

Overall, the association is consistently weak and the majority of studies have found no association. Although drinking alcohol excessively is a major cause of chronic pancreatitis, which in turn predisposes to pancreatic cancer, chronic pancreatitis associated with alcohol consumption is less frequently a precursor for pancreatic cancer than other types of chronic pancreatitis.

Some studies suggest a relationship, the risk increasing with increasing amount of alcohol intake. The risk is greatest in heavy drinkers, mostly on the order of four or more drinks per day. There appears to be no increased risk for people consuming up to 30g of alcohol a day, which is approximately 2 alcoholic beverages/day, so most people who take alcohol do so at a level that "is probably not a risk factor for pancreatic cancer". A pooled analysis concluded, "Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day".

Several studies caution that their findings could be due to confounding factors. Even if a link exists, it "could be due to the contents of some alcoholic beverages" other than the alcohol itself. One Dutch study even found that drinkers of white wine had lower risk.

"About 7 out of 10 cases of chronic pancreatitis are due to long term heavy drinking. Chronic pancreatitis is a known risk factor for cancer of the pancreas. But chronic pancreatitis that is due to alcohol doesn't increase risk as much as other types of chronic pancreatitis. So if there is a link with alcohol and pancreatic cancer risk, it is only very slight."

"Our findings indicate that alcohol drinking at the levels typically consumed by the general population of the United States is probably not a risk factor for pancreatic cancer. Our data suggest, however, that heavy alcohol drinking may be related to pancreatic cancer risk."

"Relative risks of pancreatic cancer increased with the amount of alcohol consumed (Ptrend = 0.11) after adjustment for age, smoking status, and pack-years of smoking."

"Alcoholics had only a modest 40% excess risk of pancreatic cancer … The excess risk for pancreatic cancer among alcoholics is small and could conceivably be attributed to confounding by smoking."

"It was shown that the relative risk of cancer of the pancreas increases with fat and alcohol intakes, … Alcohol may be not directly involved in the aetiology of cancer of the pancreas: its effect could be due to the contents of some alcoholic beverages."

"When compared with data from non-drinkers, the cumulative lifetime consumption of all types of alcohol in grams of ethanol… beer, spirits, red wine and fortified wine was not related to risk. The consumption of white wine was inversely associated with risk…. The uniformly reduced risk estimates for the lifetime number of drinks of white wine were based on small numbers…."

"For the most part, consumption of total alcohol, wine, liquor and beer was not associated with pancreatic cancer."

"Data from these two large cohorts do not support any overall association between coffee intake or alcohol intake and risk of pancreatic cancer."

"Our findings are consistent with a modest increase in risk of pancreatic cancer with consumption of 30 or more grams of alcohol per day."

Drinking may be a cause of earlier onset of colorectal cancer. The evidence that alcohol is a cause of bowel cancer is convincing in men and probable in women.

The National Institutes of Health, the National Cancer Institute, Cancer Research, the American Cancer Society, the Mayo Clinic, and the Colorectal Cancer Coalition, American Society of Clinical Oncology and the Memorial Sloan-Kettering Cancer Center list alcohol as a risk factor.

A WCRF panel report finds the evidence "convincing" that alcoholic drinks increase the risk of colorectal cancer in men at consumption levels above 30 grams of absolute alcohol daily. The National Cancer Institute states, "Heavy alcohol use may also increase the risk of colorectal cancer"

A 2011 meta-analysis found that alcohol consumption was associated with an increased risk of colorectal cancer.