Little research is conducted on these cancers due to their relative rarity when compared to the more common colorectal cancers. APC-min mice which carry a gene deficiency corresponding to that of humans with FAP also go on to develop small intestinal tumors, though humans do not.

The two major risk factors for esophageal squamous-cell carcinoma are tobacco (smoking or chewing) and alcohol. The combination of tobacco and alcohol has a strong synergistic effect. Some data suggest that about half of all cases are due to tobacco and about one-third to alcohol, while over three-quarters of the cases in men are due to the combination of smoking and heavy drinking. Risks associated with alcohol appear to be linked to its aldehyde metabolite and to mutations in certain related enzymes. Such metabolic variants are relatively common in Asia.

Other relevant risk factors include regular consumption of very hot drinks (over 65 °C)(149 Fahrenheit) and ingestion of caustic substances. High levels of dietary exposure to nitrosamines (chemical compounds found both in tobacco smoke and certain foodstuffs) also appear to be a relevant risk factor. Unfavorable dietary patterns seem to involve exposure to nitrosamines through processed and barbecued meats, pickled vegetables, etc., and a low intake of fresh foods. Other associated factors include nutritional deficiencies, low socioeconomic status, and poor oral hygiene. Chewing betel nut (areca) is an important risk factor in Asia.

Physical trauma may increase the risk. This may include the drinking of very hot drinks.

Cancer of the stomach, also called gastric cancer, is the fourth-most-common type of cancer and the second-highest cause of cancer death globally. Eastern Asia (China, Japan, Korea, Mongolia) is a high-risk area for gastric cancer, and North America, Australia, New Zealand and western and northern Africa are areas with low risk. The most common type of gastric cancer is adenocarcinoma, which causes about 750,000 deaths each year. Important factors that may contribute to the development of gastric cancer include diet, smoking and alcohol consumption, genetic aspects (including a number of heritable syndromes) and infections (for example, "Helicobacter pylori" or Epstein-Barr virus) and pernicious anemia. Chemotherapy improves survival compared to best supportive care, however the optimal regimen is unclear.

Risk factors for small intestine cancer include:

- Crohn's disease

- Celiac disease

- Radiation exposure

- Hereditary gastrointestinal cancer syndromes: familial adenomatous polyposis, hereditary nonpolyposis colorectal cancer, Peutz-Jeghers syndrome

- Males are 25% more likely to develop the disease

Benign tumours and conditions that may be mistaken for cancer of the small bowel:

- Hamartoma

- Tuberculosis

Male predominance is particularly strong in this type of esophageal cancer, which occurs about 7 to 10 times more frequently in men. This imbalance may be related to the characteristics and interactions of other known risk factors, including acid reflux and obesity.

The long-term erosive effects of acid reflux (an extremely common condition, also known as gastroesophageal reflux disease or GERD) have been strongly linked to this type of cancer. Longstanding GERD can induce a change of cell type in the lower portion of the esophagus in response to erosion of its squamous lining. This phenomenon, known as Barrett's esophagus, seems to appear about 20 years later in women than in men, maybe due to hormonal factors. Having symptomatic GERD or bile reflux makes Barrett's esophagus more likely, which in turn raises the risk of further changes that can ultimately lead to adenocarcinoma. The risk of developing adenocarcinoma in the presence of Barrett's esophagus is unclear, and may in the past have been overestimated.

Being obese or overweight both appear to be associated with increased risk. The association with obesity seems to be the strongest of any type of obesity-related cancer, though the reasons for this remain unclear. Abdominal obesity seems to be of particular relevance, given the closeness of its association with this type of cancer, as well as with both GERD and Barrett's esophagus. This type of obesity is characteristic of men. Physiologically, it stimulates GERD and also has other chronic inflammatory effects.

"Helicobacter pylori" infection (a common occurrence thought to have affected over half of the world's population) is not a risk factor for esophageal adenocarcinoma and actually appears to be protective. Despite being a cause of GERD and a risk factor for gastric cancer, the infection seems to be associated with a reduced risk of esophageal adenocarcinoma of as much as 50%. The biological explanation for a protective effect is somewhat unclear. One explanation is that some strains of "H. pylori" reduce stomach acid, thereby reducing damage by GERD. Decreasing rates of "H. pylori" infection in Western populations over recent decades, which have been linked to better hygiene and increased refrigeration of food, could be a factor in the concurrent increase in esophageal adenocarcinoma.

Female hormones may also have a protective effect, as EAC is not only much less common in women but develops later in life, by an average of 20 years. Although studies of many reproductive factors have not produced a clear picture, risk seems to decline for the mother in line with prolonged periods of breastfeeding.

Tobacco smoking increases risk, but the effect in esophageal adenocarcinoma is slight compared to that in squamous cell carcinoma, and alcohol has not been demonstrated to be a cause.

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).

Pancreatic cancer is the fifth-most-common cause of cancer deaths in the United States, and the seventh most common in Europe. In 2008, globally there were 280,000 new cases of pancreatic cancer reported and 265,000 deaths. These cancers are classified as endocrine or nonendocrine tumors. The most common is ductal adenocarcinoma. The most significant risk factors for pancreatic cancer are advanced age (over 60) and smoking. Chronic pancreatitis, diabetes or other conditions may also be involved in their development. Early pancreatic cancer does not tend to result in any symptom, but when a tumor is advanced, a patient may experience severe pain in the upper abdomen, possibly radiating to the back. Another symptom might be jaundice, a yellowing of the skin and eyes.

Pancreatic cancer has a poor prognosis, with a five-year survival rate of less than 5%. By the time the cancer is diagnosed, it is usually at an advanced, inoperable stage. Only one in about fifteen to twenty patients is curative surgery attempted. Pancreatic cancer tends to be aggressive, and it resists radiotherapy and chemotherapy.

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.

The cancerous mass tends to block food from getting to the small intestine. If food cannot get to the intestines, it will cause pain, acid reflux, and weight loss because the food cannot get to where it is supposed to be processed and absorbed by the body.

Patients with duodenal cancer may experience abdominal pain, weight loss, nausea, vomiting, and chronic GI bleeding.

Primary signet ring cell carcinoma of the colon and rectum (PSRCCR) is rare, with a reported incidence of less than 1 percent. It has a poor prognosis because symptoms often develop late and it is usually diagnosed at an advanced stage. Five-year survival rates in previous studies ranged from nine to 30 percent. Average survival was between 20 and 45 months. It tends to affect younger adults with higher likelihood of lymphovascular invasion. It is worth noting that the overall survival rate of patients with SRCC was significantly poorer than that of patients with mucinous or poorly differentiated adenocarcinoma.

In advanced gastric cancers, the prognosis for patients with the SRCCs was significantly worse than for the other histological types, which can be explained by the finding that advanced SRCC gastric cancers have a larger tumor size, more lymph node metastasis, a deeper invasive depth and more Borrmann type 4 lesions than other types.

Duodenal cancer is a cancer in the beginning section of the small intestine. It is relatively rare compared to gastric cancer and colorectal cancer. Its histology is usually adenocarcinoma.

Familial adenomatous polyposis (FAP), Gardner syndrome, Lynch syndrome, Muir–Torre syndrome, celiac disease, Peutz–Jeghers syndrome, Crohn's disease and juvenile polyposis syndrome are risk factors for developing this cancer.

The duodenum is the first part of the small intestine. It is located between the stomach and the jejunum. After foods combine with stomach acid, they descend into the duodenum where they mix with bile from the gallbladder and digestive juices from the pancreas.

Barrett's esophagus is a premalignant condition. Its malignant sequela, oesophagogastric junctional adenocarcinoma, has a mortality rate of over 85%. The risk of developing esophageal adenocarcinoma in people who have Barrett's esophagus has been estimated to be 6–7 per 1000 person-years, however a cohort study of 11,028 patients from Denmark published in 2011 showed an incidence of only 1.2 per 1000 person-years (5.1 per 1000 person-years in patients with dysplasia, 1.0 per 1000 person-years in patients without dysplasia). The relative risk of esophageal adenocarcinoma is approximately 10 in those with Barret's esophagus, compared to the general population. Most patients with esophageal carcinoma survive less than one year.

Primary signet-ring cell carcinoma of the urinary bladder is extremely rare and patient survival is very poor and occurs mainly in men ages 38 to 83. However, one such patient treated with a radical cystectomy followed by combined S-1 and Cisplatin adjuvant chemotherapy did demonstrate promising long-term survival of 90 months.

OGJ adenocarcinoma is a highly mutated and heterogeneous disease. Microsatellite instability (MSI) can be observed and coincides with an elevated number of somatic mutations. Potentially actionable coding mutations have been identified in 67 genes, including those in CR2, HGF, FGFR4 and ESRRB. Numerous genes harbouring somatic coding mutations and copy number changes in the microsatellite stable (MSS) OGJA are also known to be altered with similar predicted functional consequence in other tumour types. TP53, SYNE1, and ARID1A are among the most frequently mutated genes.

Oesophagogastric junctional adenocarcinoma is a cancer of the lower part of the oesophagus, often linked to a Barrett's oesophagus.

The incidence of oesophagogastric junctional adenocarcinoma is rising rapidly in western countries, in contrast to the declining frequency of distal gastric adenocarcinoma. Treatment options for adenocarcinomas involving the oesophagogastric junction are limited and the overall prognosis is extremely poor.

The incidence in the United States among Caucasian men is eight times the rate among Caucasian women and five times greater than African American men. Overall, the male to female ratio of Barrett's esophagus is 10:1. Several studies have estimated the prevalence of Barrett's esophagus in the general population to be 1.3% to 1.6% in two European populations (Italian and Swedish), and 3.6% in a Korean population.

Examples of cancers where adenocarcinomas are a common form:

- esophageal cancer; most cases in the developed world are adenocarcinomas.

- pancreas; over 80% of pancreatic cancers are ductal adenocarcinomas.

- prostate cancer is nearly always adenocarcinoma

- cervical cancer: most is squamous cell cancer, but 10–15% of cervical cancers are adenocarcinomas

- stomach cancer

Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, or both. Adenocarcinomas are part of the larger grouping of carcinomas, but are also sometimes called by more precise terms omitting the word, where these exist. Thus invasive ductal carcinoma, the most common form of breast cancer, is adenocarcinoma but does not use the term in its name—however, esophageal adenocarcinoma does to distinguish it from the other common type of esophageal cancer, esophageal squamous cell carcinoma. Several of the most common forms of cancer are adenocarcinomas, and the various sorts of adenocarcinoma vary greatly in all their aspects, so that few useful generalizations can be made about them.

In the most specific usage (narrowest sense), the glandular origin or traits are exocrine; endocrine gland tumors, such as a VIPoma, an insulinoma, or a pheochromocytoma, are typically not referred to as adenocarcinomas but rather are often called neuroendocrine tumors. Epithelial tissue sometimes includes, but is not limited to, the surface layer of skin, glands, and a variety of other tissue that lines the cavities and organs of the body. Epithelial tissue can be derived embryologically from any of the germ layers (ectoderm, endoderm, or mesoderm). To be classified as adenocarcinoma, the cells do not necessarily need to be part of a gland, as long as they have secretory properties. Adenocarcinoma is the malignant counterpart to adenoma, which is the benign form of such tumors. Sometimes adenomas transform into adenocarcinomas, but most do not.

Well differentiated adenocarcinomas tend to resemble the glandular tissue that they are derived from, while poorly differentiated adenocarcinomas may not. By staining the cells from a biopsy, a pathologist can determine whether the tumor is an adenocarcinoma or some other type of cancer. Adenocarcinomas can arise in many tissues of the body owing to the ubiquitous nature of glands within the body, and, more fundamentally, to the potency of epithelial cells. While each gland may not be secreting the same substance, as long as there is an exocrine function to the cell, it is considered glandular and its malignant form is therefore named adenocarcinoma.

The incidence of the mutation is between 1 in 10,000 and 1 in 15,000 births.

By age 35 years, 95% of individuals with FAP (>100 adenomas) have polyps. Without colectomy, colon cancer is virtually inevitable. The mean age of colon cancer in untreated individuals is 39 years (range 34–43 years).

Attentuated FAP arises when APC is defective but still somewhat functional. As a result, it retains part of its ability to suppress polyps. Therefore, attenuated FAP manifests as colorectal cancer unusually late (age 40–70, average=55), and typically with few, or at least far fewer polyps (typically 30), than the more usual version of FAP, at an age when FAP is no longer considered much of a likelihood or risk according to usual FAP epidemiology.

Most patients will develop flat, brownish spots (melanotic macules) on the skin, especially on the lips and oral mucosa, during the first year of life, and a patient’s first bowel obstruction due to intussusception usually occurs between the ages of six and 18 years. The cumulative lifetime cancer risk begins to rise in middle age. Cumulative risks by age 70 for all cancers, gastrointestinal (GI) cancers, and pancreatic cancer are 85%, 57%, and 11%, respectively.

A 2011 Dutch study followed 133 patients for 14 years. The cumulative risk for cancer was 40% and 76% at ages 40 and 70, respectively. 42 (32%) of the patients died during the study, of which 28 (67%) were cancer related. They died at a median age of 45. Mortality was increased compared with the general population.

A family with sinonasal polyposis were followed up for 28 years. Two cases of sinonasal type adenocarcinoma developed. This is a rare cancer. This report suggested that follow up of sinus polyps in this syndrome may be indicated.

In most series, LCLC's comprise between 5% and 10% of all lung cancers.

According to the Nurses' Health Study, the risk of large cell lung carcinoma increases with a previous history of tobacco smoking, with a previous smoking duration of 30 to 40 years giving a relative risk of approximately 2.3 compared to never-smokers, and a duration of more than 40 years giving a relative risk of approximately 3.6.

Another study concluded that cigarette smoking is the predominant cause of large cell lung cancer. It estimated that the odds ratio associated with smoking two or more packs/day for current smokers is 37.0 in men and 72.9 in women.

Adenocarcinoma of the lung (pulmonary adenocarcinoma) is a common histological form of lung cancer that contains certain distinct malignant tissue architectural, cytological, or molecular features, including gland and/or duct formation and/or production of significant amounts of mucus.

The overall incidence is 0.5 to 1 cases per 100,000 people per year. It is slightly more common in women than men (male:female ratio = 9:11). The median age at presentation is typically about 50 years with a range of 20–25 years.

Accurate incidence statistics on MCACL are unavailable. It is a very rare tumor, with only a few dozen cases reported in the literature to date.

In the few cases described in the literature to date, the male-to-female ratio is approximately unity, and right lung lesions occurred twice as commonly as left lung lesions. Approximately 2/3 of cases have been associated with tobacco smoking. Cases have been reported in patients as young as 29.

Acinar cell carcinoma of the pancreas, also acinar cell carcinoma, is a rare malignant exocrine tumour of the pancreas. It represents 5% of all exocrine tumours of the pancreas, making it the second most common type of pancreatic cancer. It is abbreviated ACC. It typically has a guarded prognosis.