Smoking increases the risk of developing gastric cancer significantly, from 40% increased risk for current smokers to 82% increase for heavy smokers. Gastric cancers due to smoking mostly occur in the upper part of the stomach near the esophagus. Some studies show increased risk with alcohol consumption as well.

Dietary factors are not proven causes, but some foods including smoked foods, salt and salt-rich foods, red meat, processed meat, pickled vegetables, and bracken are associated with a higher risk of stomach cancer. Nitrates and nitrites in cured meats can be converted by certain bacteria, including "H. pylori", into compounds that have been found to cause stomach cancer in animals.

Fresh fruit and vegetable intake, citrus fruit intake, and antioxidant intake are associated with a lower risk of stomach cancer. A Mediterranean diet is associated with lower rates of stomach cancer, as is regular aspirin use.

Obesity is a physical risk factor that has been found to increase the risk of gastric adenocarcinoma by contributing to the development of gastroesophageal reflux disease (GERD). The exact mechanism by which obesity causes GERD is not completely known. Studies hypothesize that increased dietary fat leading to increased pressure on the stomach and the lower esophageal sphincter, due to excess adipose tissue, could play a role, yet no statistically significant data has been collected. However, the risk of gastric cardia adenocarcinoma, with GERD present, has been found to increase more than 2 times for an obese person. There is a correlation between iodine deficiency and gastric cancer.

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.

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

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.

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.

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.

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.

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.

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.

Digestive system neoplasms are tumors which affect the digestive system. Types include:

- esophageal cancer

- gastric cancer

- small intestinal cancer

- colorectal cancer

- anal cancer

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.

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.

The median age at diagnosis is 38 years. Women are at higher risk for developing breast cancer.

Alcohol is a risk factor for breast cancer in women.

A woman drinking an average of two units of alcohol per day has an 8% higher risk of developing breast cancer than a woman who drinks an average of one unit of alcohol per day. A study concluded that for every additional drink regularly consumed per day, the incidence of breast cancer increases by 11 per 1000. Approximately 6% (between 3.2% and 8.8%) of breast cancers reported in the UK each year could be prevented if drinking was reduced to a very low level (i.e. less than 1 unit/week). Moderate to heavy consumption of alcoholic beverages (at least three to four drinks per week) is associated with a 1.3-fold increased risk of the recurrence of breast cancer. Further, consumption of alcohol at any quantity is associated with significantly increased risk of relapse in breast cancer survivors.

Alcohol has been suggested as a risk factor for gall bladder cancer. Evidence suggests that a high intake of alcohol is associated with gall bladder cancer. Men may be at a higher risk of alcohol-related gallbladder cancer than women.

Smoking has been linked to a variety of disorders of the stomach. Tobacco is known to stimulate acid production and impairs production of the protective mucus. This leads to development of ulcers in the majority of smokers.

Chronic stomach problems have also been linked to excess intake of alcohol. It has been shown that alcohol intake can cause stomach ulcer, gastritis and even stomach cancer. Thus, avoidance of smoking and excess alcohol consumption can help prevent the majority of chronic stomach disorders.

One of the most causes of chronic stomach problems is use of medications. Use of aspirin and other non-steroidal anti-inflammatory drugs to treat various pain disorders can damage lining of the stomach and cause ulcers. Other medications like narcotics can interfere with stomach emptying and cause bloating, nausea, or vomiting.

The majority of chronic stomach problems are treated medically. However, there is evidence that a change in life style may help. Even though there is no specific food responsible for causing chronic stomach problems, experts recommend eating a healthy diet which consists of fruits and vegetables. Lean meat should be limited. Moreover, people should keep a diary of foods that cause problems and avoid them.

Worldwide approximately 18% of cancer deaths are related to infectious diseases. This proportion ranges from a high of 25% in Africa to less than 10% in the developed world. Viruses are the usual infectious agents that cause cancer but cancer bacteria and parasites may also play a role.

"Oncovirus"es (viruses that can cause cancer) include human papillomavirus (cervical cancer), Epstein–Barr virus (B-cell lymphoproliferative disease and nasopharyngeal carcinoma), Kaposi's sarcoma herpesvirus (Kaposi's sarcoma and primary effusion lymphomas), hepatitis B and hepatitis C viruses (hepatocellular carcinoma) and human T-cell leukemia virus-1 (T-cell leukemias). Bacterial infection may also increase the risk of cancer, as seen in "Helicobacter pylori"-induced gastric carcinoma. Parasitic infections associated with cancer include "Schistosoma haematobium" (squamous cell carcinoma of the bladder) and the liver flukes, "Opisthorchis viverrini" and "Clonorchis sinensis" (cholangiocarcinoma).

Cancers of the stomach are rare and the incidence has been declining worldwide. Stomach cancers usually occur due to fluctuations in acidity level and may present with vague symptoms of abdominal fullness, weight loss and pain. The actual cause of stomach cancer is not known but has been linked to infection with "Helicobacter pylori", pernicious anemia, Menetriere's disease, and nitrogenous preservatives in food.

Diet, physical inactivity and obesity are related to up to 30–35% of cancer deaths. In the United States excess body weight is associated with the development of many types of cancer and is a factor in 14–20% of cancer deaths. A UK study including data on over 5 million people showed higher body mass index to be related to at least 10 types of cancer and responsible for around 12,000 cases each year in that country. Physical inactivity is believed to contribute to cancer risk, not only through its effect on body weight but also through negative effects on the immune system and endocrine system. More than half of the effect from diet is due to overnutrition (eating too much), rather than from eating too few vegetables or other healthful foods.

Some specific foods are linked to specific cancers. A high-salt diet is linked to gastric cancer. Aflatoxin B1, a frequent food contaminant, causes liver cancer. Betel nut chewing can cause oral cancer. National differences in dietary practices may partly explain differences in cancer incidence. For example, gastric cancer is more common in Japan due to its high-salt diet while colon cancer is more common in the United States. Immigrant cancer profiles develop mirror that of their new country, often within one generation.

Safety regulations from US accreditor the Joint Commission may have unintentionally decreased digital rectal examination and FOBT in hospital settings such as Emergency Departments.

Linitis plastica, also known as Brinton's disease or leather bottle stomach, is a morphological variant of diffuse (or infiltrating) stomach cancer.

Causes of linitis plastica could be lye ingestion or metastatic infiltration of the stomach, particularly breast and lung carcinoma. It is not associated with H. pylori infection or chronic gastritis. The risk factors are undefined, except for rare inherited mutations in E-cadherin, which are found in about 50% of diffuse-type gastric carcinomas.

Conditions such as ulcerative colitis or certain types of relapsing infectious diarrhea can vary in severity over time, and FOBT may assist in assessing the severity of the disease. Medications associated with gastrointestinal bleeding such as Bortezomib are sometimes monitored by FOBT.

In the United States, about 160,000 new cases of colorectal cancer are diagnosed each year. Hereditary nonpolyposis colorectal cancer is responsible for approximately 2 percent to 7 percent of all diagnosed cases of colorectal cancer. The average age of diagnosis of cancer in patients with this syndrome is 44 years old, as compared to 64 years old in people without the syndrome.

Napoleon Bonaparte and many members of his family are thought to have died from this type of cancer, although it is believed by others that he may have died from arsenic poisoning.