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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.
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 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).
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.
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.
Most juvenile polyps are benign, however, malignancy can occur. The cumulative lifetime risk of colorectal cancer is 39% in patients with juvenile polyposis syndrome.
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 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.
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.
Hereditary nonpolyposis colorectal cancer (HNPCC) or Lynch syndrome is an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers including endometrial cancer (second most common), ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin. The increased risk for these cancers is due to inherited mutations that impair DNA mismatch repair. It is a type of cancer syndrome.
Cholangiocarcinoma is a relatively rare form of cancer; each year, approximately 2,000 to 3,000 new cases are diagnosed in the United States, translating into an annual incidence of 1–2 cases per 100,000 people. Autopsy series have reported a prevalence of 0.01% to 0.46%. There is a higher prevalence of cholangiocarcinoma in Asia, which has been attributed to endemic chronic parasitic infestation. The incidence of cholangiocarcinoma increases with age, and the disease is slightly more common in men than in women (possibly due to the higher rate of primary sclerosing cholangitis, a major risk factor, in men). The prevalence of cholangiocarcinoma in patients with primary sclerosing cholangitis may be as high as 30%, based on autopsy studies.
Multiple studies have documented a steady increase in the incidence of intrahepatic cholangiocarcinoma over the past several decades; increases have been seen in North America, Europe, Asia, and Australia. The reasons for the increasing occurrence of cholangiocarcinoma are unclear; improved diagnostic methods may be partially responsible, but the prevalence of potential risk factors for cholangiocarcinoma, such as HIV infection, has also been increasing during this time frame.
Some suggestions for surveillance for cancer include the following:
- Small intestine with small bowel radiography every 2 years,
- Esophagogastroduodenoscopy and colonoscopy every 2 years,
- CT scan or MRI of the pancreas yearly,
- Ultrasound of the pelvis (women) and testes (men) yearly,
- Mammography (women) from age 25 annually livelong, and
- Papanicolaou smear (Pap smear) every year
Follow-up care should be supervised by a physician familiar with Peutz–Jeghers syndrome. Genetic consultation and counseling as well as urological and gynecological consultations are often needed.
People with juvenile polyps may require yearly upper and lower endoscopies with polyp excision and cytology. Their siblings may also need to be screened regularly. Malignant transformation of polyps requires surgical colectomy.
Treatment is variable, both due to its rarity and to its frequently slow-growing nature. Treatment ranges from watchful waiting to debulking and hyperthermic intraperitoneal chemotherapy (HIPEC, also called intraperitoneal hyperthermic chemotherapy, IPHC) with cytoreductive surgery.
Approximately 15,000 new cases of liver and biliary tract carcinoma are diagnosed annually in the United States, with roughly 10% of these cases being Klatskin tumors. Cholangiocarcinoma accounts for approximately 2% of all cancer diagnoses, with an overall incidence of 1.2/100,000 individuals. Two-thirds of cases occur in patients over the age of 65, with a near ten-fold increase in patients over 80 years of age. The incidence is similar in both men and women.
Krukenberg tumors can be seen in all age groups, with an average age of 45 years. In most countries, cancer that has metastasized to the ovary accounts for only about 1 to 2% of ovarian cancer; in the remainder, the ovary itself is the primary cancer site. However, in Japan they represent a much higher percentage of malignancies in the ovary (almost 20%) due to the increased prevalence of gastric cancer.
Krukenberg tumors account for about 15% of metastatic cancers that initially appear to have arisen in the ovary, and as such is less common than metastasis arising from ovarian epithelial and germ-cell tumors.
In people who have had nongynecologic malignancy, approximately 20% of adnexal masses are malignant, and 60% of these are Krukenberg tumors.
Although most patients present without any known risk factors evident, a number of risk factors for the development of cholangiocarcinoma have been described. In the Western world, the most common of these is primary sclerosing cholangitis (PSC), an inflammatory disease of the bile ducts which is closely associated with ulcerative colitis (UC). Epidemiologic studies have suggested that the lifetime risk of developing cholangiocarcinoma for a person with PSC is on the order of 10%–15%, although autopsy series have found rates as high as 30% in this population.
Certain parasitic liver diseases may be risk factors as well. Colonization with the liver flukes "Opisthorchis viverrini" (found in Thailand, Laos PDR, and Vietnam) or "Clonorchis sinensis" (found in China, Taiwan, eastern Russia, Korea, and Vietnam) has been associated with the development of cholangiocarcinoma. Patients with chronic liver disease, whether in the form of viral hepatitis (e.g. hepatitis B or hepatitis C), alcoholic liver disease, or cirrhosis of the liver due to other causes, are at significantly increased risk of cholangiocarcinoma. HIV infection was also identified in one study as a potential risk factor for cholangiocarcinoma, although it was unclear whether HIV itself or other correlated and confounding factors (e.g. hepatitis C infection) were responsible for the association.
Infection with the bacteria "Helicobacter bilis" and "Helicobacter hepaticus" species can cause biliary cancer.
Congenital liver abnormalities, such as Caroli's syndrome (a specific type of five recognized choledochal cysts), have been associated with an approximately 15% lifetime risk of developing cholangiocarcinoma. The rare inherited disorders Lynch syndrome II and biliary papillomatosis have also been found to be associated with cholangiocarcinoma. The presence of gallstones (cholelithiasis) is not clearly associated with cholangiocarcinoma. However, intrahepatic stones (called hepatolithiasis), which are rare in the West but common in parts of Asia, have been strongly associated with cholangiocarcinoma. Exposure to Thorotrast, a form of thorium dioxide which was used as a radiologic contrast medium, has been linked to the development of cholangiocarcinoma as late as 30–40 years after exposure; Thorotrast was banned in the United States in the 1950s due to its carcinogenicity.
Around 75% of cases are caused by alcohol and tobacco use.
Tobacco smoke is one of the main risk factors for head and neck cancer and one of the most carcinogenic compounds in tobacco smoke is acrylonitrile. (See Tobacco smoking). Acrylonitrile appears to indirectly cause DNA damage by increasing oxidative stress, leading to increased levels of 8-oxo-2'-deoxyguanosine (8-oxo-dG) and formamidopyrimidine in DNA (see image). Both 8-oxo-dG and formamidopyrimidine are mutagenic. DNA glycosylase NEIL1 prevents mutagenesis by 8-oxo-dG and removes formamidopyrimidines from DNA.
However, cigarette smokers have a lifetime increased risk for head and neck cancers that is 5- to 25-fold increased over the general population.
The ex-smoker's risk for squamous cell cancer of the head and neck begins to approach the risk in the general population twenty years after smoking cessation. The high prevalence of tobacco and alcohol use worldwide and the high association of these cancers with these substances makes them ideal targets for enhanced cancer prevention.
Smokeless tobacco is cause of oral and pharyngeal cancers (oropharyngeal cancer). Cigar smoking is an important risk factor for oral cancers as well.
Other environmental carcinogens suspected of being potential causes of head and neck cancer include occupational exposures such as nickel refining, exposure to textile fibers, and woodworking. Use of marijuana, especially while younger, is linked to an increase in squamous-cell carcinoma cases while other studies suggest use is not shown to be associated with oral squamous cell carcinoma, or associated with decreased squamous cell carcinoma.
Because of their location, these tumors tend to become symptomatic late in their development and therefore are not usually resectable at the time of presentation. This is variable as, due to obstruction, jaundice may present early and compel the patient to seek help. Complete resection of the tumor offers hope of long-term survival, and of late there has been renewed interest in liver transplantation from deceased donors along with add on therapy. Prognosis remains poor.
Monitoring involves the provision of outpatient colonoscopy, and occasionally upper gastric tract esophagogastroduodenoscopy (EGD, to search for premalignant gastric or duodenal tumors), typically once every 1–3 years, and/or a genetic blood test to definitively confirm or deny susceptibility. A small number of polyps can often be excised (removed) during the procedure, if found, but if there are more severe signs or numbers, in patient surgery may be required.
NCBI states that when an individual is identified as having FAP, or the mutations resulting in FAP: "It is appropriate to evaluate the parents of an affected individual (a) with molecular genetic testing of APC if the disease-causing mutation is known in the proband [person first identified with the condition] or (b) for clinical manifestations of APC-associated polyposis conditions".
Excessive consumption of processed meats and red meat were associated with increased rates of cancer of the head and neck in one study, while consumption of raw and cooked vegetables seemed to be protective.
Vitamin E was not found to prevent the development of leukoplakia, the white plaques that are the precursor for carcinomas of the mucosal surfaces, in adult smokers.
Another study examined a combination of Vitamin E and beta carotene in smokers with early-stage cancer of the oropharynx, and found a worse prognosis in the vitamin users.
Adenomatoid tumor is a benign mesothelial tumor, which arises from the lining of organs. It generally presents in the genital tract, in regions such as the testis and epididymis. It is the second most common extratesticular scrotal mass, after lipoma, and accounts for 30% of these masses. It also has been found in the pancreas.
In the female, it has been found in the body of the uterus and the fallopian tube.
Because Cowden syndrome can be difficult to diagnose, the exact prevalence is unknown; however, it probably occurs in at least 1 in 200,000 people.
A 2010 review of 211 patients (21 from one center, and the remaining 190 from the external literature) studied the risks for cancer and Lhermitte-Duclos disease in Cowden syndrome patients.
The cumulative lifetime (age 70 years) risks were 89% for any cancer diagnosis (95% confidence interval (CI) = 80%,95%), breast cancer [female] 81% (CI = 66%,90%), LDD 32% (CI = 19%,49%), thyroid cancer 21% (CI = 14%,29%), endometrial cancer 19% (CI = 10%,32%) and renal cancer 15% (CI = 6%,32%). A previously unreported increased lifetime risk for colorectal cancer was identified (16%, CI = 8%,24%). Male CS patients had fewer cancers diagnosed than female patients and often had cancers not classically associated with CS.