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Genetic Testing and Management of Hereditary Gastrointestinal Cancer Syndromes
- A family history of cancer and premalignant GI conditions that provides sufficient information to develop a preliminary determination of the risk of a familial predisposition to cancer should be obtained for all patients being evaluated in outpatient gastroenterology and endoscopy practices.
- Essential elements of a family history include presence and type of cancer diagnoses in first- and second-degree relatives, and presence and (ideally) type of polyps in first-degree relatives; age and lineage should be noted for each diagnosis.
- All newly diagnosed colorectal cancers (CRCs) should be evaluated for mismatch repair deficiency.
- Analysis may be done by immunohistochemical testing for the MLH1/MSH2/MSH6/PMS2 proteins and/or testing for microsatellite instability. Tumors that demonstrate loss of MLH1 should undergo BRAF testing or analysis for MLH1 promoter hypermethylation.
- Individuals who have a personal history of a tumor showing evidence of mismatch repair deficiency (and no demonstrated BRAF mutation or hypermethylation of MLH1), a known family mutation associated with LS, or a risk of ≥5% chance of LS based on risk prediction models should undergo genetic evaluation for LS.
- Genetic testing of patients with suspected LS should include germline mutation genetic testing for the MLH1, MSH2, MSH6, PMS2, and/or EPCAM genes or the altered gene(s) indicated by immunohistochemical (IHC) testing.
- Individuals who have a personal history of >10 cumulative colorectal adenomas, a family history of one of the adenomatous polyposis syndromes, or a history of adenomas and FAP-type extracolonic manifestations (duodenal/ampullary adenomas, desmoid tumors (abdominal>peripheral), papillary thyroid cancer, congenital hypertrophy of the retinal pigment epithelium ((CHRPE), epidermal cysts, osteomas) should undergo assessment for the adenomatous polyposis syndromes.
- Genetic testing of patients with suspected adenomatous polyposis syndromes should include APC and MUTYH gene mutation analysis.
- Individuals with perioral or buccal pigmentation and/or two or more histologically characteristic gastrointestinal hamartomatous polyp(s) or a family history of PJS should be evaluated for PJS.
- Genetic evaluation of a patient with possible PJS should include testing for STK11 mutations.
- Individuals with five or more juvenile polyps in the colorectum or any juvenile polyps in other parts of the GI tract should undergo evaluation for JPS.
- Genetic evaluation of a patient with possible JPS should include testing for SMAD4 and BMPR1A mutations.
- Individuals with multiple gastrointestinal hamartomas or ganglioneuromas should be evaluated for Cowden syndrome and related conditions.
- Genetic evaluation of a patient with possible Cowden syndrome should include testing for PTEN mutations.
- Individuals who meet at least one of the following criteria have the clinical diagnosis of serrated polyposis syndrome (SPS):
- at least 5 serrated polyps proximal to the sigmoid colon with ≥2 of these being >10 mm;
- any number of serrated polyps proximal to the sigmoid colon in an individual who has a first-degree relative (FDR) with serrated polyposis; and
- >20 serrated polyps of any size, distributed throughout the large intestine.
- A clear genetic etiology has not yet been defined for SPS, and therefore genetic testing is currently not routinely recommended for SPS patients; testing for MUTYH mutations may be considered for SPS patients with concurrent adenomas and/or a family history of adenomas.
- Individuals should be considered to be at risk for familial pancreatic adenocarcinoma if they
- have a known genetic syndrome associated with pancreatic cancer, including hereditary breast-ovarian cancer syndrome, familial atypical multiple melanoma and mole syndrome (FAMMM), PJS, LS, or other gene mutations associated with an increased risk of pancreatic adenocarcinoma; or
- have two relatives with pancreatic adenocarcinoma, where one is a FDR;
- have three or more relatives with pancreatic cancer; or
- have a history of hereditary pancreatitis.
- Genetic testing of patients with suspected familial pancreatic cancer should include analysis of BRCA1/2, CDKN2A, PALB2, and ATM. Evaluation for PJS, LS, and hereditary pancreatitis-associated genes should be considered if other component personal and/or family history criteria are met for the syndrome.
- Individuals with
- ≥2 cases of diffuse gastric cancer, with at least one diagnosed at <50 years;
- ≥3 cases of documented diffuse cancer in first- or second degree relatives independent of age of onset;
- diffuse gastric cancer diagnosed at <40 years;
- a personal or family history of diffuse gastric cancer and lobular breast cancer with one diagnosed at <50 years should be evaluated for HDGC.
- Genetic testing of individuals who fulfill HDGC clinical criteria should include analysis of CDH1 mutations.
- In individuals at risk for or affected with LS, screening for colorectal cancer by colonoscopy should be performed at least every 2 years, beginning between ages 20 and 25 years. Annual colonoscopy should be considered in confirmed mutation carriers.
- Colectomy with ileorectal anastomosis (IRA) is the preferred treatment of patients affected with LS with colon cancer or colonic neoplasia not controllable by endoscopy. Segmental colectomy is an option in patients unsuitable for total colectomy if regular postoperative surveillance is conducted.
- Hysterectomy and bilateral salpingo-oophorectomy should be offered to women who are known LS mutation carriers and who have finished child bearing, optimally at age 40–45 years.
- Screening for endometrial cancer and ovarian cancer should be offered to women at risk for or affected with LS by endometrial biopsy and transvaginal ultrasound annually, starting at age 30 to 35 years before undergoing surgery or if surgery is deferred.
- Screening for gastric and duodenal cancer can be considered in individuals at risk for or affected with LS by baseline esophagogastroduodenoscopy (EGD) with gastric biopsy at age 30–35 years, and treatment of H.pylori infection when found. Data for ongoing regular surveillance are limited, but ongoing surveillance every 3–5 years may be considered if there is a family history of gastric or duodenal cancer.
- Screening beyond population-based recommendations for cancers of the urinary tract, pancreas, prostate, and breast is not recommended unless there is a family history of the specific cancers.
- Although data suggest that daily aspirin may decrease the risk of colorectal and extracolonic cancer in LS, currently the evidence is not sufficiently robust or mature to make a recommendation for its standard use.
- In individuals at risk for or affected with the classic AP syndromes, screening for colorectal cancer by annual colonoscopy or flexible sigmoidoscopy should be performed, beginning at puberty. In families with attenuated familial adenomatous polyposis (AFAP) or MAP, surveillance should be by colonoscopy.
- Absolute indications for immediate colectomy in FAP, AFAP, and MAP include: documented or suspected cancer or significant symptoms. Relative indications for surgery include the presence of multiple adenomas >6 mm, a significant increase in adenoma number, and inability to adequately survey the colon because of multiple diminutive polyps.
- Screening for gastric and proximal small bowel tumors should be done using upper endoscopy including duodenoscopy starting at age 25–30 years. Surveillance should be repeated every 0.5–4 years depending on Spigelman stage of duodenal polyposis: 0=4 years; I=2–3 years, II=1–3 years, III=6–12 months, and IV=surgical evaluation. Examination of the stomach should include random sampling of fundic gland polyps. Low-grade dysplasia is common in fundic gland polyps, and surgery should be reserved for high-grade dysplasia or cancer.
- Annual thyroid screening by ultrasound should be recommended to individuals affected with FAP, MAP, and attenuated polyposis.
- Biannual screening should be offered to affected infants until age 7 years with α-fetoprotein and ultrasounds.
- Postsurgical surveillance should include yearly endoscopy of rectum or ileal pouch, and examination of an ileostomy every 2 years.
- Surveillance in affected or at-risk PJS patients should include monitoring for colon, stomach, small bowel, pancreas, breast, ovary, uterus, cervix, and testes cancers. Risk for lung cancer is increased, but no specific screening has been recommended. It would seem wise to consider annual chest radiograph or chest computed tomography (CT) in smokers.
- Surveillance of the gastrointestinal (GI) tract in affected or at-risk JPS patients should include screening for colon, stomach, and small bowel cancers.
- Colectomy and ileorectal anastomosis or proctocolectomy and ileal pouch-anal anastomosis is indicated for polyp-related symptoms, or when the polyps cannot be managed endoscopically.
- Cardiovascular examination for and evaluation for hereditary hemorrhagic telangiectasia should be considered for SMAD4 mutation carriers.
- Surveillance in affected or at-risk Cowden syndrome patients should include screening for colon, stomach, small bowel, thyroid, breast, uterine, kidney, and skin (melanoma) cancers.
- Patients with serrated polyposis should undergo colonoscopies every 1–3 years with attempted removal of all polyps >5 mm diameter.
- Indications for surgery for serrated polyposis syndrome (SPS) include an inability to control the growth of serrated polyps, or the development of cancer. Colectomy and ileorectal anastomosis is a reasonable option given the risks of metachronous neoplasia.
- There is no evidence to support extracolonic cancer surveillance for SPS at this time. Screening recommendations for family members are currently unclear pending further data and should be individualized based on results of baseline evaluations in family members.
- Surveillance of individuals with a genetic predisposition for pancreatic adenocarcinoma should ideally be performed in experienced centers utilizing a multidisciplinary approach and under research conditions. These individuals should be known mutation carriers from hereditary syndromes associated with increased risk of pancreatic cancer (Peutz-Jeghers, hereditary pancreatitis, familial atypical multiple melanoma and mole syndrome (FAMMM)) or members of familial pancreatic cancer kindreds with a pancreatic cancer affected first-degree relative. Because of a lower relative risk for pancreatic adenocarcinoma development in BRCA1, BRCA2, PALB2, ATM, and LS families, surveillance should be limited to mutation carriers with a first or second-degree relative affected with pancreatic cancer.
- Surveillance for pancreatic cancer should be with endoscopic ultrasound (EUS) and/or magnetic resonance imaging (MRI) of the pancreas annually starting at age 50 years, or 10 years younger than the earliest age of pancreatic cancer in the family. Patients with PJS should start surveillance at age 35 years.
- Because of the increased risk for pancreatic cancer development when compared with a pancreatic cyst in the sporadic setting, cystic lesion(s) of the pancreas detected during surveillance of a hereditary pancreatic cancer-prone family member requires evaluation by centers experienced in the care of these high-risk individuals. Determining when surgery is required for pancreatic lesions is difficult and is best individualized after multidisciplinary assessment.
- Management for patients with hereditary diffuse gastric cancer should include:
- prophylactic gastrectomy after age 20 years (>80% risk by age 80);
- breast cancer surveillance in women beginning at age 35 years with annual mammography and breast MRI and clinical breast examination every 6 months; and
- colonoscopy beginning at age 40 years for families that include colon cancer.
- At least three relatives with colorectal cancer (CRC); all of the following criteria should be present:
- One should be a first-degree relative of the other two;
- At least two successive generations must be affected;
- At least one of the relatives with CRC must have received the diagnosis before the age of 50 years;
- Familial adenomatous polyposis should be excluded;
- Tumors should be verified by pathologic examination.
- At least three relatives must have a cancer associated with Lynch syndrome (colorectal, cancer of the endometrium, small bowel, ureter, or renal-pelvis); all of the following criteria should be present:
- One must be a first-degree relative of the other two;
- At least two successive generations must be affected;
- At least one relative with cancer associated with Lynch syndrome (LS) should be diagnosed before age 50;
- Familial adenomatous polyposis should be excluded in the CRC case(s) (if any);
- Tumors should be verified whenever possible.
- Tumors from individuals should be tested for microsatellite instability (MSI) in the following situations:
- CRC diagnosed in a patient who is younger than 50 years of age
- Presence of synchronous, or metachronous, colorectal or other LS-related tumors, regardless of age
- CRC with MSI-high histology diagnosed in a patient who is younger than 60 years of age
- CRC diagnosed in a patient with one or more first-degree relatives with an LS-related cancer, with one of the cancers being diagnosed under age 50 years
- CRC diagnosed in a patient with two or more first- or second-degree relatives with LS-related cancer regardless of age
- Do you have a first-degree relative (mother, father, brother, sister, or child) with any of the following conditions diagnosed before age 50?
- Colon or rectal cancer
- Cancer of the uterus, ovary, stomach, small intestine, urinary tract (kidney, ureter, bladder), bile ducts, pancreas, or brain
- Have you had any of the following conditions diagnosed before age 50 years?
- Colon or rectal cancer
- Colon or rectal polyps
- Do you have three or more relatives with a history of colon or rectal cancer? (This includes parents, brothers, sisters, children, grandparents, aunts, uncles, and cousins)
- Lynch syndrome-related cancers include colorectal, endometrial, gastric, ovarian, pancreas, ureter and renal pelvis, biliary tract, brain (usually glioblastoma), small intestinal cancers, as well as sebaceous gland adenomas and keratoacanthomas.
- Presence of tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucionous/signet-ring differentiation, or medullary growth pattern.
- Information on the specific genetic mutation(s) or genomic variant(s) being tested, including whether or not the range of risk associated with the variant will affect medical care.
- Implications of positive and negative results.
- Possibility that the test will not be informative.
- Options for risk estimation without genetic or genomic testing.
- Risk of passing a genetic variant to children.
- Technical accuracy of the test, including, where required by law, licensure of the testing laboratory
- Fees involved in testing and counseling and, for direct to consumer testing, whether the counselor is employed by the testing company.
- Psychological implications of test results (benefits and risks).
- Risks and protections against genetic discrimination by employers or insurers.
- Confidentiality issues, including, for direct-to-consumer testing companies, polices related to privacy and data security.
- Possible use of DNA testing samples in future research.
- Options and limitations of medical surveillance and strategies for prevention after genetic or genomic testing.
- Importance of sharing genetic and genomic test results with at-risk relatives so that they may benefit from this information.
- Plans for follow-up after testing.
Spigelman Duodenal adenomatosis staging system
Polyps 1 Point 2 Points 3 Points
Number <4 5–20 >20
Size 0-4mm 5-10mm >10
Histology Tubular Tubulovillous Villous
Dysplasia Mild Moderate Severe
Recommended duodenal surveillance frequency
Spigelman stage Total points Frequency of surveillance
0 0 Every 4 years
I ≤4 Every 2–3 years
II 5-6 Every 1–3 years
III 7-8 Every 6–12 months
IV 9-12 Expert surveillance every 3- 6 months
Surgical evaluation, complete mucosectomy or duodenectomy or Whipple procedure if
duodenal papilla is involved
Guidelines for Follow-up of Colorectal Cancer Patients
- Which evaluations (eg, colonoscopy, computed tomography [CT], carcinoembryonic antigen [CEA], liver function, complete blood count [CBC], chest x-ray, history, and physical examination) should be performed for surveillance for recurrence of cancer?
- What is a reasonable frequency of these evaluations for surveillance?
- Which symptoms and/or signs potentially signify a recurrence of CRC and warrant investigation?
- What are the common and/or significant long-term and late effects of CRC treatment?
- On what secondary prevention measures should CRC survivors be counseled?
- The target population for these guidelines included CRC survivors (adult patients who have completed primary treatment for stage II or III CRC and who are without evidence of disease). Whether these recommendations are extrapolated to stage I patients or a patient with metastatic CRC who underwent metastatectomy and is currently without evidence of disease, is left to the discretion of the health care provider.
- The target audience for these guidelines include clinicians (eg, medical oncologist, radiation oncologist, surgeon, advanced practice nurse, physician assistant, primary care provider [family physician, nurse practitioner, family practice nurse]) involved in the delivery of care for CRC patients, families of patients who have survived CRC, and health care organizations and system leaders responsible for offering, monitoring, or providing resources for CRC survivorship protocols.
- Surveillance should be guided by presumed risk of recurrence and functional status of patient where early detection would lead to aggressive treatment including surgery. It is especially important in the first 2 to 4 years, when the risk of recurrence is the greatest.
- A medical history, physical examination, and CEA testing should be performed every 3 to 6 months for 5 years. The frequency of visits and testing should be driven by the data showing that 80% of recurrences occur in the first 2 to 2.5 years from date of surgery and 95% occur by 5 years. Patients at a higher risk of recurrence should be considered for testing in the more frequent end of the range.
- Abdominal and chest imaging using a CT scan is recommended annually for 3 years. For high-risk patients, it is reasonable to consider imaging every 6 to 12 months for the first 3 years. Outside of a clinical trial, PET scans are not recommended for surveillance.
- For patients with rectal cancer, a pelvic CT is also recommended. Clinician judgment, considering risk status, should be used to determine the frequency of pelvic scans (eg, annually for 3 to 5 years). For those patients who have not received pelvic radiation, a rectosigmoidoscopy should be performed every 6 months for 2 to 5 years.
- A surveillance colonoscopy should be performed approximately 1 year after the initial surgery. The frequency of subsequent surveillance colonoscopies should be dictated by the findings of the previous one, but they generally should be performed every 5 years if the findings of the previous one are normal. If a complete colonoscopy was not performed before diagnosis, a colonoscopy should be done as soon as reasonable after completion of adjuvant therapy and not necessarily at the 1-year time point.
- Any new and persistent or worsening symptoms warrant the consideration of a recurrence.
- Despite the lack of high-quality evidence on secondary prevention in CRC survivors, it is reasonable to counsel patients on maintaining a healthy body weight, being physically active, and eating a healthy diet.
- A treatment plan from the specialist should be sent to the patient’s other providers, particularly the primary care physician, and it should have clear directions on appropriate follow-up.
- If a patient is not a surgical candidate or a candidate for systemic therapy because of severe comorbid conditions, surveillance tests should not be performed.
The ASCO Panel wants to highlight that the recommendations are primarily for patients with stage II or III cancer. There are insufficient data to provide guidance for follow-up for stage I patients or patients with resected metastatic disease with no evidence of disease. The ASCO Panel emphasizes that surveillance tests should only be performed in patients in whom the results will change treatment decisions. If a patient is not a surgical candidate or a candidate for systemic therapy because of severe co-morbid conditions, surveillance tests should not be performed.
Lynch Syndrome (Hereditary Nonpolyposis Colorectal Cancer)
Guidelines for the management of Lynch syndrome (HNPCC) are summarized and adapted from recommendations of US and European experts.
Introduction
Although a family history of colon cancer increases an individual’s risk of colon cancer by two-to-threefold, some families have a very significantly increased cancer risk due to proven genetic mutations. While most patients with a family history of colon cancer may be surveilled with a 5-yearly screening protocol (typically starting at age 40 or 10 years before the index relative’s disease), these special families require a much closer surveillance interval and consideration for multiple other cancers. Two major genetic conditions to be considered are Familial Adenomatous Polyposis (FAP) and Lynch Syndrome (LS).
Lynch syndrome (LS), also called hereditary nonpolyposis colorectal cancer (HNPCC), is an autosomal dominant disorder caused by a germline mutation in one of several DNA mismatch repair (MMR) genes. It is the most common inherited colon cancer susceptibility syndrome, accounting for approximately 1–3% of all colorectal cancers (CRC). The name HNPCC can be misleading as this disorder predisposes to multiple cancers:
- colon cancer (risk ~25–70%)
- endometrial cancer (EC) (risk ~30–70%)
- stomach cancer
- ovarian cancer
- bladder cancer
- upper urologic tract cancers (renal pelvis, ureter)
- small bowel cancer
- biliary/pancreatic cancer
- skin cancer (sebaceous adenomas, carcinomas and keratoacanthomas)
- brain cancers
- possible prostate cancer
The frequency of extracolonic cancers in LS varied from 2-20%. LS is responsible for about 2 percent of all endometrial cancers. There is some debate whether even breast cancers may be part of the LS.
Clinical features/genetics
Early age of onset and multiplicity of cancers have been considered hallmarks of LS. 7-10% of LS patients have more than one cancer at diagnosis (i.e. synchronous CRC), metachronous CRC are also common (developing another CRC after an initial resection if a subtotal colectomy is not performed). The overall CRC rate appears moderately higher for men than women. LS is an autosomal dominant disorder caused by a defect in one of the mismatch repair (MMR) genes: MLH1, MSH2, MSH6 or PMS2.
- MLH1 (MutL homolog 1), located on chromosome 3p21
- MSH2 (MutS homolog 2), located on chromosome 2p16
- MSH6 (MutS homolog 6), located on chromosome 2p16
- PMS1 and PMS2 (postmeiotic segregation 1 and 2), located on chromosomes 2q31 and 7p22, respectively
These gene defects lead to a loss of MMR function and result in an accumulation of microsatellite mutations. These microsatellite instabilities (MSI) refer to an expansion or contraction of short repetitive DNA sequences (microsatellites) due to loss of DNA mismatch repair. These mutations lead to alterations in cancer related genes, likely driving the process of carcinogenesis. The overall cancer risk (~80%) and the colorectal cancer risk (50-70%) are similar in MLH1 and MSH2 families, but the risks of endometrial and other extracolonic cancers appear to be substantially higher in MSH2 families. Families with MSH6 and possibly PMS2 mutations appear to have an attenuated cancer phenotype (later age of cancer diagnosis and lower penetrance) compared to MLH1 and MSH2 families. Homozygous or compound heterozygous carriers of MLH1, MSH2, MSH6, or PMS2 often develop hematologic and brain malignancies during childhood. Most had a family history of LS on both the maternal and paternal sides of their families.
The term Lynch syndrome should only be used in individuals and families known to have a detectable MMR gene mutation. Individuals without gene testing are no longer labeled as having LS even if Amsterdam criteria are met.
Amsterdam criteria have been used to identify patients and families at risk for LS.
- “3-2-1 rule”: 3 affected members, 2 generations, 1 under age 50 – (3 or more relatives with LS-associated cancers (colorectal, endometrial or small bowel cancers, transitional cell carcinoma of the ureter or renal pelvis), one being a first degree relative of the other two, involvement of at least two generations, one or more cancers diagnosed before the age of 50).
Bethesda guidelines identify individuals with LS-associated cancers who should be tested for microsatellite instability (and MMR gene testing in those with MSI-H tumors). LS is suggested in colon cancer patients if certain characeristics are present such as young age and strong familial clustering of colon cancer. LS cancers appear to evolve from adenomas, tend to be larger, flatter, more proximal, and have high-grade dysplasia and/or villous histology, with a more rapid progression of the adenoma-carcinoma sequence. Cancers are more proximal, poorly differentiated , and often mucinous. Histologic features such as tumor-infiltrating lymphocytes, Crohn’s-like lymphocytic reaction, mucin/signet ring cell differentiation, and medullary growth pattern can be used to select patients who might have LS. These patients should have their colon cancers tested for microsatellite instability (if positive, proceed with germline MMR gene testing).
- Benefits of genetic testing in high risk families including a more accurate diagnosis and risk assessment as well as better implementation of surveillance protocols.
- Family members who do not need intensive surveillance can also be better identified; these members without high risk mutations carry a similar cancer risk as the general population and do not need heightened surveillance.
- Once high risk individuals are identified, germline testing is recommended in the affected individual. If possible, gene testing should be performed on the family member most likely to have the syndrome (i.e. the youngest family member with colorectal cancer).
- Practitioners should ensure that patients received appropriate counseling. Informed consent should include a general description of the test, the disorder to be tested for, the meaning of positive and negative results, and the level of certainty that a positive or negative test is a predictor of disease. Counseling about benefits of early cancer detection and prevention or treatment modalities should be offered.
Muir-Torre and Turcot Syndrome
Two variants of Lynch syndrome had been considered distinct entities: Muir-Torre (Lynch syndrome with associated sebaceous tumors, cutaneous keratoacanthomas, and visceral carcinomas) and Turcot syndrome (Lynch syndrome with associated brain tumors, typically gliomas). These families with extracolonic cancers (brain, sebaceous tumors, skin acanthomas, and visceral carcinomas) are considered part of the spectrum of LS.
General cancer surveillance in LS
Analysis of all causes of cancer deaths in LS revealed that 61% of cancer deaths were associated with non-CRC non-EC cancers. Testing of all patients (<70 years) with CRC or EC for loss of MMR function by means of MSI or immunohistochemistry has been recommended, as testing remains one of the first steps to identify individuals who are at increased risk for LS.
CRC surveillance
- Colorectal surveillance by regular colonoscopy is the only surveillance protocol proven to be effective. Due to advanced CRC in LS detected between 2 and 3 years after surveillance colonoscopy, an interval of 1-2 years is recommended. Colonoscopy is recommended to begin at age 20-25, or 10 years prior to the earliest age of colon cancer in the family (whichever comes first). In families with MSH6 mutations, surveillance starts at age 30, since onset of colon cancer is seen later in these families. Since the risk of developing a second CRC after partial colectomy for primary CRC is estimated at approximately 16% after 10 years (despite following close surveillance), more extensive surgery(total or subtotal colectomy) for the primary CRC might be considered.
EC surveillance
- Although the value of surveillance for EC is unclear, routine annual surveillance (gynecological exam, transvaginal ultrasound, biopsy starting at age of 35–40, or 5-10 years earlier than the earliest age of diagnosis of these cancers) may lead to early detection of premalignant disease or cancers and should be offered to mutation carriers. A CA 125 may be of benefit. Hysterectomy and bilateral oophorectomy prevents the development of endometrial and ovarian cancer and could be discussed with patients after the age of 35-40, who have completed their family planning. If CRC surgery is scheduled, prophylactic hysterectomy and bilateral oophorectomy at the same time should be considered.
Gastric cancer surveillance
- The cumulative risk of developing gastric cancer in LS by the age of 70 is approximately 5%. Most gastric cancers in LS are of the intestinal type, so regular EGDs may be of benefit. Given the relatively low risk of gastric cancer and the lack of established surveillance benefit, European guidelines advise against surveillance for gastric cancer.
Small bowel cancer surveillance
- The risk of developing small bowel cancer in carriers of an MLH1 or MSH2 mutation is approximately 5%. Currently European guidelines advise against surveillance for small bowel cancer, but inspection of the distal duodenum during upper endoscopy and ileum during colonoscopy (if performed) is recommended. Evaluation of the small bowel in patients with unexplained abdominal complaints or iron deficiency anemia has been suggested.
Urinary tract cancer surveillance
- Increased risks of bladder cancer as well as urothelial cancers of the upper urinary tract in LS have been demonstrated. Given lack of evidence of surveillance benefits for urinary tract cancer, European guidelines advise against surveillance for urinary tract cancer in LS.
Prostate cancer surveillance
- European guidelines do not recommend increased surveillance for prostate cancer in LS families outside of appropriate research studies.
Pancreatic cancer surveillance
- Recent studies have revealed an increased risk of developing pancreatic cancer in LS. Still, the benefit of surveillance for pancreatic cancer in high-risk groups is unknown and European guidelines advise against surveillance for this cancer in LS families.
Breast cancer surveillance
- Whether breast cancer is part of the tumor spectrum of LS is controversial. The cumulative risk by the age of 70 years may be 14% in all female carriers, with the highest risk in MLH1 carriers (MLH1: 17%; MSH2: 14.4%; MSH6: 11%). At present, female carriers of an MMR gene mutation should be advised to participate in population screening programs for breast cancer (biannual mammography from the age of 45 or 50) as per European guidelines. Since most patients with Lynch syndrome who develop breast cancer do so after the age of 50 years, standard screening approaches for breast cancer are likely appropriate.
In summary
As a practical expert opinion approach to surveillance strategies in LS, the reviewers for UpToDate® suggest annual colonoscopy starting at age 20-25 (or 10 years prior to the earliest age of colon cancer in a given family), annual screening for EC with endometrial biopsy and ovarian cancer with CA 125 as well as transvaginal ultrasound beginning at age 30-35 (or 5 to 10 years earlier than the earliest age of first diagnosis of these cancers, whichever is earlier), discussion of prophylactic hysterectomy and salpingo-oophorectomy at the end of childbearing, annual urinalysis beginning at age 25-35, annual skin surveillance and periodic upper endoscopy.
Colon Cancer – A Few Facts To Remember
- One in four people in the US will die from cancer.
- Colon Cancer is a treatable and preventable disease.
- Colon cancer is the leading GI cancer and second leading cause of cancer death for both men and women, the third leading cancer for men (after lung and prostate) and third leading cancer for women (after lung and breast cancer)
- Colon cancer has no early symptoms.
- Colon Cancer rates and deaths have dropped by 20% due to better screening implementations.
- An estimated 150,000 people will be diagnosed with colorectal cancer in the US in 2013 and an estimated 50,000 people will die from it in 2013.
- One out of twenty people will get colon cancer (~5.1% chance), yet colon cancer is a preventable disease.
- Any screening is better than none; screening starts typically at age 50 unless an individual is at high risk (family history of colon cancer or inherited genes)
- A colonoscopy is the most effective screening tool.
- It is a treatable disease if found early and a preventable disease if polyps are noted and removed.
- The life saving screening colonoscopy procedure is safe and easy, although time consuming. It is private and not embarrassing.
- Other less defined risk factors for colon cancer may be:Smoking
Diabetes
Sedentary life style
High meat- and processed meat-diet
African American race
Obesity
Heavy alcohol consumption - Signs and symptoms of colon cancer:
- Pain
- Anemia
- Rectal bleeding
- Change in bowel habits
- Urgency
- Weight loss
Colon Cancer Screening
Although screening for colon cancer is recommended starting at age 50, as of 2008, only about 63% of Americans between the ages of 50-75 years of age underwent this recommended screening. This article will address some commonly asked questions regarding colon cancer and the screening guidelines in place to prevent deaths from this serious disease.
1. Why do I need to be screened? Colon cancer is the second leading cause of cancer deaths in America (lung cancer is still number one). In 2009, colon cancer killed almost 52,000 Americans. It affects both genders and all races. Screening for colorectal cancer helps prevent this disease and greatly lessens the likelihood of dying from colon cancer. The goal of screening is to find precancerous polyps (abnormal growths) so they can be removed before they turn into cancer. Screening can also identify colon cancer in its early stages when it can be more effectively treated and potentially cured.
2. Do I really need a colonoscopy if I feel fine and have no symptoms? Colon cancer is generally slow growing. It can take many years for a precancerous polyp to progress into a malignant tumor. Unfortunately, once a person exhibits actual symptoms of colon cancer, the disease is often too advanced to be cured. Symptoms associated with colon cancer include blood in the stool, change in size of stool, abdominal pain, unintentional weight loss, and worsening constipation or diarrhea. More often, however, patients with early stage colon cancer have no symptoms and feel like their normal selves.
3. What are my screening options and which option is best for me? This decision should ultimately be made between you and your primary care physician. Screening options available include simple stool tests looking for blood, flexible sigmoidoscopy (looking just at the left side of the large colon), standard colonoscopy (looking at the entire large colon), and virtual colonoscopy (done with a CT scanner). Virtual colonoscopy often seems appealing because it does not require the bowel preparation that traditional colonoscopy does, and it appears to be as good as standard colonoscopy for detecting cancers and large precancerous polyps. Unfortunately, it is expensive, not covered by insurances, and associated with radiation exposure. In addition, if any polyps or tumors are identified, the patient must also undergo a standard colonoscopy as a virtual colonoscopy cannot biopsy or remove any detected polyps or tumors.
4. I have a family member with colon cancer or polyps. When should I start my screening? While we do not fully understand all of the factors that can contribute to the development of colon cancer, it is clear that genetics play a role. The guidelines recommend that anyone with a single first degree relative or two second degree relatives with a history of colon cancer or colon polyps should start their screening at age 40, or ten years prior to the relative’s earliest diagnosed polyp or tumor, whichever comes first. For example, if your mother was diagnosed with colon cancer at age 65, you should start your screening at age 40. If, however, your mother’s tumor was found at age 45, then your screening should start at age 35.
5. How often do I need to be screened? If no polyps are found during your initial screening, then you do not need a colonoscopy more frequently than every 10 years. That means that most patients only require a total of four screening colonoscopies in their lives. If, however, you have a family history of colon cancer or polyps, or if polyps are found on your initial colonoscopy, then you will need to be screened more regularly.
6. What can I do to prevent colon cancer? While there is no foolproof method to preventing colon cancer, colon cancer has been associated with smoking, excessive alcohol (more than one drink a day), lack of exercise, obesity, and a high fat, low fiber diet. Ultimately though, the best prevention against colon cancer is catching and removing precancerous polyps early, before they have the chance to progress to malignancy. Please be sure to talk to your primary care physician about colon cancer screening to determine when and how this is right for you.
Utah Gastroenterology Blog 