Archive for

Variants of Unknown Significance (VUS): A new trial for Lynch Syndrome patients


Uncertain Genetic Test Results for Lynch Syndrome



  • Individuals have varying tolerances for receiving ambiguous information. However, not much is known about how ambiguous genetic testing information is received. Also, not much is known about how at-risk individuals internalize and process these results. More information is needed about how this information affects a person’s life.
  • Lynch Syndrome is a genetic condition that carries a high risk of colon cancer and other cancers. Individuals at risk for Lynch Syndrome can have genetic testing for it. The test may confirm a diagnosis and determine actions that can be taken. Results from genetic testing can also affect the perspectives of relatives who might also be affected. However, genetic testing can also produce variants of unknown significance (VUS). VUS are data that may not provide enough information to make decisions. Researchers want to study people who have received a VUS result for genetic testing for Lynch Syndrome.


– To learn more about the impact and experience of receiving a VUS for Lynch Syndrome genetic testing.


– Individuals at least 18 years of age who have recently had a VUS result on a genetic test for Lynch Syndrome.


  • Participants will be asked to answer demographic questions. They will also have a 45- to 60-minute phone interview.
  • During the phone interview, participants will be asked a series of questions about their diagnosis. They will be asked about how they received the result and how they felt right after receiving it. They will also discuss who they have spoken to about the result.
Study Type: Observational
Study Design: Time Perspective: Retrospective
Official Title: Living in Lynch Syndrome Limbo: Exploring the Meaning of Uncertain Genetic Test Results
Further study details as provided by National Institutes of Health Clinical Center (CC):
Estimated Enrollment: 40
Study Start Date: April 2012

Detailed Description:

In the field of cancer genetics, clinicians and patients have encountered challenges related to the significance of unclassified genetic variants (UV) or variants of unknown significance (VUS). As the field of medical genetics moves toward whole genome sequencing (WGS), these challenges will inevitably become more frequent. VUS represent ambiguous and uncertain data, for which pathogenicity has not been demonstrated or excluded in published literature, mutation databases or on the basis of other clinical findings. Such variants present a clinical interpretation challenge and also evoke new counseling dilemmas for the understanding and psychosocial impact of uncertain genetic test results. This exploratory study aims to seek insight into the psychological impact of receiving a VUS through semi-structured interviews with 30 to 40 individuals who have received a VUS test result for one of the Lynch Syndrome/Hereditary Nonpolyposis Colorectal Cancer (HNPCC) mismatch repair genes. The interviews will focus on the experience of receiving this result and any cognitive, affective or behavioral effects related to the uncertainty of the result. Interviews will be transcribed and subjected to thematic analysis to identify themes running through the interviews. Understanding the impact of receiving a VUS may identify areas for future intervention studies to minimize negative effects of these events. Additionally, these data may contribute to the formulation of guidelines surrounding the consent for and disclosure of VUS’s for other diseases and ultimately for WGS.


Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: Yes

Individuals who have received a VUS for Lynch Syndrome must be over 18, have telephone access and speak English. Individuals will be excluded if they’ve received their results less than 3 months earlier or more than 6 years ago.

  Contacts and Locations

Please refer to this study by its identifier: NCT01646112

Contact: Barbara B Biesecker (301) 496-3979

United States, Maryland
National Human Genome Research Institute (NHGRI), 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Principal Investigator: Barbara B Biesecker National Human Genome Research Institute (NHGRI)

  More Information
Publications: Identifier: NCT01646112     History of Changes
Other Study ID Numbers: 999912126, 12-HG-N126
Study First Received: July 18, 2012
Last Updated: July 18, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):

Lynch Syndrome
Genetic Tests

Additional relevant MeSH terms:

Colorectal Neoplasms, Hereditary Nonpolyposis
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplastic Syndromes, Hereditary
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Genetic Diseases, Inborn
DNA Repair-Deficiency Disorders
Metabolic Diseases processed this record on September 27, 2012



ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making

English: Original Logo of the Society

English: Original Logo of the Society (Photo credit: Wikipedia)

Colorectal cancer (CRC) is the most common tumour type in both sexes combined in Western countries. Although screening programmes including the implementation of faecal occult blood test and colonoscopy might be able to reduce mortality by removing precursor lesions and by making diagnosis at an earlier stage, the burden of disease and mortality is still high. Improvement of diagnostic and treatment options increased staging accuracy, functional outcome for early stages as well as survival. Although high quality surgery is still the mainstay of curative treatment, the management of CRC must be a multi-modal approach performed by an experienced multi-disciplinary expert team. Optimal choice of the individual treatment modality according to disease localization and extent, tumour biology and patient factors is able to maintain quality of life, enables long-term survival and even cure in selected patients by a combination of chemotherapy and surgery. Treatment decisions must be based on the available evidence, which has been the basis for this consensus conference-based guideline delivering a clear proposal for diagnostic and treatment measures in each stage of rectal and colon cancer and the individual clinical situations. This ESMO guideline is recommended to be used as the basis for treatment and management decisions.

3 Diagnosis, management and counselling of hereditary colorectal cancer

All patients with CRC should have a collection of family history regarding polyps and any type of cancer (at least first and second-degree relatives) [V, A]. About 5% of CRC are of hereditary origin. If a clinical suspicion of polyposis or Lynch syndrome is made, the patient should be referred to a specialist in human genetics [V, C]. Average-risk populations should have an organized access to population-CRC screening, if resources are available at national level [V, A]. Methodology and choice of screening modality is a matter of discussion. An overview of management of hereditary CRC syndromes is summarized in Table 2.

View this table:

Table 2.

Management of hereditary colorectal cancer

3.1 Lynch syndrome

Clinical suspicion is based on fulfilment of clinical criteria (Amsterdam, Bethesda) or on an altered molecular screening [microsatellite instability (MSI) and/or immunohistochemistry (IHC) for mismatch repair proteins (MMR)] in the context of a suggestive personal or family history [III, B].

3.1.1 Detection of mutation

Germline genetic testing will be performed according to the results of molecular screening (MSI and/or IHC of MMR). If a tumour block is not available, the gene-specific prediction models may help to guide a genetic strategy [III, B].

If loss of MLH1 expression is observed (especially in non-familial cases), somatic hypermethylation of the MLH1 promoter should be considered, which can be ruled out by testing the somatic BRAF V600E mutation or analysis of hypermethylation of the MLH1 promoter [III, B].

Full germline genetic testing should include DNA sequencing and large rearrangement analysis of the MMR genes [I, A]. Adequate pre- and post-test genetic counselling should always be performed.

3.1.2 Surveillance for healthy mutation carriers

For individuals with Lynch syndrome carrying an MLH1 or MSH2 mutation, colonoscopy should start at the age of 20–25 years and should be repeated every 1–2 years [II, A].

No specific upper limit for surveillance endoscopies is established and it should be based on the individual’s health status.

For healthy individuals with Lynch syndrome carrying an MSH6 or PMS2 mutation, colonoscopy should start at the age of 30 years and be repeated every 1–2 years. Again, no specific upper limit is established [II, A].

Endometrial and ovarian cancer screening may be performed on a yearly basis starting at the age of 30–35 years with gynaecological examination, pelvic ultrasound, analysis of CA125 and aspiration biopsy [IV, C]. Pros and cons should be adequately discussed with the individual subject at risk given the evidence of benefit only from observational studies.

Surveillance for other Lynch-associated cancers is recommended on the basis of the family history and may include upper endoscopy, abdominal ultrasound and urine cytology from the age of 30–35 years in a 1–2-year interval [IV, C].

3.1.3 Chemoprevention

Neither specific chemoprevention nor specific dietary interventions is being recommended at the current time in individuals with Lynch syndrome to prevent CRC, although data are emerging supporting the use of aspirin [7] [II, B].

3.1.4 Risk reduction: prophylactic surgical options

Prophylactic colectomy in healthy mutation carriers is not recommended. Prophylactic gynaecological surgery might be an option in female carriers from the age of 35 onwards and after childbearing is completed [IV, C].

3.1.5 Cancer treatment

The need for intensive surveillance after surgery versus the option of an extended colectomy should be discussed at the time of diagnosis of an advanced adenoma or CRC, especially in young patients [IV, C]. For female CRC patients with good prognosis, surveillance/surgical options for gynecological cancer should also be discussed. Chemotherapy regimens are the same as those for sporadic CRC.

3.2 Familial colorectal cancer × syndrome

Relatives of individuals with CRC who fulfil the Amsterdam criteria and who do not exhibit MMR deficiency have a moderate risk of CRC. Surveillance would include colonoscopy at a 3–5-year interval, starting 5–10 years before the youngest case in the family. Surveillance of extra-colonic cancers is not recommended.

3.3 FAP

Clinical diagnosis of classical familial adenomatous polyposis (FAP) is based on the identification of >100 colorectal adenomas. Lifetime risk of development of CRC is 100%.

3.3.1 Attenuated FAP

Clinical diagnosis of attenuated FAP is based on the following criteria:

  • at least two patients with 10–99 adenomas at age >30 years; or

  • one patient with 10–99 adenomas at age >30 years, a first-degree relative with CRC and few adenomas and no family members with >100 adenomas before the age of 30 years.

3.3.2 Genetics

Genetic testing (germline adenomatous-polyposis-coli (APC) mutation) should start by investigating the affected individual. If the causative mutation is detected, pre-symptomatic diagnosis can be offered to at-risk family members. When the causative mutation is not identified, all at-risk family members should undergo colorectal endoscopic screening [V, C].

3.3.3 Colorectal screening

In families with classic FAP, flexible sigmoidoscopy is an adequate technique and it should be performed every 2 years, starting at the age of 12–14 years, and continued lifelong in mutation carriers [V, C]. If adenomas are found, colonoscopy should be done annually until colectomy.

In families without an identified APC mutation, surveillance should be performed every 2 years until the age of 40, and be repeated every 3–5 years between 40 and 50 years and may continue with general screening at age 50 if no polyposis has developed [V, C]. When an attenuated form is suspected, total colonoscopy is needed. In this setting, examination should be performed every 2 years until polyposis is diagnosed. Screening should be started at the age of 18–20 years and continued lifelong.

3.3.4 Screening for extra-colonic manifestations

It should start when colorectal polyposis is diagnosed or at the age of 25–30 years, whichever comes first [V, C].

Gastroduodenal endoscopy should be performed every 5 years until adenomas are detected [V, C]. Screening for thyroid cancer should be performed by annual sonography of the neck [V, C]. Regular physical examination and if indicated abdominal CT should be performed in search for desmoid tumours [V, C]. Screening for other extra-colonic manifestations is not justified because of their low prevalence and/or limited clinical impact. Since gastrointestinal adenomas may also develop in the jejunum and ileum, it has been suggested that regular screening by barium contrast series or wireless capsule endoscopy could be performed [V, C].

3.3.5 Treatment

Surgical resection is the standard of care in patients with classical FAP [IV, A]. It can be considered in some patients with an attenuated form. Surgical resection includes either total colectomy with ileoanal pouch anastomosis or subtotal colectomy with ileorectal anastomosis, once adenomas are detected [IV, C]. Duodenal adenomas are managed with endoscopic polypectomy, and in Spigelman stage IV (see below), duodenal–pancreatectomy may be considered. Because of the high recurrence rate of desmoid tumours, surgical resection should be delayed unless complications occur. The first-line treatment in patients with large or growing intra-abdominal or abdominal wall desmoid tumours is based on, e.g COX 2 inhibitors, tamoxifen and tyrosine kinase inhibitors.

3.3.6 Surveillance for healthy mutation carriers


Regular endoscopic surveillance every 6–12 months after subtotal colectomy is recommended to detect rectal adenoma recurrence [V, C]. When total colectomy is performed, surveillance of the pouch can be repeated every 1–2 years. In patients with attenuated FAP conservative management with endoscopic polypectomy, examination of the entire colon and rectum should be performed annually [V, C].


Surveillance of duodenal manifestation will depend on its extension. When it corresponds to Spigelman stage I or II, upper endoscopy should be performed every 5 or 3 years, respectively, and every 1–2 years in stage III or every 6 months in stage IV [IV, C].

3.4 MUTYH-associated polyposis

MUTYH-associated polyposis (MAP) is inherited as an autosomal recessive trait with high penetrance. Clinically, MAP resembles the attenuated form of FAP syndrome, with an average age of onset around the mid-50s with often <100 adenomas and, accordingly, patient management is very similar.

3.4.1 Screening for family members

Individuals should undergo total colonoscopy every 2 years, starting at the age of 18–20 years and continuing lifelong [V, C]. Genetic testing allows the most cost-effective screening to be performed by focussing colorectal examinations only on gene carriers. However, when the causative mutation is not identified, all at-risk family members should undergo colorectal screening.

3.4.2 Treatment for healthy gene carriers

Colorectal management is similar to that proposed for patients with attenuated FAP.

ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making

Table 2.

Management of hereditary colorectal cancer

Syndrome Diagnosis of index case (with cancer) Management of the affected individual (with cancer) Management of individuals at high risk (healthy mutation carriers or individuals at 50% risk of being mutation carrier)
Clinical Molecular screening (tumour tissue) Germline genetic testing (blood) Treatment Follow-up Cancer risk Surveillance Germline genetic testing (blood)
Lynch Amsterdam, Bethesda MSI and/or IHC for MMR proteins MLH1, MSH2
  • Tumour resection

  • Discuss colectomy, especially in young patients

Yearly endoscopy of the remnant colon or rectum High
  • Colonoscopy q 1–2 years, starting age 25 (30 years in case of MSH6 or PMS2 mutations)

  • Annual pelvic examinations, transvaginal ultrasound, ca125, endometrial biopsy in females, starting age 30–35 years

Direct genetic testing of the mutation identified in the family
Familial CRC X Amsterdam, Bethesda No MMR deficiency Unknown As average population As average population Moderate only CRC
  • Colonoscopy 1 3–5 years, starting 5–10 years before youngest case in the family.

FAP Colonoscopy: >100 adenomas none APC
  • Total or subtotal colectomy when adenomas occur

  • Endoscopic removal of duodenal adenomas

  • After subtotal colectomy: rectal examination q 6–12 m

  • After total colectomy: pouch exam. q 1–2 years

  • Duodenoscopy from 6 months to 5 years according to Spigelman stage

  • Thyroid examination yearly

  • Flexible sigmoidoscopy q 2 years, starting age 12–14 years until diagnosis of adenomas

  • If no mutation identified in the family: Flexible sigmoidoscopy q 2 years until 40 years, then q 3–5 years until 50, then general population screening

Attenuated FAP (aFAP) Colonoscopy:

  1. 2 relatives 10–99 adenomas (>30 years of age)

  2. 1 relative of CRC patient with 10–99 adenomas (>30 years of age)

  • Total or subtotal colectomy when adenomas occur.

  • Endoscopic removal of duodenal adenomas

As above High
  • Colonoscopy q 2 years, starting age 18–20 years, lifelong in mutation carriers.

  • APC, adenomatous-polyposis-coli; MSI, microsatellite instability; MMR, mismatch repair proteins; CRC, colorectal cancer; FAP, familial adenomatous polyposis; aFAP, attenuated FAP; MAP, MUTYH-associated polyposis.

via ESMO Consensus Guidelines for management of patients with colon and rectal cancer. A personalized approach to clinical decision making.

My Semicolon Life: Good news on the cancer front


USA Today

USA Today (Photo credit: Wikipedia)

My Semicolon Life: Good news on the cancer front

Brian Mansfield

Music critic compares his CT, pathology reports

Chemo’s off the table for now

6:00AM EST September 29. 2012 – When USA TODAY‘s Nashville music critic Brian Mansfield was diagnosed with colon cancer at age 48, he figured that a lifetime of Southern-fried foods, extra-large sodas and stress eating on deadline had brought it on. Turned out he had a genetic syndrome that gave him an 80% chance of developing colon cancer. He’ll chronicle his life with the disease — and with only a small part of his colon — in a series of weekly installments.

I thought by now I would have seen an oncologist.

It’s the weirdest thing: When I got diagnosed with colon cancer back in June, every doctor I saw told me about these great oncologists they could send me to. Then, after the surgery, they just quit talking about them. Nobody ever told me not to see an oncologist, they just stopped bringing up the subject.

When my surgeon visited me in my hospital room after the operation, he said that I might not have to undergo chemotherapy. But I figured I’d at least consult with an oncologist. After all, I had a doctor — my gastroenterologist — in charge of finding the cancer. I had another — the surgeon — in charge of removing it. Surely it was a good idea to have a doctor in charge of the cancer itself. That only made sense, right?

COLUMN: Last week’s installment

MORE: Follow Brian on Twitter

MORE: ‘Music that makes me want to live’ playlist

Now, I have a natural inclination to want to avoid people who can pump poisons into my body, even if those poisons might help me in the long run. But oncologists were on my mind last week after I finally thought to ask for a copy of my post-surgery pathology report. I had gotten great pictures, some of which would make wonderful Halloween avatars for my Facebook page, but for some reason it had never occurred to me to look at the report about what my surgeon had found when he cut me open.

The report from my CT scan and my pathology report sound like they’re talking about two different cases.

My stomach sank after I saw my CT report. It talked of enlarged lymph nodes and suggested my tumor might have extended beyond the bowel wall. Based on that report, my surgeon anticipated at least a Stage II cancer. I would have considered myself fortunate to get Stage IIIA, where the cancer’s either in the muscle layers of the colon and one to three lymph nodes or it’s in four to six lymph nodes but not in the muscle. The more I read the report, the more I steeled myself for worse news.

The pathology report, by contrast, read like the next best thing to “happily ever after.” The tumor didn’t get beyond the wall. It didn’t get into any of the 36 lymph nodes removed and tested. It didn’t get into the blood vessels. There were no signs of cancer in the surgical margins.

Basically, it was just a big ol’ tumor that hadn’t gone anywhere. No wonder I had friends tell me my surgeon came into the waiting room practically skipping.

The only thing in the pathology report that threw up a red flag was a separate polyp that my colonoscopy hadn’t caught. But my surgeon had taken that out along with my tumor, my appendix and most of my colon, so it wasn’t going to be creating any problems in the future.

At my two-month post-surgery checkup, I asked my surgeon if he planned to send me to an oncologist. He shrugged off the idea. He’d send me to one if it eased my mind, but he’d be perfectly happy to handle all the necessary future screenings in his office.

As for treatment, “there’s some debate about whether Stage II patients should have chemotherapy,” he says. “Nobody thinks Stage I patients should.”

Well, OK, then.

Until cancer decides to pop back up inside my body — and that could be a year from now, or 15, or 40, or never — I’m done with treatment.

We’ll keep a vigilant eye out for potential trouble, and we’ll start with the findings of that first CT report. My right kidney has a nice-sized cyst on it, but that’s probably no big deal. More worrisome is the “nodular focus” near the base of my right lung. “A metastatic focus cannot be excluded,” the report states. In other words, might be nothing, might be cancer.

In three months, I’ll get another CT scan to take a second look at my lung. Six months after that, I’ll be coming up on my one-year cancer anniversary, which we’ll celebrate with two big jugs of Gatorade and another colonoscopy.

Those things are months away, though, and I can’t do a thing about either of them right now. I can, however, help a 10-year-old plan her long-awaited and once-delayed trip to New York.

We leave next Saturday.

Music that makes me want to live

Cancer has changed the way I hear music, more than any other life event except marriage. Songs I once appreciated only on a surface level now strike deep at the core of my soul. Some inspire me; some terrify me. Others that I might have liked before I’ve got no use for now. I’ve also got more time to listen, whether it’s during my morning exercise time or while lying in a hospital bed. These songs form part of the soundtrack to my cancer story.

1. Thankful N’ Thoughtful, Bettye LaVette

2. Founding Fathers, Will Hoge

3. Every Road Leads Back to You, Richie Sambora

4. Live in This City, Dragonette

5. Lover of the Light, Mumford and Sons

via My Semicolon Life: Good news on the cancer front.


Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome

JNCI J Natl Cancer Inst From Win et al Journal of the National Cancer Institute September 2012

Background Lynch syndrome is a highly penetrant cancer predisposition syndrome caused by germline mutations in DNA mismatch repair (MMR) genes. We estimated the risks of primary cancers other than colorectal cancer following a diagnosis of colorectal cancer in mutation carriers.

Methods We obtained data from the Colon Cancer Family Registry for 764 carriers of an MMR gene mutation (316 MLH1, 357 MSH2, 49 MSH6, and 42 PMS2), who had a previous diagnosis of colorectal cancer. The Kaplan–Meier method was used to estimate their cumulative risk of cancers 10 and 20 years after colorectal cancer. We estimated the age-, sex-, country- and calendar period–specific standardized incidence ratios (SIRs) of cancers following colorectal cancer, compared with the general population.

Results Following colorectal cancer, carriers of MMR gene mutations had the following 10-year risk of cancers in other organs: kidney, renal pelvis, ureter, and bladder (2%, 95% confidence interval [CI] = 1% to 3%); small intestine, stomach, and hepatobiliary tract (1%, 95% CI = 0.2% to 2%); prostate (3%, 95% CI = 1% to 5%); endometrium (12%, 95% CI = 8% to 17%); breast (2%, 95% CI = 1% to 4%); and ovary (1%, 95% CI = 0% to 2%). They were at elevated risk compared with the general population: cancers of the kidney, renal pelvis, and ureter (SIR = 12.54, 95% CI = 7.97 to 17.94), urinary bladder (SIR = 7.22, 95% CI = 4.08 to 10.99), small intestine (SIR = 72.68, 95% CI = 39.95 to 111.29), stomach (SIR = 5.65, 95% CI = 2.32 to 9.69), and hepatobiliary tract (SIR = 5.94, 95% CI = 1.81 to 10.94) for both sexes; cancer of the prostate (SIR = 2.05, 95% CI = 1.23 to 3.01), endometrium (SIR = 40.23, 95% CI = 27.91 to 56.06), breast (SIR = 1.76, 95% CI = 1.07 to 2.59), and ovary (SIR = 4.19, 95% CI = 1.28 to 7.97).

Conclusion Carriers of MMR gene mutations who have already had a colorectal cancer are at increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers.

Risks of Primary Extracolonic Cancers Following Colorectal Cancer in Lynch Syndrome

Table 2.

Cumulative risks (percent) and corresponding 95% confidence intervals (CIs) of primary extracolonic cancers during the 10 and 20 years following diagnosis of colorectal cancer for carriers of mismatch repair gene mutations

Cancer site 10 years 20 years
Risk, % (95% CI) Risk,% (95% CI)
Both sexes
    Kidney etc.*
(0.87 to 3.17) 5.15 (2.86 to 7.68)
    Urinary bladder 1.61 (0.65 to 2.75) 3.15 (1.37 to 5.20)
    Small intestine 0.92 (0.28 to 1.73) 4.00 (1.92 to 6.41)
    Stomach 0.66 (0.13 to 1.40) 1.15 (0.19 to 2.48)
    Hepatobiliary tract 0.83 (0.16 to 1.69) 1.42 (0.42 to 2.73)
    Prostate 2.74 (0.86 to 4.77) 5.90 (2.69 to 9.76)
    Endometrium 12.12 (7.66 to 17.11) 23.99 (16.79 to 32.84)
    Breast 1.94 (0.58 to 3.83) 11.38 (0.63 to 16.69)
    Ovary 0.94 (0.00 to 2.11) 2.08 (0.50 to 4.14)
  • * Kidney etc. included kidney, renal pelvis, ureter and other and unspecified urinary organs.

  • † Hepatobiliary tract included liver and intrahepatic bile duct, gall bladder, and other and unspecified parts of biliary tract.


    Patients who have had colorectal cancer and who are carriers of the DNA mismatch repair gene mutations that cause Lynch syndrome “have an increased risk of a greater range of cancers than the recognized spectrum of Lynch syndrome cancers, including breast and prostate cancers,” according to a study in the Journal of the National Cancer Institute.

    Previous studies had shown that mutation carriers “are at a substantially increased risk of cancers of the colon, rectum, endometrium, stomach, ovary, ureter, renal pelvis, brain, small bowel, hepatobiliary tract, and pancreas,” the authors noted. A major inherited cancer syndrome, Lynch syndrome is also known as hereditary nonpolyposis colorectal cancer (HNPCC).

    The study was based on data for 764 patients from the Colon Cancer Family Registry, evenly divided between men and women, who were carriers of the mismatch repair gene mutation and previously diagnosed with colorectal cancer. Most of the carriers (52%) were recruited in Australia and New Zealand, with 33% from the United States and 15% from Canada. The average age at diagnosis of colorectal cancer was 44 years.

    Compared with the general population, following colorectal cancer, carriers of mismatch repair gene mutations had a 70-fold increased risk for cancer of the small intestine, a 13-fold increased risk for cancer of the kidney, renal pelvis, and ureter or urethra, a 7-fold increased risk for cancer of the bladder, a 6-fold increased risk for hepatobiliary tract cancer, and a nearly 6-fold increased risk for gastric cancer. Men had a 2-fold increased risk of prostate cancer. The most common primary cancer following colorectal cancer for women with Lynch syndrome was endometrial cancer, with a 40-fold increased risk compared to the general population. There were 20 breast cancers and 6 ovarian cancers in the study population.

    “These new data provide further determination of cancer risks, potentially informing and justifying ongoing studies to create the evidence for effective screening methodologies and intervals in [mismatch repair] gene mutation carriers,” the researchers concluded. “Larger studies are needed to refine risk estimates separately for specific [mismatch repair] gene mutations to best inform policies on clinical risk management.” ■


Much Of The Population Genetic Risk Of Colorectal Cancer Is Likely To Be Mediated Through Susceptibility To Adenomas

Gastroenterology (journal)

Gastroenterology (journal) (Photo credit: Wikipedia)

Several single nucleotide polymorphisms (SNPs) have been associated with colorectal cancer (CRC) susceptibility. Most CRCs arise from adenomas, and SNPs might therefore affect predisposition to CRC by increasing adenoma risk. We found that 8 of 18 known CRC-associated SNPs (rs10936599, rs6983267, rs10795668, rs3802842, rs4444235, rs1957636, rs4939827, and rs961253) were over-represented in CRC-free patients with adenomas, compared with controls. Ten other CRC-associated SNPs (rs6691170, rs6687758, rs16892766, rs7136702, rs11169552, rs4779584, rs9929218, rs10411210, rs4813802, and rs4925386) were not significantly associated with adenoma risk. Genetic susceptibility to CRC in the general population is likely to be mediated in part by predisposition to adenomas. – Gastroenterology – Much Of The Population Genetic Risk Of Colorectal Cancer Is Likely To Be Mediated Through Susceptibility To Adenomas. Carvajal-Carmona et al In Press September 2012

My Semicolon Life: Tracing my family’s cancer history – by Brian Mansfield


My Semicolon Life: Tracing my family’s cancer history –


USA Today

USA Today (Photo credit: Wikipedia)


When USA TODAY‘s Nashville music critic Brian Mansfield was diagnosed with colon cancer at age 48, he figured that a lifetime of Southern-fried foods, extra-large sodas and stress eating on deadline had brought it on. Turned out he had a genetic syndrome that gave him an 80% chance of developing colon cancer. He’ll chronicle his life with the disease — and with only a small part of his colon — in a series of weekly installments.


Every time my older son gets an upset stomach, he gets a little spooked.


This summer, he didn’t seem worried. My surgery and recovery went well enough that he didn’t have to spend much time wondering if things might go badly. Besides, people brought food.


Now that he’s back at college and on his own, he’s thinking less about my short-term issues and more about his long-term ones.


Like, when’s he going to get cancer?


COLUMN: Last week’s installment


MORE: Follow Brian on Twitter


MORE: ‘Music that makes me want to live’ playlist


As the son of someone with Lynch syndrome — a hereditary genetic disorder that exponentially increases one’s susceptibility to cancer — it’s not an unreasonable question. He knows he’s got a 50/50 chance of carrying the same mutation I do, and he knows that my own digestive problems led to my colon cancer diagnosis. He wants to get screened for Lynch, and he’d rather do it sooner than later.


So this week I went to see someone who could help me get a handle on the genealogical aspect of the situation. An advanced practice nurse in genetics, she’d typically walk someone — my son, for instance — through his likelihood of having a genetic disorder, then take a DNA sample to have it tested. Since I already had tested positive for Lynch, she created a family tree showing our cancer history, then outlined the steps I should take to alert and protect both my immediate and extended family.


In order to rule out additional syndromes, she asked questions about sebaceous skin tumors, thyroid glands, fibroid tumors and my ancestry of origin. Lynch doesn’t appear to be a respecter of ethnicities, but other mutations are: For instance, the BRCA mutations, which can produce a hereditary breast-ovarian cancer syndrome, are common among Ashkenazi Jews. She also measured my head: A larger-than-normal measurement could signify Cowden syndrome, a much rarer hereditary disorder that often results in multiple benign tumors and an increased cancer risk.


As for the family history, cancer showed up occasionally on my mother’s side, like the great-aunt who died of breast cancer in the mid-1950s after having worked in the Oak Ridge, Tenn., nuclear program during World War II, but no patterns emerged. My father’s side of the family, however, told a different story.


On our own, my family had focused the search on the Carter/Geralds side of my father’s lineage. When we put the Mansfields on paper, though, there was plenty of evidence to suggest troubles of their own. My grandfather, a heavy smoker, had oat-cell lung cancer when he died at 62. He had two brothers — and maybe a third — who died from colon cancer. Also, I have a second cousin on that side diagnosed with colon cancer at age 50.


Still, it’s my paternal grandmother’s branch that most strongly suggests Lynch. When Granny was in her 50s, she had a hysterectomy. She didn’t talk about it then, and she can’t tell us much about it now. As we’ve pieced together family lore, we’ve come to believe her doctors were concerned about uterine or ovarian cancer (both Lynch-related), so they removed the organs most at risk. One sister also had a hysterectomy after being diagnosed with endometrial cancer; when a malignancy recurred in her kidneys, it spread throughout her body and took her life. A brother died of lung cancer in 2009. Ovarian took the youngest sister this spring.


In the next generation, colon cancer hit three first cousins, all when they were in their 40s. Now, there’s me.


Facebook helped me gather these stories. This weekend, it’ll help me spread a message that’ll read something like this:


Dear ______,


As you know, I had surgery for colon cancer this summer. During the course of my treatment, I learned that I carry an hereditary genetic mutation called Lynch syndrome that greatly increases the likelihood of developing cancer in the colon, stomach, uterus, ovary and other places.


After looking through our family’s history with a cancer genetics professional, we’ve determined that the disorder came from my father’s side of the family. You probably already know how prevalent those cancers have been across our generations. Because of that, I’d like to suggest that you contact a cancer genetics professional in your community to help you assess your own risk of carrying the mutation.


While a Lynch diagnosis can be a scary thing, it also brings empowering knowledge. With proper screening, the most common Lynch-related cancers can be discovered early, even prevented.


The National Center for Biotechnology Information website has a section that you can use to find cancer genetic counseling near you. If you decide to get screened, I’ll be happy to send you a copy of my genetic test result and my pathology report. Soon, I should also have a pedigree that shows our family cancer history.


Since my surgery, I have recovered nicely. But few things would make me feel better than knowing I kept somebody else in our family from going through the same thing I did.






Meanwhile, I’m calling my father and my sons to help them make their own appointments. They’ve got tests to take.




Using food as medicine: The fibre challenge from Channel 4’s food hospital


The Fibre Challenge

If there’s one thing most of us don’t like talking about, it’s our bowel movements. However, your stools (that’s poo to you and me) can be a clear indicator of how healthy your insides are, particularly problems with your digestive system. Many of us are too embarrassed to talk about discomfort of going to the toilet. But even short-term problems can indicate longer-term health risks that can go undiagnosed if you don’t do anything about them.
The Food Hospital Fibre Challenge aims to tackle the toilet taboo and encourage people to make simple changes in their diet that could have significant benefits to their bowel and overall health.
Find out more about our approach.

Fresh vegetables are important components of a...

Fresh vegetables are important components of a healthy diet. (Photo credit: Wikipedia)

Take the Fibre Challenge

The Fibre Challenge has been devised by specialist dietitians and is a mass participation initiative to assess the effect of fibre on the nation’s bowel health. For 21 days, you’ll eat extra dietary fibre and send information about your bowel movements (anonymously) to our expert team for analysis. The results will help us to better understand whether a high fibre diet significantly improves short-term bowel health and general well-being. There are some people who shouldn’t take part for health reasons, but the rest of you can download the app, check out the assortment of fibre foods to add to your diet, print-out our stool chart and monitor the effects of eating extra fibre over the next few weeks. Find out more about the challenge.


Screening helps early diagnosis of bowel cancer


Cancer Research UK

Cancer Research UK (Photo credit: Wikipedia)


Screening helps early diagnosis of bowel cancer


National Cancer Intelligence Network Press Release


PATIENTS who attend bowel screening are more likely to be diagnosed with bowel cancer at an early stage – when there is a better chance of survival – than those who wait until they have symptoms of the disease.


These are the findings of new data presented at the annual National Cancer Intelligence Network (NCIN) conference in Birmingham.


Researchers say the study shows that the NHS Bowel Cancer Screening Programme is working towards its aim to reduce deaths from bowel cancer.


Using data from the West Midlands Cancer Intelligence Unit, the study looked at bowel cancers diagnosed in the region between January 2006 and September 2011 in people aged 60 – 69 years.


Researchers compared the stage at diagnosis of bowel cancers picked up through screening and those diagnosed from symptoms.


The results showed that 18.5 per cent of bowel cancers detected through screening were at the earliest stages compared with 9.4 per cent of cancers diagnosed through symptomatic routes.**


In contrast, late stage tumours were more common in patients diagnosed through symptomatic routes compared with those diagnosed through screening.***


Sam Johnson, lead researcher based at the West Midlands Cancer Intelligence Unit, said: “When bowel cancer is diagnosed at an earlier stage, it’s easier to treat, has a lower chance of coming back and better survival rates.


“Our research shows that screening can play an important role in improving bowel cancer survival by picking up cancers at an earlier stage.”


Bowel cancer is the third most common cancer in the UK – around 40,000 people are diagnosed with the disease each year.


Researchers said that once the NHS Bowel Cancer Screening Programme has been established for several more years, and has been rolled out completely to people aged 60 – 74 years old, they would expect to see fewer late stage cancers.


Chris Carrigan, head of the NCIN, said: “When bowel cancer is found at the earliest stage, there is an excellent chance of survival, with more than 90 per cent of people surviving the disease at least five years.


“Compared with breast and cervical cancers, bowel cancer tends to have a lower five-year survival rate.


“This study highlights the potential improvements we can make through encouraging more people to take-up their screening invitation so the disease is diagnosed earlier.”




Study to test spice curcumin’s ability to fight bowel cancer

Cancer Research UK

Cancer Research UK (Photo credit: Wikipedia)

A UK trial is investigating whether a curry ingredient can improve the treatment of patients with advanced bowel cancer.

Scientists will supplement standard chemotherapy with pills containing curcumin, a compound found in the yellow curry spice turmeric.

Laboratory tests have suggested that curcumin can boost the ability of chemotherapy drugs to kill bowel cancer cells. The compound is known to have powerful anti-inflammatory properties and also acts as an antioxidant.

Turmeric powder 薑黃粉

Turmeric powder 薑黃粉 (Photo credit: Wikipedia)

Some studies have indicated it may slow the spread of cancer, improve the effectiveness of chemotherapy and protect healthy cells from the effects of radiotherapy. However, hard evidence from properly conducted scientific trials is lacking.

The two-year trial, by scientists from Cancer Research UK and the University of Leicester, aims to recruit about 40 patients with bowel cancer that has spread to the liver.

Trial leader Professor William Steward, director of the Experimental Cancer Medicine Centre at the University of Leicester, said: “The prospect that curcumin might increase the sensitivity of cancer cells to chemotherapy is exciting because it could mean giving lower doses, so patients have fewer side-effects and can keep having treatment for longer.”

Read more here

Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests — Logan et al. Gut 2012

Gut (journal)

Gut (journal) (Photo credit: Wikipedia)

Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests


Introduction The Bowel Cancer Screening Programme in England began operating in 2006 with the aim of full roll out across England by December 2009. Subjects aged 60–69 are being invited to complete three guaiac faecal occult blood tests (6 windows) every 2 years. The programme aims to reduce mortality from colorectal cancer by 16% in those invited for screening.

Methods All subjects eligible for screening in the National Health Service in England are included on one database, which is populated from National Health Service registration data covering about 98% of the population of England. This analysis is only of subjects invited to participate in the first (prevalent) round of screening.

Results By October 2008 almost 2.1 million had been invited to participate, with tests being returned by 49.6% of men and 54.4% of women invited. Uptake ranged between 55–60% across the four provincial hubs which administer the programme but was lower in the London hub (40%). Of the 1.08 million returning tests 2.5% of men and 1.5% of women had an abnormal test. 17 518 (10 608 M, 6910 F) underwent investigation, with 98% having a colonoscopy as their first investigation. Cancer (n=1772) and higher risk adenomas (n=6543) were found in 11.6% and 43% of men and 7.8% and 29% of women investigated, respectively. 71% of cancers were ‘early’ (10% polyp cancer, 32% Dukes A, 30% Dukes B) and 77% were left-sided (29% rectal, 45% sigmoid) with only 14% being right-sided compared with expected figures of 67% and 24% for left and right side from UK cancer registration.

Conclusion In this first round of screening in England uptake and fecal occult blood test positivity was in line with that from the pilot and the original European trials. Although there was the expected improvement in cancer stage at diagnosis, the proportion with left-sided cancers was higher than expected.

Significance of this study

What is already known about this subject?

Randomised trials of colorectal (bowel) cancer screening have indicated that a biennial guaiac-based faecal occult blood test has the potential to reduce colorectal cancer mortality by about 25% in those accepting screening and by 16% in those offered screening.

In the UK trials and pilot studies uptake was between 50% and 60%.

Factors such as age, ethnic background, deprivation and gender are known to influence uptake.

What are the new findings?

Overall uptake in this first round of screening was 55–60% in the provinces in keeping with previous studies but was much lower in the London area at only 40%.

Uptake of the offer of colonoscopy in those with an abnormal test was high but only 83% of those with abnormal tests underwent colonoscopy.

Early cancer (Dukes A or B) was found in 70% of those with cancer.

The proportion of screen-detected cancers that were found in the right colon was lower than expected.

How might these impact on clinical practice in the foreseeable future?

If these early results are maintained the Bowel Cancer Screening Programme will achieve the intended 16% reduction in overall bowel cancer mortality.

Different screening strategies may be required to effectively screen for right-sided bowel cancer.

via Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests — Logan et al. 61 (10): 1439 — Gut.

Enter your email address to follow this blog and receive notifications of new posts by email.

Join 1,483 other followers

Live twitter feed

RSS CRUK Bowel Cancer Blog

  • An error has occurred; the feed is probably down. Try again later.

RSS Pubmed New Publications

RSS Familial Cancer

  • An error has occurred; the feed is probably down. Try again later.


Google Plus

%d bloggers like this: