This tag is associated with 8 posts

Guest blog from Georgia Hurst, Lynch Syndrome ‘previvor’: “I will not get sick”

A guest blog from Georgia Hurst, as she worries about the impact of her diagnosis of Lynch Syndrome on her son.  Read more at

“I will not get sick, but if I do…

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…I will have the strength to endure it.”

This is my new mantra. The above photo is the view from my zafu when I go to Buddhist Temple for meditation; the solace this gives me is immeasurable. I have been finding myself at Temple a lot lately, meditating and reaching for my internal strength to deal with the unbearable anxiety and stress which currently confront me. I’m trying not to discuss it with people; it’s too much for me to process, let alone them. Besides, I feel as though I put them into a precarious position if I do bring it up because there are no words available to them which can possibly comfort me at this time. I am going to Mayo Clinic in 11 days and the anxiety is increasing by the minute. I am expecting the worst, whilst hoping for the best. I’m sure I am not the only one with Lynch syndrome that feels this way when it’s close to testing time. The plethora of emotions are running rampant in me little head. I feel guilt. My oldest brother did not have a chance, my second brother does not have a colon – and then I think of all of the people I’ve met through my blog and Facebook and other forms of social media who are fighting for their lives because they, too, have been blindsided by this genetic curse. Damn you, Lynch syndrome. I feel anger because I may have given this to my beautiful little boy. If I knew for sure that this monster ended with me with 100% certainty, I would at least not have to fret about my child. I also feel anger for all the children who are watching their parents suffer and die, leaving them with a life of endless uncertainties and insecurities. I feel sad, not for myself, but for my family, my dog, and my friends; because I know that part of you dies when someone you love dies. I feel lucky; I’m fortunate to know I have this genetic mutation, have insurance, and have the ability to exhibit some control of it; I get to go Mayo and get see the Rock Star Doctors of Lynch syndrome. I feel confident; I keep reminding myself that I eat well, exercise, surround myself with loving, nourishing people, animals, books, etc., and have eliminated every imaginable toxin in my life. I feel fearless and empowered in many ways; yet, helpless in so many others. I vacillate between optimism and negativity; perhaps I should simply stop it and end up somewhere in the middle. I am exhausted, whilst I exhibit every possible emotion known to humanity. I long for the days when I didn’t know of my charming genetic nemesis and wasn’t emotionally imprisoned by Lynch syndrome. I would give everything I have to simply appreciate a few minutes of life sans Lynch. Two weeks from today, I will know if everything I talk about truly matters or if my genetics will trump everything I think and do. I just want spend the next several days being fearless. Fearless. Fearless. Fearless. In the eloquent words of Tagore: Let me not pray to be sheltered from dangers but to be fearless in facing them. Let me not beg for the stilling of my pain but for the heart to conquer it. Let me not look for allies in life’s battlefield but to my own strength. Let me not cave in… Yours, Georgia Hurst, MA This post was written in late April before I went to the Mayo Clinic in early May for my annual testing; I received a clean bill of health and not even one little polyp was found in my colon.


Guest blog from Georgia Hurst ( Matroyoshka Nesting Dolls

Thanks to Georgia Hurst for this insightful article based on her personal experiences as someone diagnosed with Lynch Syndrome.  She describes some of the barriers she has faced with this diagnosis.  Her blog is available at

Matroyoshka Nesting Dolls by Georgia Hurst –

Georgia Hurst with her son

Georgia Hurst with her son

I cannot help but think of those adorable Matryoshka nesting dolls when considering Lynch syndrome and its implications. Matryoshka nesting dolls are those cute, wooden Russian figures which separate, top from bottom, to reveal a smaller figure of the same sort inside, which, in turn, reveals another figure inside that, and so on. I think of those dolls as a metaphor for Lynch syndromesans the cuteness. The emotional toll of knowing you hold a deleterious gene mutation can be quite challenging and one Lynch syndrome issue leads to another, to another, and so forth. With that introduction, I am simply trying to raise consciousness in the elusive Lynch syndrome world about topics which are rarely discussed amongst the professionals who deal with Lynch syndrome patients. Doctors, genetic counselors, psychiatrists, psychologists, and others need to be cognizant that people with Lynch syndrome are dealing with a constellation of emotional and possibly physiological issues as a result of this diagnosis and the recommended surgeries.

Lynch syndrome, also known as Hereditary Non-Polyposis Colorectal Cancer: HNPCC, affects approximately 600,000 people in the United States; yet, only approximately only 5% of us know it. Lynch syndrome is typically associated with a significantly increased risk for colorectal and endometrial cancers and is caused by mutations in following genes: MLH1, MSH2, MSH6, PMS2, and EPCAM.  Cancers potentially stemming from Lynch syndrome include: colorectal, endometrial, gastric, ureter/renal, pelvis, biliary tract, small bowel, pancreas, brain, sebaceous carcinomas ovarian, prostate in men, and breast, endometrial and ovarian cancer in women. Lynch syndrome warning signs include early onset cancers (<50y) in one’s family history, specifically colon cancer, endometrial cancer, and/or two or more other cancers in the same individual, or among their close relatives.

My Lynch Matryoshka dolls exposed a plethora of new challenges and I did not have even one of those cancers. I took the prophylactic measure of removing my reproductive organs to prevent malignancy to them and was fortunate enough to ‘only’ have a hysterectomy and bilateral salpingo-oophorectomy. At the time of the surgery, I was a healthy, fit 40-year-old-woman – ten years, or more, away from menopause and doctors completely minimized what was to happen to me with this surgery, assuming that the “one size fits all approach” to medicine would with work with me. I was told that a hysterectomy and bilateral salpingo-oophorectomy were not such a big deal for a woman of my age and that I would be fine with a low dose of estrogen and an antidepressant. Unbeknownst to me, my physiological and psychological response to the surgery would end up highly taxing to say the least. The convalescence from surgery and further testing for Lynch syndrome screenings required a number of doctors’ visits – to some doctors who did not know about Lynch syndrome, nor would they take the time to find out, or were too arrogant to refer me elsewhere. A physician’s lack of knowledge regarding a deleterious gene mutation can only fuel a patient’s existing fears and anxiety. It is comparable to throwing the patient into dark, shark infested waters, and not telling them which way to swim; a very frightening position to be in for a person who already feels like a walking time bomb.

My first, big doll is the Lynch diagnosis of MLH1 followed by the dolls of: doctors who do not know what Lynch syndrome entails; depression; anxiety (especially over the thought of the gene mutation being passed onto my child); surgery; hormone replacement (over several months); antidepressants (and their charming side effects); hot flashes; frustration over family members ignoring pleas to get tested; loss of appetite; lethargy; stressors on family; personality changes; feelings of despair, isolation, frustration, anger; insomnia; debilitating nausea; vomiting; headaches; hair loss; and the anxiety of annual testing. Each doll is either an emotional manifestation of knowing I have Lynch syndrome, or a physical manifestation of the prophylactic surgery, and occasionally, a doll can be a result of both.

I am not your typical patient and am probably considered an anomaly in the medical world as far as patients are concerned; I have always been vigilant with my health due to my extensive background in biology and have become my greatest advocate against Lynch syndrome. Even though I live in Chicago and have access to exceptional healthcare, I still had to find doctors who knew more about Lynch than I did. Of course, I know there are thousands of genetic mutations, I could not expect every doctor to be familiar with every single one, but there should be some measure in place for physicians, at the very least, to provide patients in such precarious circumstances with some level of care, whether it be a referral, or through some other form of support. A number of doctors I sought out for the various required screenings did not know what Lynch syndrome entails and what screening involves, or bothered to find out. Frustrated I sought a referral from a friend of mine, who happens to be a neurologist; he referred me to one of the top oncologists in Chicago, and thought this oncologist could help me in taking preventative measures against Lynch syndrome. They knew I was there for Lynch syndrome and yet the oncologist had not known, or researched Lynch syndrome prior to my visit, and told me there was nothing they could do for me. I refused to believe them and continued my search beyond Chicago.

Georgia with Dr Henry Lynch

Georgia with Dr Henry Lynch

Through research, I found a specialist at Mayo Clinic and have the good fortune to visit her and the rest of my ‘team’ on an annual basis. I make one phone call when need to come in for my annual testing for Lynch syndrome and they take care of the rest.  My screening at Mayo Clinic consists of: a CT scan, an annual colonoscopy, an upper endoscopy with extended duodenoscopy, CA-125, a urinalysis with cytology and renal ultrasound, a mammogram, and a dermatological exam to screen for sebaceous adenomas, carcinomas, keratoacanthomas. Currently there is no screening for brain cancer because the screening modality for it has not been shown to be effective at detecting cancers early or reducing morbidity and mortality if detected early. The physicians at Mayo know which tests to conduct, how frequently they must be done, which doctors are best suited for each test, and are capable of completing the various scopes and tests within of two days. My medical care requires a huge collaboration amongst doctors who know their stuff. I take great comfort in knowing that I am in stellar hands, within the confines of leading medical facility, and this in turn relieves a great deal of my anxiety.

This combination of specialists, each highly knowledgeable about Lynch syndrome, and who can discuss each patient’s unique circumstance among themselves is, I have found, an exceptional reassurance. I hope that many more such ‘teams’ will be set up for those who have Lynch syndrome.

There are several proactive measures one can take to prevent cancer and influence their gene expression.

I believe, and mounting evidence supports this, there is a constellation of factors regarding whether or not one develops cancer. Along with annual screenings and stellar medical care, I believe a healthy plant-based diet, exercise, stress reduction, meditation, and a sanguine personality will combat my deleterious gene mutation. There are many factors which effect your gene expression and whether or not you survive cancer, and I use Stephen J. Gould as my best model.

Gould was an esteemed evolutionary biologist from Harvard and was diagnosed with peritoneal mesothelioma and even with surgery, his prognosis was not good – according to the statistics, those with this particular disease typically have eight months to live. Fortunately, his professional training as an evolutionary biologist required a strong familiarity with statistics and he knew how to decipher the data. This inspired him to write an article for Discover magazine entitled, The Median Isn’t the Message, discussing how statistical averages are simply abstractions – they do not include the full range of variation. Gould applied this thinking to his medical situation and figured out that his circumstances would put him in the upper statistical range for a number of reasons: his cancer was detected early, he was young, had access to great medical care, possessed a positive attitude and was willing to take risks with experimental treatments. Gould managed to survive for 20 years until another cancer, metastatic adenocarcinoma of the lung, ended his life on May 20, 2002. His story and thoughts have been inspirational for many cancer patients.

My most recent Lynch doll was the result of the psychological toll of knowing I have Lynch syndrome. The physiological toll and the physicians’ minimization of having the oophorectemy at a young age, and having experienced menopausal shock, prompted me to create a website called: I have tried to create a site mostly for previvors, people who have Lynch syndrome but do not have cancer; a site I would have liked to have found when I was diagnosed, where nothing is sugar-coated and where others may seek validation for the myriad of emotions as a result of the diagnosis. I deal with the daily, complex, emotional aspects of having a deleterious gene mutation; and yet, at the same time, try to provide my readers with some solace and encourage them to make positive changes to their lifestyle. My most recent doll has provided me with a cathartic outlet, whilst helping others who are coming to terms with their diagnosis. It has provided me with a platform to give a voice to an elusive, heinous syndrome, which can be controlled to some degree, with endless vigilance, screenings and living well.

Georgia Hurst, MA

Chicago, IL.


Georgia Hurst’s blog:

Information about Lynch Syndrome

Variants of Uncertain Significance (VUS) and Lynch Syndrome (Patient Information Sheet)

This information sheet is available in pdf form by clicking this link Variants of Uncertain Significance

Lynch Syndrome is a genetic condition that carries a high risk of colorectal (bowel) 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.

What is a VUS? A variant of uncertain significance (VUS) is a genetic sequence change whose association with disease risk is currently unknown.

Most genetic test results are either ‘positive for a deleterious mutation,’ or ‘no mutation detected.’ However, as in many areas of medicine, results are occasionally inconclusive; consequently, medical management decisions are based on other contributing factors.

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). VUS are data that may not provide enough information to make decisions.  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.

How do I manage a patient with a VUS? Since it is not possible to classify the genetic change as deleterious or benign, the patient should be managed based on personal and family history.

Individualized management may include increased surveillance and possibly other interventions, such as surgery or chemoprevention. Consider reviewing the case with your specialist to discuss appropriate management in the context of the specific patient and family history, and to explore whether additional work-up is indicated for the patient or family.

In  practice, patients may be screened as usual for Lynch Syndrome if the clinical history was suggestive of this, but we would currently be unable to offer presymptomatic genetics testing to unaffected relatives, unless the variant  was reclassified as a probable pathogenic mutation.

Result  No mutation detected (about 90% of results)  Variant, favor polymorphism (rare)  Genetic Variant of Uncertain Significance (rare)  Variant, suspected deleterious (rare)
 Negative  Almost certainly negative  Inconclusive  Almost certainly positive  Positive
 Cause of cancer in family has not been determined; patient may have increased cancer risk, but hereditary cancer less likely  Cause of cancer in family not likely due to this variant; patient may have increased cancer risk, but hereditary cancer less likely  May turn out to be positive or negative; physician will be notified once reclassified  Patient likely has the syndrome with cancer risks defined by the syndrome  Patient is confirmed to have the syndrome; cancer risks defined by the syndrome
 Manage based on personal and family history  Manage based on personal and family history  Manage based on personal and family history; provider should receive invitation for patient to participate in Variant Classification Program  Manage according to guidelines for syndrome; suggest single site testing for family members  Manage according to guidelines for syndrome; suggest single site testing for family members
What happens once a variant is reclassified?

Over time, a variant will often get reclassified as either a benign polymorphism or a deleterious mutation. When this occurs, an amended report is sent to the original ordering provider. While most clinical genetics centres proactively reclassify variants and communicates new findings to the original ordering providers, it is important to urge your patients with VUSs to keep in contact with your office or to notify the laboratory of an alternative provider if they move, so that they and their family can benefit from new information as it becomes available. 

Squaring Genetic vs Clinical Findings in Familial Polyposis

Journal CoverPrevalence and Phenotypes of APC and MUTYH Mutations in Patients With Multiple Colorectal Adenomas

Grover S, Kastrinos F, Steyerberg EW, et al

JAMA. 2012;308:485-492


Familial adenomatous polyposis (FAP) is caused by mutations in the APC gene and 2 different, or biallelic mutations, in the MUTYH gene. However, not all patients with colorectal polyposis are found to carry mutations on these genes. In addition, it is unclear how the extent of polyp burden or the age at development of the first adenoma corresponds to the likelihood of finding mutations in either of these 2 genes.

In an effort to better characterize the mutation frequency in patients with multiple colorectal adenomas, this study tested for APC and MUTYH mutations in 8676 individuals over 8 years. Each person’s cancer history, adenoma count, and family history of cancer or colorectal adenomas was reported by clinicians ordering the genetic testing.

The study found that patients with classic polyposis were very likely to carry an APC mutation: 80% of those with ≥ 1000 colorectal adenomas and 56% of those with 100-999 adenomas carried an APC mutation. APC mutations were prevalent even in individuals with fewer than 100 adenomas, with mutations seen in 10% of those with 20-99 adenomas and in 5% of those with 10-19 adenomas.

With regard to MUTYH mutations, the frequency was low in individuals with≥ 1000 adenomas (2%) but was fairly consistent in those with 10 colonic adenomas, those who present with multiple adenomas at an unusually young age, or those who have a family history consistent with FAP. The findings of the current study support testing in these individuals and demonstrate that the greater the number of polyps, the greater the likelihood of identifying a mutation.

However, multiple factors can complicate the value of genetic testing in clinical practice. The clinical phenotype of biallelic MUTYH mutations is quite varied; reports show that some mutation carriers can have hundreds of polyps, whereas others with colon cancer have no reported polyps.[2] Also, overlap among the clinical phenotypes of Lynch syndrome, MUTYH-associated disease, and attenuated FAP or other polyposis conditions may require clinical expertise for appropriate diagnosis and management. Finally, some controversy remains with regard to risk (if any) for colon cancer in persons with only 1 MUTYH mutation, and management in these patients is uncertain.[3]

At the same time, not all individuals manifesting colonic polyposis harbor a mutation in APC or MUTYH, and management is not straightforward in patients with polyposis but no identified mutation. Clearly, there are cases of unknown etiology, and there are probably as-yet unidentified genes that may predispose to adenomatosis. But changing technologies and testing standards can also affect interpretation of genetic test results. For example, polyposis testing was once only pursued in persons with > 20 polyps, whereas guidelines now recommend that testing be done in all patients who have ≥ 10 adenomas,[1] so historically “negative” tests may need to be revisited in the future.

Similarly, individuals tested before the availability of APC deletion/duplication analysis and MUTYH testing must be reassessed. Indeed, in the past few months, new and more efficient molecular testing modalities, so-called next-generation sequencing, have allowed the commercial launch of several cost-efficient gene panels that can test multiple genes at once for polyposis and nonpolyposis mutations. This may prove particularly helpful in evaluating patients with low polyp counts.

Current recommendations note that individuals with multiple adenomas or a family history of colon cancer be referred for genetic counseling. However, a lack of family history does not exclude the possibility of FAP, because an individual can harbor a de novo mutation; genetic testing for a hereditary cancer syndrome can thus be pursued on the basis of age, polyp count, and family history. In the absence of an identified mutation, family history as well as clinical presentation can be used to determine whether the individual may be at increased risk for other syndromes, and an empiric screening and prevention protocol can be established.

via Squaring Genetic vs Clinical Findings in Familial Polyposis.

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.” ■


Genetic variant in the telomerase gene modifies cancer risk in Lynch syndrome.

European Journal of Human Genetics

European Journal of Human Genetics (Photo credit: Wikipedia)

Genetic variant in the telomerase gene modif… [Eur J Hum Genet. 2012] – PubMed – NCBI.

Genetic variant in the telomerase gene modifies cancer risk in Lynch syndrome.

Bellido F, Guinó E, Jagmohan-Changur S, Seguí N, Pineda M, Navarro M, Lázaro C, Blanco I, Vasen HF, Moreno V, Capellá G, Wijnen JT, Valle L.


Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, L’Hospitalet de Llobregat, Spain.


Lynch syndrome (LS) is an inherited cancer-predisposing disorder caused by germline mutations in the mismatch repair (MMR) genes. The high variability in individual cancer risk observed among LS patients suggests the existence of modifying factors. Identifying genetic modifiers of risk could help implement personalized surveillance programs based on predicted cancer risks. Here we evaluate the role of the telomerase (hTERT) rs2075786 SNP as a cancer-risk modifier in LS, studying 255 and 675 MMR gene mutation carriers from Spain and the Netherlands, respectively. The study of the Spanish sample revealed that the minor allele (A) confers increased cancer risk at an early age. The analysis of the Dutch sample confirmed the association of the A allele, especially in homozygosity, with increased cancer risk in mutation carriers under the age of 45 (relative risk(LSca<45_AA)=2.90; 95% confidence interval=1.02-8.26). Rs2075786 is associated with colorectal cancer (CRC) risk neither in the general population nor in non-Lynch CRC families. In silico studies predicted that the SNP causes the disruption of a transcription binding site for a retinoid receptor, retinoid X receptor alpha, probably causing early telomerase activation and therefore accelerated carcinogenesis. Notably, cancer-affected LS patients with the AA genotype have shorter telomeres than those with GG. In conclusion, MMR gene mutation carriers with hTERT rs2075786 are at high risk to develop a LS-related tumor at an early age. Cancer-preventive measures and stricter cancer surveillance at early ages might help prevent or early detect cancer in these mutation carriers.European Journal of Human Genetics advance online publication, 5 September 2012; doi:10.1038/ejhg.2012.204.

Hereditary Breast and Colorectal Cancer – what is the genetic link?

The association between breast and colorectal cancer in not clear.  There is an increased incidence of breast cancer and colorectal hamartomas which may lead to colorectal cancer in PTEN-mutation spectrum disorders such as Cowden’s Syndrome, and in Peutz-Jeghers Syndrome.  Data from genome-wide association studies demonstrates association of a common but low penetrance (weak) risk locus at chromosome 8q24.

Lynch Syndrome
The link between Lynch Syndrome has been controversial, but two recent studies have added weight to Lynch Syndrome as a risk factor for breast cancer.  A recent study in JNCI (Win et al 2012) suggests that amongst Lynch Syndrome patients the risk of breast cancer as a second cancer after a diagnosis of colorectal cancer may be increased by about 76%.  An earlier study this year suggests that their is molecular evidence for this association (Buerki et al Genes Chromosomes Cancer 2012).


Some studies in Li-Fraumeni Syndrome families identified mutations in CHEK2 as possible cause for this condition (Bell et al Science 1999).  This link has not been reproducible but the variant 1100 may be a population variant which increases risk in Ashkenazi Jewish populations.

Families with Li-Fraumeni Syndrome and CHEK2 mutations

Evidence demonstrates that a subset of families with hereditary breast and colon cancer may have a cancer family syndrome caused by a mutation in the CHEK2 gene. Although the penetrance of CHEK2 mutations is clearly less than 100%, additional studies are needed to determine the risk of breast, colon, and other cancers associated with CHEK2 germline mutations. One large study showed that truncating mutations in CHEK2 were not significantly associated with CRC; however, a specific missense mutation (I157T) was associated with modest increased risk (odds ratio [OR], 1.5; 95% CI, 1.2–3.0) of CRC.

Similar results were obtained in another study conducted in Poland. In this study, 463 probands from LS and LS–related families and 5,496 controls were genotyped for four CHEK2 mutations, including I157T. The missense I157T allele was associated with LS–related cancer only for MMR mutation-negative cases (OR, 2.1; 95% CI, 1.4–3.1). There was no association found with the truncating mutations. Further studies are needed to confirm this finding and to determine whether they are related to familial CRC type X.

A Family History of Bowel Cancer?

Many people worry about getting bowel cancer, sometimes because a relative has had it. About 1 in 20 people will get bowel cancer in their lifetime.

Bowel cancer is the third most common cancer in the UK for men and the second most common cancer for women. Every year more than 30,000 people will develop it.

The cause of most bowel cancers is not known, but we do know that some risk factors can increase your chances of developing cancer.

Having a particular risk factor for cancer, or being exposed to one, doesn’t mean that you will definitely get cancer – just as not having it doesn’t mean that you won’t. For example if you just have one elderly relative who had bowel cancer, it’s unlikely that you will have a significantly increased risk.

How does family history affect my bowel cancer risk?

Genes carry the biological information we inherit from our parents. They affect the way our bodies grow, work and look.

Changes (mutations) in certain genes can increase the risk of bowel cancer in family members who inherit the genetic change. However, only a small number of bowel cancers are thought to be due to an inherited altered gene (genetic mutation) running in the family.

A genetic mutation that could increase your risk of developing bowel cancer is only likely to be present in your family if you have:

  • One close relative who had bowel cancer at a young age (under 50). Your close relatives are your parents, children, brothers and sisters. They are also sometimes called your first degree relatives.
  • At least two first degree relatives on the same side of the family who developed bowel cancer.
  • Cases of bowel and womb cancer on the same side of your family.
  • Relatives with multiple (over 10) pre-cancerous growths (polyps) in the bowel.

If any of these apply to your family and you’re worried about your risk of developing bowel cancer, you may want to talk to your GP. If your GP thinks there’s a chance you may have an increased risk of developing bowel cancer because of your family history, they can refer you to a family history of bowel cancer clinic at West Middlesex University Hospital or elsewhere.

Inherited conditions which increase the risk of bowel cancer

Up to 30 per cent of people will have a close relative with bowel cancer, however, the degree of risk varies between individuals.  There are some conditions in which inherited genetic changes greatly increase the risk of bowel cancer developing, such as polyposis and Lynch syndrome, where many people in a single family can be affected.  Only about 5 per cent of bowel cancer cases occur in people who have a very strong inherited predisposition.  On the other hand, if only one elderly relative has had bowel cancer, this does not greatly increase your risk.

How can screening reduce my risk of bowel cancer?

The Bowel Cancer Screening Programme (BCSP)

Everyone in England between the ages of 60 and 75 years of age is invited to take part in the National BCSP.  This involves 2 yearly stool tests which are sent through the post, the Faecal Occult Blood Test (FOBT).  People with an abnormal FOBT test will have a colonoscopy.

During a colonoscopy a long, flexible tube is inserted gently into the back passage to look at the inside of the bowel. Bowel screening aims to detect any precancerous changes to the bowel (known as polyps) that could develop into cancer.  These polyps can be removed and cancer prevented.  More information about the BCSP can be found at

People with a stronger family history

For most people with a family history of bowel cancer the BCSP is an adequate level of screening.  For some people with a stronger family history we recommend screening with colonoscopy directly rather than the stool tests.  For example this may be from the age of 50 years and every five years for people with 2 close relatives with bowel cancer at a young age.  The type of screening for an individual does vary depending on the degree of risk.  We can discuss this with you in detail in the family history of bowel cancer clinic and work out what suits you best.

Think you have a strong family history of bowel cancer?

Do you know if anyone in your family has had bowel or any other kind of cancer? Talk to your family and make sure you all know your family history.  This would for example be particularly important for those people with a history of bowel cancer diagnosis under age 50 years, or with 2 people in their family affected with bowel cancer.

If you think you have a strong family history of bowel cancer, you should make an appointment with your GP to talk about your concerns. If your GP agrees with you, they can refer you to a specialist family history of bowel cancer clinic at West Middlesex University Hospital. The specialist will go through your family history with you in great detail and ask you to provide accurate information about who has been affected, how old they were when they were diagnosed, and the site where their cancer developed. You may also have to have blood tests as part of this investigation.

You will talk about what types of screening they would recommend, at what age you (and/or other family members) should start being screened and how often you should be screened. Regular screening will ensure that any signs of bowel changes and early cancer are spotted and treated quickly.  You can also discuss other ways to reduce your risk through your lifestyle.

Who we are

Dr Kevin J Monahan (Service lead) spent three years working at Cancer Research UK where I completed my PhD in cancer genetics with funding from the Bobby Moore Fund for Bowel Cancer Research.  I worked in the Family Cancer Clinic at St Mark’s Hospital in Harrow during this time.  I work with Dr Iain Beveridge, Dr Carole Collins, Dr Joel Mawdsley and Dr Krishna Sundaram in the Gastroenterology Department.
Athalie Melville is a Genetic Counsellor from the Kennedy Galton Clinical Genetics Centre in Northwick Park, Harrow.  She sepnd time also within the clinic seeing patients before they have genetic testing.

The other members of the team are from the Departments of Gastroenterology, Endoscopy, Colorectal Surgery and Cancer Services at West Middlesex University Hospital.

Familial Adenomatous Polyposis (FAP)

FAP (familial adenomatous polyposis) is a rare genetic disease that causes a family history of cancer and multiple polyps in the bowel.

Lynch Syndrome

Lynch Syndrome (also known as hereditary non-polyposis colorectal cancer or HNPCC) is a rare condition that may cause a family history of bowel cancer, and causes 1000 cases of bowel cancer in the UK annually. Anybody diagnosed with bowel cancer under 50 years of age should be tested for this condition (unless they have over 10 polyps)

Endoscopic procedures

Sigmoidoscopy patient information sheet

Gastroscopy patient information sheet

Colonoscopy patient information sheet

Information for GPs

Click here to download information sheet for GPs

Contact details

The Family History of Bowel Cancer Clinic,
Gastroenterology Department
West Middlesex University Hospital,
Twickenham Road, Isleworth,
London TW7 6AF.
Telephone: 020 8321 5351
Fax: 020 8321 5024

Useful web pages

Beating Bowel Cancer

Bowel Cancer UK

Cancer Research UK: High risk groups for bowel cancer

Macmillan: Information about bowel cancer

West Middlesex University Hospital – Department of Gastroenterology

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