Lynch Syndrome Explainer: A Common Cancer Risk Few Have Heard Of

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Lynch syndrome is a common, inherited condition that affects thousands of Australians and greatly increases the risk of developing cancer. Yet 95% of those who have it dont know about it.

Lynch syndrome is the most prevalent inherited cancer syndrome affecting both men and women. It is caused by an inherited gene mutation affecting one of four mismatch repair or cancer protection genes (MLH1, MSH2, MSH6, PMS2).

Mismatch repair genes should repair mistakes that can occur when DNA is copied for cell division. Faulty mismatch repair genes allow errors to accumulate in cells, which can lead to uncontrolled cell growth and cancer.

Up to one in 250 people may carry a mismatch repair gene fault. As many as one in 280 carry a fault in a Lynch syndrome gene.

A parent with Lynch syndrome has a 50% chance of passing on the faulty gene to their children, regardless of gender. However, because a carrier inherits one faulty gene and one properly functioning gene, some people with Lynch syndrome may never develop cancer.

Lynch syndrome does not cause cancer and has no readily identified symptoms, but the faulty gene predisposes carriers to a dramatically increased risk of developing one or more primary cancers over their lifetime. As this tool shows, the risk varies by type of tumour, age, gender and the particular mismatch repair gene that is affected. In people with the syndrome, cancers are often fast growing, may occur simultaneously and tend to occur from a much younger age (under 50 and sometimes in the 20s or earlier).

If an individual knows they have Lynch syndrome, they can adopt life-saving strategies for cancer prevention, early detection and treatment.

^{Lynch syndrome awareness video}

What Cancers Are Associated With Lynch Syndrome?

Patterns of Lynch syndrome cancers in families were first observed by Dr Aldred Warthin in the 1890s. However, the condition is named after Dr Henry Lynch, who persisted against the prevailing wisdom of the 1960s-70s which disputed a hereditary basis for cancer to document, describe and establish the genetic basis for Lynch syndrome.

For a time, Lynch syndrome was called hereditary non-polyposis colon cancer. That was an unfortunate misnomer because Lynch syndrome cancers can involve polyps and dont just involve colon cancers.

Lynch syndrome is most commonly associated with colorectal and endometrial cancers. It also significantly increases the risk of cancer of the ovary, stomach, hepatobiliary tract (liver/gallbladder), urinary tract, pancreas, brain, skin, oesophagus and small bowel.

Some tumours may also present differently in individuals with Lynch syndrome. Examples include the unusually flat, difficult-to-detect polyps and tumours sometimes observed in bowel and breast cancers.

How Is Lynch Syndrome Diagnosed?

GPs should suspect an individual may carry a Lynch syndrome gene when there is a compelling family history of cancer. This means three or more family members have been diagnosed with cancers identified above, two consecutive generations or more are affected by those cancers, and one of those affected family members was diagnosed with cancer before 50 years of age. It should also be suspected where a patient has little or no access to their familys health history information and has already had one or more relevant cancers before age 50.

^{Family history of cancer as above could signify Lynch syndrome. Source: Lynch syndrome Australia.}

If Lynch syndrome is not identified and the patient develops cancer, they will typically require surgery to remove the tumour. Current best practice for all colon and endometrial tumours for patients under age 50, or who have a strong family cancer history, is for the treating team to order a pathology test to check mismatch repair genes are functioning properly.

Unfortunately, research reveals less than half of these tumours are tested and patient follow-up is confusing and inconsistent.

Any patient suspected of carrying Lynch syndrome should be referred to a family cancer clinic. There, a genetic counsellor will conduct a thorough assessment and explain the gene-testing process and its implications. With patient consent, the clinic will arrange testing of a tissue sample from a past tumour (either the patients or another family members) to search for a mismatch repair gene mutation.

If a gene mutation is detected, risk-reducing strategies are discussed. Diagnosis for other family members then involves a relatively simple blood test, which looks for the same mutation.

How Is Lynch Syndrome Managed?

Managing Lynch syndrome involves a surveillance plan of regular tests to detect problems early. Then polyps can be removed before they become cancerous or cancers can be removed at an early stage. The potential for risk-reducing surgery (to remove organs, such as ovaries, that are high risk yet difficult to screen) or supplements such as aspirin (which longitudinal studies suggest may significantly reduce the incidence of Lynch syndrome cancer) may also be considered.

Guidelines recommend annual colonoscopies (from age 25 or 30, depending on the gene mutation, or five years younger than youngest relative diagnosed with bowel cancer) and prophylactic removal of the uterus, fallopian tubes, ovaries and cervix be considered after childbearing is complete, or by age 40.

Frequent colonoscopies are important because the average time from polyp to bowel cancer reduces from ten years in the general population to just 35 months in patients with Lynch syndrome. Similarly, the average age for developing uterine cancer reduces from 64 years to 42-46 years.

An individuals surveillance plan may be further tailored to address specific cancer risks for them, based on family history or environmental factors. For example, a family history of gastric or skin cancers may justify including annual endoscopy or dermatological reviews.

Effective diagnosis and management of individuals with Lynch syndrome can be life-saving. Unfortunately, this is not the experience for thousands of Australian families. Its important we raise awareness of this condition among medical professionals, health organisations and the general public.

Sharron O’Neill, Researcher, International Governance and Performance (IGAP) Research Centre and Natalie Taylor, Senior Research Fellow in Behaviour Change and Implementation Science

Read more: http://www.iflscience.com/health-and-medicine/lynch-syndrome-explainer-common-cancer-risk-few-have-heard