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Young people often present with concerns that they could have symptoms that represent an underlying cancer diagnosis. Thankfully, this is rarely the case. However, this recently updated GPnotebook page on Lynch syndrome, a familial condition associated with cancer, reminded me that asking about family history is a powerful tool in picking out rare cases.

I have only seen one case of Lynch syndrome in my patient population, and the lady in question attended about a year ago. She was in her early 40s and presented with unusually persistent rectal bleeding and blood mixed in with the stool. She also had weight loss and right iliac fossa pain. Luckily, she saw a consultant quite quickly; unluckily, her colonoscopy revealed colorectal cancer (CRC). In the midst of her treatment, another letter arrived stating that she had a diagnosis of Lynch syndrome, or hereditary non-polyposis colorectal cancer (HNPCC).

What is Lynch syndrome?

Well, it is a condition first identified nearly a century ago and characterised by a familial clustering of cancers, particularly those of the colon, small intestine, stomach, endometrium, upper urinary tract and sebaceous tumours of the skin. The cancers are not related to polyposis, hence the term HNPCC.

A striking point is that Lynch syndrome accounts for approximately 2–5% of all cases of CRC. As the most common genetic syndrome associated with an increased susceptibility to CRC, I think it is something worth having on our radar as GPs.

When I reviewed the referral letter that I sent for my patient, I did note a family history of colorectal cancer in her mother, when she was in her 40s; however, reading about Lynch syndrome has convinced me to widen the net a little in asking about the family history of cancer.

The implications of a diagnosis of Lynch syndrome are significant and listed below.

• The first thing to note is the 60–80% risk of the person developing CRC at some point in their lives.
• The CRC is often located in the right or proximal colon, in contrast to a predominance of sigmoid/distal carcinomas in sporadic disease. This can make it more difficult to pick up and increases the risk of a later presentation.
• Other gastrointestinal (GI) tract malignancies are also more common, including gastric cancer, cancer of the small bowel, cancer of the biliary tract and pancreatic cancer.
• Endometrial cancer is the second most common malignancy in Lynch syndrome, with a lifetime risk between 40% and 60%, often occurring before CRC in females.
• There is also a higher risk of ovarian cancer, of cancer of the renal pelvis and of cancer of the brain.
• There is a suggestion that breast cancer risk is increased, although this remains controversial.

A unifying feature for all of these cancers is that they tend to develop earlier in life. For example, the average age of onset for CRC and endometrial cancer for individuals with Lynch syndrome is approximately 44 and 48 years, respectively, compared with 65 years for CRC and 60 years for endometrial cancer. The risk of people with Lynch syndrome getting more than one type of cancer is 50%, and some even get multiple cancers at the same time.

The underlying pathology in Lynch syndrome is a genetic condition – Mendelian autosomal dominant in pattern – and affects genes that protect the integrity of DNA. Individuals are born with a normal-functioning gene on one chromosome and a mutated gene on the other chromosome. The one functioning gene can be enough to stave off the cancer risk in some, explaining the unpredictable presence of cancers in people with Lynch syndrome.

From a clinical point of view, the change in my practice will be to ask more broadly about family history of cancers, especially in people presenting with GI or gynaecological symptoms.

If a suspicion of Lynch syndrome is raised on this one question, it is useful to know that there are two sets of criteria to spot those who need testing – the Amsterdam criteria and the Bethesda criteria.

Both sets of criteria are found on the updated GPnotebook page, but I have only included the Bethesda criteria below as I found it slightly easier to make sense of.

Bethesda criteria

Individuals are at risk if they:

• Have been diagnosed with CRC or uterine cancer and are younger than 50 years.
• Have been diagnosed with a second CRC or another cancer associated with Lynch syndrome.
• Are younger than 60 years and have a cancer that is characteristic of Lynch syndrome when viewed under a microscope.
• Have a first-degree relative (parent, sibling or child) younger than 50 years who was diagnosed with CRC or another cancer associated with Lynch syndrome.
• Have two or more first- or second-degree relatives (aunt, uncle, niece, nephew or grandparent) with CRC or another Lynch syndrome-related cancer at any age.

Naturally, where we become suspicious, the appropriate path is onward referral for diagnosis, management and familial screening. If a diagnosis is confirmed, the electronic patient record becomes our best friend, where we can make note of the diagnosis and highlight the future red-flag presentations to look out for.

This topic is large in scope and very interesting, but I will stop writing before losing your attention!

For more information on the role of aspirin in Lynch syndrome and endometrial cancer in Lynch syndrome, click here and here, respectively.

Many thanks for reading this, and I look forward to writing for you again next month.