What is Lynch syndrome?

Lynch syndrome (LS) is a genetic disorder that causes an increase in certain cancers at an earlier age than usual. There about 12 cancers that can be affected, the commonest are large bowel cancer and rectal cancer. After that, the next most common is womb cancer. LS tends to run in families so it is usual to find than people in different generations have one of these cancers. Find out more on our website lynch-syndrome-uk.org

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Lynch syndrome gene mutations are inherited in an "autosomal dominant" pattern. That means either sex can get it and it can pass from parent to child. There is a 50% chance that children of someone with LS will inherit the abnormal genes. It cannot skip generations.

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The cancers that occur in Lynch syndrome families can come from this list (the commonest ones are first) : large bowel (or colon) and rectum, womb (uterus), ovary, urological cancers (kidney, ureter and bladder), stomach, small bowel, pancreas, biliary tract, some skin cancers, some breast cancers, prostate and some brain cancers.

[Suziewoozi]

Hi I'm suzie LS+ MLH1 I'm 30 years old. I'd like to get as much information as possible on LS raise awareness and learn more about any prophylactic surgeries available. It'd also be nice to find some new friends who understand the brevity of being diagnosed LS.

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Hi Suzi, I expect you know a lot about MLH1 but this is a quick resume. Women should have 1-2 yearly colonoscopies from 25 years old and the risk of cancers of the uterus and womb means you should seek gynaecological advice at 30-35 years. The safest option is to have HBSO - hysterectomy and ovaries removed around 40 depending if you have finished having children. It is possible to have screening of these organs but not all gynaecologists do it and it therefore isn't routinely available. The risk of breast cancer is higher than the general population in women with MLH1 and so earlier mammograms at 40 years are advised in the UK. Other cancers such as skin, kidneys/ureter/bladder, stomach, small bowel, pancreas and brain are not high enough to be screened routinely by family history can make a difference. If you go to our website we have information in detail that can be downloaded - go to the learning section.

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Are you thinking of having hysterectomy Suzi?

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The "fault" in Lynch syndrome lies in a mutation in the "mismatch repair" system of cells' DNA. DNA is the helical structure in the nuclei of cells that ensures that replication of chromosomes is performed accurately. People who have LS are not able to rectify faults that happen on a regular basis when cells divide and multiply. Eventually this can lead to cancerous changes.

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lynch-syndrome-uk.org If you're interested in learning a lot of detail about LS - go to our website. There are documents about genetics, bowel cancer and uterine cancer in the learning centre that cover everything you need to know and can be taken to your GP. Or you can just get to grips with the essentials, learning just what you need to know. Firstly, do you know what gene mutation you are? If you do, fill out our quick poll above.

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There are 5 main gene mutation (or alteration) groups in LS. The two most common ones are MLH1 and MSH2. MSH6 and PMS2 are less common and (usually) cause less trouble than the other two. EPCAM is a small group of people who have mutations or deletions of the MSH2 gene. There are also lots of "variants" to the usual picture of gene mutations - there are several thousand of these world wide. That is why when you have tests for LS it is not just a quick "yes" or "no" test. In some cases it takes months.

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Lynch syndrome (LS) is a "autosomal dominant" inherited gene. That means it passes from a parent to a child. It can affect both sexes. Offspring each have a 50% chance of inheriting LS from their parent. It does not skip generations. Children born with one of the Lynch syndrome mutations do not have any outward stigmata of the disease but if their blood was tested it would already have the tell-tale LS mutations. Fortunately, nearly all children do not have any problems until they are adults but just occasionally a family has a youngster who gets cancer below the age of 18 years old.

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The spread of mutations among the LS community is uneven. About 40% have MLH1, 40% have MSH2 or Epcam, 11% have MSH6 and 6% have PMS2. Each of the gene mutations has a different pattern of cancers but on the whole, MSH6 and PMS2 have fewer cancers. Research studies in the past had vastly different proportions of the genes. That was because the research was often done on LS patient registries and they often had a disproportionate number of MLH1 and MSH2 patients with bowel and rectal cancer. Recent research such as Moller P, "Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance . . . gut.bmj.com/content/early/2... is an example of gene specific research that is done prospectively not retrospectively. Even so they don't have enough PMS2 cases to make some of the findings statistically significant. The lesson here is beware of old research papers about LS - anything over 10 years old use their figures with caution. Make sure what you are looking at is "gene specific" - that is the genes have different figures, not all lumped together. Try to use review articles from the UK, Europe or US. If papers are all saying the same thing it is probably correct. All articles from Henry Lynch are well written, plain English and good science.

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Always check your Lynch syndrome mutation group with your genetic counsellor. Not only are the groups basically different but there are "variants" of each of the main mutations or deletions that change the behavior of the genes in the formation of cancers. There are several thousand LS variants all over the world. They don't all cause trouble - some are "non-pathological". It means that LS gene results might have to be chased around the world if your relatives have come from far and wide. The world-wide collection of LS gene mutations put together by InSight an international organization for genetic bowel diseases has helped this enormously. You can help this process, whether you are in the UK or abroad by letting your genetic counsellor know that you want your genetic results sent to InSight database. Put a knot in your hankie!