MSH6

So Lynch is not a classic polyposis syndrome because patients do not develop hundreds of polyps, but it is a major hereditary colorectal cancer syndrome and an important contrast to FAP.

So Lynch syndrome results from mutations in DNA mismatch repair genes, including the MLH1, MSH2, MSH6, and PMS and PMS2.

Patients may only have a few adenomas, but the progression from adenoma to cancer can happen more quickly.

Think early onset and often right-sided colorectal cancer, plus a family history of endometrial, ovarian, gastric, urinary tract, or other related cancers.

Yeah, well, we already do in the UK because we're a little bit ahead of the curve.

So our new UK recommendation is that you start aspirin at 20 for the two big genes and you start at 30 for MSH6 and PMS2.

The MSH6 group are easily included.

It's slightly less penetrant.

More than 20% of our participants were MSH6.

So I think it's okay for the big three genes.

I always say that PMS2 is the drummer in the band.

The typical MMR evaluation, MLH1, PMS2.

MSH6, MSH2.

When there's loss of expression, that means there's an abnormality.

We're going to talk about the therapeutic implications, but we also could talk about the, it's also a triage tool for germline mutational status for those patients with Lynch syndrome.

Okay

... are the proteins MSH2 and MSH6, coded for by the genes MSH2 and MSH6.

Mm-hmm.

Now, here's what matters for you.

Okay.

The reason that matters is because Lynch syndrome is actually caused by genetic changes in multiple different genes.

MSH2 and MSH6 are on that list.

Okay.