S1E3: Endometrial Cancer - Risk Factors, Pathophysiology & Types

This is the most common gynaecological cancer in Australia and Aotearoa, New Zealand, so worth paying attention

to.

Now the good news is this is one of the cancers where an early diagnosis can make a huge difference and luckily enough it often gives us signs and symptoms which helps with early diagnosis and therefore treatment.

So let's start with the risk factors.

Yes, we've already discussed them in the last two episodes, but we're going to go through them in a little bit more detail and talk about why they make sense.

First, let's talk more broadly about risk factors for cancer in general, age, personal history, family history and immunodeficiency.

Chloe, can you talk us through why each of these are relevant?

Yeah, so firstly, age makes sense as a risk factor because it takes time for cell mutations to develop and turn into cancer.

So the longer you've been around, the higher the risk of developing cancer.

Personal history is explained because if a patient has developed a cancer before, they're more likely to develop it again.

either by cancer occurrence or individual propensity to DNA damage.

And if they already have a pre-malignant disease, it's at risk of progressing to malignancy as well, like endometrial hyperplasia becoming endometrial adenocarcinoma.

Now, family history can be explained by genetically inherited cancer syndromes, but even without genetic syndromes, there seem to be some families who are more prone to developing malignancies.

And finally, immunodeficiency.

Now, this is because the immune system can help to destroy DNA-mutated cells.

If there's a significant immunodeficiency, then these systems fail, so mutated cells are allowed to proliferate into cancers.

As for risk factors for endometrial cancer specifically, we're talking about unopposed estrogen, and this is because estrogen is the hormone which drives endometrial proliferation, until changing progesterone levels cause stabilisation, then shedding of the endometrium.

With unchecked proliferation comes the risk of cell damage and therefore development of cancer.

On the other hand, progesterone is protective as it suppresses endometrial growth and encourages its shedding.

And as we remember, the causes of unopposed estrogen include taking estrogen or estrogen-like medications such as tamoxifen, estrogen-secreting tumors, obesity because adipose tissue produces estrogen, early menarche, late menopause, and nulliparity because these patients have been exposed to more estrogen in their lives.

and PMOS, where cycles are anovulatory, and therefore there is a relative lack of progesterone, and endometrial proliferation therefore goes unchecked for longer cycles.

Now, other risk factors also include diabetes and hypertension, in keeping with a metabolic syndrome phenotype.

On the other hand, taking progesterone, the contraceptive pill, increased gravity and parity, breastfeeding, and increased physical activity are considered protective against endometrial cancer.

Now when you're reviewing the risk factors for endometrial cancer, a common trick is to mention smoking.

Smoking is a common risk factor for a lot of different cancer types, but it's actually protective for endometrial cancer.