So, this is indeed an interesting finding (though the linked does not provide access to the entire manuscript, which was hard to find), but it should be taken alongside the entirety of the LDL/Cancer relationship data.

An extended thread:
A bit of background first-- LDL levels in the context of chronic disease are a bit tricky. (Chronic) Inflammatory conditions decrease LDL levels (via IL-6, TNFa, other cytokines), making it essential to consider the role of reverse causation in these types of analysis.
In the context of things like metabolic syndrome (which, remember, is also an inflammatory condition), this can be challenging, as there are forces pushing LDL in either direction. In cancer, though, it is a bit more clear cut--chronic inflammatory conditions decreases LDL levels…

Interestingly, the % of sdLDL particles often **increases** in the context of inflammatory disease despite an LDL-C decrease, but that's a topic for another thread.

Anyway, this phenomenon is well-characterized in inflammatory diseases, including cancer
The study linked originally suggests that lower LDL levels can predict risk for cancer incidence almost 19 years in advance-- a compelling finding. This study also found that some association was suggested between some types of cancer and low LDL levels in a population study…

This study did look at total serum cholesterol, though, which adds together HDL, LDL, and Trigs/5 . LDL is the largest contributor to this number, but the directions of the vectors in the TSC variables are not unidirectional-- a non-trivial limitation.
It should be noted, also, that this study (I believe) did not stratify or control for lipid-lowering medications (i.e. statin use).
A significant degree of associations disappeared when reverse causation was attempted to be accounted for, including a lag-time analysis, but associations did persist for several types of cancers, including for general risk of cancer in women (did not persist in men).
So far, it looks like we might be onto something, right? Immune cells use cholesterol liberally for immune function, why wouldn't more = better surveillance, less cancer incidence? Well, we can go into why the mechanistic data really support this in a separate thread...
For now, let's continue to focus on the outcomes data.

If low LDL was a causal factor in increased cancer incidence, we would expect genetically lower cholesterol levels (and therefore lower lifetime exposure) to result in a significant increase in cancer incidence--
almost as a reverse of the increase in ASCVD seen with lifelong exposure to high LDL (i.e. FH).

However, this doesn't happen. Lifelong lower levels of LDL confer no difference in cancer incidence (0.96 (95% CI = 0.87 to 1.05)).
Even those with PCSK9 variants (a strong genetic LDL-C reducer) did not have a greater number of events.…
Furthermore, analysis of 175,000 individuals showed that use of statin medications and concurrent reduction in LDL levels did not impact cancer incidence rates (RR=1, exactly the same risk).…
Notably, " In particular, among individuals with low baseline LDL-C (<2 mmol/L), there was no evidence that further LDL-C reduction (from about 1.7 to 1.3 mmol/L) increased cancer risk (381 [1.6% py] versus 408 [1.7% py]; RR 0.92 [99% CI 0.76–1.10])."
Further, observation of cancer incidence and progression suggests a significant LDL lowering effect of pre-clinical neoplasm, which leads to a lead-time bias like effect in terms of incidence and mortality in many population based considerations.…
So, we are left with a lack of dose response and no apparent temporal component. This makes the claim that LDL plays a causal protective role in preventing cancer an extremely difficult sell.
Now, I know I said mechanistic considerations would be left for another thread, but let's consider that for just a moment.

We must always remember that mechanistic speculation goes both ways. There is some very loose mechanistic cases that LDL is used in immunologic processes
and therefore increasing levels of it demonstrate improved immune function (this is not how substrate sufficiency works, but okay). Let's take a look at the mechanistic evidence to say this is a reductionist characterization (warning-- these strongly suggest the opposite):
I can link many more, but I think I've made my point.

Anyway, I look forward to additional, well-designed analysis of the subject, as it certainly is warranted, but from the available data, it is irresponsible to call LDL a causal protective agent in the prevention of neoplasms
/End Scene

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17 Oct
I’d like to use this to highlight why defining terms matters, and refusing to do so severely reduces the utility of such conversations.

LDL risk stratification are best predicted by AUC. Point/cross-sectional sampling is only weakly predictive....
Therefore, proposing this as a hypothetical without specification of age, first and foremost, limits the ability to extrapolate conclusions extensively. Is the person 70 with no history of events? Likely very mild difference? 30, with family history of ischemic events?
It is challenging to engage these types of arguments with data-driven follow up and analysis because terms and specifications are rarely provided. In exercises that are driven by cumulative statistics, which is exactly what this is, these sorts of specifications are **essential**
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