A largely Swedish study using UK data [1].
The only thing that experts agree on concerning the causes of PCA, is that risk increases with chronicological age. The new study used three different calculations of "biological" age, expecting to get a better age measure for the risk of various cancers. Unexpectedly, biological age [BA] was inversely associated with PCa risk.
"... we observed an inverse association between BA measures and prostate cancer, although it was attenuated after removing glycated hemoglobin and serum glucose from the BA algorithms."
...
"... as we found an unexpected protective effect of BA measures for prostate cancer and that HbA1c and serum glucose may be associated with reduced prostate cancer risk, we repeated the analysis using modified versions of KDM, PhenoAge, and HD computed from 16 biomarkers (i.e., removing HbA1c and serum glucose) to further examine whether the observed inverse relationship may be influenced by these two biomarkers."
...
"The inverse association between BA and prostate cancer found in our primary analysis is somewhat in line with previous studies which showed indications of a protective effect of the GrimAge clock for prostate cancer. Interestingly, in our study, this association was slightly attenuated after adjusting for prostate cancer-specific factors such as diabetes and having prostate-specific antigen (PSA) test, and was further attenuated to non-statistically significance after removing HbA1c and serum glucose from the BA algorithms. Diabetes, as well as HbA1c and serum glucose levels, have been linked to a lower incidence of prostate cancer, partly because of the lower level of insulin-like growth factor-1 levels in diabetic patients, and partly because of the potential detection bias due to the lower PSA level in diabetic men. We therefore speculate that the apparent protective effect of higher BA for prostate cancer could be confounded by diabetes and altered glucose metabolism, which are also closely related to aging."
...
A number of studies have reported that diabetics have a higher risk of every cancer type other than PCa, for which they have lower risk.
My interpretation has been that insulin resistance is, uniquely, a risk factor for PCa. Two significant things have happened to diabetics: (i) production of insulin has been much reduced, due to beta cell burnout, & (ii) Metformin, which is standard treatment for the newly diabetic, controls glucose spikes without the need for insulin medication.
In other words, if men with insulin resistance were to be given Metformin, the number of PCa cases would fall and the apparent protection of diabetes would disappear.
-Patrick
[1] full text: nature.com/articles/s41416-...
