On statins: a race-related update

It is relatively common knowledge — although never actually proven in a large, randomized, placebo-controlled trial — that statins like rosuvastatin (Crestor) and atorvastatin (Lipitor) may be helpful in the management of prostate cancer.

Specifically, the use of statins has been associated with clear indications that they may be able to lower risk for diagnosis with prostate cancer (and high-risk prostate cancer in particular); lower risk for prostate cancer recurrence after first-line therapy; and lower risk for prostate cancer-specific mortality among men diagnosed with prostate cancer.

Of course what we really need are the large-scale clinical trials that could actually prove these effects, but the cost of such trials would be high.

What we have not ever had, until now, are data indicating whether these apparent effects of statins are observed in men of ethnic/racial groups other than Caucasians. Two of the three findings mentioned above come from retrospective analyses of the large Danish national health-care databases, and non-Caucasians are not exactly commonplace in the Danish population. However, …

In a presentation given at the annual meeting of the American Urological Association (AUA) earlier this year, Allott et al. reported findings from a retrospective study of information from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, which compiles data from eight different VA hospitals across the country and consequently includes data for a high percentage of African-American males.

Allott et al. were able to identify 570 prostate cancer patients in this database who had been started on androgen deprivation therapy (ADT) after initial treatment (by radical prostatectomy) for a diagnosis with prostate cancer. They were then able to use electronic medical records to identify a spectrum of other data about these patients, including the use of a statin prior to initiation of ADT.

Here is what they found:

  • 308/570 men (54 percent) were taking a statin prior to starting ADT.
  • 239/570 patients (42 percent) were African American.
  • Statin users were slightly older, on average, than non-users (65 vs. 63 years)
  • Statin users had a higher body mass index (BMI), on average, than non-users
  • Statin use, overall, was not associated with risk for
    • Prostate cancer metastasis
    • Onset of castration-resistant prostate cancer (CRPC)
    • Prostate cancer-specific mortality (PCSM)
    • All-cause mortality

However, they also found, on univariable analysis, that

  • White men demonstrated clear inverse associations between statin use and risk for
    • Prostate cancer metastasis (hazard ratio [HR] = 0.57; p = 0.037)
    • Onset of CRPC (HR = 0.58; p = 0.048
    • PCSM (HR = 0.46; p = 0.04)
  • African-American men showed no comparable associations.

In other words, in men with higher-risk forms of prostate cancer who went on to have ADT after their first-line therapy, statin use prior to initiation of ADT (and presumably ongoing afterwards) seems to have had a definable impact on lowering risk for metastasis and later consequences in whites, but no such impact in African Americans.

One has to wonder whether this finding is in any way associated with other data, reported at the ASCO annual meeting this year, suggesting that African-American men being treated for metastatic prostate cancer often seem to do better, on average, than Caucasian and Hispanic patients.

13 Responses

  1. African American is a social term, not a genetic term, dubious it should be a medical term. Obama was a “black” man at 50%. Is the child of a “white” mother and a “black” African man at 50% “white”? How low a percentage does it take to become “white”? Are you still a black man at 10%?

    Not trying to make a social comment, but as a medical risk factor “black” has not much of a scientific basis. Were I “black” I would be feeling my “medical studies” were being analyzed rather unscientifically.

  2. We have seen data that African Americans tend to get a more virulent form of prostate cancer, which may have something to do with it. Also, as we saw in PIVOT, men treated at the VA (at least in that trial) had lower than expected survival, so results may not be generalizable to the US population.

    There have been dozens of retrospective studies on statins with some unable to find an effect, and some finding a positive effect. But since low-dose statins are cheap, have few adverse effects, and may be good in older men for other reasons, my opinion is why not take it (along with low dose aspirin and metformin)?

  3. Dear Mike H.

    Well, using your argument, exactly the same complaint can be made about the use of the term “white”. And yet we use these terms all the time. Do you have a better suggestion? I know of no one specific gene that could be used to define “race”. We use the terms “Caucasian”, “Hispanic”, “Asian”, and “Native American” with an equal degree of inaccuracy.

  4. Dear Allen:

    I was being very careful not to comment on the issue of whether one should or should not be taking a cholesterol-lowering agent specifically to manage one’s prostate cancer if one had high-risk disease like the men in this study. My comments were confined to an interesting finding.

  5. Sitemaster,

    My complaint is not about the use of the term, it is about the loose treatment of data and what it means.

    The study attempts to find the risk factors for “African Americans”. It is the equivalent to a study of obesity that fails to define obesity.

    Being “African American” is a linear risk? I do not think so, any more than being 5 lbs overweight to 500 lbs is a linear risk.

    The extent of “African American” genes and it’s risks factors seems to be a basic question of research. “All the same” is simply a basic flaw in the research.

    The European white argument is not wrong, it just has a longer period of genetic mixing than the “African American”.

  6. Dear Mike:

    You didn’t answer my question. We have well-defined categories for body mass index (albeit still rather “gross”). We do not have (and perhaps can’t easily develop) similarly well-defined categories for “degree” of any particular “race”.

    I would also seriously question your statement about white Europeans having had “a longer period of genetic mixing” than African Americans. What genetic mixing are you referring to? There were subtypes of the species Homo sapiens in Africa at least a hundred thousand years before any of them made it to Europe and Asia, let alone the Americas. And that’s before we start to worry about those of us who carry clear genetic traits of Homo neanderthalensis (or perhaps Homo sapiens neanderthalensis, depending on whose taxonomic classification one chooses to adhere to) among the European and Asian racial groupings.

    The classification of individuals by skin type is probably most sophisticated in its use by dermatologists, for a whole variety of reasons (see here, for example), but even then it is by no means definitive in any way, shape, or form.

  7. Yet we are able to determine an increased risk for “African Americans”. Not that mixed from that standard. How much of which pool appears to me to be a logical step towards “why”. If you are going to study a genetic pool, defining the pool is critical.

    Here being defined a “African American” and having been in what was then a rather segregated military may well be no more of an influence than being a private loading Agent Orange or walking through sprayed fields. Genetic risk or rank risk? Both.

    Perhaps there is a clue (and here I am clueless) in sickle cell. Does risk vary with heritage? Linear or weighted scale?

    Really, the pool was not well genetically defined (skin color? self identity?) and one should not read it as more than there is. On that I believe we agree.

  8. Race is always self-defined. If a man considers himself to be African American, there is no researcher who will say he is not. So to be precise, this study found that there was no effect of statins in men at the VA who self-identify as African American, and there was an effect in men at the VA who self-identify as Caucasian. So it doesn’t really matter which genetic characteristics one may or may not have, these results are true for anyone who self-identifies for one or the other race group.

  9. Sorry, can’t go there.

    Self-identity is is not a valid biological marker for making a medical decision. It is a social marker. There is a strong reaction to morphine in some natives , unlike whites. Self identity there can kill you. In mother -in law’s case, case assigned identity, not self -assigned.

    Self-identifying oneself as white will not prevent sickle cell. Self-identify does not change the individual’s reaction to statins. Overly simplistic classification.

    Is the effect of statins identical between being 5% African and 90% African? Shouldn’t we find out?

  10. Dear Mike:

    You still aren’t answering my question. What is “5% African” or “90% African”? These are no more “valid biological markers” than self-identification unless you can provide me with a biologically accurate and consistent set of descriptors. You seem to think there is something fundamentally misleading about “social” markers. But we have been using these for tens of thousands of years and most of us accept them for what they are — one form of categorization that (like all the other ones) is less than perfect.

    I can assure you that, genetically, a man from the Ibo tribal group in eastern Nigeria has very clear genetic and physiological differences when compared to a man who is from the Hausa tribal group in northern Nigeria, and the same is true for men of long-term Cornish ethnicity in England as compared to men with long-term origins in Eastern Yorkshire. How can you possibly know that it isn’t some of these types of genetic marker that are involved in determining who responds to cholesterol-lowering agents? Alternatively, maybe it is just their diets!

  11. There is something fundamentally wrong with using social markers as the basis of medical decisions. Repeating that often does not change that. The difficulty of finding an alternate pool does not change that.

    You, a strong advocate for establishing a valid pool of similar cases are here resistant to the same argument. As you close it could be just the diet. Then what is the value of the findings? Limited.

    Simply smacks me of the old put down: “They all look alike to me”.

    I self identify as Irish. Does not change the fact my mother was thoroughly English and my father’s surname came from Normandy. so I could self Identify as French. In my opinion including myself in a study of Statins on the Irish would be a social study not a medical study.

    I think you know what I mean by 10% or 90% without my doing the math.

    Yes, I do agree it could be the diet. My point exactly.

  12. Self identification is actually the best way, If you self-identify as African American, you now have information that will inform your decision. Studies predict for groups, not individuals. You don’t need genetic analysis. In fact, genetic information will likely prove useless and will cloud what is otherwise a very easy marker to use. As the Sitemaster has reported, there are about 170 different genes that have been implicated in one way or another (including in various combinations) in prostate cancer. If such analysis were done on African Americans, some super computer could possibly arrive at probabilities that each combination of those genes will result in cancer. Because it is a probabilistic estimate, it gets one no further towards knowing one’s individual risk. Self-identification draws a clearer and more easily attained line than genetic analysis ever can. It will be right more often than it is wrong, which is the best we can hope for for any prognostic marker.

  13. Dear Mike:

    The fact that you self-identify as Irish is apparently a misleading statement. I had a thoroughly Irish mother and a thoroughly English father and I self-identify as Anglo-Irish (accurate back for at least four generations that I am certain of). Someone who self-identifies as African American likely has one or more good reasons to do so. This has absolutely nothing to do with “They all look alike to me”. That’s an insulting comment to all concerned, for the very simple reason (as I pointed out before) that “they” don’t all look the same at all. The descriptor “African American” encompasses a vast swath of possibilities (as do “white” and “Caucasian” and many other social markers).

    You are entirely entitled to your opinion that “There is something fundamentally wrong with using social markers as the basis of medical decisions.” But no, I absolutely don’t know what you mean by 10% or 90% “white” or “black” or anything else. Do you mean genetically, or by lifestyle, or by the way someone speaks, or by what side of town they live on, or what? Genetic make-up is far from being the only factor that affects risk for diagnosis with prostate cancer and probably, also, far from being the only reason why someone does or doesn’t benefit from using a cholesterol-lowering agent.

    I am also not “resistant” in any way to attempts to establish “a valid pool of similar cases”. I simply reported some data published in a reputable scientific journal by a group of pretty well-respected physicians. And I have no idea how else they could have established a better validated pool based on the data available to them. I have asked you three times if you could suggest a better way to do this, and so far you have ignored my request. If you take the position that there is something fundamentally wrong, then please offer a better hypothesis. Without a better hypothesis, this is a pointless discussion. I have never even implied that you are required to accept the authors’ reported findings.

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