Refining knowledge about familial risk for prostate cancer


We have known for years that if your father or your brother is diagnosed with prostate cancer, it affects your own risk for prostate cancer … but what sorts of prostate cancer are we talking about? Aggressive, indolent, metastatic, localized, what?

A newly published study by Bratt et al. in the Journal of the National Cancer Institute has provided us with the first set of data that helps us to appreciate the possible answers to this question — and the answers aren’t necessarily quite what one might have expected.

Perhaps not surprisingly, these early data come from the national, long-term Swedish National Prostate Cancer database (PCBaSe). Bratt et al. were able to use this large national database to investigate the risk for diagnosis with prostate cancer in > 22,500 brothers of 13,975 men (“index patients”) who had already been given such a diagnosis.

Basically, what they found was the following:

  • 30 percent of men that had one brother only with prostate cancer were also diagnosed with prostate cancer by age 75 years.
    • This risk is about double the national Swedish average for risk of diagnosis with prostate cancer.
    • The brothers of index patients were all at increased risk for a diagnosis of cancer (standardized incidence ratio [SIR] = 3.1)
  • Among the brothers of the index patients, the risk for diagnosis with clinical stage T1c tumors (SIR = 3.4) was higher than risk for diagnosis with metastatic tumors (SIR = 2.0).
  • This increased risk for diagnosis with prostate cancer was associated with an increased likelihood of diagnostic activity among the relatives of the index cases.
  • Risk for diagnosis with T1c tumors was
    • Higher during the first year after the diagnosis of the index patient (SIR = 4.3)
    • Lower in following years (SIR range, 2.8 to 3.3)
    • Higher for brothers of index patients who had a higher socioeconomic status (SIR = 4.2)
    • Lower for brothers of index patients with lower socioeconomic status (SIR = 2.8)
  • Risk for diagnosis with aggressive prostate cancer was much lower, at 9 percent (compared to the national average risk of 5 percent).
  • In men who had a father and a brother with prostate cancer,
    • The risk for diagnosis with any form of prostate cancer was up to 48 percent.
    • The risk for diagnosis with an aggressive form of prostate cancer was 14 percent.

According to Dr. Bratt, in a media release from Lund University,

We expected that the risk of aggressive prostate cancer would not be much increased in brothers of men with the indolent form [of prostate cancer], but it turned out to almost as high as the risk among men with aggressive prostate cancer in the family.  This is an important finding that needs to be disseminated to the general public and to healthcare professionals. Men whose father or brother have an indolent, untreated prostate cancer are probably not aware that this increases their own risk of developing aggressive prostate cancer. They might not even know that there is prostate cancer in the family.

Bratt et al. conclude that, based on their study data:

Increased diagnostic activity among men with a family history of prostate cancer appears to contribute to their increased risk of prostate cancer and to lead to detection bias in epidemiological and genetic studies of familial prostate cancer.

In other words, while there is certainly an increase in risk for prostate cancer among first-degree relatives (brothers and sons) of men diagnosed with prostate cancer, some of this increase in risk (relative to the general population) may be a direct consequence of increased diagnostic activity among the brothers and sons of the index patients, leading to findings of prostate cancer that might never otherwise have been diagnosed (and which have therefore been diagnosed unnecessarily).

One of the learnings from this study is that just because your brother has a form of prostate cancer that really does need early treatment does not mean that the form of prostate cancer that you get diagnosed with afterwards also needs immediate treatment. Conversely, however, the fact that your brother was diagnosed with an indolent and low-risk prostate cancer does not mean that, if you are also diagnosed with prostate cancer, that your form of prostate cancer is also going to be indolent and low-risk.

3 Responses

  1. Please help me understand this study. I looked at the link to the study and their conclusion was that some degree of the risk of diagnosis of prostate cancer in a person who had a brother with prostate cancer is related to more intense PSA screening in those men.

    How do they draw the conclusion that patients with a brother or father with low-grade prostate cancer have almost as high a risk for aggressive prostate cancer as men who have a brother or father with aggressive prostate cancer?

  2. Dear Mark:

    Look at Table 1 of the study and then at the data (about half way down the table) that deal specifically with the likelihood of the second brother getting diagnosed with prostate cancer after the first brother based on the Gleason score of the first brother (the “index patient”). These data show the following

    — When the index patient is diagnosed with a Gleason score of 2-6, the ratio of observed to expected cases of T1c cancers was 567/185 for an SIR of 3.1 and the ratio of observed to expected cases of metastatic cancers was 30/16 for an SIR of 1.9.
    — When the index patient is diagnosed with a Gleason score of 7, the ratio of observed to expected cases of T1c cancers was 303/92 for an SIR of 3.3 and the ratio of observed to expected cases of metastatic cancers was 17/8.1 for an SIR of 2.1.
    — When the index patient is diagnosed with a Gleason score of 8-10, the ratio of observed to expected cases of T1c cancers was 135/48 for an SIR of 2.8 and the ratio of observed to expected cases of metastatic cancers was 11/4.3 for an SIR of 2.6.

    In other words, the SIR values for risk of metastatic prostate cancer for the second brother were all of a similar order of magnitude (at 1.9, 2.1, and 2.6) as opposed to being different by an order of magnitude (e.g., 0.1, 1.0, and 10.0).

    However, one has to be very careful in the interpretation of retrospective data like these, especially when (in the case of the numbers of metastatic patients) we are talking about very small numbers of individuals. The authors are very clear about this in the full text of the paper, but they are correct when they state that these data were not what most of us would have expected.

  3. Thanks, that helps.

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