A new study from Sweden suggests that the of risk of prostate cancer in men with a known family history of the disease could be inflated because such men are more likely to seek a diagnosis, further intensifying the controversial debate on whether PSA testing does more harm than good.

Experts writing in the same journal propose that if you consider that many men in the population at large may have the disease but don’t take a test to find it, then cases of men who seek a diagnosis because a brother or father has tested positive, will exaggerate any familial link.

You can read a paper on the study and the accompanying editorial in the 19 August advanced online issue of Journal of the National Cancer Institute .

Dr Ola Bratt, from the Department of Urology at Helsingborg Hospital, and colleagues wrote in their background information that epidemiological and other studies suggest family history is a stronger risk for prostate cancer than many other cancers.

However, since the PSA (prostate-specific antigen) test came into use in the early 1990s, men whose fathers and brothers have been diagnosed with the disease have been the most likely group to take the test, so the researchers decided to investigate whether increased diagnostic activity is linked in any way to the incidence of prostate cancer among brothers of men with the disease.

For the study, they examined data on patients diagnosed with prostate cancer between 1996 to 2006 recorded in Sweden’s nationwide population-based Prostate Cancer Database (PCBaSe Sweden), which includes cases registered in the National Prostate Cancer Register and other sources.

First they looked for “index” patients: prostate cancer patients recorded in the National Prostate Cancer Register, for whom they could also identify at least one brother and their father from Sweden’s Multi-Generation Register, which includes family information for Swedish residents born since 1932.

Altogether they found data on 22,511 brothers of 13,975 index patients in the PCBaSe Sweden database.

They gathered a range of information on each index patient’s brother, such as type of tumor, time elapsed between their diagnosis and that of the index patient, calendar period, socioeconomic status and geographical situation and compared it to their incidence of prostate cancer.

The researchers found that:

  • Brothers of index patients with prostate cancer were at increased risk for a diagnosis of prostate cancer than same-age men in the general Swedish population (standardized incidence ratio SIR = 3.1, 95% confidence interval CI ranged from 2.9 to 3.3).
  • The risk was even higher among brothers of index patients whose fathers also had prostate cancer.
  • The risk was highest among men with two brothers with prostate cancer.
  • However, the type of cancer most often detected was early stage, which is typically diagnosed via PSA test and may or may not become clinically relevant.
  • Rate of prostate cancer diagnosis among brothers of index patients was highest in the first year following the index patient’s diagnosis.
  • The rate was also highest among brothers with a higher socioeconomic status.

Bratt and colleagues concluded that:

“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 an accompanying editorial, Dr Ian M. Thompson of the Department of Urology at the University of Texas Health Science Center in San Antonio, and colleagues, commented that the idea that family history of prostate cancer increases a man’s risk of being diagnosed of the disease is firmly entrenched in the minds of doctors and public alike.

The rate at which papers have emerged linking family medical history to prostate cancer has vastly accelerated pace since the introduction of the PSA test.

Is it possible, therefore, as Thompson and colleagues suggest, that because of the PSA, a “man with a brother or father with prostate cancer was more likely to be screened”, thus resulting in a scenario where this “simple decision could lead to a prostate biopsy and exaggerate the link between family history and prostate cancer” especially against a background of many undetected but diagnosable cases in the population at large?

“Effects of Prostate-Specific Antigen Testing on Familial Prostate Cancer Risk Estimates.”
Ola Bratt, Hans Garmo, Jan Adolfsson, Anna Bill-Axelson, Lars Holmberg, Mats Lambe, and Pär Stattin.
J Natl Cancer Inst, Advance Access published on 19 August 2010.
DOI:10.1093/jnci/djq265

“Prostate-Specific Antigen, Risk Factors, and Prostate Cancer: Confounders Nestled in an Enigma.”
Ian M. Thompson, Donna P. Ankerst, and Catherine M. Tangen.
J Natl Cancer Inst, Advance Access published on 19 August 2010.
DOI:10.1093/jnci/djq313

Written by: Catharine Paddock, PhD