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Evidence that Increased Prostate Cancer Risk in Brothers of Men with the Disease Relate to Increased Diagnosis, Not Genetic Factors

doi: 10.1097/

Increased diagnostic activity, rather than genetic mutations, may be the cause of the increased prostate cancer risk observed in the brothers of men diagnosed with the disease, according to a study published in the Journal of the National Cancer Institute (2010;102:1336-1343).

Researchers led by Ola Bratt, MD, of the Department of Urology at Helsingborg Hospital in Sweden looked at data from the Prostate Cancer Database Sweden of patients who were diagnosed with prostate cancer between 1996 and 2006 and who were registered in the National Prostate Cancer Registry to determine whether or not estimates of the familial risk of prostate cancer may be at least partially inflated by detection bias from increased diagnostic activity.

Included in the analysis were 22,511 brothers of 13,975 “index patients,” who were prostate cancer patients with one or more brother and their fathers registered in Sweden's Multi-Generation Register.

The incidence of prostate cancer was higher among brothers of prostate cancer patients than men of the same age, and the incidence was higher still among men with both a brother and father with prostate cancer. The incidence was highest among men who had two brothers with prostate cancer.

The type of cancer most often detected was early-stage prostate cancer, which is typically detected by a PSA test and may or may not be clinically relevant, the authors noted.

“PSA testing (screening) of men who have no clinical symptoms of prostate disease may lead to detection of prostate cancer in men who would not develop symptomatic prostate cancer during their lifetime. The increased diagnostic activity among men with a family history of prostate cancer, which we observed, will inflate family history as a risk factor for prostate cancer in populations of men who commonly receive PSA testing.”

The researchers also found that the incidence of prostate cancer diagnosis among brothers of index patients was highest during the first year after the index patient's diagnosis. Overall, the incidence of prostate cancer increased sharply between 1999 and 2006, and a higher socioeconomic status was associated with a statistically significant increased risk of a prostate cancer diagnosis.

As for the clinical implication, the authors wrote, “When counseling men about their risk of hereditary predisposition to prostate cancer, one should consider the possibility that a familial aggregation of prostate cancer may be at least partially caused by increased diagnostic activity.”

In an accompanying editorial, Ian M. Thompson, MD, and Donna P. Ankerst, PhD, of the University of Texas Health Science Center at San Antonio, along with Catherine M. Tangen, DrPH, of Fred Hutchinson Cancer Research Center, wrote that assessments of variables affecting prostate cancer risk are subject to unknown biases in most studies.

“Perhaps the best tactic would be to change our approach from seeking risk factors for prostate cancer to an assessment of factors related to biologically consequential prostate cancer,” the three coauthors concluded.

© 2010 Lippincott Williams & Wilkins, Inc.
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