FAMILY HISTORY AND PROSTATE CANCER RISK

August 30, 2010 — Increased diagnostic activity among men who have a brother with prostate cancer appears to contribute to their increased risk for prostate cancer, say Swedish researchers.

The incidence of prostate cancer was higher among brothers of index patients than among men of the same age in the general Swedish population (standardized incidence ratio [SIR], 3.1; 95% confidence interval [CI], 2.9 - 3.3).

However, this 3-fold increased incidence was accompanied by increased diagnostic activity, the researchers report.

This increased diagnostic activity will "inflate" family history as a risk factor, say the authors, led by Ola Bratt, MD, from Helsingborg Hospital in Sweden. Their findings were published online August 19 in the Journal of the National Cancer Institute.

To dramatically illustrate their point, the authors highlighted cases in which 2 brothers in a family had been diagnosed with prostate cancer.

The risk was "very high" that a third brother would also be diagnosed with prostate cancer, particularly a T1c tumor (which is prostate-specific antigen [PSA]-detected by definition), within the first year after the second brother's diagnosis (SIR, 22; 95% CI, 15 - 31).

"This result must not be interpreted as meaning that men with 2 brothers with prostate cancer have a 22-fold increased risk of developing symptomatic prostate cancer, compared with the general population," the authors write. "But rather that such men are very likely to undergo PSA testing."

Notably, the researchers acknowledge that genetic factors are very important in prostate cancer.

"Hereditary factors may be more important in the etiology of prostate cancer than of any other cancer," they write, citing a study of twins (N Engl J Med. 2000;343:78-85).

However, there is no biomarker that indicates a genetic predisposition to clinically consequential prostate cancer.

Thus, the authors want clinicians to know that, when counseling men with prostate cancer in the family, "familial aggregation of prostate cancer may be at least partially caused by increased diagnostic activity."

In an editorial that accompanies the study, a trio of experts suggest that the only way to circumvent such bias is to find new ways to evaluate prostate cancer.

"Perhaps the best tactic would be to change our approach from seeking risk factors for prostate cancer (a disease that is ubiquitous, with many patients probably being better off if it were not detected by screening) to an assessment of factors related to biologically consequential prostate cancer (i.e., metastatic disease or prostate-cancer-specific death)," write editorialists Ian Thompson, MD, Donna P. Ankerst, PhD, and Catherine M. Tangen, DrPH.

They are all from the Cancer Therapy and Research Center of the University of Texas Health Science Center at San Antonio.

An "Entrenched" Risk, But How So?

In their editorial, Dr. Thompson and his colleagues say that the connection between family history and increased prostate risk is well established — and then some.

"That a family history of prostate cancer increases a man's risk of a diagnosis of this disease is now entrenched in the medical literature," the editorialists write.

Dr. Thompson, who is known for "rethinking" prostate cancer issues, and his colleagues explore when this entrenchment came to be.

They review published papers on the association between family history and prostate neoplasms.

In the 10 years from 1977 to 1986, there were 7 publications on the subject — a rate of 0.7 articles per year.

After 1986, there was an ongoing uptick in the published research.

From 1987 to 1996, there were 79 articles, a rate of 7.9 articles per year. From 1997 to 2006, there were 45.8 articles per year; and in the past 4 years or so, there were 65 articles per year.

"Why did it take us until the mid-1980s to fully recognize or explore adequately the familial association?" ask the editorialists.

They then answer their own question — somewhat.

"Certainly, the explosion in total numbers of prostate cancers has drawn our attention to the disease and provided the data to explore this association," they write, noting that the time of the research uptick — the mid-1980s — is the "PSA era," when widespread PSA testing began in the United States.

However, the editorialists also say that the study from Sweden provides "another explanation" for how the link between family history and prostate neoplasms came to be "entrenched" in the literature starting in the mid-1980s.

The Swedish study shows how, "in the PSA era, a man with a brother or father with prostate cancer was more likely to be screened for prostate cancer by PSA testing. Against the background of an enormous number of undiagnosed (but diagnosable) prostate cancers, this simple decision could lead to a prostate biopsy and exaggerate the link between family history and prostate cancer."

Findings

Their new findings are not entirely novel, admit Dr. Bratt and his coauthors.

Other researchers have found that there is an increased detection of prostate cancer shortly after a diagnosis of the disease in a family (J Natl Cancer Inst. 2005;97:1575-1579).

However, in their study, the Swedes added a few more details to what is understood about how PSA testing influences familial prostate cancer risk.

The study involved 22,511 brothers of 13,975 index patients with prostate cancer in the National Prostate Cancer Register of Sweden.

The investigators found, for the first time, that brothers of index patients who had a higher socioeconomic status (SIR, 4.2; 95% CI, 3.7 - 4.7) were more likely to be diagnosed with prostate cancer than brothers of index patients with a lower socioeconomic status (SIR, 2.8; 95% CI, 2.4 - 3.2).

The risk for T1c tumors (SIR, 3.4; 95% CI, 3.2 - 3.8), which are by definition diagnosed after a PSA test, was higher than for metastatic tumors (SIR, 2.0; 95% CI, 1.5 - 2.6), report the study authors.

And the risk for T1c tumors was highest during the first year after the diagnosis of the index patient (SIR, 4.3; 95% CI, 3.8 - 4.9), compared with the risk in the following years (SIR range, 2.8 to 3.3).

"The diagnostic activity among brothers of prostate cancer patients was especially high during the first year after a prostate cancer diagnosis in the family," the authors point out.

The study was funded by the Swedish Research Council, the Swedish Cancer Society, and Vasterbotten County Council. The authors have disclosed no relevant financial relationships.

J Natl Cancer Inst. Published online August 19, 2010. Abstract