Elsevier

European Urology

Volume 62, Issue 4, October 2012, Pages 656-661
European Urology

Prostate Cancer
Concordance of Tumor Differentiation Among Brothers with Prostate Cancer

https://doi.org/10.1016/j.eururo.2012.02.032Get rights and content

Abstract

Background

Genetic factors seem to be of greater importance in prostate cancer than in other forms of cancer. Studies have suggested familial concordance in survival, but the extent to which that is due to tumor characteristics is not known.

Objective

We hypothesized that a brother of an index case with prostate cancer is at particularly increased risk of prostate cancer with the same tumor differentiation as the index case.

Design, setting and participants

We identified 21 930 brothers of index cases with prostate cancer in the Prostate Cancer Data Base Sweden and followed them up for incidence of prostate cancer.

Outcome measurements and statistical analysis

The relative risk of Gleason score–specific prostate cancer in the cohort of brothers was estimated by using the standardized incidence ratio (SIR) stratified by Gleason score of the index case. We estimated 95% confidence intervals (CIs) assuming a Poisson distribution.

Results and limitations

Among brothers of index cases with Gleason score 8–10 cancer, the SIR was 2.53 (95% CI, 1.97–3.21) for a Gleason score 2–6 cancer and 4.00 (95% CI, 2.63–5.82) for a Gleason score 8–10 cancer. SIR for Gleason score 2–6 cancer among brothers decreased with time since the date of the index cases’ diagnoses, whereas the risk of Gleason 8–10 cancer increased over time for brothers of index cases with Gleason 8–10 cancer (p for trend = 0.009).

Conclusions

Brothers of men with high-grade prostate cancer are at particularly increased risk of high-grade prostate cancer. Likewise, there is a concordance of less malignant prostate cancers within families. These findings may have direct clinical relevance for counseling men with a family history of prostate cancer.

Introduction

Genetic factors seem to be stronger determinants of prostate cancer risk than for risk of any other cancer [1], [2], [3]. Although genetic factors have been extensively studied as determinants of disease incidence, little is known of the concordance in tumor aggressiveness within families [4]. Three recent studies from Sweden suggested that there is a familial concordance in cancer-specific mortality for several cancers, including prostate cancer [5], [6], [7]. Survival among cancer patients is determined not only by tumor characteristics but also by host-related factors such as general health, immunologic response, socioeconomic factors related to health awareness and behavior, early diagnosis and treatment, and chance of cure. The extent to which familial concordance in prostate cancer survival is attributable to concordance in tumor aggressiveness is unknown.

The strongest predictor of prostate cancer aggressiveness is tumor differentiation assessed by Gleason score [8]. We hypothesized that brothers of index cases are at particularly increased risk of a cancer with the same Gleason score category as the index cases. To test this hypothesis, we used the large population-based cohort of the Prostate Cancer Data Base Sweden (PCBaSe) to estimate relative risk of prostate cancer with specific Gleason score categories in a cohort of brothers of men diagnosed with prostate cancer with a known Gleason score.

Section snippets

The registers

PCBaSe is a nationwide database encompassing 80 079 men diagnosed with prostate cancer between January 1, 1996, and December 31, 2006, and registered in the National Prostate Cancer Register (NPCR). The creation of the PCBaSe cohort has previously been described in detail [9]. In brief, using the individually unique personal identity number assigned to all residents in Sweden since 1947, the data in the NPCR were linked to several other population-based national registries. In the present

Results

Among 21 930 brothers of index cases, 1022 were diagnosed with prostate cancer, resulting in an overall SIR for prostate cancer of 3.1 (95% CI, 2.9–3.3) A higher proportion of prostate cancer was detected through health check-ups among brothers than among index cases (44.1% vs 31.9%). The brothers also had a lower proportion of metastatic disease and a higher proportion of low-risk cancers than the index cases (Table 1).

Table 2 presents the SIR for prostate cancer with high and low Gleason score

Discussion

In this large, nationwide, population-based study, brothers of men with high-grade prostate cancer had a more pronounced increased risk of high-grade than low-grade prostate cancer. We also found a concordance of less aggressive tumors among brothers. For less aggressive tumors, the risk among brothers decreased with time since the index cases’ diagnoses, indicating that part of the increased risk is caused by an increased diagnostic intensity during the first years after the diagnosis of the

Conclusions

Our study provides evidence of concordance in tumor differentiation among brothers with prostate cancer. Brothers of men with poorly differentiated prostate cancer are themselves at particularly increased risk of poorly differentiated prostate cancer. Whereas the concordance in low-grade tumors, at least to some extent, may be caused by increased diagnostic activity among brothers of an index case, the concordance of high-grade, potentially lethal prostate cancer is more likely explained by

References (26)

  • Statistics Sweden, Population and Welfare Department. Statistics Sweden, background facts, population and welfare...
  • A.V. D’Amico et al.

    Biochemical outcome after radical prostatectomy, external beam radiation therapy, or interstitial radiation therapy for clinically localized prostate cancer

    JAMA

    (1998)

    • Cited by (0)

    View full text
    Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.