Height, Obesity, and the Risk of TMPRSS2:ERG -Defined Prostate Cancer

• Published in: Cancer epidemiology, biomarkers & prevention biomarkers & prevention, 2018-02, Vol.27 (2), p.193-200
• Main Authors: Graff, Rebecca E, Ahearn, Thomas U, Pettersson, Andreas, Ebot, Ericka M, Gerke, Travis, Penney, Kathryn L, Wilson, Kathryn M, Markt, Sarah C, Pernar, Claire H, Gonzalez-Feliciano, Amparo G, Song, Mingyang, Lis, Rosina T, Schmidt, Daniel R, Vander Heiden, Matthew G, Fiorentino, Michelangelo, Giovannucci, Edward L, Loda, Massimo, Mucci, Lorelei A
• Format: Article
• Language: English
• Subjects: Body mass; Body mass index; ERG gene; ERG protein; Gene fusion; Health risk assessment; Health risks; Medical personnel; Medicin och hälsovetenskap; Obesity; Prostate cancer; Risk factors
• ISSN: 1055-9965; 1538-7755; 1538-7755
• DOI: 10.1158/1055-9965.EPI-17-0547

The largest molecular subtype of primary prostate cancer is defined by the gene fusion. Few studies, however, have investigated etiologic differences by status. Because the fusion is hormone-regulated and a man's hormonal milieu varies by height and obesity status, we hypothesized that both may be differentially associated with risk of -defined disease. Our study included 49,372 men from the prospective Health Professionals Follow-up Study. Participants reported height and weight at baseline in 1986 and updated weight biennially thereafter through 2009. Tumor ERG protein expression (a marker) was immunohistochemically assessed. We used multivariable competing risks models to calculate HRs and 95% confidence intervals (CIs) for the risk of ERG-positive and ERG-negative prostate cancer. During 23 years of follow-up, we identified 5,847 incident prostate cancers, among which 913 were ERG-assayed. Taller height was associated with an increased risk of ERG-positive disease only [per 5 inches HR 1.24; 95% confidence interval (CI), 1.03-1.50; = 0.07]. Higher body mass index (BMI) at baseline (per 5 kg/m HR 0.75; 95% CI, 0.61-0.91; = 0.02) and updated BMI over time (per 5 kg/m HR 0.86; 95% CI, 0.74-1.00; = 0.07) were associated with a reduced risk of ERG-positive disease only. Our results indicate that anthropometrics may be uniquely associated with -positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk. Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes. .