Background: The largest molecular subtype of primary prostate cancer is defined by the TMPRSS2:ERG gene fusion. Few studies, however, have investigated etiologic differences by TMPRSS2:ERG 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 TMPRSS2:ERG-defined disease.
Methods: 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 TMPRSS2:ERG 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.
Results: 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; Pheterogeneity = 0.07]. Higher body mass index (BMI) at baseline (per 5 kg/m2 HR 0.75; 95% CI, 0.61–0.91; Pheterogeneity = 0.02) and updated BMI over time (per 5 kg/m2 HR 0.86; 95% CI, 0.74–1.00; Pheterogeneity = 0.07) were associated with a reduced risk of ERG-positive disease only.
Conclusions: Our results indicate that anthropometrics may be uniquely associated with TMPRSS2:ERG-positive prostate cancer; taller height may be associated with greater risk, whereas obesity may be associated with lower risk.
Impact: Our study provides strong rationale for further investigations of other prostate cancer risk factors that may be distinctly associated with subtypes.
|Published In||Cancer Epidemiology, Biomarkers & Prevention|
|Date||Feb 1, 2018|
Graff RE, Ahearn TU, Pettersson A, Ebot EM, Gerke TA, Penney KL, Wilson KM, Markt S, Pernar CH, Gonzalez-Feliciano AG, Song M, Lis R, Schmidt DR, Vander Heiden MG, Fiorentino M, Giovannucci EL, Loda M, Mucci LA. Height, obesity, and the risk of TMPRSS2:ERG-defined prostate cancer. Cancer Epidemiol Biomarkers Prev 2018; 27(2): 193--200. PMID: 29167279 PMCID: PMC5809280.