title: Smoking and risk of low- and high-grade prostate cancer: results from the REDUCE study.
abstract: OBJECTIVE
  Although the relationship between smoking and prostate cancer risk is inconsistent, some studies show that smoking is associated with prostate cancer mortality. Whether this reflects delayed diagnosis or direct smoking-related effects is unknown. REDUCE, which followed biopsy-negative men with protocol-dictated prostate-specific antigen (PSA)-independent biopsies at 2 and 4 years, provides an opportunity to evaluate smoking and prostate cancer diagnosis with minimal confounding from screening biases.
  
  
  METHODS
  Logistic regression was conducted to test the association between smoking and cancer on the first on-study biopsy (no cancer, low-grade Gleason 4-6, high-grade Gleason 7-10) in REDUCE.
  
  
  RESULTS
  Of 6,240 men with complete data and ≥1 on-study biopsy, 2,937 (45.8%) never smoked, 929 (14.5%) were current smokers, and 2,554 (39.8%) were former smokers. Among men with negative first on-study biopsies, smokers were 36% less likely to receive a second on-study biopsy (P < 0.001). At first on-study biopsy, 941 (14.7%) men had cancer. Both current and former smoking were not significantly associated with either total or low-grade prostate cancer (all P > 0.36). Current (OR = 1.44, P = 0.028) but not former smokers (OR = 1.21, P = 0.12) were at increased risk of high-grade disease. On secondary analysis, there was an interaction between smoking and body mass index (BMI; Pinteraction = 0.017): current smokers with BMI ≤ 25 kg/m(2) had an increased risk of low-grade (OR = 1.54, P = 0.043) and high-grade disease (OR = 2.45, P = 0.002), with null associations for BMI ≥ 25 kg/m(2).
  
  
  CONCLUSIONS
  Among men with elevated PSA and negative pre-study biopsy in REDUCE, in which biopsies were largely PSA independent, smoking was unrelated to overall prostate cancer diagnosis but was associated with increased risk of high-grade prostate cancer.
authors.affiliation: Duke University School of Medicine, Durham, North Carolina. Urology Section, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Tammy
authors.initials: T
authors.lastname: Ho
authors.affiliation: Urology Section, Durham Veterans Affairs Medical Center, Durham, North Carolina. Division of Urology, Department of Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Howard
authors.affiliation: Urology Section, Durham Veterans Affairs Medical Center, Durham, North Carolina. Division of Urology, Department of Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Vidal
authors.affiliation: Urology Section, Durham Veterans Affairs Medical Center, Durham, North Carolina. Division of Urology, Department of Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, North Carolina.
authors.forename: Leah
authors.initials: L
authors.lastname: Gerber
authors.affiliation: Arthur Smith Institute for Urology, North Shore-Long Island Jewish Health System, New Hyde Park, New York.
authors.forename: Daniel
authors.initials: D
authors.lastname: Moreira
authors.affiliation: Urology Section, Durham Veterans Affairs Medical Center, Durham, North Carolina.
authors.forename: Madeleine
authors.initials: M
authors.lastname: McKeever
authors.affiliation: Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine in St. Louis, St. Louis, Missouri. Prostate Study Center, Barnes-Jewish Hospital, St. Louis, Missouri.
authors.forename: Gerald
authors.initials: G
authors.lastname: Andriole
authors.affiliation: GlaxoSmithKline Oncology R&D, Collegeville, Pennsylvania.
authors.forename: Ramiro
authors.initials: R
authors.lastname: Castro-Santamaria
authors.affiliation: Urology Section, Durham Veterans Affairs Medical Center, Durham, North Carolina. Division of Urology, Department of Surgery, Duke Prostate Center, Duke University School of Medicine, Durham, North Carolina. Department of Pathology, Duke University Medical Center, Durham, North Carolina. steve.freedland@duke.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Freedland
mesh_terms: D000368:Aged; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D011471:Prostatic Neoplasms / Q000209:etiology* / Q000473:pathology* / Q000628:therapy; D012306:Risk; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*