Susan Chadid1, John R Barber1, William G Nelson2,3, Bora Gurel4, M Scott Lucia5, Ian M Thompson6,7, Phyllis J Goodman8,9, Frank Z Stanczyk10, Howard L Parnes11, Scott M Lippman12, Angelo M De Marzo2,3,13, Elizabeth A Platz1,2,3. 1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 2. Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland. 3. Department of Urology, The James Buchanan Brady Urological Institute and Johns Hopkins School of Medicine, Baltimore, Maryland. 4. The Institute of Cancer Research, The Royal Marsden, London, UK. 5. Department of Pathology, University of Colorado School of Medicine, Aurora, Colorado. 6. The Cancer Therapy and Research Center, CHRISTUS Santa Rosa Hospital-Medical Center, San Antonio, Texas. 7. Department of Urology, University of Texas Health Sciences Center San Antonio, San Antonio, Texas. 8. SWOG Statistical Center, Fred Hutchinson Cancer Research Center, Seattle, Washington. 9. Cancer Prevention Program, Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington. 10. Departments of Obstetrics and Gynecology, and Preventive Medicine, University of Southern California Keck School of Medicine, Los Angeles, California. 11. Division of Cancer Prevention, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland. 12. Moores Cancer Center, University of California San Diego, La Jolla, California. 13. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Abstract
BACKGROUND: Intraprostatic inflammation is an emerging prostate cancer risk factor. Estrogens are pro-inflammatory while androgens are anti-inflammatory. Thus, we investigated whether serum sex steroid hormone concentrations are associated with intraprostatic inflammation to inform mechanistic links among hormones, inflammation, and prostate cancer. METHODS: We conducted a cross-sectional study among 247 men in the placebo arm of the Prostate Cancer Prevention Trial who had a negative end-of-study biopsy, most (92.7%) performed without clinical indication per trial protocol. Serum estradiol, estrone, and testosterone were previously measured by immunoassay in pooled baseline and Year 3 serum. Free estradiol and free testosterone were calculated. Inflammation was visually assessed (median of three prostate biopsy cores per man). Polytomous or logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of some or all cores inflamed (both vs none) or any core inflamed (vs none) by hormone tertile, adjusting for age, race, and family history. We evaluated effect modification by waist circumference and body mass index (BMI). RESULTS: In all, 51.4% had some and 26.3% had all cores inflamed. Free (P-trend = .11) but not total estradiol was suggestively inversely associated with all cores inflamed. In men with waist circumference greater than or equal to 102 cm (P-trend = .021) and BMI ≥ 27.09 kg/m2 (P-trend = .0037) free estradiol was inversely associated with any core inflamed. Estrone was inversely associated with all cores inflamed (T3: OR = 0.36, 95% CI 0.14-0.95, P-trend = .036). Total (T3: OR = 1.91, 95% CI 0.91-4.02, P-trend = .11) and free (T3: OR = 2.19, 95% CI 1.01-4.74, P-trend = .05) testosterone were positively associated with any core inflamed, especially free testosterone in men with waist circumference less than 102 cm (T3: OR = 3.51, 95% CI 1.03-12.11, P-trend = .05). CONCLUSIONS: In this first study in men without prostate cancer and irrespective of clinical indication for biopsy, contrary to the hypothesis, circulating estrogens appeared to be inversely associated, especially in heavy men, whereas androgens appeared to be positively associated with intraprostatic inflammation.
BACKGROUND: Intraprostatic inflammation is an emerging prostate cancer risk factor. Estrogens are pro-inflammatory while androgens are anti-inflammatory. Thus, we investigated whether serum sex steroid hormone concentrations are associated with intraprostatic inflammation to inform mechanistic links among hormones, inflammation, and prostate cancer. METHODS: We conducted a cross-sectional study among 247 men in the placebo arm of the Prostate Cancer Prevention Trial who had a negative end-of-study biopsy, most (92.7%) performed without clinical indication per trial protocol. Serum estradiol, estrone, and testosterone were previously measured by immunoassay in pooled baseline and Year 3 serum. Free estradiol and free testosterone were calculated. Inflammation was visually assessed (median of three prostate biopsy cores per man). Polytomous or logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI) of some or all cores inflamed (both vs none) or any core inflamed (vs none) by hormone tertile, adjusting for age, race, and family history. We evaluated effect modification by waist circumference and body mass index (BMI). RESULTS: In all, 51.4% had some and 26.3% had all cores inflamed. Free (P-trend = .11) but not total estradiol was suggestively inversely associated with all cores inflamed. In men with waist circumference greater than or equal to 102 cm (P-trend = .021) and BMI ≥ 27.09 kg/m2 (P-trend = .0037) free estradiol was inversely associated with any core inflamed. Estrone was inversely associated with all cores inflamed (T3: OR = 0.36, 95% CI 0.14-0.95, P-trend = .036). Total (T3: OR = 1.91, 95% CI 0.91-4.02, P-trend = .11) and free (T3: OR = 2.19, 95% CI 1.01-4.74, P-trend = .05) testosterone were positively associated with any core inflamed, especially free testosterone in men with waist circumference less than 102 cm (T3: OR = 3.51, 95% CI 1.03-12.11, P-trend = .05). CONCLUSIONS: In this first study in men without prostate cancer and irrespective of clinical indication for biopsy, contrary to the hypothesis, circulating estrogens appeared to be inversely associated, especially in heavy men, whereas androgens appeared to be positively associated with intraprostatic inflammation.
Authors: M H Umbehr; B Gurel; T J Murtola; S Sutcliffe; S B Peskoe; C M Tangen; P J Goodman; I M Thompson; S M Lippman; M S Lucia; H L Parnes; C G Drake; W G Nelson; A M De Marzo; E A Platz Journal: Prostate Cancer Prostatic Dis Date: 2015-05-05 Impact factor: 5.554
Authors: K K Tsilidis; S Rohrmann; K A McGlynn; S J Nyante; D S Lopez; G Bradwin; M Feinleib; C E Joshu; N Kanarek; W G Nelson; E Selvin; E A Platz Journal: Andrology Date: 2013-09-30 Impact factor: 3.842
Authors: Sabine Rohrmann; Meredith S Shiels; David S Lopez; Nader Rifai; William G Nelson; Norma Kanarek; Eliseo Guallar; Andy Menke; Corinne E Joshu; Manning Feinleib; Siobhan Sutcliffe; Elizabeth A Platz Journal: Cancer Causes Control Date: 2011-06-16 Impact factor: 2.506
Authors: Elizabeth A Platz; Ibrahim Kulac; John R Barber; Charles G Drake; Corinne E Joshu; William G Nelson; M Scott Lucia; Eric A Klein; Scott M Lippman; Howard L Parnes; Ian M Thompson; Phyllis J Goodman; Catherine M Tangen; Angelo M De Marzo Journal: Cancer Epidemiol Biomarkers Prev Date: 2017-07-28 Impact factor: 4.254
Authors: Angelo M De Marzo; Elizabeth A Platz; Siobhan Sutcliffe; Jianfeng Xu; Henrik Grönberg; Charles G Drake; Yasutomo Nakai; William B Isaacs; William G Nelson Journal: Nat Rev Cancer Date: 2007-04 Impact factor: 60.716
Authors: Sabine Rohrmann; Elizabeth A Platz; Elizabeth Selvin; Meredith S Shiels; Corinne E Joshu; Andy Menke; Manning Feinleib; Shehzad Basaria; Nader Rifai; Adrian S Dobs; Norma Kanarek; William G Nelson Journal: Clin Endocrinol (Oxf) Date: 2011-08 Impact factor: 3.478
Authors: Eleanor L Watts; Paul N Appleby; Aurora Perez-Cornago; H Bas Bueno-de-Mesquita; June M Chan; Chu Chen; Barbara A Cohn; Michael B Cook; Leon Flicker; Neal D Freedman; Graham G Giles; Edward Giovannucci; Randi E Gislefoss; Graeme J Hankey; Rudolf Kaaks; Paul Knekt; Laurence N Kolonel; Tatsuhiko Kubo; Loïc Le Marchand; Robert N Luben; Tapio Luostarinen; Satu Männistö; E Jeffrey Metter; Kazuya Mikami; Roger L Milne; Kotaro Ozasa; Elizabeth A Platz; J Ramón Quirós; Harri Rissanen; Norie Sawada; Meir Stampfer; Frank Z Stanczyk; Pär Stattin; Akiko Tamakoshi; Catherine M Tangen; Ian M Thompson; Konstantinos K Tsilidis; Shoichiro Tsugane; Giske Ursin; Lars Vatten; Noel S Weiss; Bu B Yeap; Naomi E Allen; Timothy J Key; Ruth C Travis Journal: Eur Urol Date: 2018-08-01 Impact factor: 20.096