Adela Ramirez-Torres1, Allison L Reagan2,3, Lauren E Howard2,3, Emily Wiggins3, Adriana C Vidal1, Junxiang Wan4, Brendan Miller4, Stephen J Freedland1,3, Pinchas Cohen4. 1. Department of Surgery, Center for Integrated Research on Cancer and Lifestyle, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA. 2. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, North Carolina, USA. 3. Division of Urology, Veterans Affairs Health Care System, VA Medical Center, Durham, North Carolina, USA. 4. Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California, USA.
Abstract
INTRODUCTION: The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race. METHODS: Plasma SHLP2, humanin, and MOTS-c were measured in 198 men (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) undergoing biopsy. Logistic and multinomial regression models tested associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5). Models were adjusted for age, body mass index, digital rectal examination, and prostate specific antigen (PSA). We tested interactions between MDPs and race. RESULTS: Among controls, humanin was similar by race (p = 0.60), but both SHLP2 (p = 0.007) and MOTS-c (p = 0.026) were lower in AAM controls versus EAM controls. Among EAM, higher MDP values were associated with lower PC risk (all p ≤ 0.001), with null associations in AAM (all p-interactions ≤ 0.01). Similarly, higher MDP expression was associated with decreased risk of low- and high-grade PC in EAM (all p ≤ 0.005) with null associations in AAM. CONCLUSIONS: Higher MDP levels were associated with lower PC risk in EAM but not AAM. Generally, AAM controls had lower MDP levels. These data support MDPs and mitochondrial dysfunction in PC, suggesting greater dysfunction in AAM may contribute to excess PC risk. Future larger studies are needed to confirm these results.
INTRODUCTION: The mitochondrial genome has small open reading frames (sORF) which produce measurable mitochondrial-derived peptides (MDPs), including humanin, SHLP2, and MOTS-c. Previously, among men undergoing prostate biopsy, we found higher serum SHLP2 was linked with lower prostate cancer (PC) risk in European American men (EAM), while null associations were found in African American men (AAM). Here, in different patients undergoing prostate biopsy, we tested the link between SHLP2, humanin and MOTS-c and PC risk by race. METHODS: Plasma SHLP2, humanin, and MOTS-c were measured in 198 men (50/49 EAM/AAM cases; 50/49 EAM/AAM controls) undergoing biopsy. Logistic and multinomial regression models tested associations between each MDP and PC diagnosis, low-grade (grade group, GG1) and high-grade (GG2-5). Models were adjusted for age, body mass index, digital rectal examination, and prostate specific antigen (PSA). We tested interactions between MDPs and race. RESULTS: Among controls, humanin was similar by race (p = 0.60), but both SHLP2 (p = 0.007) and MOTS-c (p = 0.026) were lower in AAM controls versus EAM controls. Among EAM, higher MDP values were associated with lower PC risk (all p ≤ 0.001), with null associations in AAM (all p-interactions ≤ 0.01). Similarly, higher MDP expression was associated with decreased risk of low- and high-grade PC in EAM (all p ≤ 0.005) with null associations in AAM. CONCLUSIONS: Higher MDP levels were associated with lower PC risk in EAM but not AAM. Generally, AAM controls had lower MDP levels. These data support MDPs and mitochondrial dysfunction in PC, suggesting greater dysfunction in AAM may contribute to excess PC risk. Future larger studies are needed to confirm these results.
Authors: Vittorio Fasulo; Janet E Cowan; Martina Maggi; Samuel L Washington; Hao G Nguyen; Katsuto Shinohara; Massimo Lazzeri; Paolo Casale; Peter R Carroll Journal: Eur Urol Oncol Date: 2020-10-14
Authors: Alexis R Gaines; Elizabeth L Turner; Patricia G Moorman; Stephen J Freedland; Christopher J Keto; Megan E McPhail; Delores J Grant; Adriana C Vidal; Cathrine Hoyo Journal: Cancer Causes Control Date: 2014-05-31 Impact factor: 2.506
Authors: David V Conti; Burcu F Darst; Lilit C Moss; Edward J Saunders; Xin Sheng; Alisha Chou; Fredrick R Schumacher; Ali Amin Al Olama; Sara Benlloch; Tokhir Dadaev; Mark N Brook; Ali Sahimi; Thomas J Hoffmann; Atushi Takahashi; Koichi Matsuda; Yukihide Momozawa; Masashi Fujita; Kenneth Muir; Artitaya Lophatananon; Peggy Wan; Loic Le Marchand; Lynne R Wilkens; Victoria L Stevens; Susan M Gapstur; Brian D Carter; Johanna Schleutker; Teuvo L J Tammela; Csilla Sipeky; Anssi Auvinen; Graham G Giles; Melissa C Southey; Robert J MacInnis; Cezary Cybulski; Dominika Wokołorczyk; Jan Lubiński; David E Neal; Jenny L Donovan; Freddie C Hamdy; Richard M Martin; Børge G Nordestgaard; Sune F Nielsen; Maren Weischer; Stig E Bojesen; Martin Andreas Røder; Peter Iversen; Jyotsna Batra; Suzanne Chambers; Leire Moya; Lisa Horvath; Judith A Clements; Wayne Tilley; Gail P Risbridger; Henrik Gronberg; Markus Aly; Robert Szulkin; Martin Eklund; Tobias Nordström; Nora Pashayan; Alison M Dunning; Maya Ghoussaini; Ruth C Travis; Tim J Key; Elio Riboli; Jong Y Park; Thomas A Sellers; Hui-Yi Lin; Demetrius Albanes; Stephanie J Weinstein; Lorelei A Mucci; Edward Giovannucci; Sara Lindstrom; Peter Kraft; David J Hunter; Kathryn L Penney; Constance Turman; Catherine M Tangen; Phyllis J Goodman; Ian M Thompson; Robert J Hamilton; Neil E Fleshner; Antonio Finelli; Marie-Élise Parent; Janet L Stanford; Elaine A Ostrander; Milan S Geybels; Stella Koutros; Laura E Beane Freeman; Meir Stampfer; Alicja Wolk; Niclas Håkansson; Gerald L Andriole; Robert N Hoover; Mitchell J Machiela; Karina Dalsgaard Sørensen; Michael Borre; William J Blot; Wei Zheng; Edward D Yeboah; James E Mensah; Yong-Jie Lu; Hong-Wei Zhang; Ninghan Feng; Xueying Mao; Yudong Wu; Shan-Chao Zhao; Zan Sun; Stephen N Thibodeau; Shannon K McDonnell; Daniel J Schaid; Catharine M L West; Neil Burnet; Gill Barnett; Christiane Maier; Thomas Schnoeller; Manuel Luedeke; Adam S Kibel; Bettina F Drake; Olivier Cussenot; Géraldine Cancel-Tassin; Florence Menegaux; Thérèse Truong; Yves Akoli Koudou; Esther M John; Eli Marie Grindedal; Lovise Maehle; Kay-Tee Khaw; Sue A Ingles; Mariana C Stern; Ana Vega; Antonio Gómez-Caamaño; Laura Fachal; Barry S Rosenstein; Sarah L Kerns; Harry Ostrer; Manuel R Teixeira; Paula Paulo; Andreia Brandão; Stephen Watya; Alexander Lubwama; Jeannette T Bensen; Elizabeth T H Fontham; James Mohler; Jack A Taylor; Manolis Kogevinas; Javier Llorca; Gemma Castaño-Vinyals; Lisa Cannon-Albright; Craig C Teerlink; Chad D Huff; Sara S Strom; Luc Multigner; Pascal Blanchet; Laurent Brureau; Radka Kaneva; Chavdar Slavov; Vanio Mitev; Robin J Leach; Brandi Weaver; Hermann Brenner; Katarina Cuk; Bernd Holleczek; Kai-Uwe Saum; Eric A Klein; Ann W Hsing; Rick A Kittles; Adam B Murphy; Christopher J Logothetis; Jeri Kim; Susan L Neuhausen; Linda Steele; Yuan Chun Ding; William B Isaacs; Barbara Nemesure; Anselm J M Hennis; John Carpten; Hardev Pandha; Agnieszka Michael; Kim De Ruyck; Gert De Meerleer; Piet Ost; Jianfeng Xu; Azad Razack; Jasmine Lim; Soo-Hwang Teo; Lisa F Newcomb; Daniel W Lin; Jay H Fowke; Christine Neslund-Dudas; Benjamin A Rybicki; Marija Gamulin; Davor Lessel; Tomislav Kulis; Nawaid Usmani; Sandeep Singhal; Matthew Parliament; Frank Claessens; Steven Joniau; Thomas Van den Broeck; Manuela Gago-Dominguez; Jose Esteban Castelao; Maria Elena Martinez; Samantha Larkin; Paul A Townsend; Claire Aukim-Hastie; William S Bush; Melinda C Aldrich; Dana C Crawford; Shiv Srivastava; Jennifer C Cullen; Gyorgy Petrovics; Graham Casey; Monique J Roobol; Guido Jenster; Ron H N van Schaik; Jennifer J Hu; Maureen Sanderson; Rohit Varma; Roberta McKean-Cowdin; Mina Torres; Nicholas Mancuso; Sonja I Berndt; Stephen K Van Den Eeden; Douglas F Easton; Stephen J Chanock; Michael B Cook; Fredrik Wiklund; Hidewaki Nakagawa; John S Witte; Rosalind A Eeles; Zsofia Kote-Jarai; Christopher A Haiman Journal: Nat Genet Date: 2021-01-04 Impact factor: 38.330