Justin C Brown1,2, Bette J Caan3, Carla M Prado4, Elizabeth M Cespedes Feliciano3, Jingjie Xiao4, Candyce H Kroenke3, Jeffrey A Meyerhardt5. 1. Department of Population and Public Health Science, Pennington Biomedical Research Center, Baton Rouge. 2. Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans. 3. Kaiser Permanente Northern California, Oakland, CA. 4. University of Alberta, Edmonton, AB, Canada. 5. Dana-Farber Cancer Institute, Boston, MA.
Abstract
BACKGROUND: The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancer patients, and such associations may vary by patient sex. METHODS: This cohort included 3262 stage I-III colorectal cancer patients. Visceral and subcutaneous adipose tissues were quantified using computed tomography. The primary endpoint was all-cause mortality. Restricted cubic splines estimated statistical associations with two-sided P values. RESULTS: Visceral adipose tissue was prognostic of mortality in a reverse L-shaped pattern (nonlinear P = .02); risk was flat to a threshold (∼260 cm2) then increased linearly. Subcutaneous adipose tissue was prognostic of mortality in a J-shaped pattern (nonlinear P < .001); risk was higher at extreme (<50 cm2) but lower at intermediate values (>50 to ≤560 cm2). Patient sex modified the prognostic associations between visceral adipose tissue (Pinteraction = .049) and subcutaneous adipose tissue (Pinteraction = .04) with mortality. Among men, visceral adiposity was associated with mortality in a J-shaped pattern (nonlinear P = .003), whereas among women, visceral adiposity was associated with mortality in a linear pattern (linear P = .008). Among men, subcutaneous adiposity was associated with mortality in an L-shaped pattern (nonlinear P = .01), whereas among women, subcutaneous adiposity was associated with mortality in a J-shaped pattern (nonlinear P < .001). CONCLUSIONS: Visceral and subcutaneous adipose tissue were prognostic of mortality in patients with colorectal cancer; the shape of these associations were often nonlinear and varied by patient sex. These results offer insight into the potential biological mechanisms that link obesity with clinical outcomes in patients with cancer, suggesting that the dysregulated deposition of excess adiposity is prognostic of mortality.
BACKGROUND: The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancerpatients, and such associations may vary by patient sex. METHODS: This cohort included 3262 stage I-III colorectal cancerpatients. Visceral and subcutaneous adipose tissues were quantified using computed tomography. The primary endpoint was all-cause mortality. Restricted cubic splines estimated statistical associations with two-sided P values. RESULTS: Visceral adipose tissue was prognostic of mortality in a reverse L-shaped pattern (nonlinear P = .02); risk was flat to a threshold (∼260 cm2) then increased linearly. Subcutaneous adipose tissue was prognostic of mortality in a J-shaped pattern (nonlinear P < .001); risk was higher at extreme (<50 cm2) but lower at intermediate values (>50 to ≤560 cm2). Patient sex modified the prognostic associations between visceral adipose tissue (Pinteraction = .049) and subcutaneous adipose tissue (Pinteraction = .04) with mortality. Among men, visceral adiposity was associated with mortality in a J-shaped pattern (nonlinear P = .003), whereas among women, visceral adiposity was associated with mortality in a linear pattern (linear P = .008). Among men, subcutaneous adiposity was associated with mortality in an L-shaped pattern (nonlinear P = .01), whereas among women, subcutaneous adiposity was associated with mortality in a J-shaped pattern (nonlinear P < .001). CONCLUSIONS: Visceral and subcutaneous adipose tissue were prognostic of mortality in patients with colorectal cancer; the shape of these associations were often nonlinear and varied by patient sex. These results offer insight into the potential biological mechanisms that link obesity with clinical outcomes in patients with cancer, suggesting that the dysregulated deposition of excess adiposity is prognostic of mortality.
Authors: Chun Seng Lee; David J Murphy; Colm McMahon; Blathnaid Nolan; Garret Cullen; Hugh Mulcahy; Kieran Sheahan; Elizabeth Barnes; David Fennelly; Elizabeth J Ryan; Glen A Doherty Journal: J Gastrointest Cancer Date: 2015-09
Authors: David B Liesenfeld; Dmitry Grapov; Johannes F Fahrmann; Mariam Salou; Dominique Scherer; Reka Toth; Nina Habermann; Jürgen Böhm; Petra Schrotz-King; Biljana Gigic; Martin Schneider; Alexis Ulrich; Esther Herpel; Peter Schirmacher; Oliver Fiehn; Johanna W Lampe; Cornelia M Ulrich Journal: Am J Clin Nutr Date: 2015-07-08 Impact factor: 7.045
Authors: Karen L Shea; Kathleen M Gavin; Edward L Melanson; Ellie Gibbons; Anne Stavros; Pamela Wolfe; John M Kittelson; Sheryl F Vondracek; Robert S Schwartz; Margaret E Wierman; Wendy M Kohrt Journal: Menopause Date: 2015-10 Impact factor: 2.953
Authors: Aaron S Rickles; James C Iannuzzi; Oleg Mironov; Andrew-Paul Deeb; Abhiram Sharma; Fergal J Fleming; John R T Monson Journal: J Gastrointest Surg Date: 2012-10-23 Impact factor: 3.452
Authors: Jennifer H Lin; Shumin M Zhang; Kathryn M Rexrode; Joann E Manson; Andrew T Chan; Kana Wu; Shelley S Tworoger; Susan E Hankinson; Charles Fuchs; J Michael Gaziano; Julie E Buring; Edward Giovannucci Journal: Clin Gastroenterol Hepatol Date: 2012-11-28 Impact factor: 11.382
Authors: Lindsay A Renfro; Fotios Loupakis; Richard A Adams; Matthew T Seymour; Volker Heinemann; Hans-Joachim Schmoll; Jean-Yves Douillard; Herbert Hurwitz; Charles S Fuchs; Eduardo Diaz-Rubio; Rainer Porschen; Christophe Tournigand; Benoist Chibaudel; Alfredo Falcone; Niall C Tebbutt; Cornelis J A Punt; J Randolph Hecht; Carsten Bokemeyer; Eric Van Cutsem; Richard M Goldberg; Leonard B Saltz; Aimery de Gramont; Daniel J Sargent; Heinz-Josef Lenz Journal: J Clin Oncol Date: 2015-10-26 Impact factor: 44.544
Authors: Justin C Brown; Michael H Rosenthal; Chao Ma; Sui Zhang; Halla S Nimeiri; Nadine J McCleary; Thomas A Abrams; Matthew B Yurgelun; James M Cleary; Douglas A Rubinson; Deborah Schrag; Andrea J Bullock; Jill Allen; Dan Zuckerman; Emily Chan; Jennifer A Chan; Brian Wolpin; Michael Constantine; Douglas J Weckstein; Meredith A Faggen; Christian A Thomas; Chryssanthi Kournioti; Chen Yuan; Hui Zheng; Bruce W Hollis; Charles S Fuchs; Kimmie Ng; Jeffrey A Meyerhardt Journal: Cancers (Basel) Date: 2020-11-20 Impact factor: 6.639
Authors: Elizabeth M Cespedes Feliciano; Karteek Popuri; Dana Cobzas; Vickie E Baracos; Mirza Faisal Beg; Arafat Dad Khan; Cydney Ma; Vincent Chow; Carla M Prado; Jingjie Xiao; Vincent Liu; Wendy Y Chen; Jeffrey Meyerhardt; Kathleen B Albers; Bette J Caan Journal: J Cachexia Sarcopenia Muscle Date: 2020-04-20 Impact factor: 12.910
Authors: In Kyu Park; Song Soo Yang; Eric Chung; Eun-Suk Cho; Hye Sun Lee; Su-Jin Shin; Yeong Cheol Im; Eun Jung Park; Seung Hyuk Baik; Kang Young Lee; Jeonghyun Kang Journal: Cancer Med Date: 2021-10-13 Impact factor: 4.452