S Uccella1, A Mariani1, A H Wang2, R A Vierkant2, K Robien3, K E Anderson3, J R Cerhan4. 1. Department of Obstetrics and Gynecology, Division of Gynecologic Surgery. 2. Department of Health Sciences Research, Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester. 3. Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis. 4. Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine, Rochester, USA. Electronic address: cerhan.james@mayo.edu.
Abstract
BACKGROUND: Type I and II endometrial cancer are biologically and clinically distinct, with type II cancers having a high frequency of p53 mutations and an association with chromosomal instability. This raises the hypothesis that one-carbon nutrients (folate, methionine, and the enzymic cofactors vitamins B2, B6, and B12), which mediate chromosomal stability and DNA methylation, may be protective for type II but not type I endometrial cancer. METHODS: Using a prospective cohort of 23 356 postmenopausal women followed 20 years, we estimated the relative risks (RRs) of type I (N = 471) and II (N = 71) endometrial cancers according to intake of one-carbon nutrients, adjusting for confounders. RESULTS: No associations were observed between dietary or supplemental intake of any one-carbon nutrient and risk of type I cancer. For type II cancer, positive associations were due to supplemental, rather than dietary, intake of these nutrients: supplemental folate (RR = 1.80 for >228.6 versus 0 μg/day; P trend = 0.027) and vitamins B2 (RR = 1.94 for >1.70 versus 0 mg/day; P trend = 0.011), B6 (RR = 2.08 for >2.00 versus 0 mg/day; P trend = 0.012), and B12 (RR = 2.10 for >3.43 versus 0 μg/day; P trend = 0.0060). CONCLUSION: Contrary to our hypothesis, use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.
BACKGROUND: Type I and II endometrial cancer are biologically and clinically distinct, with type II cancers having a high frequency of p53 mutations and an association with chromosomal instability. This raises the hypothesis that one-carbon nutrients (folate, methionine, and the enzymic cofactors vitamins B2, B6, and B12), which mediate chromosomal stability and DNA methylation, may be protective for type II but not type I endometrial cancer. METHODS: Using a prospective cohort of 23 356 postmenopausal women followed 20 years, we estimated the relative risks (RRs) of type I (N = 471) and II (N = 71) endometrial cancers according to intake of one-carbon nutrients, adjusting for confounders. RESULTS: No associations were observed between dietary or supplemental intake of any one-carbon nutrient and risk of type I cancer. For type II cancer, positive associations were due to supplemental, rather than dietary, intake of these nutrients: supplemental folate (RR = 1.80 for >228.6 versus 0 μg/day; P trend = 0.027) and vitamins B2 (RR = 1.94 for >1.70 versus 0 mg/day; P trend = 0.011), B6 (RR = 2.08 for >2.00 versus 0 mg/day; P trend = 0.012), and B12 (RR = 2.10 for >3.43 versus 0 μg/day; P trend = 0.0060). CONCLUSION: Contrary to our hypothesis, use of supplements containing folate and vitamins B2, B6, and B12 was associated with an increased risk of type II endometrial cancer.
Authors: Rachael Z Stolzenberg-Solomon; Shih-Chen Chang; Michael F Leitzmann; Karen A Johnson; Christine Johnson; Saundra S Buys; Robert N Hoover; Regina G Ziegler Journal: Am J Clin Nutr Date: 2006-04 Impact factor: 7.045
Authors: Michael Yeh; Kirsten B Moysich; Vijayvel Jayaprakash; Kerry J Rodabaugh; Saxon Graham; John R Brasure; Susan E McCann Journal: J Nutr Date: 2008-12-11 Impact factor: 4.798
Authors: Jane C Figueiredo; Maria V Grau; Robert W Haile; Robert S Sandler; Robert W Summers; Robert S Bresalier; Carol A Burke; Gail E McKeown-Eyssen; John A Baron Journal: J Natl Cancer Inst Date: 2009-03-10 Impact factor: 13.506
Authors: Ross L Prentice; Cynthia A Thomson; Bette Caan; F Allan Hubbell; Garnet L Anderson; Shirley A A Beresford; Mary Pettinger; Dorothy S Lane; Lawrence Lessin; Shagufta Yasmeen; Baljinder Singh; Janardan Khandekar; James M Shikany; Suzanne Satterfield; Rowan T Chlebowski Journal: J Natl Cancer Inst Date: 2007-10-09 Impact factor: 13.506
Authors: Adriana M Coletta; Susan K Peterson; Leticia A Gatus; Kate J Krause; Susan M Schembre; Susan C Gilchrist; Mala Pande; Eduardo Vilar; Y Nancy You; Miguel A Rodriguez-Bigas; Larkin L Strong; Patrick M Lynch; Karen H Lu; Karen Basen-Engquist Journal: Fam Cancer Date: 2019-06-24 Impact factor: 2.375
Authors: Veronica Wendy Setiawan; Hannah P Yang; Malcolm C Pike; Susan E McCann; Herbert Yu; Yong-Bing Xiang; Alicja Wolk; Nicolas Wentzensen; Noel S Weiss; Penelope M Webb; Piet A van den Brandt; Koen van de Vijver; Pamela J Thompson; Brian L Strom; Amanda B Spurdle; Robert A Soslow; Xiao-ou Shu; Catherine Schairer; Carlotta Sacerdote; Thomas E Rohan; Kim Robien; Harvey A Risch; Fulvio Ricceri; Timothy R Rebbeck; Radhai Rastogi; Jennifer Prescott; Silvia Polidoro; Yikyung Park; Sara H Olson; Kirsten B Moysich; Anthony B Miller; Marjorie L McCullough; Rayna K Matsuno; Anthony M Magliocco; Galina Lurie; Lingeng Lu; Jolanta Lissowska; Xiaolin Liang; James V Lacey; Laurence N Kolonel; Brian E Henderson; Susan E Hankinson; Niclas Håkansson; Marc T Goodman; Mia M Gaudet; Montserrat Garcia-Closas; Christine M Friedenreich; Jo L Freudenheim; Jennifer Doherty; Immaculata De Vivo; Kerry S Courneya; Linda S Cook; Chu Chen; James R Cerhan; Hui Cai; Louise A Brinton; Leslie Bernstein; Kristin E Anderson; Hoda Anton-Culver; Leo J Schouten; Pamela L Horn-Ross Journal: J Clin Oncol Date: 2013-06-03 Impact factor: 44.544
Authors: Maki Inoue-Choi; Kim Robien; Andrea Mariani; James R Cerhan; Kristin E Anderson Journal: Cancer Epidemiol Biomarkers Prev Date: 2013-11-22 Impact factor: 4.254
Authors: S Uccella; A Mariani; A H Wang; R A Vierkant; W A Cliby; K Robien; K E Anderson; J R Cerhan Journal: Br J Cancer Date: 2013-09-10 Impact factor: 7.640