Keming Yang1, Michele R Forman2, Brett H Graham3, Patrick O Monahan4, Edward L Giovannucci5, Immaculata De Vivo6, Andrew T Chan7, Hongmei Nan8. 1. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. 2. Department of Nutrition Science, College of Health and Human Science, Purdue Center for Cancer Research, Purdue University, West Lafayette, IN, USA. 3. Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. 4. Department of Biostatistics, School of Medicine and Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA. 5. Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 6. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 7. Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA; Clinical and Translational Epidemiology Unit and Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. Electronic address: ACHAN@mgh.harvard.edu. 8. Department of Epidemiology, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA; Department of Global Health, Richard M. Fairbanks School of Public Health, Indiana University, Indianapolis, IN, USA; IU Melvin and Bren Simon Cancer Center, Indiana University, Indianapolis, IN, USA. Electronic address: hnan@iu.edu.
Abstract
BACKGROUND: Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colorectal cancer (CRC) diagnosis and CRC prognosis, findings have been inconsistent, and no study has specifically investigated the association of pre-diagnostic mtDNAcn with CRC survival. METHODS: We examined the association of pre-diagnostic leukocyte mtDNAcn (measured by qPCR) with overall and CRC-specific survival among 587 patients in Nurses' Health Study and Health Professionals Follow-Up Study. Cox models were constructed to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). RESULTS: During a mean follow-up of 10.5 years, 395 deaths were identified; 180 were due to CRC. Overall, we did not observe significant associations between mtDNAcn and either overall or CRC-specific survival among all cases or by cancer location, grade, or stage. In an exploratory stratified analysis, a suggestive inverse association of mtDNAcn and overall death risk appeared among current smokers [HR (95 % CI) for 1 SD decrease in mtDNAcn = 1.50 (0.98, 2.32), P-trend = 0.06]. Reduced mtDNAcn and lower CRC-specific death risk was observed among patients aged ≤ 70.5 at diagnosis [HR (95 % CI) for 1 SD decrease of mtDNAcn = 0.71 (0.52, 0.97), P-trend = 0.03], ≤ 5 years from blood collection to diagnosis [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.65 (0.44, 0.96), P-trend = 0.03] and those consuming a low-inflammatory diet [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.61 (0.42, 0.88), P-trend = 0.009]. CONCLUSION: no significant associations between pre-diagnostic leukocyte mtDNAcn and either overall or CRC-specific survival appeared but exploratory analysis identified potential sub-group associations.
BACKGROUND: Mitochondrial DNA copy number (mtDNAcn) is considered a biomarker for mitochondrial function and oxidative stress. Although previous studies have suggested a potential relationship between mtDNAcn at the time of colorectal cancer (CRC) diagnosis and CRC prognosis, findings have been inconsistent, and no study has specifically investigated the association of pre-diagnostic mtDNAcn with CRC survival. METHODS: We examined the association of pre-diagnostic leukocyte mtDNAcn (measured by qPCR) with overall and CRC-specific survival among 587 patients in Nurses' Health Study and Health Professionals Follow-Up Study. Cox models were constructed to estimate hazard ratios (HRs) and 95 % confidence intervals (95 % CIs). RESULTS: During a mean follow-up of 10.5 years, 395 deaths were identified; 180 were due to CRC. Overall, we did not observe significant associations between mtDNAcn and either overall or CRC-specific survival among all cases or by cancer location, grade, or stage. In an exploratory stratified analysis, a suggestive inverse association of mtDNAcn and overall death risk appeared among current smokers [HR (95 % CI) for 1 SD decrease in mtDNAcn = 1.50 (0.98, 2.32), P-trend = 0.06]. Reduced mtDNAcn and lower CRC-specific death risk was observed among patients aged ≤ 70.5 at diagnosis [HR (95 % CI) for 1 SD decrease of mtDNAcn = 0.71 (0.52, 0.97), P-trend = 0.03], ≤ 5 years from blood collection to diagnosis [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.65 (0.44, 0.96), P-trend = 0.03] and those consuming a low-inflammatory diet [HR (95 % CI) for 1 SD decrease in mtDNAcn = 0.61 (0.42, 0.88), P-trend = 0.009]. CONCLUSION: no significant associations between pre-diagnostic leukocyte mtDNAcn and either overall or CRC-specific survival appeared but exploratory analysis identified potential sub-group associations.
Authors: Fred K Tabung; Stephanie A Smith-Warner; Jorge E Chavarro; Kana Wu; Charles S Fuchs; Frank B Hu; Andrew T Chan; Walter C Willett; Edward L Giovannucci Journal: J Nutr Date: 2016-06-29 Impact factor: 4.798
Authors: Keming Yang; Xin Li; Michele R Forman; Patrick O Monahan; Bret H Graham; Amit Joshi; Mingyang Song; Dong Hang; Shuji Ogino; Edward L Giovannucci; Immaculata De Vivo; Andrew T Chan; Hongmei Nan Journal: Carcinogenesis Date: 2019-12-31 Impact factor: 4.944
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