Association between pre-diagnostic leukocyte mitochondrial DNA copy number and survival among colorectal cancer patients

Keming Yang, Michele R. Forman, Brett H. Graham, Patrick O. Monahan, Edward L. Giovannucci, Immaculata De Vivo, Andrew T. Chan, Hongmei Nan

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number101778
JournalCancer Epidemiology
Volume68
DOIs
StatePublished - Oct 2020
Externally publishedYes

Keywords

  • Colorectal cancer
  • Leukocyte
  • Mitochondria
  • Mitochondrial DNA
  • Mitochondrial DNA copy number
  • Survival

ASJC Scopus subject areas

  • Epidemiology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Association between pre-diagnostic leukocyte mitochondrial DNA copy number and survival among colorectal cancer patients'. Together they form a unique fingerprint.

  • Cite this