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Yang K, Forman MR, Graham BH, Monahan PO, Giovannucci EL, De Vivo I, Chan AT, Nan H. Association between pre-diagnostic leukocyte mitochondrial DNA copy number and survival among colorectal cancer patients. Cancer epidemiology. 2020 Oct 1; 68:101778.
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.