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

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.

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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.