Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer

Abstract

BackgroundAlterations of mitochondrial DNA (mtDNA) have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA). We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters.MethodsPeripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu protein.ResultsThe content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023). Reduced mtDNA was found often in post menopausal cancer group (P = 0.024). No difference in mtDNA content, in regards to age (p = 0.564), lymph node involvement (p = 0.673), ER (p = 0.877), PR (p = 0.763), and Her-2/neu expression (p = 0.335), was observed.ConclusionEarly detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer.

Circulating Mitochondrial DNA Level, a Noninvasive Biomarker for the Early Detection of Gastric Cancer

“…A lower blood mtDNA level has been described in stage I breast cancer than in advanced stages II to IV, leading to suggest that cancer cells deplete a larger amount of mtDNA in circulating cells at an early stage of cancer development. The initial decline in mtDNA content should be compensated at later stage of the cancer process to restore respiratory functions (34), which is in agreement with the increase we observed in many of the gastric cancer cases studied. This kinetic of mtDNA levels during the carcinogenic process would also be in agreement with results from cohort 2 patients showing significant lower mtDNA levels in NAG and in patients with precancerous intestinal metaplasia, compared with most patients with gastric cancer.…”

“…Levels of circulating mtDNA were found significantly higher in patients with various type of tumors (29)(30)(31)(32)44). Peripheral mtDNA content has also been proposed as a novel molecular marker for tracing tumor progression (34). In the present study, we found more variation of circulating leukocytes mtDNA level in patients with NAG or gastric cancer than in healthy subjects.…”

“…These studies indicated that increased mtDNA content in peripheral blood is associated with elevated cancer risk. However, contrasting reports have found mtDNA depletion in the blood of patients with stage I breast tumors (34). A recent large prospective cohort study in women from Shanghai found no association between the leukocyte mtDNA copy number and the presence of gastric tumor (35).…”

Germline HVR-II mitochondrial polymorphisms associated with breast cancer in Tunisian women

“…Similar results were obtained by Bragoszewski and collaborators (2008) in studies on ovarian cancer risk assessment. However, the significance of these results is still a subject of some controversy, since 1) low mtDNA content was identified in tumor specimens of BC at an early TNM stage (stage I) as compared with more advanced stages, suggesting that it may be essential in the early progression of BC (Xia et al, 2009), and 2) reduced mtDNA content shows a significant correlation with BC patient's ER or PR status (Yu et al, 2007). Therefore, the relationship between mtDNA content/ polymorphisms and clinicopathological characteristics of cancers remains unclear and needs further investigation, because they may influence the outcome of BC therapy, particularly endocrine treatments.…”

Monitoring Genetic Population Biomarkers for Wastewater-Based Epidemiology

“…It is used as a biomarker in a number of cancers including breast, renal and gastric cancers. 13 We recently proposed the use of community sewage sensors as rapid and inexpensive alternatives to classical analytical methods for the detection of sewage biomarkers. 7 We have previously also demonstrated that community sewage sensors are able to detect a wide range of markers (e.g., prostate specific antigen 14 and illicit drugs such as cocaine 15 ).…”