TY - JOUR
T1 - Reduced mitochondrial DNA copy number in peripheral blood leukocytes increases the risk of soft tissue sarcoma
AU - Xie, Hui
AU - Lev, Dina
AU - Gong, Yilei
AU - Wang, Shui
AU - Pollock, Raphael E.
AU - Wu, Xifeng
AU - Gu, Jian
PY - 2013/5
Y1 - 2013/5
N2 - Mitochondrial DNA (mtDNA) has increased susceptibility to damage due to its close proximity to the site of reactive oxygen species production, lack of introns and protective histones, and less efficient DNA repair mechanisms than nuclear DNA. The relationship between mtDNA copy number in peripheral blood leukocytes (PBLs) and the risk of soft tissue sarcoma (STS) has not been investigated. In this study, we determined the relative mtDNA copy number in PBLs of 325 patients (cases) with histologically confirmed STS and 330 healthy controls that were frequency matched to cases according to age, sex and ethnicity. Cases had a significantly lower mtDNA copy number than controls (0.93 ± 0.49 for cases versus 1.23 ± 0.59 for controls; P < 0.001). In analyses stratified by sex, ethnicity and smoking status, mtDNA copy number was lower in the cases than in controls in any stratum. Using the median mtDNA copy number in controls as a cutoff, individuals with lower mtDNA copy number were associated with a significantly increased risk of STS compared with those with higher mtDNA copy number (adjusted odds ratio, 2.71; 95% confidence interval, 1.94-3.82). There was a significant dose-response relationship between reduced mtDNA copy number and increased risk of STS in tertile and quartile analyses. The present study provides the first epidemiologic evidence that reduced mtDNA copy number in PBLs is significantly associated with an increased risk of STS, thereby suggesting an important role of mtDNA in STS development.
AB - Mitochondrial DNA (mtDNA) has increased susceptibility to damage due to its close proximity to the site of reactive oxygen species production, lack of introns and protective histones, and less efficient DNA repair mechanisms than nuclear DNA. The relationship between mtDNA copy number in peripheral blood leukocytes (PBLs) and the risk of soft tissue sarcoma (STS) has not been investigated. In this study, we determined the relative mtDNA copy number in PBLs of 325 patients (cases) with histologically confirmed STS and 330 healthy controls that were frequency matched to cases according to age, sex and ethnicity. Cases had a significantly lower mtDNA copy number than controls (0.93 ± 0.49 for cases versus 1.23 ± 0.59 for controls; P < 0.001). In analyses stratified by sex, ethnicity and smoking status, mtDNA copy number was lower in the cases than in controls in any stratum. Using the median mtDNA copy number in controls as a cutoff, individuals with lower mtDNA copy number were associated with a significantly increased risk of STS compared with those with higher mtDNA copy number (adjusted odds ratio, 2.71; 95% confidence interval, 1.94-3.82). There was a significant dose-response relationship between reduced mtDNA copy number and increased risk of STS in tertile and quartile analyses. The present study provides the first epidemiologic evidence that reduced mtDNA copy number in PBLs is significantly associated with an increased risk of STS, thereby suggesting an important role of mtDNA in STS development.
UR - http://www.scopus.com/inward/record.url?scp=84877104879&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84877104879&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgt023
DO - 10.1093/carcin/bgt023
M3 - Article
C2 - 23349016
AN - SCOPUS:84877104879
SN - 0143-3334
VL - 34
SP - 1039
EP - 1043
JO - Carcinogenesis
JF - Carcinogenesis
IS - 5
ER -