title: Constitutive mitochondrial DNA copy number in peripheral blood of melanoma families with and withoutCDKN2Amutations.
abstract: Quantitative changes in mitochondrial DNA (mtDNA) have been associated with the risk of a number of human cancers; however, the relationship between constitutive mtDNA copy number in blood and the risk of familial cutaneous malignant melanoma (CMM) has not been reported. We measured mtDNA copy number using quantitative PCR in blood-derived DNA from 136 CMM cases and 302 controls in 53 melanoma-prone families (23 segregatingCDKN2Agermline mutations). MtDNA copy number did not vary by age, sex, pigmentation characteristics, or CMM status. However, germlineCDKN2Amutation carriers had significantly higher mean mtDNA copy number compared to non-carriers, particularly among CMM cases (geometric mean mtDNA copy number of 144 and 111 for carrier versus non-carrier, respectively; P= 0.02). When adjusting for age, sex, and familial correlation, having increasing mtDNA copy number was significantly associated withCDKN2Amutation status among CMM cases (OR=1.47,Ptrend=0.024). In particular, individuals with specificCDKN2Amutations with the potential to inactivate or reduce the level of the p16-INK4 reactive oxygen species (ROS) protective function had significantly increased mtDNA copy number levels (P=0.035). Future research in prospective studies is required to validate these findings and to further investigate mtDNA copy number in both blood and melanoma tissues in relation to CMM risk andCDKN2Amutation status.
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Paula L
authors: PL
authors: Hyland
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Melissa
authors: M
authors: Rotunno
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Jonathan N
authors: JN
authors: Hofmann
authors: Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors: Chin-San
authors: CS
authors: Liu
authors: Vascular and Genomic Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
authors: Wen-Ling
authors: WL
authors: Cheng
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Jeff
authors: J
authors: Yuenger
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Qing
authors: Q
authors: Lan
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Margaret A
authors: MA
authors: Tucker
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Alisa M
authors: AM
authors: Goldstein
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD.
authors: Xiaohong R
authors: XR
authors: Yang
keywords: CDKN2A; Familial melanoma; mtDNA copy number; peripheral blood