Sonja Berndt

NCI

Investigator

PLCO (Learn more about this study)

PLCO-140

Apr 3, 2015

An analysis of the association between genetic variants and mitochondrial DNA copy number.

Mitochondria have been implicated in playing a critical role carcinogenesis because of their central role in energy production and apoptosis. Mitochondrial DNA lacks both the DNA repair capacity and cytogenetic protections found in nuclear DNA, making it more susceptible to DNA damage and an attractive candidate in the study of cancer etiology. Indeed, previous epidemiologic studies have reported associations between mitochondrial DNA copy number in peripheral blood or buccal cells and risk of several cancers. Mitochondrial DNA copy number has been shown to be approximately 65% heritable [1], and a previous study of the genetic variation contributing to mitochondrial DNA copy number has implicated the nuclear gene STAT3 [2]. A recent familial GWAS of the nuclear genome and mitochondrial DNA levels uncovered suggestive sex-specific associations in intronic variants of PARK2 and MRPL37 [3]. Several nested case-control studies of mtDNA copy number and cancer risk have been conducted in the PLCO Cancer Screening Trial. We propose to explore the association between genetic variants across the genome and mitochondrial DNA copy number among PLCO participants, adjusting for confounders such as age,sex, and smoking status, using the available genotyping from GWAS and data on DNA mitochondrial copy number in this cohort.

References:
[1] Xing, J., et al. Mitochondrial DNA content: its genetic heritability and association with renal cell carcinoma. J Natl Cancer Inst. 2008;100(15):1104-1112.

[2] Gianotti, T.F., et al. Mitochondrial DNA copy number is modulated by genetic variation in the signal transducer and activator of transcription 3 (STAT3). Metabolism. 2011;60(8):1142-9.

[3] López, S., et al. A genome-wide association study in the genetic analysis of idiopathic thrombophilia project suggests sex-specific regulation of mitochondrial DNA levels. Mitochondrion. 2014;18:34-40.