title: Mitochondrial DNA copy number and risk of gastric cancer: a report from the Shanghai Women's Health Study.
abstract: BACKGROUND
  Mitochondrial DNA (mtDNA) is an approximately 16,000-bp circular double-stranded DNA molecule that is a prime target of oxidative damage. Several somatic mutations in mtDNA have been observed in gastric tumors, suggesting an involvement in gastric cancer risk and progression. mtDNA copy number in leukocyte DNA has also been linked to several other cancers, although the temporal relationship between mtDNA and cancer has not been adequately explored.
  
  
  METHODS
  Using a nested case-control study design, we examined the association between mtDNA copy number in 162 gastric cancer cases and 299 matched controls within the Shanghai Women's Health Study, a large population-based prospective cohort. Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay in peripheral leukocytes.
  
  
  RESULTS
  mtDNA copy number levels were comparable among cases and controls, with a median of 1.04 [interquartile range (IQR), 0.87-1.25] and 1.06 (IQR, 0.88-1.29), respectively. Overall, mtDNA was not associated with gastric cancer risk. However, the association differed when stratified by the time between sample collection and cancer diagnosis. An association between low levels of mtDNA copy number (<median) and gastric cancer risk was apparent among earlier diagnosed cases, in particular, those diagnosed within 2 years of sample collection (OR = 5.32; 95% CI = 1.03-27.60). This association was not present as the time between sample collection and cancer diagnosis increased.
  
  
  CONCLUSIONS
  Our findings suggest that there is no association between leukocyte mtDNA copy number and risk of developing gastric cancer; however, we observed a possible early disease effect on mtDNA copy number levels.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, 6120 Executive Blvd, EPS 8003, MSC 7240, Bethesda, MD 20892, USA. donglm@mail.nih.gov
authors.forename: Linda M
authors.initials: LM
authors.lastname: Liao
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.forename: Xiao-Ou
authors.initials: XO
authors.lastname: Shu
authors.forename: Yu-Tang
authors.initials: YT
authors.lastname: Gao
authors.forename: Bu-Tian
authors.initials: BT
authors.lastname: Ji
authors.forename: Gong
authors.initials: G
authors.lastname: Yang
authors.forename: Hong-Lan
authors.initials: HL
authors.lastname: Li
authors.forename: Mirjam
authors.initials: M
authors.lastname: Hoxha
authors.forename: Laura
authors.initials: L
authors.lastname: Dioni
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Wei
authors.initials: W
authors.lastname: Zheng
authors.forename: Wong-Ho
authors.initials: WH
authors.lastname: Chow
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008875:Middle Aged; D011446:Prospective Studies; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000235:genetics*; D016387:Women's Health
chemical_list: D004272:DNA, Mitochondrial