title: Association of mitochondrial DNA variations with lung cancer risk in a Han Chinese population from southwestern China.
abstract: Mitochondrial DNA (mtDNA) is particularly susceptible to oxidative damage and mutation due to the high rate of reactive oxygen species (ROS) production and limited DNA-repair capacity in mitochondrial. Previous studies demonstrated that the increased mtDNA copy number for compensation for damage, which was associated with cigarette smoking, has been found to be associated with lung cancer risk among heavy smokers. Given that the common and "non-pathological" mtDNA variations determine differences in oxidative phosphorylation performance and ROS production, an important determinant of lung cancer risk, we hypothesize that the mtDNA variations may play roles in lung cancer risk. To test this hypothesis, we conducted a case-control study to compare the frequencies of mtDNA haplogroups and an 822 bp mtDNA deletion between 422 lung cancer patients and 504 controls. Multivariate logistic regression analysis revealed that haplogroups D and F were related to individual lung cancer resistance (OR = 0.465, 95%CI = 0.329-0.656, p<0.001; and OR = 0.622, 95%CI = 0.425-0.909, p = 0.014, respectively), while haplogroups G and M7 might be risk factors for lung cancer (OR = 3.924, 95%CI = 1.757-6.689, p<0.001; and OR = 2.037, 95%CI = 1.253-3.312, p = 0.004, respectively). Additionally, multivariate logistic regression analysis revealed that cigarette smoking was a risk factor for the 822 bp mtDNA deletion. Furthermore, the increased frequencies of the mtDNA deletion in male cigarette smoking subjects of combined cases and controls with haplogroup D indicated that the haplogroup D might be susceptible to DNA damage from external ROS caused by heavy cigarette smoking.
authors.affiliation: Institute of Human Respiratory Disease, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Shizhen
authors.initials: S
authors.lastname: Zheng
authors.forename: Pin
authors.initials: P
authors.lastname: Qian
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Li
authors.forename: Guisheng
authors.initials: G
authors.lastname: Qian
authors.forename: Changzheng
authors.initials: C
authors.lastname: Wang
authors.forename: Guoming
authors.initials: G
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Haining
authors.initials: H
authors.lastname: Li
authors.forename: Binfeng
authors.initials: B
authors.lastname: He
authors.forename: Fuyun
authors.initials: F
authors.lastname: Ji
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D020029:Base Pairing / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D002681:China; D004272:DNA, Mitochondrial / Q000235:genetics*; D004587:Electrophoresis, Agar Gel; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D012307:Risk Factors; D017384:Sequence Deletion / Q000235:genetics; D012907:Smoking / Q000235:genetics
chemical_list: D004272:DNA, Mitochondrial