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Associations of mitochondrial DNA copy number with incident risks of gastrointestinal cancers: A prospective case–cohort study
Author(s) -
Guan Xin,
Li Mengying,
Bai Yansen,
Feng Yue,
Li Guyanan,
Wei Wei,
Fu Ming,
Li Hang,
Wang Chenming,
Jie Jiali,
Meng Hua,
Wu Xiulong,
Deng Qilin,
Li Fangqing,
Yang Handong,
Zhang Xiaomin,
He Meian,
Guo Huan
Publication year - 2023
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.23478
Subject(s) - prospective cohort study , hazard ratio , quartile , cohort , medicine , confidence interval , cancer , proportional hazards model , colorectal cancer , cohort study , oncology
Epidemiological investigations implied that mitochondrial DNA copy number (mtDNAcn) variations could trigger predisposition to multiple cancers, but evidence regarding gastrointestinal cancers (GICs) was still uncertain. We conducted a case‐cohort study within the prospective Dongfeng‐Tongji cohort, including incident cases of colorectal cancer (CRC, n = 278), gastric cancer (GC, n = 138), and esophageal cancer (EC, n = 72) as well as a random subcohort ( n = 1173), who were followed up from baseline to the end of 2018. We determined baseline blood mtDNAcn and associations of mtDNAcn with the GICs risks were estimated by using weighted Cox proportional hazards models. Significant U ‐shaped associations were observed between mtDNAcn and GICs risks. Compared to subjects within the second quartile (Q2) mtDNAcn subgroup, those within the 1st (Q1), 3rd (Q3), and 4th (Q4) quartile subgroups showed increased risks of CRC (hazard ratio [HR] [95% confidence interval, CI] = 2.27 [1.47–3.52], 1.65 [1.04–2.62], and 2.81 [1.85–4.28], respectively) and total GICs (HR [95%CI] = 1.84 [1.30–2.60], 1.47 [1.03–2.10], and 2.51 [1.82–3.47], respectively], and those within Q4 subgroup presented elevated GC and EC risks (HR [95% CI] = 2.16 [1.31–3.54] and 2.38 [1.13–5.02], respectively). Similar associations of mtDNAcn with CRC and total GICs risks remained in stratified analyzes by age, gender, smoking, and drinking status. This prospective case‐cohort study showed U ‐shaped associations between mtDNAcn and GICs risks, but further research works are needed to uncover underlying biological mechanisms.