title: Measurement of DNA damage in peripheral blood by the γ-H2AX assay as predictor of colorectal cancer risk.
abstract: The detection of γ-H2AX focus is one of the most sensitive ways to monitor DNA double-strand breaks (DSBs). Although changes in γ-H2AX activity have been studied in tumor cells in colorectal cancer (CRC), changes in peripheral blood lymphocytes (PBLs) have not been examined previously. We hypothesize that higher levels of irradiation-induced γ-H2AX in PBLs may be associated with an elevated risk of colorectal cancer (CRC). In a case-control study, the baseline and ionizing radiation (IR)-induced γ-H2AX levels in PBLs from frequency-matched 320 untreated CRC patients and 320 controls were detected by a laser scanning cytometer-based immunocytochemical method. We used unconditional multivariable logistic regression to evaluate CRC risk by using the ratio of IR-induced γ-H2AX to the baseline levels with adjustment of age, sex and smoking status. We found CRC cases had significantly higher γ-H2AX ratio (1.5 vs. 1.41, P<0.0001) compared with controls. When using the median γ-H2AX ratio of controls as a cutoff point, we found higher γ-H2AX ratio was significantly associated with an increased risk of CRC (OR=6.72, 95% CI=4.54-9.94). Quartile analyses also showed significant dose-response relationship between higher γ-H2AX ratio and increased risk of CRC (P for trend<0.0001). Age, sex, BMI and smoking status also influenced the association of γ-H2AX ratio with CRC risk; however, no interactions with γ-H2AX ratio were observed. These results support the premise that DSBs in peripheral blood as measured by γ-H2AX level might represent an intermediate phenotype to assess the risk of CRC. Future prospective studies are necessary to confirm our findings in independent populations.
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi Province, 710032, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: Chang
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Yilei
authors.initials: Y
authors.lastname: Gong
authors.affiliation: Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Cathy
authors.initials: C
authors.lastname: Eng
authors.affiliation: Departments of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA. Electronic address: xwu@mdanderson.org.
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics; D004247:DNA / Q000378:metabolism / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D005260:Female; D006657:Histones / Q000032:analysis / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016015:Logistic Models; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D011839:Radiation, Ionizing; D012306:Risk; D044465:White People
chemical_list: C468783:H2AX protein, human; D006657:Histones; D004247:DNA
keywords: Colorectal cancer risk; DNA repair; Double-strand break; Gamma H2AX