TY - JOUR
T1 - Increased risk of cancer mortality by smoking-induced aryl hydrocarbon receptor repressor DNA hypomethylation in Japanese population
T2 - A long-term cohort study
AU - Tsuboi, Yoshiki
AU - Yamada, Hiroya
AU - Munetsuna, Eiji
AU - Fujii, Ryosuke
AU - Yamazaki, Mirai
AU - Ando, Yoshitaka
AU - Mizuno, Genki
AU - Hattori, Yuji
AU - Ishikawa, Hiroaki
AU - Ohashi, Koji
AU - Hashimoto, Shuji
AU - Hamajima, Nobuyuki
AU - Suzuki, Koji
N1 - Funding Information:
We thank the participants and staff of the health examination program, Yakumo, Hokkaido, Japan. This study was supported by the Japan Society for the Promotion of Science (JSPS) under Grants-in-Aid for Scientific Research (Nos. 26293144, 17K09139, 16H06277 , and 20K10515 ).
Publisher Copyright:
© 2022
PY - 2022/6
Y1 - 2022/6
N2 - Background: Smoking is well known to be a major risk factor for cancer, and to decrease the levels of aryl hydrocarbon receptor repressor (AHRR) DNA methylation. AHRR is a key regulator for AHR signaling, which is involved in chemical metabolism and cancer development. Therefore, smoking-induced AHRR DNA hypomethylation may be associated with cancer development. However, it has not been reported that association between AHHR DNA methylation and cancer mortality in Asian population. Hence, we examined whether AHRR DNA methylation levels were associated with cancer mortality in a Japanese population. Methods: This study was conducted with 812 participants (aged 38–80 years) who received a health check-up in 1990, and did not have a clinical histories. We followed up the participants until the end of 2019 (median: 27.8 years), and 100 participants died from cancer. The AHRR DNA methylation levels in peripheral blood mononuclear cells (PBMCs) were measured by the pyrosequencing method. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for cancer mortality according to the baseline levels of AHRR DNA methylation. Results: We found that AHRR DNA hypomethylation was associated with a higher risk of all cancer mortality, especially smoking related cancers and lung cancer. (all cancer: HR, 1.28, 95% CI, 1.09–1.51; smoking-related cancers: HR, 1.35, 95% CI, 1.12–1.62; lung cancer: HR, 1.68, 95% CI, 1.24–2.26). Conclusions: Smoking-induced AHRR DNA hypomethylation in PBMCs was associated with the risk of cancer mortality in Japanese population; therefore, hypomethylation of AHRR may be a useful biomarker of cancer mortality risk.
AB - Background: Smoking is well known to be a major risk factor for cancer, and to decrease the levels of aryl hydrocarbon receptor repressor (AHRR) DNA methylation. AHRR is a key regulator for AHR signaling, which is involved in chemical metabolism and cancer development. Therefore, smoking-induced AHRR DNA hypomethylation may be associated with cancer development. However, it has not been reported that association between AHHR DNA methylation and cancer mortality in Asian population. Hence, we examined whether AHRR DNA methylation levels were associated with cancer mortality in a Japanese population. Methods: This study was conducted with 812 participants (aged 38–80 years) who received a health check-up in 1990, and did not have a clinical histories. We followed up the participants until the end of 2019 (median: 27.8 years), and 100 participants died from cancer. The AHRR DNA methylation levels in peripheral blood mononuclear cells (PBMCs) were measured by the pyrosequencing method. We calculated the hazard ratio (HR) and 95% confidence interval (CI) for cancer mortality according to the baseline levels of AHRR DNA methylation. Results: We found that AHRR DNA hypomethylation was associated with a higher risk of all cancer mortality, especially smoking related cancers and lung cancer. (all cancer: HR, 1.28, 95% CI, 1.09–1.51; smoking-related cancers: HR, 1.35, 95% CI, 1.12–1.62; lung cancer: HR, 1.68, 95% CI, 1.24–2.26). Conclusions: Smoking-induced AHRR DNA hypomethylation in PBMCs was associated with the risk of cancer mortality in Japanese population; therefore, hypomethylation of AHRR may be a useful biomarker of cancer mortality risk.
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U2 - 10.1016/j.canep.2022.102162
DO - 10.1016/j.canep.2022.102162
M3 - Article
C2 - 35461154
AN - SCOPUS:85128484821
VL - 78
JO - Cancer Epidemiology
JF - Cancer Epidemiology
SN - 1877-7821
M1 - 102162
ER -