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Published on: June 16, 2017
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AHRR DNA Methylation Levels in Leukocytes Identify People at Risk for Cancer Mortality Overlooked by
Yoshiki Tsuboi1, Hiroya Yamada2, Ryosuke Fujii1
1Department of Preventive Medical Sciences, Fujita Health University School of Medical Sciences, Toyoake, Japan.
Summary
Low aryl hydrocarbon receptor repressor DNA methylation (AHRR DNAm) levels indicate a higher cancer mortality risk, even with low smoking exposure. This biomarker may identify at-risk individuals missed by traditional smoking assessments.
Area of Science:
- Epigenetics
- Cancer Epidemiology
- Biomarker Discovery
Background:
- Aryl hydrocarbon receptor repressor DNA methylation (AHRR DNAm) levels are linked to increased cancer mortality risk.
- Low AHRR DNAm may indicate a more vulnerable population than traditional smoking indices.
- Integrating AHRR DNAm with smoking data can refine cancer risk assessment.
Purpose of the Study:
- To identify high-risk groups for cancer mortality by combining smoking history and leukocyte AHRR DNAm levels in a Japanese population.
- To evaluate the utility of AHRR DNAm as a biomarker for cancer mortality risk, particularly in individuals with low smoking exposure.
Main Methods:
- A cohort of 795 participants without prior clinical history was followed for up to 30 years for mortality.
- Leukocyte AHRR DNAm levels were quantified using pyrosequencing.
- Cox proportional hazards models were employed to calculate hazard ratios (HRs) for cancer mortality.
Main Results:
- Elevated cancer mortality HRs were observed in individuals with low AHRR DNAm, irrespective of smoking intensity (e.g., Pack-years < 20: HR 3.69; Pack-years ≥ 20: HR 2.13).
- High AHRR DNAm was associated with significantly lower cancer mortality HRs in former smokers, regardless of years since quitting (YSQ ≤ 10: HR 0.13; YSQ > 10: HR 0.28).
- No significant cancer mortality risk reduction was found in former smokers with low AHRR DNAm, even after more than 10 years of quitting.
Conclusions:
- Low AHRR DNAm levels are associated with increased cancer mortality risk, even in individuals with minimal smoking exposure.
- Leukocyte AHRR DNAm levels may serve as a valuable biomarker to identify individuals at risk for cancer mortality who might be overlooked by conventional smoking questionnaires.
- The findings highlight the potential of epigenetic markers in refining cancer risk stratification and personalized prevention strategies.
