Blood Leukocyte AHRR Methylation and Risk of Non-smoking-associated Cancer: A Case-cohort Study of Non-Hodgkin Lymphoma
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Blood Leukocyte AHRR Methylation and Risk of Non-smoking-associated Cancer : A Case-cohort Study of Non-Hodgkin Lymphoma. / Dahl, Christina; Hvidtfeldt, Ulla A; Tjønneland, Anne; Guldberg, Per; Raaschou-Nielsen, Ole.
I: Cancer research communications, Bind 3, Nr. 9, 2023, s. 1781-1787.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Blood Leukocyte AHRR Methylation and Risk of Non-smoking-associated Cancer
T2 - A Case-cohort Study of Non-Hodgkin Lymphoma
AU - Dahl, Christina
AU - Hvidtfeldt, Ulla A
AU - Tjønneland, Anne
AU - Guldberg, Per
AU - Raaschou-Nielsen, Ole
N1 - © 2023 The Authors; Published by the American Association for Cancer Research.
PY - 2023
Y1 - 2023
N2 - UNLABELLED: Aryl-hydrocarbon receptor repressor (AHRR) hypomethylation in peripheral blood is tightly linked with tobacco smoking and lung cancer. Here, we investigated AHRR methylation in non-Hodgkin lymphoma (NHL), a non-smoking-associated cancer. In a case-cohort study within the population-based Danish Diet, Cancer and Health cohort, we measured AHRR (cg23576855) methylation in prediagnostic blood from 161 participants who developed NHL within 13.4 years of follow-up (median: 8.5 years), with a comparison group of 164 randomly chosen participants. We measured DNA-methylation levels using bisulfite pyrosequencing and estimated incidence rate ratios (IRR) using Cox proportional hazards models with adjustment for baseline age, sex, educational level, smoking status, body mass index, alcohol intake, physical activity, and diet score. Global DNA-methylation levels were assessed by long interspersed nucleotide element 1 (LINE-1) analysis. Overall, the IRR for AHRR hypomethylation (lowest vs. other quartiles) was 2.52 [95% confidence interval (CI), 1.24-5.15]. When stratified according to time between blood draw and diagnosis, low AHRR methylation levels were associated with a future diagnosis of NHL [IRR: 4.50 (95% CI, 1.62-12.50) at 0-<5 years, 7.04 (95% CI, 2.36-21.02) at 5-<10 years, and 0.56 (95% CI, 0.21-1.45) at ≥10 years]. There was no association between global DNA-methylation levels and risk of NHL. Our results show that AHRR hypomethylation in blood leukocytes is associated with a higher risk of NHL in a time-dependent manner, suggesting that it occurs as a response to tumor development.SIGNIFICANCE: Our population-based study demonstrated that lower AHRR methylation levels in peripheral blood leukocytes were associated with an increased risk of NHL. This association was independent of tobacco smoking, sex, and lifestyle characteristics, but was highly dependent on time to diagnosis. These findings highlight the potential of AHRR methylation as a biomarker for NHL risk, effective up to 10 years after blood draw.
AB - UNLABELLED: Aryl-hydrocarbon receptor repressor (AHRR) hypomethylation in peripheral blood is tightly linked with tobacco smoking and lung cancer. Here, we investigated AHRR methylation in non-Hodgkin lymphoma (NHL), a non-smoking-associated cancer. In a case-cohort study within the population-based Danish Diet, Cancer and Health cohort, we measured AHRR (cg23576855) methylation in prediagnostic blood from 161 participants who developed NHL within 13.4 years of follow-up (median: 8.5 years), with a comparison group of 164 randomly chosen participants. We measured DNA-methylation levels using bisulfite pyrosequencing and estimated incidence rate ratios (IRR) using Cox proportional hazards models with adjustment for baseline age, sex, educational level, smoking status, body mass index, alcohol intake, physical activity, and diet score. Global DNA-methylation levels were assessed by long interspersed nucleotide element 1 (LINE-1) analysis. Overall, the IRR for AHRR hypomethylation (lowest vs. other quartiles) was 2.52 [95% confidence interval (CI), 1.24-5.15]. When stratified according to time between blood draw and diagnosis, low AHRR methylation levels were associated with a future diagnosis of NHL [IRR: 4.50 (95% CI, 1.62-12.50) at 0-<5 years, 7.04 (95% CI, 2.36-21.02) at 5-<10 years, and 0.56 (95% CI, 0.21-1.45) at ≥10 years]. There was no association between global DNA-methylation levels and risk of NHL. Our results show that AHRR hypomethylation in blood leukocytes is associated with a higher risk of NHL in a time-dependent manner, suggesting that it occurs as a response to tumor development.SIGNIFICANCE: Our population-based study demonstrated that lower AHRR methylation levels in peripheral blood leukocytes were associated with an increased risk of NHL. This association was independent of tobacco smoking, sex, and lifestyle characteristics, but was highly dependent on time to diagnosis. These findings highlight the potential of AHRR methylation as a biomarker for NHL risk, effective up to 10 years after blood draw.
KW - Humans
KW - Basic Helix-Loop-Helix Transcription Factors/genetics
KW - Cohort Studies
KW - DNA
KW - DNA Methylation/genetics
KW - Leukocytes
KW - Lymphoma, Non-Hodgkin/epidemiology
KW - Repressor Proteins/genetics
U2 - 10.1158/2767-9764.CRC-23-0151
DO - 10.1158/2767-9764.CRC-23-0151
M3 - Journal article
C2 - 37691855
VL - 3
SP - 1781
EP - 1787
JO - Cancer research communications
JF - Cancer research communications
SN - 2767-9764
IS - 9
ER -
ID: 379580030