TY - JOUR
T1 - Alcohol, one-carbon nutrient intake, and risk of colorectal cancer according to tumor methylation level of IGF2 differentially methylated region
AU - Nishihara, Reiko
AU - Wang, Molin
AU - Qian, Zhi Rong
AU - Baba, Yoshifumi
AU - Yamauchi, Mai
AU - Mima, Kosuke
AU - Sukawa, Yasutaka
AU - Kim, Sun A.
AU - Inamura, Kentaro
AU - Zhang, Xuehong
AU - Wu, Kana
AU - Giovannucci, Edward L.
AU - Chan, Andrew T.
AU - Fuchs, Charles S.
AU - Ogino, Shuji
AU - Schernhammer, Eva S.
PY - 2014/12/1
Y1 - 2014/12/1
N2 - Background: Although a higher consumption of alcohol, which is a methyl-group antagonist, was previously associated with colorectal cancer risk, mechanisms remain poorly understood.Objective: We hypothesized that excess alcohol consumption might increase risk of colorectal carcinoma with hypomethylation of insulinlike growth factor 2 (IGF2) differentially methylated region-0 (DMR0), which was previously associated with a worse prognosis.Design: With the use of a molecular pathologic epidemiology database in 2 prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association between alcohol intake and incident colorectal cancer according to the tumor methylation level of IGF2 DMR0. Duplication-method Cox proportional cause-specific hazards regression for competing risk data were used to compute HRs and 95% CIs. In addition, we investigated intakes of vitamin B-6, vitamin B-12, methionine, and folate as exposures.Results: During 3,206,985 person-years of follow-up, we identified 993 rectal and colon cancer cases with an available tumor DNA methylation status. Compared with no alcohol consumption, the consumption of >15 g alcohol/d was associated with elevated risk of colorectal cancer with lower levels of IGF2 DMR0 methylation [within the first and second quartiles: HRs of 1.55 (95% CI: 1.08, 2.24) and 2.11 (95% CI: 1.44, 3.07), respectively]. By contrast, alcohol consumption was not associated with cancer with higher levels of IGF2 DMR0 methylation. The association between alcohol and cancer risk differed significantly by IGF2 DMR0 methylation level (P-heterogeneity = 0.006). The association of vitamin B-6, vitamin B-12, and folate intakes with cancer risk did not significantly differ according to IGF2 DMR0 methylation level (P-heterogeneity . 0.2).Conclusions: Higher alcohol consumption was associated with risk of colorectal cancer with IGF2 DMR0 hypomethylation but not risk of cancer with high-level IGF2 DMR0 methylation. The association between alcohol intake and colorectal cancer risk may differ by tumor epigenetic features.
AB - Background: Although a higher consumption of alcohol, which is a methyl-group antagonist, was previously associated with colorectal cancer risk, mechanisms remain poorly understood.Objective: We hypothesized that excess alcohol consumption might increase risk of colorectal carcinoma with hypomethylation of insulinlike growth factor 2 (IGF2) differentially methylated region-0 (DMR0), which was previously associated with a worse prognosis.Design: With the use of a molecular pathologic epidemiology database in 2 prospective cohort studies, the Nurses' Health Study and Health Professionals Follow-up Study, we examined the association between alcohol intake and incident colorectal cancer according to the tumor methylation level of IGF2 DMR0. Duplication-method Cox proportional cause-specific hazards regression for competing risk data were used to compute HRs and 95% CIs. In addition, we investigated intakes of vitamin B-6, vitamin B-12, methionine, and folate as exposures.Results: During 3,206,985 person-years of follow-up, we identified 993 rectal and colon cancer cases with an available tumor DNA methylation status. Compared with no alcohol consumption, the consumption of >15 g alcohol/d was associated with elevated risk of colorectal cancer with lower levels of IGF2 DMR0 methylation [within the first and second quartiles: HRs of 1.55 (95% CI: 1.08, 2.24) and 2.11 (95% CI: 1.44, 3.07), respectively]. By contrast, alcohol consumption was not associated with cancer with higher levels of IGF2 DMR0 methylation. The association between alcohol and cancer risk differed significantly by IGF2 DMR0 methylation level (P-heterogeneity = 0.006). The association of vitamin B-6, vitamin B-12, and folate intakes with cancer risk did not significantly differ according to IGF2 DMR0 methylation level (P-heterogeneity . 0.2).Conclusions: Higher alcohol consumption was associated with risk of colorectal cancer with IGF2 DMR0 hypomethylation but not risk of cancer with high-level IGF2 DMR0 methylation. The association between alcohol intake and colorectal cancer risk may differ by tumor epigenetic features.
KW - Biomarker
KW - Epigenetics
KW - Imprinting
KW - Molecular pathological epidemiology
KW - One carbon metabolism
UR - http://www.scopus.com/inward/record.url?scp=84911369731&partnerID=8YFLogxK
U2 - 10.3945/ajcn.114.095539
DO - 10.3945/ajcn.114.095539
M3 - Article
C2 - 25411283
AN - SCOPUS:84911369731
SN - 0002-9165
VL - 100
SP - 1479
EP - 1488
JO - American Journal of Clinical Nutrition
JF - American Journal of Clinical Nutrition
IS - 6
ER -