RESUMO
Alcohol consumption is an established risk factor for cancer, but little is known regarding the effect of genetic polymorphisms in alcohol metabolism genes on alcohol-related cancer risk in the Japanese population. Associations between the ADH1B gene (alcohol dehydrogenase 1B), single nucleotide polymorphism (SNP) rs1229984 and cancer have been extensively studied yet evidence is inconsistent. This population-based case-control study primarily aimed to clarify any association between SNP rs1229984 in both overall and specific cancer risk in a Japanese population. The functional non-synonymous SNP rs1229984 (Arg48His) was genotyped using DNA samples from 1,359 consecutive autopsy cases registered in The Japanese Single Nucleotide Polymorphisms for Geriatric Research database. Medical and pathological record data from this database were used to categorise cases and controls. Results included 1,359 participants, 816 cases and 543 controls. Multinomial logistic regression analyses showed no significant association between rs1229984 presence and overall cancer risk in both dominant and recessive genetic inheritance models [Arg/Arg+Arg/His vs. His/His: Adjusted odds ratio (OR)=0.66 (95% CI=0.39-1.13; P=0.129), Arg/Arg vs. Arg/His+His/His: OR=0.95 (95% CI=0.75-1.20; P=0.657)]. However, results showed those homozygous for rs1229984 (genotype His/His) were at significantly decreased odds of lung cancer than other genotypes [recessive model: OR=0.64 (95% CI=0.44-0.93; P=0.020]. In conclusion, there was no significant association between rs1229984 and odds of overall or specific cancers except in lung cancer where His/His genotype decreased odds. To the best of our knowledge, the association between His/His and decreased odds of lung cancer is a novel finding. These findings require further validation in larger studies.
RESUMO
Mid-to-late gestation is a unique period in which women experience dynamic changes in lipid metabolism. Although the recent intensive epigenome-wide association studies (EWAS) using peripheral leukocytes have revealed that lipid-related traits alter DNA methylation, the influence of pregnancy-induced metabolic changes on the methylation levels of these differentially methylated sites is not well known. In this study, we performed a prospective cohort study of pregnant women (n = 52) using the MassARRAY EpiTYPER assay and analyzed the methylation levels of variably methylated sites, including CPT1A intron 1 and SREBF1 intron 1 CpGs, which were previously verified to be robustly associated with adiposity traits. Although methylation of SREBF1 was associated with body mass index (BMI) and low-density lipoprotein cholesterol at mid-gestation, this association was attenuated at late gestation, which was consistent with the metabolic switch from an anabolic to a catabolic state. However, the BMI association with CPT1A intron 1 methylation appeared to strengthen at late gestation; this association was mediated by pre-pregnancy BMI-dependent change in the leukocyte proportion during mid-to-late gestation. Thus, the methylation of adiposity-related differentially methylated regions was sensitive to metabolic and immunological changes during mid-to-late gestation.
