Polymorphisms in Alcohol Metabolism Genes <i>ADH1B</i> and <i>ALDH2</i>, Alcohol Consumption and Colorectal Cancer

<div><p>Background</p><p>Colorectal cancer (CRC) is a leading cause of cancer death worldwide. Epidemiological risk factors for CRC included alcohol intake, which is mainly metabolized to acetaldehyde by alcohol dehydrogenase and further oxidized to acetate by aldehyde dehydrogenase; consequently, the role of genes in the alcohol metabolism pathways is of particular interest. The aim of this study is to analyze the association between SNPs in <i>ADH1B</i> and <i>ALDH2</i> genes and CRC risk, and also the main effect of alcohol consumption on CRC risk in the study population.</p><p>Methodology/Principal Findings</p><p>SNPs from <i>ADH1B</i> and <i>ALDH2</i> genes, included in alcohol metabolism pathway, were genotyped in 1694 CRC cases and 1851 matched controls from the Molecular Epidemiology of Colorectal Cancer study. Information on clinicopathological characteristics, lifestyle and dietary habits were also obtained. Logistic regression and association analysis were conducted. A positive association between alcohol consumption and CRC risk was observed in male participants from the Molecular Epidemiology of Colorectal Cancer study (MECC) study (OR = 1.47; 95%CI = 1.18-1.81). Moreover, the SNPs rs1229984 in <i>ADH1B</i> gene was found to be associated with CRC risk: under the recessive model, the OR was 1.75 for A/A genotype (95%CI = 1.21-2.52; p-value = 0.0025). A path analysis based on structural equation modeling showed a direct effect of <i>ADH1B</i> gene polymorphisms on colorectal carcinogenesis and also an indirect effect mediated through alcohol consumption.</p><p>Conclusions/Significance</p><p>Genetic polymorphisms in the alcohol metabolism pathways have a potential role in colorectal carcinogenesis, probably due to the differences in the ethanol metabolism and acetaldehyde oxidation of these enzyme variants.</p></div

Additional file 2: of A quantitative assessment of the evolution of cerebellar syndrome in children with phosphomannomutase-deficiency (PMM2-CDG)

Cerebellar volumetric study, molecular and clinical characteristics of Patients 3, 5 and 7. (TIFF 3555 kb

Association between polymorphisms in alcohol metabolism genes and colorectal cancer risk (men only).

1<p>OR adjusted for age, ethnicity, religion, energy intake and physical activity.</p

Forest Plot for percentage of improvement in Y-BOCS scores.

<p>Forest Plot for percentage of improvement in Y-BOCS scores.</p

Forest Plot for percentage of responders according to standardized criteria (> 35% reduction in post-treatment Y-BOCS scores).

<p>Forest Plot for percentage of responders according to standardized criteria (> 35% reduction in post-treatment Y-BOCS scores).</p

Adverse effects of DBS reported in the studies included in the meta-analysis.

<p>*Not fullfilling criteria for hypomanic episode</p><p>** Without other symptoms of a panick attack</p><p>Adverse effects of DBS reported in the studies included in the meta-analysis.</p

Flow of information according to PRISMA statement, study selection and reasons for exclusion.

<p>Flow of information according to PRISMA statement, study selection and reasons for exclusion.</p

Potential GxG associated with breast cancer risk in <i>BRCA1/2</i> mutation carriers.

<p>*Each estimate is derived from the interaction term of a Cox regression model.</p><p>Potential GxG associated with breast cancer risk in <i>BRCA1/2</i> mutation carriers.</p

The <i>HMMR</i> locus and breast cancer risk in <i>BRCA1</i> mutation carriers.

<p>(<b>A</b>) Forest plots showing rs299290 HRs and 95% CIs (retrospective likelihood trend estimation) for participating countries (relatively small sample sets are not shown) ordered by sample size. Left and right panels show results for <i>BRCA1</i> and <i>BRCA2</i> mutation carriers, respectively. The sizes of the rectangles are proportional to the corresponding country/study precision. (<b>B</b>) The rs299290-containing region, including the genes, variation and regulatory evidence mentioned in HMECs. Exons are marked by black-filled rectangles and the direction of transcription is marked by arrows in the genomic structure. The chromosome 5 positions (base pairs (bp)) and linkage disequilibrium structure from Caucasian HapMap individuals are also shown.</p

Gene expression interactions in breast cancer survival.

<p>(<b>A</b>) Kaplan–Meier survival curves based on categorization of <i>HMMR</i> (probe NM_012484) and <i>AURKA</i> (NM_003600) expression in tertiles (low, medium or high expression). For simplicity, only the tertiles for “high” <i>AURKA</i> are shown. The tumours with high expression levels for both genes were not those with the poorest prognosis. (<b>B</b>) Kaplan–Meier survival curves based on categorization of <i>HMMR</i> (NM_012484) and <i>TUBG1</i> (NM_016437) expression in tertiles (low, medium or high expression). For simplicity, only the tertiles for “high” <i>HMMR</i> are shown. The cases with high expression levels for both genes were those with the poorest prognosis.</p