Aldehyde Dehydrogenase 2 and Head and Neck Cancer: A Meta-analysis Implementing a Mendelian Randomization Approach

Abstract

Alcohol drinking at high doses is a risk factor for head and neck cancer, and exposure to acetaldehyde, the principle metabolite of alcohol, is supposed to account for the increased risk. Individuals homozygous for the *2 variant allele of aldehyde dehydrogenase 2 (ALDH2) are unable to metabolize acetaldehyde, which prevents them from alcohol drinking, whereas *1*2 have 6-fold higher blood acetaldehyde concentration postalcohol consumption with respect to *1*1. According to the concept of Mendelian randomization, because this polymorphism is distributed randomly during gamete formation, its association with head and neck cancer should be not confounded by smoking. We carried out a meta-analysis of ALDH2 and head and neck cancer searching for relevant studies on Medline and Embase up to January 31, 2008, and investigated the consistency between the expected odds ratio (OR) among drinkers from the largest pooled analysis among never smokers and the observed OR from this meta-analysis by an interaction test. Six studies were selected (945 cases, 2,917 controls). The OR of head and neck cancer among *2*2 was 0.53 [95% confidence interval (95% CI), 0.28-1.00] relative to *1*1 and 1.83 (95% CI, 1.21-2.77) among *1*2. The expected OR for head and neck cancer due to alcohol intake among *1*1 was 1.38 (95% CI, 0.88-2.17) and the observed OR among *1*1 compared with 2*2 from this meta-analysis was 1.88 (95% CI, 1.00-3.57; P for interaction = 0.43). Besides showing the effectiveness of the Mendelian randomization approach, these findings support the theory that alcohol increases head and neck cancer risk through the carcinogenic action of acetaldehyde. (Cancer Epidemiol Biomarkers Prev 2009;18(1):248-54)

Use of genetic markers and gene-diet interactions for interrogating population-level causal influences of diet on health

“…The reduction in risk is close to that predicted from the size of effect of genotype on alcohol consumption and the dose-response association of alcohol and oesophageal cancer risk [80]. A similar picture is seen when head and neck cancer is the outcome [81].…”

“…8). A similar analysis has been performed for head and neck cancer and again demonstrates no association of genotype and cancer risk in never drinkers and a graded association according to level of alcohol intake among alcohol drinkers [81].…”

NMR and FTIR Analysis of Overheated Cooking Oil

“…The presence of carbonyl groups in overheated oil may constitute a serious risk to the human body. It was reported that aldehydes are potentially toxic substances with possibility to induce different cancers when consumed [26][27][28] . Furthermore, it is known that asparagine and reducing sugars are relatively in high amount in potatoes, and that both compounds are the main precursors of acrylamide, which is formed during frying, baking, grilling or toasting carbohydrates rich foods 19,29,30 .…”

A Case-Control Study on the Effect of Apoliprotein E Genotype on Head and Neck Cancer Risk

“…Study participants were recruited among patients admitted to the teaching hospital "Agostino 15.9% oral cavity, and 21.3% pharyngeal. Controls were selected from among cancer-free patients admitted to the same hospital during the same time period with a broad range of diagnoses.…”

“…Generally speaking, studying the association between sequence variants of genes (e.g., apoE) known to be related to an intermediate phenotype (e.g., serum cholesterol level) and a disease has the advantage of being less prone to the confounding effect of lifestyle factors or disease stage that might affect the association between the intermediate phenotype and the disease itself. This approach has been called "Mendelian randomization" (14,15), and it has been recently adopted to evaluate the association between cholesterol levels and cancer risk by using the apoE genotype as a surrogate for cholesterol levels. Results, however, are largely conflicting (7,(16)(17)(18).…”