Reference
Complete the bibliographic reference for the article according to AJE format.
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Yokoyama T, et al. Alcohol Flushing, Alcohol and Aldehyde Dehydrogenase Genotypes, and Risk for Esophageal Squamous Cell Carcinoma in Japanese Men. CEBP. 2003 Nov; 12: 1227-1233.
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Category of HuGE information
Specify the types of information (from the list below) available in the article:
- Prevalence of gene variant
- Gene-disease association
- Gene-environment interaction
- Gene-gene interaction
- Genetic test evaluation/monitoring
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- Prevalence of gene variant: ADH2 and ALDH2
- Gene-disease association: esophageal cancer and surrogate for ALDH2
- Gene-environment interaction: surrogate for ALDH2 and alcohol drinking
- Gene-gene interaction: ADH2 and ALDH2
- Genetic test evaluation: questionnaire
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Study hypotheses or purpose
The authors study hypotheses or main purpose for conducting the study
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- Evaluate the reliability of an alcohol flushing questionnaire for detecting inactive ALDH2 ( genotype ) – sensitivity and specificity.
- Evaluate predictive model of esophageal cancer risk based on this questionnaire.
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Gene(s)
Identification of the following:
- Gene name
- Chromosome location
- Gene product/function
- Alleles
- OMIM #
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- Gene name: ALDH2, Aldehyde Dehydrogenase 2
- Chromosome location: 12q24.2
- Gene product/function: ethanol metabolism
- Alleles: 2*1/2*1, 2*1/2*2, 2*2/2*2
- OMIM#:100650
- Gene name: ADH2, Alcohol Dehydrogenase 2
- Chromosome location: 4q22
- Gene product/function: ethanol metabolism
- Alleles: 2*1/2*1, 2*1/2*2, 2*2/2*2
- OMIM#:103720
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Environmental factor(s)
Identification of the major environmental factors studied (infectious, chemical, physical, nutritional, and behavioral) |
- drinking alcohol ( never/rare, light, moderate, heavy, ex-drinker )
- frequency of drinking strong alcoholic beverages straight ( frequently, sometimes,never) ( No further description of this measure is given )
- smoking ( pack-years: 0, < 30, ≥ 30)
- Green-yellow vegetable intake ( 5 levels )
- Fruits intake ( 5 levels )
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Health outcome(s)
Identification of the major health outcome(s) studied
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- esophageal cancer
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Study design
Specification of the type of study design(s)
- Case-control
- Cohort
- Cross-sectional
- Descriptive or case series
- Clinical trial
- Population screening
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- Case-control Study
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Case definition
For study designs 1, 4, and 5, define the following if available:
- Disease case definition
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants (% of total eligible)
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1. Disease case definition: male Japanese patients with primary esophageal squamous cell carcinomas undergoing treatment at four major Japanese Hospitals and registered between September 2000 and December 2001.
2a. Inclusion Criteria: age between 40-79yr old, newly diagnosed by histology, within 3 yrs of registration
2b. Exclusion criteria: Alcoholic patients diagnosed as having esophageal cancer at the National Institute on Alcoholism, Japan; Esophageal cancer patients registered in the authors’ previous study between 1998 and 1999
3. Gender: Male
4. Race/ethnicity: Japanese
5. Age: 40-79 years
6. Time period: enrollment during September 2000 and December 2001
7. Geographic location: Tokyo, Kawasaki, Osaka Japan
8. Number of participants: N ( % of total eligible ) 234/236 patients ( 99% ) --> 233 completed the questionnaire ( 233/236 ) ( 98.7% )
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Control definition
For study design 1, define the following if available:
- Control selection criteria
- Matching variables
- Exclusion criteria
- Gender
- Race/ethnicity
- Age
- Time period
- Geographic location
- Number of participants (% of total eligible)
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1. Control selection criteria: cancer-free patients who visited two Tokyo clinics for annual health checkups between September 2000 and December 2001
2. Matching variables: none
3. Exclusion criteria: not specified
4. Gender: Male
5. Race/ethnicity: Japanese
6. Age: 40-79 years
7. Time periods: between September 2000 and December 2001
8. Geographic location: Tokyo, Japan
9. Number of participants: 634 ( 86% ) --> 610 completed the questionnaire ( 610/634= 96% ) but 83% of original eligible.
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Assessment of environment factors
For studies that include gene-environment interactions, define the following, if available:
- Environmental factor
- Exposure assessment
- Exposure definition
- Number of participants with exposure data (% of total eligible)
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Environmental factors considered for interaction:
1. Exposure assessment: self-reported questionnaire
2. Exposure definition: alcohol drinking : self-classification of never, current, ex-drinker. Current drinkers were further classified into rare, light, moderate and heavy based on the frequency and type of alcohol beverage consumed.
3. Number of participants with exposure data: N ( % of total eligible ) 234/236 patients ( 99% ) for cases and 634 ( 86% ) for controls.
Environmental factors considered as potential confounders:
1. smoking ( pack years )
2. frequency of drinking strong alcoholic beverage straight ( this is a different frequency measure than the exposure variable of alcohol drinking as described in Table 1 )
3. green-yellow vegetable intake
4. fruits intake
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Genotyping
Specify the following:
- Gene
- DNA source
- Methodology
- Number of participants genotyped (% of total eligible)
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- Gene: ALDH2, ADH2
- DNA source: lymphocyte
- Methodology: PCR-RFLP
- Number of participants genotyped: N ( % eligible ) 234/236 patients ( 99% ) for cases and 634 ( 86% ) for controls
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Results
Describe the major results under each of the following HuGE categories. Include tables when data are provided:
- Prevalence of gene variant
- Gene-disease association
- Gene-environment interaction
- Gene-gene interaction
- Genetic test evaluation/monitoring
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Conclusion
State the author's overall conclusions from the study |
- This simple questionnaire can reliably detect inactive ALDH2 and predict risk for esophageal cancer
- ADH2 modifies the association between flushing response and ALDH2 genotype
- This questionnaire may be a cost-effective approach in identifying high risk patients in clinical setting
- This questionnaire can be used in lieu of costly genetic analysis in a large epidemiologic study
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Comments
Provide additional insight, including methodologic issues and/or concerns about the study |
- Selection bias: control selection and differential participation rate
- Misclassification bias: covariates (measurement bias ), flushing response (recall bias )
- Sensitivity and specificity differ between controls and cases modified by ADH2
- Restricted homogenous population: male, 40-70 y.o. Japaneses (reduces potential for population stratification )
- Choice of study population is appropriate and relevant for the gene, environmental exposure and the outcome studied
- Strong association but wide confidence interval due to small numbers
- High prevalence of genotype and exposure in the study population
- Identifying high risk individuals for early screening of esophageal cancer is an important public health issue in this population
- This case-control study is the first large study to confirm the association of these genotypes and esophageal cancer in non-alcoholic population.
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