Reference
Complete the bibliographic reference for the article according to AJE format.

Boyapati, Sonia M., et al. Folate intake MTHFR C677T polymorphism, alcohol consumption, and risk for sporadic colorectal adenoma. Cancer Causes and Control. 2004;15:493-501. (1)

Category of HuGE information
Specify the types of information (from the list below) available in the article:

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

2. Gene-disease association
3. Gene-environment interaction

Gene(s)
Identification of the following:

1. Gene name
2. Chromosome location
3. Gene product/function
4. Alleles
5. OMIM #
6. GDPInfo link

1. Gene name: MTHFR 2
2. Chromosome location: 1p36.3
3. Gene product/function: Through the product 5-Methyltetrahydrofolate, the MTHFR gene helps regulate methylation and DNA synthesis.
4. Alleles: 677C 677T
5. OMIM #: 607093
6. Go to GDPInfo Genes A-Z result

Folate, alcohol, vitamin B2, B6, B12, methionine

Health outcome(s)
Identification of the major health outcome(s) studied

1. Case-control
2. Cohort 
3. Cross-sectional
4. Descriptive or case series
5. Clinical trial
6. Population screening

1. Disease case definition
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants

1. Disease case definition: English speaking patients diagnosed with concurrent adenomas after undergoing a voluntary colonoscopy
2. Exclusion criteria: Previous diagnosis of cancer not including non-melanoma skin cancer, established genetic syndromes known to be associated with colonic neoplasia, high risk of bleeding, and a history of ulcerative colitis or Crohn's Disease
3. Gender: Males and Females
4. Race/ethnicity: not specified
5. Age: 30 - 74
6. Time period: One year time period between 1995 and 1997
7. Geographic location: Piedmont Region of North Carolina
8. Number of participants: 184 (63%)

1. Control selection criteria
2. Matching variables
3. Exclusion criteria
4. Gender
5. Race/ethnicity
6. Age
7. Time period
8. Geographic location
9. Number of participants

1. Control selection criteria: English speaking patients that were not diagnosed with concurrent adenomas after undergoing a voluntary colonoscopy
2. Matching variables: None
3. Exclusion criteria: Same as Cases
4. Gender: Males and Females
5. Race/ethnicity: not specified
6. Age: 30-74
7. Time period: one year time period between 1995 and 1997
8. Geographic location: Piedmont Region of North Carolina
9. Number of participants: 236 (63%)

Cohort definition
For study designs 2, 3, and 6, define the following if available:

1. Cohort selection criteria
2. Exclusion criteria
3. Gender
4. Race/ethnicity
5. Age
6. Time period
7. Geographic location
8. Number of participants (% of total eligible)

1. Environmental factor
2. Exposure assessment
3. Exposure definition
4. Number of participants with exposure data (% of total eligible)

1. Environmental factor: Alcohol, folate, and other nutrients involved in the folate metabolism pathway
2. Exposure assessment: Self reported through adapted Willet semi-quantitative food frequency and Paffenbarger questionnaires
3. Exposure definition: Separated into sex-specific tertiles based on the intake
4. Number of participants with exposure data: 405 (60.7%)

1. Gene
2. DNA source
3. Methodology
4. Number of participants genotyped (% of total eligible) 

1. Gene: MTHFR
2. DNA source: Blood
3. Genotyping method: PCR and restriction enzyme digestion
4. Number of participants genotyped: 386 (57.9%)

Analysis
Comment on the analysis carried out by the author(s), e.g. matching, modeling or statistical tests used. Were the analyses appropriate?

Associations may be biased toward the null as a result of recruiting participants who were having voluntary colonoscopies since these individuals may not have been representative of the general population. A majority of the participants may have been considered at a higher risk of colorectal adenoma. Evidence of this bias can be seen the fact that controls were younger and were more likely to have had a history of colorectal cancer in their family than cases.

1. Prevalence of gene variant
2. Gene-disease association
3. Gene-environment interaction
4. Gene-gene interaction
5. Genetic test evaluation/monitoring

2. Gene-Disease Association: There was no statistically significant difference between the different genotypes and the risk of colorectal adenoma. (Table 1)

First, a statistically significant association between total intake and risk of colorectal adenoma could not be established (Table 3). Second, a higher consumption of alcohol was associated with an increased risk of colorectal adenoma regardless of folate intake (Table 4). Finally, the data were consistent, though not statistically significant, with a possible protective effect in individuals with a high folate intake and high Vitamin B consumption or homozygous for the TT allele (Tables 2 and 5).

The major limitation of this article concerned statistical low power and selection bias that could have contributed to lack of statistical significance.

In reference to public health, a lower alcohol or higher vitamin B complex consumption in the population could help decrease the incidence of colorectal adenoma and possibly colorectal cancer. As with the folate fortification of grain products, this may be accomplished by fortifying more food items with additional multinutrients. (1)

Further research could be directed toward analyzing the inconclusive associations, related to vitamins B6 and B12 and the MTHFR genotype, with greater statistical power. This could involve new studies that utilize greater sample sizes and research designs that avoid creating biases toward the null or the meta-analysis of similar studies.

• Table 1
• Table 2
• Table 3
• Table 4
• Table 5

1. Boyapati, Sonia M., et al. Folate intake MTHFR C677T polymorphism, alcohol consumption, and risk for sporadic colorectal adenoma. Cancer Causes and Control. 2004;15:493-501.
2. Weizmann Institute of Science . GeneCard for MTHFR. (last accessed 01/2008)