Question
1:
On the partner strand of DNA, the "antisense" strand,
what is the corresponding base change?
Your
answer:
The G to A SNP in
the ornithine decarboxylase (or ODC) gene occurs in an "intron" or a
non-coding region of DNA. The DNA in introns does not code for
amino acids, so it does not make protein. In this region of the ODC
gene, called intron 1, the DNA serves as a binding site for proteins
that regulate activity of the gene. Gene activity is in large part
determined by how often the gene is transcribed into mRNA: how often
the gene is turned on or shut off.
Question
2: The authors present
background material describing how intron 1, and specifically the
region where the G to A change occurs, is involved in regulation of
transcription of the ODC gene. How does this regulation occur?
Your answer:
Question
3: APC is a tumor
suppressor gene . What happens when APC is functioning normally?
Your answer:
Question
4:
What happens when APC is not functioning normally?
Your answer:
Question
5:
What happens with the ODC intron 1 G allele is changed to A?
Your answer:
Part 2.
Identifying the research questions.
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Question
6:
What do the authors hypothesize about the ODC intron 1A allele and
risk of polyps?
Your answer:
Question
7:
How does aspirin fit into the scheme?
Your answer:
Question
8:
What do the authors hypothesize about interactions between the ODC
polymorphism and aspirin?
Your answer:
Part 3.
Evaluating the study design
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The authors
genotyped 688 of 1304 participants in a randomized trial of adenoma
(polyp) recurrence. The original study randomized participants to a
wheat bran fiber intervention. However, it is important to note that
the analysis in this article is observational: the participants were
not randomized to aspirin. Participants in both arms of the fiber
trial were combined and information was collected from
self-administered questionnaires on aspirin use. It was not stated
how many participants failed to provide information on aspirin use.
A large percentage (47%) of the participants did not provide a blood
sample, and it is not known whether providing a blood sample was
related to outcome (polyp recurrence) or aspirin use or ODC
genotype.
Genotyping was
conducted using a PCT-based method known as 5'-exonuclease allele
discrimination or Taqman. Two different DNA probes were made, one
for each of the intron 1 alleles (G or A). The probes are labeled
with a fluorescent dye that is released during PCR amplification.
The validity of the assay is maintained using positive controls (DNA
standards of known sequence) and negative controls (buffer without
DNA).
Question
9:
How was the reliability of the assay determined? Do you think these
measures were adequate?
Your answer:
Question
10:
How was the
association between ODC genotype and polyp recurrence measured?
Your answer:
Question
11:
How was
interaction between aspirin use and ODC genotype assessed?
Your answer:
Part 4. Assessing
the findings
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Table 1
presented odds ratios for aspirin use and polyp recurrence, ignoring
ODC genotype. An inverse association was found: adjusted OR = 0.68
(95% CI 0.48-0.98). The association for ODC genotype and polyp
recurrence, ignoring aspirin use, was also inverse: adjusted OR =
0.48 (0.24-0.99) for A/A versus G/G genotype.
Question
12:
Are the ODC
genotypes in Hardy Weinberg equilibrium in the study population?
Your answer:
Question
13:
Interpret the
p-value for the Hardy Weinberg equilibrium test.
Your answer:
Question
14:
How does a Hardy
Weinberg equilibrium test serve as a quality control check on
genotyping procedures as well as on the underlying study design?
Your answer:
Question
15:
Figure 1
presents joint effects where both aspirin use and ODC genotype are
taken into account. How would you characterize the joint effects
of aspirin use and ODC genotype?
Your answer:
Part 5.
Implications of the study findings.
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Question
16: How
do the authors interpret the findings?
Your answer:
Question
17:
What are the
implications of the findings for public health?
Your answer:
Question
18:
Would you
recommend that aspirin use for the prevention of polyps only be
targeted to persons with ODC A/A genotype?
Your answer:
Question
19:
Should persons
with the ODC G/G or G/A genotype be targetted for increased
screening for polyps and colorectal cancer, for example, through
fecal occult blood testing or colonoscopy?
Your answer:
Question
20:
What other studies should be done?
Your answer:
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