Review for 10.1186/1471-230X-9-79 (2009)

Reviewer's report
Title:Investigation of innate immunity genes CARD4, CARD8 and CARD15 as
germline susceptibility factors for colorectal cancer
Version: 1Date:21 May 2009
Reviewer: RAJA MARRAKCHI
Reviewer's report:
The study is interesting and the size of the samples that have been analysed
important.
Three main features should be mentioned.
- The exclusion of patients with both CRC and IBD could explain the results
obtained, since CARD genes are involved in IBD and since IBD are considered
as risk factor for CRC .
- Most of the SNP studied are neutral and located in introns, with loch of effect at
functional level and hence no incidence on the disease. However , haplotype
study is pertinent since these SNP could be in disequilibrium with other marers
such as rs 6958571 (ins/del) that should have been analysed in gene CARD4
- No information is available in the paper about the patients phenotype.No
stratification following the disease presentation.
The case/control study should have included this parameter. The SNP analysed
could be not associated to CRC as risk factor but they could be associated to
disease presentation.
Background
-Since the paper is focused on three genes CARD4, CARD8 and CARD15, the
authors should have presented all the 3 genes equally in the background part.
Indeed, only one sentence in page 3 has introduced CARD4 and CARD8 .
# The sentence at the end of page 8 in results should be included in background.
# The third and fourth sentences page 9 giving information on CARD8 mutation
Cys10Ter should be moved to background
- There is too much details on the size of the samples used in other studies
.These precise data should be used in a comparative approach (a table) with the
results obtained in this paper including comparaison of allele frequencies
between populations.
- The last sentence of background should be changed.
Methods
- Patients phenotypes are not presented in Table 1 . Stratification following the
disease presentation should be given .
- What about patients with FAP?
- The figures 2 , 3, 4should be moved to methods part , since they present the
location
- Of the different SNP studied .
Moreover , it does not appear clearly if linkage disequilibrium patterns have been
established on the basis of the study sample or refers to previous studies as in
figure 2, 3 and 4 .
Results
-The power analysis should be better explained .
- Tables 2, 3, 4 should be improved and columns well separated .
# Columns HAP2 to HAP5 that refer to studing window haplotype analysis
should be better explained in the tables.
# To which genotype Pgene refers. More information should be given.
# # is not clear.
# What about EZ66K in CARD4 gene (table2).
- Table 5 : it should have been said cleary if Pall and Pgene were calculated
tacking into account 2*2 (c) , and P value 2*2 (c) genotype should be calculated .
- SNP rs 252944D in CARD8 gene is not shown in table 3 neither in figure 3 .
- Number should be the same in Tables and in the text
- There is no comment b about E266K SNP in CARD4.
- For R702 W SNP in CARD15, or rece : 2,8 should have been discussed .
Discussion
-Correct who mistakes at the last line of page 12(terms, individual)
-Add discussion about patient’s selection and SNP studied as presented in
general comments.
Sincerely
Pr RAJA MARRACHI
Speciality : Immunology
Biology Department
Université Tunis El Manar, Tunisia
Faculté des sciences de Tunis,
Laboratoire de Génétique, Immunologie et Pathologies Humaines,
Campus universitaire, El Manar I, 2092 Tunis/Tunisie,
Tel : 216 20 932 327
Email : raja.triki@laposte.net
Level of interest: An article of limited interest
Quality of written English: Acceptable
Statistical review: Yes, and I have assessed the statistics in my report.
Declaration of competing interests:
I declare no compting interest's below