Reviewer ’s report  
 
Title: Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer  
 
Version: 0 Date: 22 Jun 2017  
 
Reviewer: Manuela Gariboldi  
 
Reviewer's report:  
 
Only one SNP (rs1525489) was significantly different, although with low significance, in two of 
the four pop ulations analyzed. And overall it only showed a p -trend. The fact that the association 
was found in sub -populations from Lithuania and Spain and not in populations from Czech 
Republic and Italy, compensating the different origins in both groups, supports t he possibility 
that it is a casual interaction.  
A study aimed at evaluating the role of TAS2R16 in the context of colorectal adenomas has 
already been conducted, although on populations from different ethnicity (Schembre SM et al., 
Variations in bitter -taste receptor genes, dietary intake, and colorectal adenoma risk. Nutr 
Cancer. 2013; 65:982 -90), and should be mentioned and discussed in the text. This study found 
non association of the SNP analyzed and presence of adenomas. The sentence "The study was 
carried out in a large cohort of European individuals and it is the first to evaluate the role of this 
receptor in the context of CRC carcinogenesis" should be modified accordingly.  
The only new result emerging from here is the association of SNP rs1525489  with an increased 
risk of developing rectal cancer (p=0.007) in the whole series analyzed. Please add its association 
in each stratified population. To support the significance of rs1525489 SNP between colon and 
rectum, authors speculate that colon and re ctum may have a different expression of TAS2R16. 
Despite what they say, separate gene expression profiles of rectal and colon cancer are available 
for example at TCGA portal and should be investigated and results should be added to the text, 
to confirm wha t they say.  
Nevertheless, it has been reported that there is no overall effect of aspirin on the risk of rectal 
cancer (Garcia -Albeniz X. and A.T. Chan. Aspirin for the prevention of colorectal cancer. Best 
Pract Res Clin Gastroenterol. 2011; 25: 461 -472).  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess  any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional st atistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in t he past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisat ion that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursemen ts, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to t his paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my name d report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Reviewer ’s report  
 
Title: Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer  
 
Version: 0 Date: 22 Jun 2017  
 
Reviewer: Manuela Gariboldi  
 
Reviewer's report:  
 
Only one SNP (rs1525489) was significantly different, although with low significance, in two of 
the four pop ulations analyzed. And overall it only showed a p -trend. The fact that the association 
was found in sub -populations from Lithuania and Spain and not in populations from Czech 
Republic and Italy, compensating the different origins in both groups, supports t he possibility 
that it is a casual interaction.  
A study aimed at evaluating the role of TAS2R16 in the context of colorectal adenomas has 
already been conducted, although on populations from different ethnicity (Schembre SM et al., 
Variations in bitter -taste receptor genes, dietary intake, and colorectal adenoma risk. Nutr 
Cancer. 2013; 65:982 -90), and should be mentioned and discussed in the text. This study found 
non association of the SNP analyzed and presence of adenomas. The sentence "The study was 
carried out in a large cohort of European individuals and it is the first to evaluate the role of this 
receptor in the context of CRC carcinogenesis" should be modified accordingly.  
The only new result emerging from here is the association of SNP rs1525489  with an increased 
risk of developing rectal cancer (p=0.007) in the whole series analyzed. Please add its association 
in each stratified population. To support the significance of rs1525489 SNP between colon and 
rectum, authors speculate that colon and re ctum may have a different expression of TAS2R16. 
Despite what they say, separate gene expression profiles of rectal and colon cancer are available 
for example at TCGA portal and should be investigated and results should be added to the text, 
to confirm wha t they say.  
Nevertheless, it has been reported that there is no overall effect of aspirin on the risk of rectal 
cancer (Garcia -Albeniz X. and A.T. Chan. Aspirin for the prevention of colorectal cancer. Best 
Pract Res Clin Gastroenterol. 2011; 25: 461 -472).  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess  any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional st atistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in t he past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisat ion that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursemen ts, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to t his paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my name d report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
Please review this paper.
user
Reviewer ’s report  
 
Title: Association between polymorphisms of TAS2R16 and susceptibility to colorectal cancer  
 
Version: 0 Date: 22 Jun 2017  
 
Reviewer: Manuela Gariboldi  
 
Reviewer's report:  
 
Only one SNP (rs1525489) was significantly different, although with low significance, in two of 
the four pop ulations analyzed. And overall it only showed a p -trend. The fact that the association 
was found in sub -populations from Lithuania and Spain and not in populations from Czech 
Republic and Italy, compensating the different origins in both groups, supports t he possibility 
that it is a casual interaction.  
A study aimed at evaluating the role of TAS2R16 in the context of colorectal adenomas has 
already been conducted, although on populations from different ethnicity (Schembre SM et al., 
Variations in bitter -taste receptor genes, dietary intake, and colorectal adenoma risk. Nutr 
Cancer. 2013; 65:982 -90), and should be mentioned and discussed in the text. This study found 
non association of the SNP analyzed and presence of adenomas. The sentence "The study was 
carried out in a large cohort of European individuals and it is the first to evaluate the role of this 
receptor in the context of CRC carcinogenesis" should be modified accordingly.  
The only new result emerging from here is the association of SNP rs1525489  with an increased 
risk of developing rectal cancer (p=0.007) in the whole series analyzed. Please add its association 
in each stratified population. To support the significance of rs1525489 SNP between colon and 
rectum, authors speculate that colon and re ctum may have a different expression of TAS2R16. 
Despite what they say, separate gene expression profiles of rectal and colon cancer are available 
for example at TCGA portal and should be investigated and results should be added to the text, 
to confirm wha t they say.  
Nevertheless, it has been reported that there is no overall effect of aspirin on the risk of rectal 
cancer (Garcia -Albeniz X. and A.T. Chan. Aspirin for the prevention of colorectal cancer. Best 
Pract Res Clin Gastroenterol. 2011; 25: 461 -472).  
Are the methods appropriate and well described?  
If not, please specify what is required in your comments to the authors.  
 
Yes 
 
Does the work include the necessary controls?  
If not, please specify which controls are required in your comments to the authors.  
 
Yes 
 
Are the conclusions drawn adequately supported by the data shown?  
If not, please explain in your comments to the authors.  
 
Yes 
 
Are you able to assess  any statistics in the manuscript or would you recommend an  
additional statistical review?  
If an additional statistical review is recommended, please specify what aspects require further  
assessment in your comments to the editors.  
 
I recommend additional st atistical review  
 
Quality of written English  
Please indicate the quality of language in the manuscript:  
 
Acceptable  
 
Declaration of competing interests  
Please complete a declaration of competing interests, considering the following questions:  
 
1. Have you in t he past five years received reimbursements, fees, funding, or salary from an  
organisation that may in any way gain or lose financially from the publication of this  
manuscript, either now or in the future?  
 
2. Do you hold any stocks or shares in an organisat ion that may in any way gain or lose  
financially from the publication of this manuscript, either now or in the future?  
 
3. Do you hold or are you currently applying for any patents relating to the content of the  
manuscript?  
 
4. Have you received reimbursemen ts, fees, funding, or salary from an organization that 
holds  or has applied for patents relating to the content of the manuscript?  
 
5. Do you have any other financial competing interests?  
 
6. Do you have any non -financial competing interests in relation to t his paper?  
 
If you can answer no to all of the above, write 'I declare that I have no competing interests' 
below.  If your reply is yes to any, please give details below.  
 
I declare that I have no competing interests  
 
I agree to the open peer review policy of the journal. I understand that my name will be included  
on my report to the authors and, if the manuscript is accepted for publication, my named report  
including any attachments I upload will be posted on the websi te along with the authors'  
responses. I agree for my report to be made available under an Open Access Creative Commons  
CC-BY license ( http://creativecommons.org/licenses/by/4.0/ ). I understand that any comments  
which I do not wish to be included in my name d report can be included as confidential comments  
to the editors, which will not be published.  
 
I agree to the open peer review policy of the journal  
assistant