Reviewer ’s report  
Title : Associations between polymorphisms in folate -metabolizing genes and pancreatic c ancer 
risk in Japanese subjects  
 
Version:  0 Date:  18 Feb 2016  
 
Reviewer:  Harkirat  Singh  
 
Reviewer's report:  
This is a case control study evaluating the associati on between folate metabolizing gene 
polymorphisms and pancreatic cancer in japanese patients. Authors have done a good job.  
 
Title: Appropriate  
Introduction/Background: Adequate length, explains the reason for the study clearly and explains 
the hypothesis . One thing that can be clarified is the results of both the japanese studies on this 
topic (Suzuki et al,Ohnami et al)  instead of clubbing it with the studies in other populations (Li 
et al in non hispanic US whites, wang et al in chinese and Matsubayash i et al in americans). 
Reason being genetic polymorphisms and phenotypes and vary in different ethnic, geographic 
and racial populations.  
 
Methods: There is no description of how the sample size was determined for the main 
hypothesis. Please explain about calculation of sample size in this section. Also explain about the 
sample size needed to find interactions/effect modifications (smoking, alcohol and dietary folate 
intake) with the exposure in question (gene polymorphism) and effect (pancreatic cancer)  
 
Results:  OK 
Discussion:  
In the first paragraph, please discuss both the previous japanese studies. Please clearly mention 
that your results for MTHFR polymorphisms are not different from previous two Japanese 
studies for gentotype alone. In the 2nd paragrap h, it is stated that your results of null findings on 
association between MTHFR genotypes and panc cancer can be from difference observed in 
minor allele frequencies among ethnic populations. Are you comparing it with non -japanese 
studies or the japanese s tudy with positive association for MTRR polymorphism (Ohnami et al)? 
How is the ethnicity of your population different from other japanese studies? What reasons can 
you give for the different results from study by Ohnami et al?  
 
Overall the message from y our results is that there is no association noted for genetic 
polymorphisms alone and there is not enough data for calculating effect modification due to 
alcohol,smoking or folate intake (gene -environment interaction). I would make this more clear in 
the e nding of your discussion.  
 
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 n ecessary 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 s tatistics 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 am able to assess the statisti cs 
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 the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation 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 reimbursements, 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 com peting interests in relation to this 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 revie w 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 website 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 named report can be included as co nfidential comments 
to the editors, which will not be published.  
I agree to the open peer review policy of the journal  
Reviewer ’s report  
Title : Associations between polymorphisms in folate -metabolizing genes and pancreatic c ancer 
risk in Japanese subjects  
 
Version:  0 Date:  18 Feb 2016  
 
Reviewer:  Harkirat  Singh  
 
Reviewer's report:  
This is a case control study evaluating the associati on between folate metabolizing gene 
polymorphisms and pancreatic cancer in japanese patients. Authors have done a good job.  
 
Title: Appropriate  
Introduction/Background: Adequate length, explains the reason for the study clearly and explains 
the hypothesis . One thing that can be clarified is the results of both the japanese studies on this 
topic (Suzuki et al,Ohnami et al)  instead of clubbing it with the studies in other populations (Li 
et al in non hispanic US whites, wang et al in chinese and Matsubayash i et al in americans). 
Reason being genetic polymorphisms and phenotypes and vary in different ethnic, geographic 
and racial populations.  
 
Methods: There is no description of how the sample size was determined for the main 
hypothesis. Please explain about calculation of sample size in this section. Also explain about the 
sample size needed to find interactions/effect modifications (smoking, alcohol and dietary folate 
intake) with the exposure in question (gene polymorphism) and effect (pancreatic cancer)  
 
Results:  OK 
Discussion:  
In the first paragraph, please discuss both the previous japanese studies. Please clearly mention 
that your results for MTHFR polymorphisms are not different from previous two Japanese 
studies for gentotype alone. In the 2nd paragrap h, it is stated that your results of null findings on 
association between MTHFR genotypes and panc cancer can be from difference observed in 
minor allele frequencies among ethnic populations. Are you comparing it with non -japanese 
studies or the japanese s tudy with positive association for MTRR polymorphism (Ohnami et al)? 
How is the ethnicity of your population different from other japanese studies? What reasons can 
you give for the different results from study by Ohnami et al?  
 
Overall the message from y our results is that there is no association noted for genetic 
polymorphisms alone and there is not enough data for calculating effect modification due to 
alcohol,smoking or folate intake (gene -environment interaction). I would make this more clear in 
the e nding of your discussion.  
 
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 n ecessary 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 s tatistics 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 am able to assess the statisti cs 
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 the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation 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 reimbursements, 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 com peting interests in relation to this 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 revie w 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 website 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 named report can be included as co nfidential 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 : Associations between polymorphisms in folate -metabolizing genes and pancreatic c ancer 
risk in Japanese subjects  
 
Version:  0 Date:  18 Feb 2016  
 
Reviewer:  Harkirat  Singh  
 
Reviewer's report:  
This is a case control study evaluating the associati on between folate metabolizing gene 
polymorphisms and pancreatic cancer in japanese patients. Authors have done a good job.  
 
Title: Appropriate  
Introduction/Background: Adequate length, explains the reason for the study clearly and explains 
the hypothesis . One thing that can be clarified is the results of both the japanese studies on this 
topic (Suzuki et al,Ohnami et al)  instead of clubbing it with the studies in other populations (Li 
et al in non hispanic US whites, wang et al in chinese and Matsubayash i et al in americans). 
Reason being genetic polymorphisms and phenotypes and vary in different ethnic, geographic 
and racial populations.  
 
Methods: There is no description of how the sample size was determined for the main 
hypothesis. Please explain about calculation of sample size in this section. Also explain about the 
sample size needed to find interactions/effect modifications (smoking, alcohol and dietary folate 
intake) with the exposure in question (gene polymorphism) and effect (pancreatic cancer)  
 
Results:  OK 
Discussion:  
In the first paragraph, please discuss both the previous japanese studies. Please clearly mention 
that your results for MTHFR polymorphisms are not different from previous two Japanese 
studies for gentotype alone. In the 2nd paragrap h, it is stated that your results of null findings on 
association between MTHFR genotypes and panc cancer can be from difference observed in 
minor allele frequencies among ethnic populations. Are you comparing it with non -japanese 
studies or the japanese s tudy with positive association for MTRR polymorphism (Ohnami et al)? 
How is the ethnicity of your population different from other japanese studies? What reasons can 
you give for the different results from study by Ohnami et al?  
 
Overall the message from y our results is that there is no association noted for genetic 
polymorphisms alone and there is not enough data for calculating effect modification due to 
alcohol,smoking or folate intake (gene -environment interaction). I would make this more clear in 
the e nding of your discussion.  
 
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 n ecessary 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 s tatistics 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 am able to assess the statisti cs 
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 the past five years received reimbursements, f ees, funding, or salary from an 
organisation that may in any way gain or lose financial ly from the publication of this 
manuscript, either now or in the future?  
2. Do you hold any stocks or shares in an organisation 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 reimbursements, 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 com peting interests in relation to this 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 revie w 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 website 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 named report can be included as co nfidential comments 
to the editors, which will not be published.  
I agree to the open peer review policy of the journal  
assistant