Association of TP53 Arg72Pro (rs1042522) Polymorphism with Pancreatic Cancer Risk in a Patient Cohort

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Evaluation of paper entitled:

„TP53 Arg72Pro polymorphism and pancreatic cancer susceptibility assessing rs10442522 as a risk factor for pancreatic  cancer”

By Laura Antolino, Germana de Nucci, Stefania Scarpino, Giuseppe Bianco, Gianluca Lopez, Paolo Aurello, Niccolo Petrucciani, Roberto Santoro, Giuseppe Nigri, Salvatore Agnes, Gianpietro Manes, Francesco A. D’Angelo

This manuscript presents the original results of research  study on genetic variation in gene p53 carrying higher risk of developing the pancreatic cancer. Authors analyzed plasma samples obtained from patients with pancreatic ductal adenocarcinoma (PDAC). Extracted DNA fragments were evaluated by RT-PCR, and prepared for the analysis of genes mutations. The main genes involved in pancreatic carcinogenesis were sequenced using the next-generation sequencing (NGS) method. As a reference population was used data from  1000Genome Project on healthy subject from central Italy. The results of study revealed that variant rs1042522 of TP53 gene with homozygosity G/G is related to higher risk of developing PDAC. The limitations of this study are related to the low number of enrolled patients (35 subjects )  due to low recruitment rate.  

Comments and suggestions:

1. Results: Table 2 is presented as part a, and part b. For better clarity this table should be separately shown as   two independent tables.
2. Discussion; the TP53 gene mutation SNP variant rs1042522  is often associated with cancer risk, f.ex with prostate cancer ( Front Oncol 2024, Toscano-Guerra A et al.) and also was reported  in patients with non-Hodgkin lymphoma  (Clin.Med.Insights 2025,  Helal E.A. et al.)
3. The list of reference should be updated, because most of citated positions was published 10 or more years ago.
4. A complete list of abbreviations used in the text should be included at the end of manuscript for the readers convenience .
5. This is an interesting study and should be continued. 

Author Response

Comments and suggestions:

1. Results: Table 2 is presented as part a, and part b. For better clarity this table should be separately shown as   two independent tables.
2. Discussion; the TP53 gene mutation SNP variant rs1042522  is often associated with cancer risk, f.ex with prostate cancer ( Front Oncol 2024, Toscano-Guerra A et al.) and also was reported  in patients with non-Hodgkin lymphoma  (Clin.Med.Insights 2025,  Helal E.A. et al.)
3. The list of reference should be updated, because most of citated positions was published 10 or more years ago.
4. A complete list of abbreviations used in the text should be included at the end of manuscript for the readers convenience .
5. This is an interesting study and should be continued.

Dear Reviewer 1 we truly thank you for all your positive comments about pur work and for all the precious adjustments that you have highlighted and we tried to answer properly with some substantial changes in our work. We modified the tables, we checked for abbreviations and more we updated the references

Reviewer 2 Report

Comments and Suggestions for Authors

The preliminary nature of the findings, along with the limited sample size and methodological simplicity, does not meet the threshold for a full original article. Instead, this work would be better suited as a poster presentation or brief communication/letter, where early-stage or exploratory findings are often shared prior to full-scale validation.

Author Response

The preliminary nature of the findings, along with the limited sample size and methodological simplicity, does not meet the threshold for a full original article. Instead, this work would be better suited as a poster presentation or brief communication/letter, where early-stage or exploratory findings are often shared prior to full-scale validation.

Dear Reviewer 2 

we thank you for your proper comments about our work, that is effectively a preliminary study due to the small number of patients included. Unfortunately we had limited funds to carry on our study as a public hospital. We are looking forward to continue  the enrollment as soon as possible. In the meanwhile we have changed the type of work to communication. 

Thank you so much

Kind regards

Germana de Nucci on behalf of the authors

Reviewer 3 Report

Comments and Suggestions for Authors

The article "TP53 Arg72Pro Polymorphism and Pancreatic Cancer Susceptibility: assessing rs1042522 as a Risk Factor for Pancreatic Cancer " is a communication article, that has identified individuals with TP53 Arg72Pro and/or rs1042522 variation have a higher risk of developing the Pancreatic Cancer. It is a very preliminary results which has not yet been further validated. It is a mere observation made from a single cohort of patients. The study has limitations which authors have duly accepted and explained in brief.

It seems the draft presented for review (with lot of yellow highlights) has already been reviewed/revised/edited. Few suggestions for improving the manuscript are as follows:

1. Minimal patient characteristics are presented in table 1. There is room for adding more clinical information.
2. Patient cohort need to be added in title. As the conclusion/observation has yet not been generalized/validated, it is safe to include them at the title.
3. There is room for having some statistical calculation for data presented in table 2 which would help to make power calculations for future large-scale validation studies.
4. If possible and available, we can analyze secondary data to validate the current observations.
5. It is interesting why authors choose not to present any other results related to other mountain genes, given the trial has been stopped. 

Author Response

The article "TP53 Arg72Pro Polymorphism and Pancreatic Cancer Susceptibility: assessing rs1042522 as a Risk Factor for Pancreatic Cancer " is a communication article, that has identified individuals with TP53 Arg72Pro and/or rs1042522 variation have a higher risk of developing the Pancreatic Cancer. It is a very preliminary results which has not yet been further validated. It is a mere observation made from a single cohort of patients. The study has limitations which authors have duly accepted and explained in brief.

It seems the draft presented for review (with lot of yellow highlights) has already been reviewed/revised/edited. Few suggestions for improving the manuscript are as follows:

1. Minimal patient characteristics are presented in table 1. There is room for adding more clinical information.
2. Patient cohort need to be added in title. As the conclusion/observation has yet not been generalized/validated, it is safe to include them at the title.
3. There is room for having some statistical calculation for data presented in table 2 which would help to make power calculations for future large-scale validation studies.
4. If possible and available, we can analyze secondary data to validate the current observations.
5. It is interesting why authors choose not to present any other results related to other mountain genes, given the trial has been stopped

Dear Reviewer 3 

we truly tank you for your precise observations that surely can improve your work. as you suggested we have difficulties to retrive more informations from a cohort of patients most of them have already passed away at nowadays. We had limited fund as a public hospital and this is the reason why we had to stope the enrollment of our cohort because we had no more chance to make additional genetic analysis to make our data stronger. hoverer based on the publication of this first communications, we do believe to obtain more fund to continue and enlarge the enrollment to give to these data more strength.

Thank you so much for the chance you can give to us however we modified the communications as soon as possible folioing your suggestions

Kind regards

Germana de Nucci on behalf of all the authors

Round 2

Reviewer 3 Report

Comments and Suggestions for Authors

Sincere thanks for revising the article. Revised version of the manuscript addresses most of the comments of reviewers.