See the published version of this preprint at World Journal of Surgical Oncology.
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Research
Zhixiong Zhong
Meizhou People's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3200-3105
License:
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Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.
Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed.
Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 38.4%, 24%, and 32.7%, respectively. DPYD*2A variant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe vomiting and skin ulceration (p = 0.042 and p = 0.018, respectively). Patients with GSTP1 c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p = 0.027). Nevertheless, no significant difference was found between patients with DPYD*2A, *5A, *9A for chemotherapeutic toxicity.
Conclusions: The results demonstrated that GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of GSTP1 in colorectal cancer patients before chemotherapy may help to realize personalized therapy.
Keywords
DPYD, GSTP1, gene polymorphism, chemotherapy toxicity, Hakka population
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CURRENT STATUS: Published
View the published article at World Journal of Surgical Oncology.
Version 3
Posted 08 Dec, 2020
No community comments so far
Editorial decision: Accept
On 26 Nov, 2020
Reviewer #2 agreed
On 25 Nov, 2020
Reviewers invited
Invitations sent on 25 Nov, 2020
Reviewer #1 agreed
On 25 Nov, 2020
Review #1 received
Received 25 Nov, 2020
Review #2 received
Received 25 Nov, 2020
Editor assigned
On 23 Nov, 2020
Submission checks complete
On 23 Nov, 2020
Editor invited
On 23 Nov, 2020
No comments provided
Editorial decision: Major Revision
On 14 Oct, 2020
Review #1 received
Received 07 Oct, 2020
Review #2 received
Received 07 Oct, 2020
Review #4 received
Received 06 Oct, 2020
Review #5 received
Received 06 Oct, 2020
Review #3 received
Received 06 Oct, 2020
Reviewer #5 agreed
On 05 Oct, 2020
Reviewer #6 agreed
On 05 Oct, 2020
Reviewer #4 agreed
On 04 Oct, 2020
Reviewer #3 agreed
On 03 Oct, 2020
Editor assigned
On 02 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Reviewer #1 agreed
On 02 Oct, 2020
Reviewer #2 agreed
On 02 Oct, 2020
Submission checks complete
On 01 Oct, 2020
Editor invited
On 01 Oct, 2020
No comments provided
Editorial decision: Revise before peer review
On 10 Sep, 2020
Editor assigned
On 07 Sep, 2020
Submission checks complete
On 06 Sep, 2020
Editor invited
On 06 Sep, 2020
First submitted
On 05 Sep, 2020
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A new preprint design is coming!
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See the published version of this preprint at World Journal of Surgical Oncology.
This is a preprint, a preliminary version of a manuscript that has not completed peer review at a journal. Research Square does not conduct peer review prior to posting preprints. The posting of a preprint on this server should not be interpreted as an endorsement of its validity or suitability for dissemination as established information or for guiding clinical practice.
Learn more about In Review
Research
Zhixiong Zhong
Meizhou People's Hospital
Corresponding Author
ORCiD: https://orcid.org/0000-0002-3200-3105
Badges
Prescreen
This manuscript passed our Prescreen assessment
Complete author information
Appropriate declaration statements
Potential risks to human health
Prescreen
Peer Review Timeline
CURRENT STATUS: Published
View the published article at World Journal of Surgical Oncology.
Version 3
Posted 08 Dec, 2020
No community comments so far
Editorial decision: Accept
On 26 Nov, 2020
Reviewer #2 agreed
On 25 Nov, 2020
Reviewers invited
Invitations sent on 25 Nov, 2020
Reviewer #1 agreed
On 25 Nov, 2020
Review #1 received
Received 25 Nov, 2020
Review #2 received
Received 25 Nov, 2020
Editor assigned
On 23 Nov, 2020
Submission checks complete
On 23 Nov, 2020
Editor invited
On 23 Nov, 2020
No comments provided
Editorial decision: Major Revision
On 14 Oct, 2020
Review #1 received
Received 07 Oct, 2020
Review #2 received
Received 07 Oct, 2020
Review #4 received
Received 06 Oct, 2020
Review #5 received
Received 06 Oct, 2020
Review #3 received
Received 06 Oct, 2020
Reviewer #5 agreed
On 05 Oct, 2020
Reviewer #6 agreed
On 05 Oct, 2020
Reviewer #4 agreed
On 04 Oct, 2020
Reviewer #3 agreed
On 03 Oct, 2020
Editor assigned
On 02 Oct, 2020
Reviewers invited
Invitations sent on 02 Oct, 2020
Reviewer #1 agreed
On 02 Oct, 2020
Reviewer #2 agreed
On 02 Oct, 2020
Submission checks complete
On 01 Oct, 2020
Editor invited
On 01 Oct, 2020
No comments provided
Editorial decision: Revise before peer review
On 10 Sep, 2020
Editor assigned
On 07 Sep, 2020
Submission checks complete
On 06 Sep, 2020
Editor invited
On 06 Sep, 2020
First submitted
On 05 Sep, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
View the published article at World Journal of Surgical Oncology.
Background: Fluoropyrimidines and platinum are still widely used for colorectal cancer (CRC) management. Several studies have reported that mutations of dihydropyrimidine dehydrogenase (DPYD) and glutathione S-transferase pi-1 (GSTP1) polymorphisms are related to Chemotherapy-related adverse events. In the present study, we purposed to assess the impact of DPYD and GSTP1 variants on the toxicity of adjuvant chemotherapy risk among the Hakka population, minimize adverse events, and to maximize therapy outcome for individualized treatment.
Methods: Genotyping was examined in 104 patients diagnosed with CRC cases and receiving fluoropyrimidine and platinum drugs based chemotherapy regimen by direct sequencing of DPYD and GSTP1 polymorphisms. Three DPYD variants including *2A, *5A, *9A, and GSTP1 c.313A>G were analyzed and clinical outcomes were assessed.
Results: The data suggest that the incidence of DPYD*5A, DPYD*9A, and GSTP1 c.313A>G variants were 38.4%, 24%, and 32.7%, respectively. DPYD*2A variant was not found. A total of 23 patients (22.1%) suffered severe vomiting and 19 patients (18.3%) suffered severe anemia. DPYD*5A polymorphism was found significantly associated with grade 3/4 ulceration (p = 0.001). GSTP1 was determined to be an independent risk factor for severe vomiting and skin ulceration (p = 0.042 and p = 0.018, respectively). Patients with GSTP1 c. 313A>G mutant type contributed to a higher risk for grade severe toxicity compared with wild genotype (p = 0.027). Nevertheless, no significant difference was found between patients with DPYD*2A, *5A, *9A for chemotherapeutic toxicity.
Conclusions: The results demonstrated that GSTP1 polymorphisms were useful predictors of severe events. Screening of single nucleotide polymorphisms of GSTP1 in colorectal cancer patients before chemotherapy may help to realize personalized therapy.
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