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Research article
Polymorphisms in endoplasmic reticulum aminopeptidase genes are associated with cervical cancer risk in a Chinese Han population
Li Shi
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9508-7863
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This work is licensed under a CC BY 4.0 License. Read Full License
Background: Antigen-processing machinery molecules play crucial roles in infectious diseases and cancers. Studies have shown that polymorphisms in endoplasmic reticulum aminopeptidase (ERAP) genes can influence the enzymatic activity of ERAP proteins and are associated with the risk of diseases. In the current study, we evaluated the influence of ERAP gene (ERAP1 and ERAP2) polymorphisms on susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer.
Methods: Six single nucleotide polymorphisms (SNPs) in ERAP1 and 5 SNPs in ERAP2 were selected and genotyped in 556 CIN patients, 1072 cervical cancer patients, and 1262 healthy control individuals. Candidate SNPs were genotyped using SNaPshot assay. And the association of these SNPs with CIN and cervical cancer was analysed.
Results: The results showed that allelic and genotypic frequencies of rs26653 in ERAP1 were significantly different between cervical cancer and control groups (P=0.001 and 0.004). The allelic frequencies of rs27044 in ERAP1 and rs2287988 in ERAP2 were significantly different between control and cervical cancer groups (P=0.003 and 0.004). Inheritance model analysis showed that genotypes of rs27044, rs26618, rs26653 and rs2287988 SNPs may be associated with the risk of cervical cancer (P=0.003, 0.004, 0.001 and 0.002). Additionally, haplotype analysis results showed that the ERAP1 haplotype, rs27044C-rs30187T-rs26618T-rs26653G-rs3734016C, was associated with a lower risk of cervical cancer (P=0.001). The ERAP2 haplotypes rs2549782G- rs2548538A-rs2248374A-rs2287988G-rs1056893T (P=0.009 and 0.006) and rs2549782T-rs2548538T-rs2248374G-rs2287988A-rs1056893T (P=0.003 and 0.009) might be associated with cervical cancer and the development from CIN to cervical cancer.
Conclusion: Our results indicated that rs27044, rs26618 and rs26653 in ERAP1 and rs2287988 in ERAP2 influenced susceptibility to cervical cancer.
Keywords
Endoplasmic reticulum aminopeptidase; Single nucleotide polymorphisms; Association; Susceptibility; Cervical intraepithelial neoplasia; Cervical cancer
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On 11 Mar, 2020
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Editorial decision: Major revision
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Reviewer #5 agreed
On 29 Jan, 2020
Reviewer #4 agreed
On 25 Jan, 2020
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On 24 Jan, 2020
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This preprint is under consideration at BMC Cancer. A preprint is 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 article
Polymorphisms in endoplasmic reticulum aminopeptidase genes are associated with cervical cancer risk in a Chinese Han population
Li Shi
Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Medical Biology
Corresponding Author
ORCiD: https://orcid.org/0000-0001-9508-7863
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: Under Review
Version 4
Posted 10 Apr, 2020
No community comments so far
Submission checks complete
On 06 Apr, 2020
No comments provided
Editorial decision: Minor revision
On 02 Apr, 2020
Reviewer #2 agreed
On 31 Mar, 2020
Reviewer #3 agreed
On 31 Mar, 2020
Review #1 received
Received 31 Mar, 2020
Review #2 received
Received 31 Mar, 2020
Editor assigned
On 30 Mar, 2020
Reviewers invited
Invitations sent on 30 Mar, 2020
Reviewer #1 agreed
On 30 Mar, 2020
Submission checks complete
On 29 Mar, 2020
Editor invited
On 29 Mar, 2020
No comments provided
Editorial decision: Minor revision
On 27 Mar, 2020
Review #3 received
Received 26 Mar, 2020
Review #1 received
Received 16 Mar, 2020
Review #2 received
Received 16 Mar, 2020
Reviewer #4 agreed
On 16 Mar, 2020
Review #4 received
Received 16 Mar, 2020
Reviewer #3 agreed
On 12 Mar, 2020
Editor assigned
On 11 Mar, 2020
Reviewers invited
Invitations sent on 11 Mar, 2020
Reviewer #1 agreed
On 11 Mar, 2020
Reviewer #2 agreed
On 11 Mar, 2020
Submission checks complete
On 10 Mar, 2020
Editor invited
On 10 Mar, 2020
No comments provided
Review #4 received
Received 14 Feb, 2020
Editorial decision: Major revision
On 14 Feb, 2020
Review #3 received
Received 07 Feb, 2020
Review #1 received
Received 30 Jan, 2020
Review #2 received
Received 30 Jan, 2020
Reviewer #5 agreed
On 29 Jan, 2020
Reviewer #4 agreed
On 25 Jan, 2020
Reviewer #3 agreed
On 24 Jan, 2020
Editor assigned
On 23 Jan, 2020
Reviewers invited
Invitations sent on 23 Jan, 2020
Reviewer #1 agreed
On 23 Jan, 2020
Reviewer #2 agreed
On 23 Jan, 2020
Submission checks complete
On 17 Jan, 2020
Editor invited
On 17 Jan, 2020
First submitted
On 15 Jan, 2020
Metrics
Comments: 0
PDF Downloads: ...
HTML Views: ...
License:
This work is licensed under a CC BY 4.0 License. Read Full License
Background: Antigen-processing machinery molecules play crucial roles in infectious diseases and cancers. Studies have shown that polymorphisms in endoplasmic reticulum aminopeptidase (ERAP) genes can influence the enzymatic activity of ERAP proteins and are associated with the risk of diseases. In the current study, we evaluated the influence of ERAP gene (ERAP1 and ERAP2) polymorphisms on susceptibility to cervical intraepithelial neoplasia (CIN) and cervical cancer.
Methods: Six single nucleotide polymorphisms (SNPs) in ERAP1 and 5 SNPs in ERAP2 were selected and genotyped in 556 CIN patients, 1072 cervical cancer patients, and 1262 healthy control individuals. Candidate SNPs were genotyped using SNaPshot assay. And the association of these SNPs with CIN and cervical cancer was analysed.
Results: The results showed that allelic and genotypic frequencies of rs26653 in ERAP1 were significantly different between cervical cancer and control groups (P=0.001 and 0.004). The allelic frequencies of rs27044 in ERAP1 and rs2287988 in ERAP2 were significantly different between control and cervical cancer groups (P=0.003 and 0.004). Inheritance model analysis showed that genotypes of rs27044, rs26618, rs26653 and rs2287988 SNPs may be associated with the risk of cervical cancer (P=0.003, 0.004, 0.001 and 0.002). Additionally, haplotype analysis results showed that the ERAP1 haplotype, rs27044C-rs30187T-rs26618T-rs26653G-rs3734016C, was associated with a lower risk of cervical cancer (P=0.001). The ERAP2 haplotypes rs2549782G- rs2548538A-rs2248374A-rs2287988G-rs1056893T (P=0.009 and 0.006) and rs2549782T-rs2548538T-rs2248374G-rs2287988A-rs1056893T (P=0.003 and 0.009) might be associated with cervical cancer and the development from CIN to cervical cancer.
Conclusion: Our results indicated that rs27044, rs26618 and rs26653 in ERAP1 and rs2287988 in ERAP2 influenced susceptibility to cervical cancer.