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Historical Pathogen-Driven Selection May Contribute to Contemporary Ethnic Difference in Bladder Cancer Susceptibility

Meng, Xiang Yu ; Wang, Qiao Li LU orcid ; Shi, Ming Jun and Zhang, Hong Yu (2023) In Bladder Cancer 9(3). p.211-216
Abstract

BACKGROUND: The rationale for ethnic differences in bladder cancer (BCa) susceptibility is an important open question. In this study, we raised the hypothesis that the APOBEC3-rs1014971 variant associated with BCa risk and APOBEC-mutagenesis probably contribute to ethnic differences. METHODS: We calculated the ethnicity-stratified 5-year age-adjusted incidence rates of BCa using the US SEER database. We performed somatic mutational-signature analyses and compared the APOBEC-related mutational contribution across BCa tumors in patients of different ethnicities. We analyzed the allele frequency distribution of APOBEC3-related rs1014971 in contemporary populations of different ethnicities and in ancient human genomes. We also analyzed the... (More)

BACKGROUND: The rationale for ethnic differences in bladder cancer (BCa) susceptibility is an important open question. In this study, we raised the hypothesis that the APOBEC3-rs1014971 variant associated with BCa risk and APOBEC-mutagenesis probably contribute to ethnic differences. METHODS: We calculated the ethnicity-stratified 5-year age-adjusted incidence rates of BCa using the US SEER database. We performed somatic mutational-signature analyses and compared the APOBEC-related mutational contribution across BCa tumors in patients of different ethnicities. We analyzed the allele frequency distribution of APOBEC3-related rs1014971 in contemporary populations of different ethnicities and in ancient human genomes. We also analyzed the natural selection profiles and ages of the investigated SNPs. RESULTS: We validated the ethnic difference in BCa risk using US SEER data, revealing Caucasians to be at >2-fold greater risk than Asians / Pacific islanders. In contemporary populations, we observed a coherent ethnic distribution in terms not only of the allele frequency of APOBEC3-related rs1014971, but also the mutational contribution of APOBEC-mediated mutagenesis in BCa tumors. Population genetics and ancient genome analyses further suggested that the diverse ethnic distribution of rs1014971 could be rooted in human evolution. CONCLUSIONS: It is possible that APOBEC3-related rs1014971 is involved in the different BCa incidence across ethnic groups, and this difference is potentially derived from human evolution. Our findings suggested an evolutionary link between contemporary population-level variations in malignancy susceptibility and pathogen-driven selection in the past, not unlike previously reported cases of certain autoimmune and metabolic disorders.

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author
; ; and
publishing date
type
Contribution to journal
publication status
published
in
Bladder Cancer
volume
9
issue
3
pages
211 - 216
publisher
SAGE Publications
external identifiers
  • scopus:85174075668
ISSN
2352-3727
DOI
10.3233/BLC-230010
language
English
LU publication?
no
additional info
Publisher Copyright: © 2023 - The authors. Published by IOS Press.
id
374f7a5b-fcbe-438a-90c9-792e057a2df9
date added to LUP
2025-05-12 17:06:55
date last changed
2025-10-14 10:16:34
@article{374f7a5b-fcbe-438a-90c9-792e057a2df9,
  abstract     = {{<p>BACKGROUND: The rationale for ethnic differences in bladder cancer (BCa) susceptibility is an important open question. In this study, we raised the hypothesis that the APOBEC3-rs1014971 variant associated with BCa risk and APOBEC-mutagenesis probably contribute to ethnic differences. METHODS: We calculated the ethnicity-stratified 5-year age-adjusted incidence rates of BCa using the US SEER database. We performed somatic mutational-signature analyses and compared the APOBEC-related mutational contribution across BCa tumors in patients of different ethnicities. We analyzed the allele frequency distribution of APOBEC3-related rs1014971 in contemporary populations of different ethnicities and in ancient human genomes. We also analyzed the natural selection profiles and ages of the investigated SNPs. RESULTS: We validated the ethnic difference in BCa risk using US SEER data, revealing Caucasians to be at &gt;2-fold greater risk than Asians / Pacific islanders. In contemporary populations, we observed a coherent ethnic distribution in terms not only of the allele frequency of APOBEC3-related rs1014971, but also the mutational contribution of APOBEC-mediated mutagenesis in BCa tumors. Population genetics and ancient genome analyses further suggested that the diverse ethnic distribution of rs1014971 could be rooted in human evolution. CONCLUSIONS: It is possible that APOBEC3-related rs1014971 is involved in the different BCa incidence across ethnic groups, and this difference is potentially derived from human evolution. Our findings suggested an evolutionary link between contemporary population-level variations in malignancy susceptibility and pathogen-driven selection in the past, not unlike previously reported cases of certain autoimmune and metabolic disorders.</p>}},
  author       = {{Meng, Xiang Yu and Wang, Qiao Li and Shi, Ming Jun and Zhang, Hong Yu}},
  issn         = {{2352-3727}},
  language     = {{eng}},
  month        = {{09}},
  number       = {{3}},
  pages        = {{211--216}},
  publisher    = {{SAGE Publications}},
  series       = {{Bladder Cancer}},
  title        = {{Historical Pathogen-Driven Selection May Contribute to Contemporary Ethnic Difference in Bladder Cancer Susceptibility}},
  url          = {{http://dx.doi.org/10.3233/BLC-230010}},
  doi          = {{10.3233/BLC-230010}},
  volume       = {{9}},
  year         = {{2023}},
}