Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

Valentina A. Zavala; Sandro Casavilca-Zambrano; Jeannie Navarro-Vásquez; Carlos A. Castañeda; Guillermo Valencia; Zaida Morante; Monica Calderón; Julio E. Abugattas; Henry Gómez; Hugo A. Fuentes; Ruddy Liendo-Picoaga; Jose M. Cotrina; Claudia Monge; Silvia P. Neciosup; Scott Huntsman; Donglei Hu; Sixto E. Sánchez; Michelle A. Williams; Angel Núñez-Marrero; Lenin Godoy; Aaron Hechmer; Adam B. Olshen; Julie Dutil; Elad Ziv; Jovanny Zabaleta; Bizu Gelaye; Jule Vásquez; Marco Gálvez-Nino; Daniel Enriquez-Vera; Tatiana Vidaurre; Laura Fejerman

doi:10.1158/1055-9965.EPI-22-0069

Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

Valentina A. Zavala, Sandro Casavilca-Zambrano, Jeannie Navarro-Vásquez, Carlos A. Castañeda, Guillermo Valencia, Zaida Morante, Monica Calderón, Julio E. Abugattas, Henry Gómez, Hugo A. Fuentes, Ruddy Liendo-Picoaga, Jose M. Cotrina, Claudia Monge, Silvia P. Neciosup, Scott Huntsman, Donglei Hu, Sixto E. Sánchez, Michelle A. Williams, Angel Núñez-Marrero, Lenin GodoyAaron Hechmer, Adam B. Olshen, Julie Dutil, Elad Ziv, Jovanny Zabaleta, Bizu Gelaye, Jule Vásquez, Marco Gálvez-Nino, Daniel Enriquez-Vera, Tatiana Vidaurre, Laura Fejerman

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.

Original language	English
Pages (from-to)	1602-1609
Number of pages	8
Journal	Cancer Epidemiology Biomarkers and Prevention
Volume	31
Issue number	8 August
DOIs	https://doi.org/10.1158/1055-9965.EPI-22-0069
State	Published - Aug 2022

Bibliographical note

Funding Information:
The PEGEN-BC study was supported by the National Cancer Institute of the National Institutes of Health under award number (R01CA204797; to L. Fejerman). The PrOMIS study was supported by the National Institute of Child Health and Human Development of the National Institutes of Health under award number (R01-HD-059835; to B. Gelaye). We want to thank the biobank at the Instituto Nacional de Enfermedades Neoplásicas, Lima, Peru, for their assistance managing and storing the material for the study. We also want to thank participants from the PEGEN-BC and PrOMIS studies. Research supported by the 2021 AACR-Genentech Cancer Disparities Research Fellowship, Grant Number 21-40-18-ZAVA (to V.A. Zavala).

Funding Information:
The PEGEN-BC study was supported by the National Cancer Institute of the National Institutes of Health under award number (R01CA204797; to L. Fejerman). The PrOMIS study was supported by the National Institute of Child Health and Human Development of the National Institutes of Health under award number (R01-HD-059835; to B. Gelaye). We want to thank the biobank at the Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru, for their assistance managing and storing the material for the study. We also want to thank participants from the PEGEN-BC and PrOMIS studies. Research supported by the 2021 AACR-Genentech Cancer Disparities Research Fellowship, Grant Number 21-40-18-ZAVA (to V.A. Zavala).

Publisher Copyright:
© 2022 The Authors.

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10.1158/1055-9965.EPI-22-0069

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Zavala, V. A., Casavilca-Zambrano, S., Navarro-Vásquez, J., Castañeda, C. A., Valencia, G., Morante, Z., Calderón, M., Abugattas, J. E., Gómez, H., Fuentes, H. A., Liendo-Picoaga, R., Cotrina, J. M., Monge, C., Neciosup, S. P., Huntsman, S., Hu, D., Sánchez, S. E., Williams, M. A., Núñez-Marrero, A., ... Fejerman, L. (2022). Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women. Cancer Epidemiology Biomarkers and Prevention, 31(8 August), 1602-1609. https://doi.org/10.1158/1055-9965.EPI-22-0069

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title = "Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women",

abstract = "Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.",

author = "Zavala, {Valentina A.} and Sandro Casavilca-Zambrano and Jeannie Navarro-V{\'a}squez and Casta{\~n}eda, {Carlos A.} and Guillermo Valencia and Zaida Morante and Monica Calder{\'o}n and Abugattas, {Julio E.} and Henry G{\'o}mez and Fuentes, {Hugo A.} and Ruddy Liendo-Picoaga and Cotrina, {Jose M.} and Claudia Monge and Neciosup, {Silvia P.} and Scott Huntsman and Donglei Hu and S{\'a}nchez, {Sixto E.} and Williams, {Michelle A.} and Angel N{\'u}{\~n}ez-Marrero and Lenin Godoy and Aaron Hechmer and Olshen, {Adam B.} and Julie Dutil and Elad Ziv and Jovanny Zabaleta and Bizu Gelaye and Jule V{\'a}squez and Marco G{\'a}lvez-Nino and Daniel Enriquez-Vera and Tatiana Vidaurre and Laura Fejerman",

note = "Publisher Copyright: {\textcopyright} 2022 The Authors.",

year = "2022",

month = aug,

doi = "10.1158/1055-9965.EPI-22-0069",

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volume = "31",

pages = "1602--1609",

journal = "Cancer Epidemiology Biomarkers and Prevention",

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Zavala, VA, Casavilca-Zambrano, S, Navarro-Vásquez, J, Castañeda, CA, Valencia, G, Morante, Z, Calderón, M, Abugattas, JE, Gómez, H, Fuentes, HA, Liendo-Picoaga, R, Cotrina, JM, Monge, C, Neciosup, SP, Huntsman, S, Hu, D, Sánchez, SE, Williams, MA, Núñez-Marrero, A, Godoy, L, Hechmer, A, Olshen, AB, Dutil, J, Ziv, E, Zabaleta, J, Gelaye, B, Vásquez, J, Gálvez-Nino, M, Enriquez-Vera, D, Vidaurre, T & Fejerman, L 2022, 'Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women', Cancer Epidemiology Biomarkers and Prevention, vol. 31, no. 8 August, pp. 1602-1609. https://doi.org/10.1158/1055-9965.EPI-22-0069

TY - JOUR

T1 - Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

AU - Zavala, Valentina A.

AU - Casavilca-Zambrano, Sandro

AU - Navarro-Vásquez, Jeannie

AU - Castañeda, Carlos A.

AU - Valencia, Guillermo

AU - Morante, Zaida

AU - Calderón, Monica

AU - Abugattas, Julio E.

AU - Gómez, Henry

AU - Fuentes, Hugo A.

AU - Liendo-Picoaga, Ruddy

AU - Cotrina, Jose M.

AU - Monge, Claudia

AU - Neciosup, Silvia P.

AU - Huntsman, Scott

AU - Hu, Donglei

AU - Sánchez, Sixto E.

AU - Williams, Michelle A.

AU - Núñez-Marrero, Angel

AU - Godoy, Lenin

AU - Hechmer, Aaron

AU - Olshen, Adam B.

AU - Dutil, Julie

AU - Ziv, Elad

AU - Zabaleta, Jovanny

AU - Gelaye, Bizu

AU - Vásquez, Jule

AU - Gálvez-Nino, Marco

AU - Enriquez-Vera, Daniel

AU - Vidaurre, Tatiana

AU - Fejerman, Laura

PY - 2022/8

Y1 - 2022/8

N2 - Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.

AB - Background: Breast cancer incidence in the United States is lower in Hispanic/Latina (H/L) compared with African American/ Black or Non-Hispanic White women. An Indigenous American breast cancer-protective germline variant (rs140068132) has been reported near the estrogen receptor 1 gene. This study tests the association of rs140068132 and other polymorphisms in the 6q25 region with subtype-specific breast cancer risk in H/Ls of high Indigenous American ancestry. Methods: Genotypes were obtained for 5,094 Peruvian women with (1,755) and without (3,337) breast cancer. Associations between genotype and overall and subtype-specific risk for the protective variant were tested using logistic regression models and conditional analyses, including other risk-associated polymorphisms in the region. Results: We replicated the reported association between rs140068132 and breast cancer risk overall [odds ratio (OR), 0.53; 95% confidence interval (CI), 0.47-0.59], as well as the lower odds of developing hormone receptor negative (HR-) versus HR+ disease (OR, 0.77; 95% CI, 0.61-0.97). Models, including HER2, showed further heterogeneity with reduced odds for HR+HER2+ (OR, 0.68; 95% CI, 0.51-0.92), HR-HER2+ (OR, 0.63; 95% CI, 0.44-0.90) and HR-HER2- (OR, 0.77; 95% CI, 0.56-1.05) compared with HR+HER2-. Inclusion of other risk-associated variants did not change these observations. Conclusions: The rs140068132 polymorphism is associated with decreased risk of breast cancer in Peruvians and is more protective against HR- and HER2+ diseases independently of other breast cancer-associated variants in the 6q25 region. Impact: These results could inform functional analyses to understand the mechanism by which rs140068132-G reduces risk of breast cancer development in a subtype-specific manner. They also illustrate the importance of including diverse individuals in genetic studies.

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U2 - 10.1158/1055-9965.EPI-22-0069

DO - 10.1158/1055-9965.EPI-22-0069

M3 - Artículo

C2 - 35654312

AN - SCOPUS:85135596165

SN - 1055-9965

VL - 31

SP - 1602

EP - 1609

JO - Cancer Epidemiology Biomarkers and Prevention

JF - Cancer Epidemiology Biomarkers and Prevention

IS - 8 August

ER -

Association between Ancestry-Specific 6q25 Variants and Breast Cancer Subtypes in Peruvian Women

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