Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Women's Health
Published in: BMC Women's Health 1/2015

Open Access 01-12-2015 | Research article

Breast cancer risk and genetic ancestry: a case–control study in Uruguay

Authors: Carolina Bonilla, Bernardo Bertoni, Pedro C Hidalgo, Nora Artagaveytia, Elizabeth Ackermann, Isabel Barreto, Paula Cancela, Mónica Cappetta, Ana Egaña, Gonzalo Figueiro, Silvina Heinzen, Stanley Hooker, Estela Román, Mónica Sans, Rick A Kittles

Published in: BMC Women's Health | Issue 1/2015

Login to get access

Abstract

Background

Uruguay exhibits one of the highest rates of breast cancer in Latin America, similar to those of developed nations, the reasons for which are not completely understood. In this study we investigated the effect that ancestral background has on breast cancer susceptibility among Uruguayan women.

Methods

We carried out a case–control study of 328 (164 cases, 164 controls) women enrolled in public hospitals and private clinics across the country. We estimated ancestral proportions using a panel of nuclear and mitochondrial ancestry informative markers (AIMs) and tested their association with breast cancer risk.

Results

Nuclear individual ancestry in cases was (mean ± SD) 9.8 ± 7.6% African, 13.2 ± 10.2% Native American and 77.1 ± 13.1% European, and in controls 9.1 ± 7.5% African, 14.7 ± 11.2% Native American and 76.2 ± 14.2% European. There was no evidence of a difference in nuclear or mitochondrial ancestry between cases and controls. However, European mitochondrial haplogroup H was associated with breast cancer (OR = 2.0; 95% CI 1.1, 3.5).

Conclusions

We have not found evidence that overall genetic ancestry differs between breast cancer patients and controls in Uruguay but we detected an association of the disease with a European mitochondrial lineage, which warrants further investigation.
Appendix
Available only for authorised users
Literature
1.
Dumitrescu RG, Cotarla I. Understanding breast cancer risk – where do we stand in 2005? J Cell Mol Med. 2005;9:208–21.CrossRefPubMed
2.
DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2013;64:52–62.CrossRefPubMed
3.
Perera NMA, Gui GPH. Multi-ethnic differences in breast cancer: current concepts and future directions. Int J Cancer. 2003;106:463–7.CrossRefPubMed
4.
Barrios E, Vasallo J, Alonso R, Garau M, Mussetti C. III Atlas de incidencia de cancer en el Uruguay. 2002–2006. 2010.
5.
Barrios E, Vasallo J, Alonso R, Garau M, Mussetti C. IV Atlas de mortalidad por cancer en el Uruguay. 2004–2008. 2011.
6.
De Stefani E, Ronco A, Mendilaharsu M, Guidobono M, Deneo-Pellegrini H. Meat intake, heterocyclic amines and risk of breast cancer: a case–control study in Uruguay. Cancer Epidemiol Biomarkers Prev. 1997;6(August):573–81.PubMed
7.
De Stefani E, Deneo-Pellegrini H, Mendilaharsu M, Ronco A. Essential fatty acids and breast cancer: a case–control study in Uruguay. Int J Cancer. 1998;76:491–4.CrossRefPubMed
8.
Ronco A, De Stefani E, Boffetta P, Deneo-Pellegrini H, Mendilaharsu M, Leborgne F. Vegetables, fruits, and related nutrients and risk of breast cancer: a case–control study in Uruguay. Nutr Cancer. 1999;35:111–9.CrossRefPubMed
9.
De Stefani E, Correa P, Ronco A, Mendilaharsu M, Guidobono M, Deneo-Pellegrini H. Dietary fiber and risk of breast cancer: a case–control study in Uruguay. Nutr Cancer. 1997;28:14–9.CrossRefPubMed
10.
Ronco AL, De Stéfani E, Dáttoli R. Dairy foods and risk of breast cancer: a case–control study in Montevideo, Uruguay. Eur J Cancer Prev. 2002;11:457–63.CrossRefPubMed
11.
Ronco AL, de Stefani E, Aune D, Boffetta P, Deneo-Pellegrini H, Acosta G, et al. Nutrient patterns and risk of breast cancer in Uruguay. Asian Pacific J Cancer Prev. 2010;11:519–24.
12.
Delgado L, Fernández G, González A, Bressac-de Paillerets B, Gualco G, Bombled J, et al. Hereditary breast cancer associated with a germline BRCA2 mutation in identical female twins with similar disease expression. Cancer Genet Cytogenet. 2002;133:24–8.CrossRefPubMed
13.
Ronco AL, Stoll M, De Stéfani E, Maisonneuve JE, Mendoza BA, Deneo-Pellegrini H. Rh factor, family history and risk of breast cancer: a case–control study in Uruguay. Cancer Detect Prev. 2009;32:277–85.CrossRefPubMed
14.
Delgado L, Fernández G, Grotiuz G, Cataldi S, González A, Lluveras N, et al. BRCA1 and BRCA2 germline mutations in Uruguayan breast and breast-ovarian cancer families. Identification of novel mutations and unclassified variants. Breast Cancer Res Treat. 2011;128:211–8.CrossRefPubMed
15.
Fejerman L, John EM, Huntsman S, Beckman K, Choudhry S, Perez-Stable E, et al. Genetic ancestry and risk of breast cancer among U.S. Latinas. Cancer Res. 2008;68:9723–8.CrossRefPubMedPubMedCentral
16.
Fejerman L, Romieu I, John EM, Lazcano-Ponce E, Huntsman S, Beckman KB, et al. European ancestry is positively associated with breast cancer risk in Mexican women. Cancer Epidemiol Biomarkers Prev. 2010;2050:1–9.
17.
Hidalgo PC, Bengochea M, Abilleira D, Cabrera A, Alvarez I. Genetic admixture estimate in the Uruguayan population based on the loci LDLR, GYPA, HBGG, GC and D7S8. Int J Hum Genet. 2005;5:217–22.
18.
Bonilla C, Bertoni B, González S, Cardoso H, Brum-Zorrilla N, Sans M. Substantial Native American female contribution to the population of Tacuarembó, Uruguay, reveals past episodes of sex-biased gene flow. Am J Hum Biol. 2004;16:289–97.CrossRefPubMed
19.
Gascue C, Mimbacas A, Sans M, Gallino JP, Bertoni B, Hidalgo P, et al. Frequencies of the four major Amerindian mtDNA haplogroups in the population of Montevideo, Uruguay. Hum Biol. 2005;77:873–8.CrossRefPubMed
20.
Pagano S, Sans M, Pimenoff V, Cantera AM, Alvarez JC, Lorente JA, et al. Assessment of HV1 and HV2 mtDNA variation for forensic purposes in an Uruguayan population sample. J Forensic Sci. 2005;50:1239–42.PubMed
21.
Sans M, Merriwether DA, Hidalgo PC, Bentancor N, Weimer TA, Franco MHLP, et al. Population structure and admixture in Cerro Largo, Uruguay, based on blood markers and mitochondrial DNA polymorphisms. Am J Hum Biol. 2006;18:513–24.CrossRefPubMed
22.
Sans M, Salzano FM, Chakraborty R. Historical genetics in Uruguay: estimates of biological origins and their problems. Hum Biol. 1997;69:161–70.PubMed
23.
Sauer S, Gut I. Genotyping single-nucleotide polymorphisms by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry. J Chromatogr B. 2002;782:73–87.CrossRef
24.
Giri VN, Egleston B, Ruth K, Uzzo RG, Chen DYT, Buyyounouski M, et al. Race, genetic West African ancestry, and prostate cancer prediction by prostate-specific antigen in prospectively screened high-risk men. Cancer Prev Res. 2009;2:244–50.CrossRef
25.
Pritchard JK, Stephens M, Donnelly P. Inference of population structure using multilocus genotype data. Genetics. 2000;155:945–59.PubMedPubMedCentral
26.
Salzano FM, Sans M. Interethnic admixture and the evolution of Latin American populations. Genet Mol Biol. 2014;1(suppl):151–70.CrossRef
27.
Wallace DC, Torroni A. American Indian prehistory as written in the mitochondrial DNA: a review. Hum Biol. 1992;64:403–16.PubMed
28.
Vigilant L, Pennington R, Harpending H, Kocher TD, Wilson AC. Mitochondrial DNA sequences in single hairs from a southern African population. Proc Natl Acad Sci U S A. 1989;86:9350–4.CrossRefPubMedPubMedCentral
29.
Sans M, Figueiro G, Ackermann E, Barreto I, Egana A, Bertoni B, et al. Mitochondrial DNA in Basque-descendants from the city of Trinidad, Uruguay: Uruguayan- or Basque-like population. Hum Biol. 2011;83:55-70.
30.
Martínez-Cruzado JC, Toro-Labrador G, Viera-Vera J, Rivera-Vega MY, Startek J, Latorre-Esteves M, et al. Reconstructing the population history of Puerto Rico by means of mtDNA phylogeographic analysis. Am J Phys Anthropol. 2005;128:131–55.CrossRefPubMed
31.
Nicholas KB, Nicholas HBJ. GeneDoc: a tool for editing and annotating multiple sequence alignments. 1997.
32.
Macaulay V, Richards M, Hickey E, Vega E, Cruciani F, Guida V, et al. The emerging tree of West Eurasian mtDNAs: a synthesis of control-region sequences and RFLPs. Am J Hum Genet. 1999;64:232–49.CrossRefPubMedPubMedCentral
33.
Achilli A, Rengo C, Magri C, Battaglia V, Olivieri A, Scozzari R, et al. The molecular dissection of mtDNA haplogroup H confirms that the Franco-Cantabrian glacial refuge was a major source for the European gene pool. Am J Hum Genet. 2004;75:910–8.CrossRefPubMedPubMedCentral
34.
Achilli A, Perego UA, Bravi CM, Coble MD, Kong Q-P, Woodward SR, et al. The phylogeny of the four pan-American MtDNA haplogroups: implications for evolutionary and disease studies. PLoS One. 2008;3:e1764.CrossRefPubMedPubMedCentral
35.
Salas A, Richards M, De la Fe T, Lareu M-V, Sobrino B, Sánchez-Diz P, et al. The making of the African mtDNA landscape. Am J Hum Genet. 2002;71:1082–111.CrossRefPubMedPubMedCentral
36.
Simoni L, Calafell F, Pettener D, Bertranpetit J, Barbujani G. Geographic patterns of mtDNA diversity in Europe. Am J Hum Genet. 2000;66:262–78.CrossRefPubMed
37.
Tamm E, Kivisild T, Reidla M, Metspalu M, Smith DG, Mulligan CJ, et al. Beringian standstill and spread of Native American founders. PLoS One. 2007;2:e829.CrossRefPubMedPubMedCentral
38.
Van Oven M, Kayser M. Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Hum Mutat. 2009;30:E386–94.CrossRefPubMed
39.
Lee HY, Song I, Ha E, Cho S-B, Yang WI, Shin K-J. mtDNAmanager: a Web-based tool for the management and quality analysis of mitochondrial DNA control-region sequences. BMC Bioinformatics. 2008;9:483.CrossRefPubMedPubMedCentral
40.
Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet. 2007;81:559–75.CrossRefPubMedPubMedCentral
41.
Zeggini E, Scott LJ, Saxena R, Voight BF, Marchini JL, de Bakker PIW, et al. Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nat Genet. 2008;40:638–45.CrossRefPubMedPubMedCentral
42.
Johansson A, Marroni F, Hayward C, Franklin CS, Kirichenko AV, Jonasson I, et al. Common variants in the JAZF1 gene associated with height identified by linkage and genome-wide association analysis. Hum Mol Genet. 2009;18:373–80.CrossRefPubMed
43.
Thomas G, Jacobs KB, Yeager M, Kraft P, Wacholder S, Orr N, et al. Multiple loci identified in a genome-wide association study of prostate cancer. Nat Genet. 2008;40:310–5.CrossRefPubMed
44.
Prokunina-Olsson L, Fu Y-P, Tang W, Jacobs KB, Hayes RB, Kraft P, et al. Refining the prostate cancer genetic association within the JAZF1 gene on chromosome 7p15.2. Cancer Epidemiol Biomarkers Prev. 2010;19:1349–55.
45.
Slattery ML, John EM, Torres-Mejia G, Lundgreen A, Herrick JS, Baumgartner KB, et al. Genetic variation in genes involved in hormones, inflammation and energetic factors and breast cancer risk in an admixed population. Carcinogenesis. 2012;33:1512–21.CrossRefPubMedPubMedCentral
46.
Salas A, García-Magariños M, Logan I, Bandelt H-J. The saga of the many studies wrongly associating mitochondrial DNA with breast cancer. BMC Cancer. 2014;14:659.CrossRefPubMedPubMedCentral
47.
Bai R-K, Leal SM, Covarrubias D, Liu A, Wong L-JC. Mitochondrial genetic background modifies breast cancer risk. Cancer Res. 2007;67:4687–94.CrossRefPubMed
48.
Czarnecka AM, Krawczyk T, Plak K, Klemba A, Zdrozny M, Arnold RS, et al. Mitochondrial genotype and breast cancer predisposition. Oncol Rep. 2010;24:1521–34.PubMed
49.
Gutiérrez Povedano C, Salgado J, Gil C, Robles M, Patiño-García A, García-Foncillas J. Analysis of BRCA1 and mtDNA haplotypes and mtDNA polymorphism in familial breast cancer. Mitochondrial DNA. 2013;1736:1–5.
50.
Mosquera-Miguel A, Alvarez-Iglesias V, Carracedo A, Salas A, Vega A, Milne R, et al. Is mitochondrial DNA variation associated with sporadic breast cancer risk? Cancer Res. 2008;68:623–5. author reply 624.CrossRefPubMed
51.
Gallardo M, Silva A, Rubio L, Alvarez C, Torrealba C, Salinas M, et al. Incidence of BRCA1 and BRCA2 mutations in 54 Chilean families with breast/ovarian cancer, genotype-phenotype correlations. Breast Cancer Res Treat. 2006;95:81–7.CrossRefPubMed
52.
Tommasi S, Favia P, Weigl S, Bianco A, Pilato B, Russo L, et al. Mitochondrial DNA variants and risk of familial breast cancer: an exploratory study. Int J Oncol. 2014;44:1691–8.PubMed
53.
Salas A, Fachal L, Marcos-Alonso S, Vega A, Martinón-Torres F. Investigating the role of mitochondrial haplogroups in genetic predisposition to meningococcal disease. PLoS One. 2009;4:e8347.CrossRefPubMedPubMedCentral
54.
Campbell DD, Parra MV, Duque C, Gallego N, Franco L, Tandon A, et al. Amerind ancestry, socioeconomic status and the genetics of type 2 diabetes in a Colombian population. PLoS One. 2012;7:e33570.CrossRefPubMedPubMedCentral
55.
Ruiz-Linares A, Adhikari K, Acuña-Alonzo V, Quinto-Sanchez M, Jaramillo C, Arias W, et al. Admixture in Latin America: Geographic Structure, Phenotypic Diversity and Self-Perception of Ancestry Based on 7,342 Individuals. PLoS Genet. 2014;10:e1004572.CrossRefPubMedPubMedCentral
56.
Florez JC, Price AL, Campbell D, Riba L, Parra MV, Yu F, et al. Strong association of socioeconomic status with genetic ancestry in Latinos: implications for admixture studies of type 2 diabetes. Diabetologia. 2009;52:1528–36.CrossRefPubMedPubMedCentral
57.
Pereira L, Zamudio R, Soares-Souza G, Herrera P, Cabrera L, Hooper CC, et al. Socioeconomic and nutritional factors account for the association of gastric cancer with Amerindian ancestry in a Latin American admixed population. PLoS One. 2012;7:e41200.CrossRefPubMedPubMedCentral
58.
Hines LM, Risendal B, Slattery ML, Baumgartner KB, Giuliano AR, Sweeney C, et al. Comparative analysis of breast cancer risk factors among Hispanic and non-Hispanic white women. Cancer. 2010;116:3215–23.CrossRefPubMedPubMedCentral
Metadata
Title
Breast cancer risk and genetic ancestry: a case–control study in Uruguay
Authors
Carolina Bonilla
Bernardo Bertoni
Pedro C Hidalgo
Nora Artagaveytia
Elizabeth Ackermann
Isabel Barreto
Paula Cancela
Mónica Cappetta
Ana Egaña
Gonzalo Figueiro
Silvina Heinzen
Stanley Hooker
Estela Román
Mónica Sans
Rick A Kittles
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Women's Health / Issue 1/2015
Electronic ISSN: 1472-6874
DOI
https://doi.org/10.1186/s12905-015-0171-8

Other articles of this Issue 1/2015

BMC Women's Health 1/2015 Go to the issue

Research article

Predictors of modern contraceptive methods use among married women of reproductive age groups in Western Ethiopia: a community based cross-sectional study

Research article

Symptomatic presentation with cervical cancer in Uganda: a qualitative study assessing the pathways to diagnosis in a low-income country

Research article

Postpartum contraceptive use in Gondar town, Northwest Ethiopia: a community based cross-sectional study

Research article

Differentials in the prevalence of anemia among non-pregnant, ever-married women in Bangladesh: multilevel logistic regression analysis of data from the 2011 Bangladesh Demographic and Health Survey

Research article

Group psychological intervention for postnatal depression: a nested qualitative study with British South Asian women

Research article

Stigma against HIV/AIDS among female sex workers and general migrant women in eastern China