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Elad Ziv - One of the best experts on this subject based on the ideXlab platform.
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interaction between common breast cancer susceptibility variants Genetic Ancestry and nonGenetic risk factors in hispanic women
Cancer Epidemiology Biomarkers & Prevention, 2015Co-Authors: Laura Fejerman, Esther M. John, Elad Ziv, Mariana C. Stern, Gabriela Torresmejia, Lisa M Hines, Roger K Wolff, Kathy B Baumgartner, Anna R Giuliano, Eliseo J PerezstableAbstract:Background: Most Genetic variants associated with breast cancer risk have been discovered in women of European Ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene–environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by Ancestry interaction in this population. Methods: We estimated Genetic Ancestry with a set of 104 Ancestry-informative markers selected to discriminate between Indigenous American and European Ancestry. We used logistic regression models to evaluate main effects and interactions. Results: We found that the rs13387042–2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74–1.20), 1.20 (0.94–1.53), and 1.49 (1.28–1.75) for current, former, and never hormone therapy users, respectively, P interaction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72–1.42), 1.19 (0.98–1.45), and 1.69 (1.26–2.26) for never, 12 months breastfeeding, respectively, P interaction 0.014]. Conclusions: The correlation between Genetic Ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and Genetic Ancestry in Hispanic women. Impact: These results highlight the importance of understanding the interplay between Genetic Ancestry, Genetics, and nonGenetic risk factors and their contribution to breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1731–8. ©2015 AACR .
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Genetic Ancestry and risk of mortality among U.S. Latinas with breast cancer
Cancer research, 2013Co-Authors: Laura Fejerman, Esther M. John, Scott Huntsman, Eliseo J. Pérez-stable, Mariana C. Stern, Christopher A. Haiman, Elad ZivAbstract:Multiple studies have reported that Latina women in the United States are diagnosed with breast cancer at more advanced stages and have poorer survival than non-Latina White women. However, Latinas are a heterogeneous group with individuals having different proportions of European, Indigenous American, and African Genetic Ancestry. In this study, we evaluated the association between Genetic Ancestry and survival after breast cancer diagnosis among 899 Latina women from the San Francisco Bay area. Genetic Ancestry was estimated from single-nucleotide polymorphisms from an Affymetrix 6.0 array and we used Cox proportional hazards models to evaluate the association between Genetic Ancestry and breast cancer-specific mortality (tests were two-sided). Women were followed for an average of 9 years during which 75 died from breast cancer. Our results showed that Individuals with higher Indigenous American Ancestry had increased risk of breast cancer-specific mortality [HR: 1.57 per 25% increase in Indigenous American Ancestry; 95% confidence interval (CI): 1.08-2.29]. Adjustment for demographic factors, tumor characteristics, and some treatment information did not explain the observed association (HR: 1.75; 95%CI, 1.12-2.74). In an analysis in which Ancestry was dichotomized, the hazard of mortality showed a two-fold increase when comparing women with less than 50% Indigenous American Ancestry to women with 50% or more [HR, 1.89, 95%CI, 1.10-3.24]. This was also reflected by Kaplan-Meier survival estimates (P for log-rank test of 0.003). Overall, results suggest that Genetic factors and/or unmeasured differences in treatment or access to care should be further explored to understand and reduce ethnic disparities in breast cancer outcomes.
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Recent advances of Genetic Ancestry testing in biomedical research and direct to consumer testing
Clinical genetics, 2009Co-Authors: Marc Via, Elad Ziv, Esteban G. BurchardAbstract:In the post-Human Genome Project era, the debate on the concept of race/ethnicity and its implications for biomedical research are dependent on two critical issues: whether and how to classify individuals and whether biological factors play a role in health disparities. The advent of reliable estimates of Genetic (or biogeographic) Ancestry has provided this debate with a quantitative and more objective tool. The estimation of Genetic Ancestry allows investigators to control for population stratification in association studies and helps to detect biological causation behind population-specific differences in disease and drug response. New techniques such as admixture mapping can specifically detect population-specific risk alleles for a disease in admixed populations. However, researchers have to be mindful of the correlation between Genetic Ancestry and socioeconomic and environmental factors that could underlie these differences. More importantly, researchers must avoid the stigmatization of individuals based on perceived or real Genetic risks. The latter point will become increasingly sensitive as several 'for profit companies' are offering Ancestry and Genetic testing directly to consumers and the consequences of the spread of the services of these companies are still unforeseeable.
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Genetic Ancestry and risk of breast cancer among U.S. Latinas.
Cancer research, 2008Co-Authors: Laura Fejerman, Esteban G. Burchard, Shweta Choudhry, Esther M. John, Scott Huntsman, Kenny Beckman, Eliseo J. Pérez-stable, Elad ZivAbstract:US Latinas have a lower incidence of breast cancer compared to non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their Genetic Ancestry from Europeans and Indigenous Americans. We used Genetic markers to estimate the Ancestry of Latina breast cancer cases and controls and assessed the association with Genetic Ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 Ancestry informative markers (AIMs) in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco (SF) Bay area and estimated Genetic Ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (CI) for Ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European Ancestry was associated with increased breast cancer risk. The odds ratio for a 25% increase in European Ancestry was 1.79 (95% CI: 1.28–2.79, p
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Genetic Ancestry and risk of breast cancer among u s latinas
Cancer Research, 2008Co-Authors: Laura Fejerman, Esteban G. Burchard, Shweta Choudhry, Esther M. John, Scott Huntsman, Kenny Beckman, Eliseo J Perezstable, Elad ZivAbstract:US Latinas have a lower incidence of breast cancer compared to non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their Genetic Ancestry from Europeans and Indigenous Americans. We used Genetic markers to estimate the Ancestry of Latina breast cancer cases and controls and assessed the association with Genetic Ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 Ancestry informative markers (AIMs) in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco (SF) Bay area and estimated Genetic Ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (CI) for Ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European Ancestry was associated with increased breast cancer risk. The odds ratio for a 25% increase in European Ancestry was 1.79 (95% CI: 1.28–2.79, p<0.001). When known risk factors and place of birth were adjusted for, the association with European Ancestry was attenuated but remained statistically significant (OR=1.39; 95% CI: 1.06–2.11, p=0.013). Further work is needed to determine if the association is due to Genetic differences between populations or possibly due to environmental factors not measured.
Sunny Kim - One of the best experts on this subject based on the ideXlab platform.
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association of Genetic Ancestry with striatal dopamine d2 d3 receptor availability
Molecular Psychiatry, 2018Co-Authors: Corinde E Wiers, Par C Towb, Colin A Hodgkinson, Peihong Shen, Clara Freeman, Gregg Miller, Elsa Lindgren, Ehsan Shokrikojori, şukru Baris Demiral, Sunny KimAbstract:Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between Genetic Ancestry and striatal D2R. Here, we show that Ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes). Effects of ethnicity on D2R were not driven by variation in dopaminergic candidate genes. Instead, candidate gene associations with striatal D2R were diminished when correcting for Ancestry. These findings imply that future studies investigating D2 receptor genes should covary for Genetic Ancestry or study homogeneous populations. Moreover, Ancestry studies on human neurobiology should control for socioeconomic differences between ethnic groups.
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Association of Genetic Ancestry with striatal dopamine D2/D3 receptor availability.
Molecular psychiatry, 2017Co-Authors: Corinde E Wiers, Par C Towb, Colin A Hodgkinson, Peihong Shen, Clara Freeman, Gregg Miller, Elsa Lindgren, şukru Baris Demiral, Ehsan Shokri-kojori, Sunny KimAbstract:Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between Genetic Ancestry and striatal D2R. Here, we show that Ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P
Corinde E Wiers - One of the best experts on this subject based on the ideXlab platform.
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association of Genetic Ancestry with striatal dopamine d2 d3 receptor availability
Molecular Psychiatry, 2018Co-Authors: Corinde E Wiers, Par C Towb, Colin A Hodgkinson, Peihong Shen, Clara Freeman, Gregg Miller, Elsa Lindgren, Ehsan Shokrikojori, şukru Baris Demiral, Dardo TomasiAbstract:Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between Genetic Ancestry and striatal D2R. Here, we show that Ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes). Effects of ethnicity on D2R were not driven by variation in dopaminergic candidate genes. Instead, candidate gene associations with striatal D2R were diminished when correcting for Ancestry. These findings imply that future studies investigating D2 receptor genes should covary for Genetic Ancestry or study homogeneous populations. Moreover, Ancestry studies on human neurobiology should control for socioeconomic differences between ethnic groups.
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association of Genetic Ancestry with striatal dopamine d2 d3 receptor availability
Molecular Psychiatry, 2018Co-Authors: Corinde E Wiers, Par C Towb, Colin A Hodgkinson, Peihong Shen, Clara Freeman, Gregg Miller, Elsa Lindgren, Ehsan Shokrikojori, şukru Baris Demiral, Sunny KimAbstract:Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between Genetic Ancestry and striatal D2R. Here, we show that Ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P<0.0001), while correcting for age, sex, BMI, education, smoking status, and estimated socioeconomic status (ZIP codes). Effects of ethnicity on D2R were not driven by variation in dopaminergic candidate genes. Instead, candidate gene associations with striatal D2R were diminished when correcting for Ancestry. These findings imply that future studies investigating D2 receptor genes should covary for Genetic Ancestry or study homogeneous populations. Moreover, Ancestry studies on human neurobiology should control for socioeconomic differences between ethnic groups.
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Association of Genetic Ancestry with striatal dopamine D2/D3 receptor availability.
Molecular psychiatry, 2017Co-Authors: Corinde E Wiers, Par C Towb, Colin A Hodgkinson, Peihong Shen, Clara Freeman, Gregg Miller, Elsa Lindgren, şukru Baris Demiral, Ehsan Shokri-kojori, Sunny KimAbstract:Despite ethnic differences in allele frequencies of variants in dopaminergic genes associated with dopamine D2/D3 receptor availability (D2R), no study to date has investigated the relationship between Genetic Ancestry and striatal D2R. Here, we show that Ancestry-informative markers significantly predict dorsal striatal D2R in 117 healthy ethnically diverse residents of the New York metropolitan area using Positron Emission Tomography (PET) with [11C]raclopride (P
Rick A Kittles - One of the best experts on this subject based on the ideXlab platform.
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Leveraging Genetic Ancestry to study health disparities.
American journal of physical anthropology, 2020Co-Authors: Ken Batai, Stanley Hooker, Rick A KittlesAbstract:Research to understand human genomic variation and its implications in health has great potential to contribute in the reduction of health disparities. Biological anthropology can play important roles in genomics and health disparities research using a biocultural approach. This paper argues that racial/ethnic categories should not be used as a surrogate for sociocultural factors or global genomic clusters in biomedical research or clinical settings, because of the high Genetic heterogeneity that exists within traditional racial/ethnic groups. Genetic Ancestry is used to show variation in ancestral genomic contributions to recently admixed populations in the United States, such as African Americans and Hispanic/Latino Americans. Genetic Ancestry estimates are also used to examine the relationship between Ancestry-related biological and sociocultural factors affecting health disparities. To localize areas of genomes that contribute to health disparities, admixture mapping and genome-wide association studies (GWAS) are often used. Recent GWAS have identified many Genetic variants that are highly differentiated among human populations that are associated with disease risk. Some of these are population-specific variants. Many of these variants may impact disease risk and help explain a portion of the difference in disease burden among racial/ethnic groups. Genetic Ancestry is also of particular interest in precision medicine and disparities in drug efficacy and outcomes. By using Genetic Ancestry, we can learn about potential biological differences that may contribute to the heterogeneity observed across self-reported racial groups.
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Association of Genetic Ancestry With DNA Methylation Changes in Prostate Cancer Disparity.
Anticancer research, 2019Co-Authors: Victor Apprey, Rick A Kittles, Songping Wang, Wei Tang, William M. Southerland, Michael Ittmann, Bernard Kwabi-addoAbstract:BACKGROUND We hypothesized that Ancestry-mediated methylated DNA changes may drive racial and ethnic disparity in prostate cancer (PCa). To test this hypothesis, we analyzed Genetic Ancestry and association with DNA methylation changes in PCa disparity. MATERIALS AND METHODS Pyrosequencing and Ancestry informative markers were used for DNA methylation and Genetic Ancestry testing, respectively. RESULTS Using Spearman rho rank correlation test, the data demonstrated significant (p
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Genetic Ancestry analysis reveals misclassification of commonly used cancer cell lines
Cancer Epidemiology Biomarkers & Prevention, 2019Co-Authors: Stanley Hooker, Leanne Woodsburnham, Madhavi Bathina, Stacy M Lloyd, Priyatham Gorjala, Ranjana Mitra, Larisa Nonn, Sean K Kimbro, Rick A KittlesAbstract:Background: Given the scarcity of cell lines from underrepresented populations, it is imperative that Genetic Ancestry for these cell lines is characterized. Consequences of cell line mischaracterization include squandered resources and publication retractions. Methods: We calculated Genetic Ancestry proportions for 15 cell lines to assess the accuracy of previous race/ethnicity classification and determine previously unknown estimates. DNA was extracted from cell lines and genotyped for Ancestry informative markers (AIMs) representing West African (WA), Native American (NA), and European (EUR) Ancestry. Results: Of the cell lines tested, all previously classified as White/Caucasian were accurately described with mean EUR Ancestry proportions of 97%. Cell lines previously classified as Black/African American were not always accurately described. For instance, the 22Rv1 prostate cancer cell line was recently found to carry mixed Genetic Ancestry using a much smaller panel of markers. However, our more comprehensive analysis determined the 22Rv1 cell line carries 99% EUR Ancestry. Most notably, the E006AA-hT prostate cancer cell line, classified as African American, was found to carry 92% EUR Ancestry. We also determined the MDA-MB-468 breast cancer cell line carries 23% NA Ancestry suggesting possible Afro-Hispanic/Latina Ancestry. Conclusions: Our results suggest predominantly EUR Ancestry for the White/Caucasian-designated cell lines, yet high variance in Ancestry for the Black/African American-designated cell lines. Additionally, we revealed an extreme misclassification of the E006AA-hT cell line. Impact: Genetic Ancestry estimates offer more sophisticated characterization leading to better contextualization of findings. Ancestry estimates should be provided for all cell lines to avoid erroneous conclusions in disparities literature.
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Abstract C34: Association of Genetic Ancestry with colorectal tumor characteristics in Puerto Rican Hispanics
Epidemiology Lifestyle and Genetics, 2016Co-Authors: Julyann Pérez-mayoral, Rick A Kittles, Marievelisse Soto, Maria Gonzalez-pons, Belisa Suárez, Myrta I. Olivera, Ebony Shah, Marcia Cruz-correaAbstract:Background: Colorectal cancer (CRC) is the 1st cause of cancer deaths in Puerto Rican Hispanics (PRH). Even though PRH have a lower incidence of CRC, when compared to other ethnic groups, their mortality rates are higher. As the 2nd largest Hispanic population on the United States, the increased CRC mortality rates for this ethnic group have a large socio-economic burden. The CRC epidemiologic data supports the importance of studying this cancer as a health disparity in PRH. The Genetic background of the Puerto Rican population, which is mix of European, African and Amerindian races, could account, at least in part, for the differences observed in the CRC mortality rates for this population. The objective of this project was to assess the role of Genetic Ancestry in CRC risk and clinicopathological features of CRC tumors in the PRH population. Methods: We used a panel of 105 Ancestry informative markers (AIMs) to estimate Genetic Ancestry in 224 PRH CRC cases and 202 PRH controls. Additionally, we examined the association of Genetic Ancestry estimates with CRC risk and clinicopathological characteristics of CRC tumors in our study population using the Bayesian Markov Chain Monte Carlo method implemented in the software STRUCTURE. Logistic regression analysis was used to determine the association of Genetic Ancestry with disease risk. Pearson9s Chi-Square and Fisher9s Exact Test was used to determine the association of categorical values of Genetic Ancestry with tumor clinicopathological characteristics. Results: Our results showed that the Genetic Ancestry mean estimates for the PRH population were 60% for European, 21% for African and 19% for Amerindian. No association of Genetic Ancestry with CRC risk in the PRH population was found in our study (OR= 0.86 [0.43-1.69], p=0.655). However, Genetic Ancestry was found to have a significant role on the CRC tumor characteristics of the studied population. High African Ancestry (>21.0%) was associated with distal tumor location, when compared to low African Ancestry (≤ 21.0%) (p=0.012). Furthermore, low Amerindian Ancestry (≤ 19.2%) was associated with poorly differentiated tumors (p= 0.022). Conclusion: The preliminary results presented in this study show that Genetic Ancestry is associated with tumor location and differentiation, both associated with CRC prognosis. Additional studies are needed to fully elucidate the role of Genetic Ancestry in CRC susceptibility and prognosis. Citation Format: Julyann Perez-Mayoral, Marievelisse Soto, Maria Gonzalez-Pons, Belisa Suarez, Myrta I. Olivera, Ebony Shah, Rick Kittles, Marcia R. Cruz-Correa. Association of Genetic Ancestry with colorectal tumor characteristics in Puerto Rican Hispanics. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr C34.
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Genetic Ancestry and odds of prostate cancer diagnosis in African American and European American men.
Journal of Clinical Oncology, 2016Co-Authors: Yaw A. Nyame, Ken Batai, Ebony Shah, Adam B. Murphy, Maria Ruden, Courtney M.p. Hollowell, Andre Kajdacsy-balla, William J. Catalona, Rick A KittlesAbstract:86 Background: Although ethnic differences in disease incidence among African American (AA) men may reflect differences in screening behaviors and behavioral and socioeconomic factors, Genetic Ancestry may be a factor. This study will investigate the association between West African and Native American Genetic Ancestry and PCa diagnosis. Methods: We enrolled 40-79 year-old men who were undergoing prostate biopsy or routine PSA screening at outpatient urology clinics in Chicago, IL. Blood was drawn at the time of enrollment for the genotyping of 105 Ancestry informative markers. West African (WAA), European (EA), and Native American (NAA) Genetic Ancestry was estimated using the Bayesian Markov Chain-Monte Carlo method implemented in the program STRUCTURE. Univariate analysis was performed by Wilcoxon rank-sum test for continuous variables. Unconditional binary logistic regression models were used to estimate odds ratios for the likelihood of PCa diagnosis and for the odds of having high-risk PCa relative ...
Laura Fejerman - One of the best experts on this subject based on the ideXlab platform.
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Abstract IA12: Variation in Genetic Ancestry proportions among Latinos and its impact on cancer risk, prediction, and outcomes
Heterogeneity within US Latinos, 2017Co-Authors: Laura FejermanAbstract:Latinos are a heterogeneous group, encompassing individuals with diverse Genetic and sociocultural backgrounds. Reports on U.S. cancer incidence rates and cancer mortality in Latinos have only recently started to provide information by national origin, which has unveiled disparities that were not apparent in analyses that grouped all Latinos together. Genetic Ancestry is another important factor in the characterization of Latin American populations. Mainly composed of European, Indigenous American and African ancestral influences, it can reflect socioeconomic/sociocultural differences as well as Genetic ones. There have been studies testing the association between Genetic Ancestry and cancer risk, and Genetic Ancestry and cancer survival. However, there is a lack of published investigations assessing the performance of cancer risk prediction models in Latinos with different Ancestry proportions. In this presentation, I will provide an overview of what we know about cancer risk and mortality in Latinos with different Ancestry proportions and present preliminary results of an ongoing study of breast cancer risk prediction in U.S. Latinas. Citation Format: Laura Fejerman. Variation in Genetic Ancestry proportions among Latinos and its impact on cancer risk, prediction, and outcomes. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr IA12.
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interaction between common breast cancer susceptibility variants Genetic Ancestry and nonGenetic risk factors in hispanic women
Cancer Epidemiology Biomarkers & Prevention, 2015Co-Authors: Laura Fejerman, Esther M. John, Elad Ziv, Mariana C. Stern, Gabriela Torresmejia, Lisa M Hines, Roger K Wolff, Kathy B Baumgartner, Anna R Giuliano, Eliseo J PerezstableAbstract:Background: Most Genetic variants associated with breast cancer risk have been discovered in women of European Ancestry, and only a few genome-wide association studies (GWAS) have been conducted in minority groups. This research disparity persists in post-GWAS gene–environment interaction analyses. We tested the interaction between hormonal and lifestyle risk factors for breast cancer, and ten GWAS-identified SNPs among 2,107 Hispanic women with breast cancer and 2,587 unaffected controls, to gain insight into a previously reported gene by Ancestry interaction in this population. Methods: We estimated Genetic Ancestry with a set of 104 Ancestry-informative markers selected to discriminate between Indigenous American and European Ancestry. We used logistic regression models to evaluate main effects and interactions. Results: We found that the rs13387042–2q35(G/A) SNP was associated with breast cancer risk only among postmenopausal women who never used hormone therapy [per A allele OR: 0.94 (95% confidence intervals, 0.74–1.20), 1.20 (0.94–1.53), and 1.49 (1.28–1.75) for current, former, and never hormone therapy users, respectively, P interaction 0.002] and premenopausal women who breastfed >12 months [OR: 1.01 (0.72–1.42), 1.19 (0.98–1.45), and 1.69 (1.26–2.26) for never, 12 months breastfeeding, respectively, P interaction 0.014]. Conclusions: The correlation between Genetic Ancestry, hormone replacement therapy use, and breastfeeding behavior partially explained a previously reported interaction between a breast cancer risk variant and Genetic Ancestry in Hispanic women. Impact: These results highlight the importance of understanding the interplay between Genetic Ancestry, Genetics, and nonGenetic risk factors and their contribution to breast cancer risk. Cancer Epidemiol Biomarkers Prev; 24(11); 1731–8. ©2015 AACR .
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Genetic Ancestry and risk of mortality among U.S. Latinas with breast cancer
Cancer research, 2013Co-Authors: Laura Fejerman, Esther M. John, Scott Huntsman, Eliseo J. Pérez-stable, Mariana C. Stern, Christopher A. Haiman, Elad ZivAbstract:Multiple studies have reported that Latina women in the United States are diagnosed with breast cancer at more advanced stages and have poorer survival than non-Latina White women. However, Latinas are a heterogeneous group with individuals having different proportions of European, Indigenous American, and African Genetic Ancestry. In this study, we evaluated the association between Genetic Ancestry and survival after breast cancer diagnosis among 899 Latina women from the San Francisco Bay area. Genetic Ancestry was estimated from single-nucleotide polymorphisms from an Affymetrix 6.0 array and we used Cox proportional hazards models to evaluate the association between Genetic Ancestry and breast cancer-specific mortality (tests were two-sided). Women were followed for an average of 9 years during which 75 died from breast cancer. Our results showed that Individuals with higher Indigenous American Ancestry had increased risk of breast cancer-specific mortality [HR: 1.57 per 25% increase in Indigenous American Ancestry; 95% confidence interval (CI): 1.08-2.29]. Adjustment for demographic factors, tumor characteristics, and some treatment information did not explain the observed association (HR: 1.75; 95%CI, 1.12-2.74). In an analysis in which Ancestry was dichotomized, the hazard of mortality showed a two-fold increase when comparing women with less than 50% Indigenous American Ancestry to women with 50% or more [HR, 1.89, 95%CI, 1.10-3.24]. This was also reflected by Kaplan-Meier survival estimates (P for log-rank test of 0.003). Overall, results suggest that Genetic factors and/or unmeasured differences in treatment or access to care should be further explored to understand and reduce ethnic disparities in breast cancer outcomes.
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Genetic Ancestry and risk of breast cancer among U.S. Latinas.
Cancer research, 2008Co-Authors: Laura Fejerman, Esteban G. Burchard, Shweta Choudhry, Esther M. John, Scott Huntsman, Kenny Beckman, Eliseo J. Pérez-stable, Elad ZivAbstract:US Latinas have a lower incidence of breast cancer compared to non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their Genetic Ancestry from Europeans and Indigenous Americans. We used Genetic markers to estimate the Ancestry of Latina breast cancer cases and controls and assessed the association with Genetic Ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 Ancestry informative markers (AIMs) in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco (SF) Bay area and estimated Genetic Ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (CI) for Ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European Ancestry was associated with increased breast cancer risk. The odds ratio for a 25% increase in European Ancestry was 1.79 (95% CI: 1.28–2.79, p
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Genetic Ancestry and risk of breast cancer among u s latinas
Cancer Research, 2008Co-Authors: Laura Fejerman, Esteban G. Burchard, Shweta Choudhry, Esther M. John, Scott Huntsman, Kenny Beckman, Eliseo J Perezstable, Elad ZivAbstract:US Latinas have a lower incidence of breast cancer compared to non-Latina White women. This difference is partially explained by differences in the prevalence of known risk factors. Genetic factors may also contribute to this difference in incidence. Latinas are an admixed population with most of their Genetic Ancestry from Europeans and Indigenous Americans. We used Genetic markers to estimate the Ancestry of Latina breast cancer cases and controls and assessed the association with Genetic Ancestry, adjusting for reproductive and other risk factors. We typed a set of 106 Ancestry informative markers (AIMs) in 440 Latina women with breast cancer and 597 Latina controls from the San Francisco (SF) Bay area and estimated Genetic Ancestry using a maximum likelihood method. Odds ratios (OR) and 95% confidence intervals (CI) for Ancestry modeled as a continuous variable were estimated using logistic regression with known risk factors included as covariates. Higher European Ancestry was associated with increased breast cancer risk. The odds ratio for a 25% increase in European Ancestry was 1.79 (95% CI: 1.28–2.79, p<0.001). When known risk factors and place of birth were adjusted for, the association with European Ancestry was attenuated but remained statistically significant (OR=1.39; 95% CI: 1.06–2.11, p=0.013). Further work is needed to determine if the association is due to Genetic differences between populations or possibly due to environmental factors not measured.