Genomic Diversity in Sporadic Breast Cancer in a Latin American Population

Among Latin American women, breast cancer incidences vary across populations. Uruguay and Argentina have the highest rates in South America, which are mainly attributed to strong, genetic European contributions. Most genetic variants associated with breast cancer were described in European populations. However, the vast majority of genetic contributors to breast cancer risk remain unknown. Here, we report the results of a candidate gene association study of sporadic breast cancer in 176 cases and 183 controls in the Uruguayan population. We analyzed 141 variants from 98 loci that have been associated with overall breast cancer risk in European populations. We found weak evidence for the association of risk variants rs294174 (ESR1), rs16886165 (MAP3K1), rs2214681 (CNTNAP2), rs4237855 (VDR), rs9594579 (RANKL), rs8183919 (PTGIS), rs2981582 (FGFR2), and rs1799950 (BRCA1) with sporadic breast cancer. These results provide useful insight into the genetic susceptibility to sporadic breast cancer in the Uruguayan population and support the use of genetic risk scores for individualized screening and prevention.

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A Polygenic Risk Score for Breast Cancer in US Latinas and Latin American Women

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djz174 ◽

2019 ◽

Vol 112 (6) ◽

pp. 590-598 ◽

Cited By ~ 7

Author(s):

Yiwey Shieh ◽

Laura Fejerman ◽

Paul C Lott ◽

Katie Marker ◽

Sarah D Sawyer ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Receiver Operating Characteristic Curve ◽

Latin American ◽

Operating Characteristic ◽

Characteristic Curve ◽

Polygenic Risk ◽

Operating Characteristic Curve ◽

European Populations

Abstract Background More than 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Because most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry. Methods We conducted a pooled case-control analysis of US Latinas and Latin American women (4658 cases and 7622 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (P < 5 × 10–8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression, and assessed discrimination using an area under the receiver operating characteristic curve. We also assessed PRS performance across quartiles of Indigenous American genetic ancestry. All statistical tests were two-sided. Results Of 180 SNPs tested, 142 showed directionally consistent associations compared with European populations, and 39 were nominally statistically significant (P < .05). The PRS was associated with breast cancer risk, with an odds ratio per SD increment of 1.58 (95% confidence interval [CI = 1.52 to 1.64) and an area under the receiver operating characteristic curve of 0.63 (95% CI = 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry. Conclusions The 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry.

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A polygenic risk score for breast cancer in U.S. Latinas and Latin-American women

10.1101/598730 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yiwey Shieh ◽

Laura Fejerman ◽

Paul C. Lott ◽

Katie Marker ◽

Sarah D. Sawyer ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Latin American ◽

African Ancestry ◽

Polygenic Risk Score ◽

Control Analysis ◽

Polygenic Risk ◽

American Women ◽

European Populations

AbstractBackgroundOver 180 single nucleotide polymorphisms (SNPs) associated with breast cancer susceptibility have been identified; these SNPs can be combined into polygenic risk scores (PRS) to predict breast cancer risk. Since most SNPs were identified in predominantly European populations, little is known about the performance of PRS in non-Europeans. We tested the performance of a 180-SNP PRS in Latinas, a large ethnic group with variable levels of Indigenous American, European, and African ancestry.MethodsWe conducted a pooled case-control analysis of U.S. Latinas and Latin-American women (4,658 cases, 7,622 controls). We constructed a 180-SNP PRS consisting of SNPs associated with breast cancer risk (p < 5 × 10−8). We evaluated the association between the PRS and breast cancer risk using multivariable logistic regression and assessed discrimination using area under the receiver operating characteristic curve (AUROC). We also assessed PRS performance across quartiles of Indigenous American genetic ancestry.ResultsOf 180 SNPs tested, 142 showed directionally consistent associations compared with European populations, and 39 were nominally significant (p < 0.05). The PRS was associated with breast cancer risk, with an odds ratio (OR) per standard deviation increment of 1.58 (95% CI 1.52 to 1.64) and AUCROC of 0.63 (95% CI 0.62 to 0.64). The discrimination of the PRS was similar between the top and bottom quartiles of Indigenous American ancestry.ConclusionsThe 180-SNP PRS predicts breast cancer risk in Latinas, with similar performance as reported for Europeans. The performance of the PRS did not vary substantially according to Indigenous American ancestry.

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Do Breast Cancer Risk Scores Work for You?

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/djab052 ◽

2021 ◽

Author(s):

Kathleen E Houlahan

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Scores

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Cases in Precision Medicine: The Role of Polygenic Risk Scores in Breast Cancer Risk Assessment

Annals of Internal Medicine ◽

10.7326/m20-5874 ◽

2020 ◽

Author(s):

Nur Zeinomar ◽

Wendy K. Chung

Keyword(s):

Breast Cancer ◽

Risk Assessment ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Precision Medicine ◽

Cancer Risk Assessment ◽

Risk Scores ◽

Polygenic Risk ◽

Breast Cancer Risk Assessment

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Identification of novel common breast cancer risk variants at the 6q25 locus among Latinas

Breast Cancer Research ◽

10.1186/s13058-018-1085-9 ◽

2019 ◽

Vol 21 (1) ◽

Cited By ~ 12

Author(s):

Joshua Hoffman ◽

◽

Laura Fejerman ◽

Donglei Hu ◽

Scott Huntsman ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Variants

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Glutathione S-transferase M1 (GSTM1) and T1 (GSTT1) variants and breast cancer risk in Burkina Faso

BioMolecular Concepts ◽

10.1515/bmc-2019-0020 ◽

2019 ◽

Vol 10 (1) ◽

pp. 175-183 ◽

Cited By ~ 1

Author(s):

Isabelle Touwendpoulimdé Kiendrebeogo ◽

Abdou Azaque Zoure ◽

Pegdwendé Abel Sorgho ◽

Albert Théophane Yonli ◽

Florencia Wendkuuni Djigma ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Patients ◽

Sporadic Breast Cancer ◽

Disease Stage ◽

Breast Cancer Patients ◽

Glutathione S Transferase ◽

Increased Risk ◽

Increased Susceptibility

AbstractBackground and objectiveBreast cancer remains the most common cause of cancer mortality in women. The aim of this study was to investigate associations between genetic variability in GSTM1 and GSTT1 and susceptibility to breast cancer.MethodsGenomic DNA was extracted from blood samples for 80 cases of histologically diagnosed breast cancer and 100 control subjects. Genotyping analyses were performed by PCR-based methods. Associations between specific genotypes and the development of breast cancer were examined using logistic regression to calculate odds ratios [1] and 95% confidence intervals (95%CI).ResultsNo correlation was found between GSTM1-null and breast cancer (OR = 1.83; 95%CI 0.90-3.71; p = 0.10), while GSTT1-null (OR = 2.42; 95%CI 1.17-5.02; p= 0.01) was associated with increased breast cancer risk. The GSTM1/GSTT1 double null was not associated with an increased risk of developing breast cancer (OR = 2.52; 95%CI 0.75-8.45; p = 0.20). Furthermore, analysis found no association between GSTM1-null (OR =1.12; 95%CI 0.08-15.50; p = 1.00) or GSTT1-null (OR = 1.71; 95%CI 0.13-22.51; p = 1.00) and the disease stage of familial breast cancer patients or sporadic breast cancer patients (GSTM1 (OR = 0.40; 95%CI 0.12-1.32; p = 0.20) and GSTT1 (OR = 1.41; 95%CI 0.39-5.12; p = 0.75)). Also, body mass index (BMI) was not associated with increased or decreased breast cancer risk in either GSTM1-null (OR = 0.60; 95%CI 0.21-1.68; p = 0.44) or GSTT1-null (OR = 0.60; 95%CI 0.21-1.68; p =0.45).ConclusionOur results suggest that only GSTT1-null is associated with increased susceptibility to breast cancer development.

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