Publications by authors named "Esther John"
Genome-wide association studies have identified approximately 200 genetic risk loci for breast cancer, but the causal variants and target genes are mostly unknown. We sought to fine-map all known breast cancer risk loci using genome-wide association study data from 172,737 female breast cancer cases and 242,009 controls of African, Asian and European ancestry. We identified 332 independent association signals for breast cancer risk, including 131 signals not reported previously, and for 50 of them, we narrowed the credible causal variants down to a single variant.
View Article and Find Full Text PDFMenopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.
View Article and Find Full Text PDFEvaluation of multiple breast cancer polygenic risk score panels in women of Latin American heritage.
Cancer Epidemiol Biomarkers Prev
December 2024
Background: A substantial portion of the genetic predisposition for breast cancer is explained by multiple common genetic variants of relatively small effect. A subset of these variants, which have been identified mostly in individuals of European and Asian ancestry, have been combined to construct a polygenic risk score (PRS) to predict breast cancer risk, but the prediction accuracy of existing PRSs in Hispanic/Latinx individuals (H/L) remain relatively low. We assessed the performance of several existing PRS panels with and without addition of H/L specific variants among self-reported H/L women.
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- A study analyzed liver cancer death rates (specifically hepatocellular carcinoma or HCC) in the U.S. from 2006 to 2022, revealing a concerning upward trend in mortality.* -
- Out of 188,280 deaths recorded, most victims were male, with overall liver cancer mortality rates projected to rise from 5.03 per 100,000 in 2022 to 6.39 by 2040.* -
- While deaths from hepatitis-related liver cancer are declining, those associated with alcohol and metabolic diseases are rising, with metabolic dysfunction expected to become a leading cause of HCC-related death in the future.*
Purpose: To determine the relationship between germline pathogenic variants (PV) in cancer predisposition genes and the risk of ductal carcinoma in situ (DCIS).
Experimental Design: Germline PV frequencies in breast cancer predisposition genes (ATM, BARD1, BRCA1, BRCA2, CDH1, CHEK2, PALB2, RAD51C, and RAD51D) were compared between DCIS cases and unaffected controls and between DCIS and invasive ductal breast cancer (IDC) cases from a clinical testing cohort (n = 9,887), a population-based cohort (n = 3,876), and the UK Biobank (n = 2,421). The risk of contralateral breast cancer (CBC) for DCIS cases with PV was estimated in the population-based cohort.
Genetic variation at the 19q13.3 KLK locus is linked with prostate cancer susceptibility in men. The non-synonymous KLK3 single nucleotide polymorphism (SNP), rs17632542 (c.
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- Pathogenic variants (PVs) in certain genes like BRCA1 and BRCA2 increase breast cancer risk, but it's unclear how risk varies based on the type and location of these variants.
- This study analyzed breast cancer risks associated with different PV types and locations using data from 12 US studies and clinical cohorts involving over 64,000 women.
- Results showed that women with specific exon PTVs had higher breast cancer risks, lower rates of ER-negative breast cancer, and were diagnosed at younger ages compared to those with other variants, with these patterns observed across multiple cohorts.
Physical activity during adolescence and early adulthood and breast cancer risk before age 40 years.
Cancer Epidemiol Biomarkers Prev
October 2024
Article Synopsis
- The study investigates the relationship between recreational physical activity (RPA) in adolescence and early adulthood and breast cancer (BC) risk in women under 40 years old, using data from a large international family cohort.
- Results indicate that higher levels of RPA are linked to reduced BC risk, with a 12% lower risk during adolescence and a 16% lower risk during early adulthood for women in the highest activity quartiles.
- The findings suggest that encouraging more physical activity in young women could be a crucial strategy for lowering the increasing incidence of breast cancer in this age group.
Article Synopsis
- - The study analyzed a diverse group of 9,639 women with first primary invasive breast cancer to identify risk factors for second primary breast cancer (SBC), focusing on both contralateral and ipsilateral cases.
- - Results showed that younger women with ER/PR-negative cancer and family history had increased risk of contralateral SBC, while older women showed higher risk linked to family history and lifestyle factors like being overweight and alcohol consumption.
- - The research highlighted persistent elevated risks for SBC among African American, Asian American, and Hispanic women compared to non-Hispanic White women, suggesting the need for better screening and tailored risk assessments for different racial and ethnic groups.
Article Synopsis
- The study investigates the relationship between hormonal contraceptive use and breast cancer risk in both unaffected women and mutation carriers.
- Out of the participants, it was found that hormonal contraceptive use was linked to a higher breast cancer risk in mutation carriers, particularly with longer duration of use.
- The findings suggest that decisions regarding hormonal contraceptive use for women with genetic mutations should consider individual risk factors and benefits.
Development of a Breast Cancer Risk Prediction Model Integrating Monogenic, Polygenic, and Epidemiologic Risk.
Cancer Epidemiol Biomarkers Prev
November 2024
Article Synopsis
- - The study aimed to enhance breast cancer risk modeling by integrating pathogenic variants (PVs) in specific genes, a polygenic risk score (PRS), and an epidemiologic risk score (ERS) using data from over 23,000 breast cancer cases and controls.
- - The results showed that postmenopausal women with no PVs but high ERS had a 4.4-fold increase in breast cancer risk, while some CHEK2 PV carriers had a predicted lifetime risk below 20%, indicating potential over-screening in certain groups.
- - The findings suggest that combining these risk factors can improve risk assessment and possibly lead to more tailored screening and prevention strategies for breast cancer.
Importance: Few studies have investigated whether the associations between pregnancy-related factors and breast cancer (BC) risk differ by underlying BC susceptibility. Evidence regarding variation in BC risk is critical to understanding BC causes and for developing effective risk-based screening guidelines.
Objective: To examine the association between pregnancy-related factors and BC risk, including modification by a of BC where scores are based on age and BC family history.
Article Synopsis
- Scientists looked at the timing of when girls start their periods (called menarche) and how it can affect their health later in life.
- They studied about 800,000 women and found over a thousand genetic signals that influence when menstruation starts.
- Some women have a much higher chance of starting their periods too early or too late based on their genetic makeup, suggesting that genes play a big role in this process!
Background: Medical record abstraction (MRA) and self-report questionnaires are two methods frequently used to ascertain cancer treatment information. Prior studies have shown excellent agreement between MRA and self-report, but it is unknown how a recall window longer than 3 years may affect this agreement.
Methods: The Women's Environmental Cancer and Radiation Epidemiology (WECARE) Study is a multicenter, population-based case-control study of controls with unilateral breast cancer individually matched to cases with contralateral breast cancer.
Breast cancer includes several subtypes with distinct characteristic biological, pathologic, and clinical features. Elucidating subtype-specific genetic etiology could provide insights into the heterogeneity of breast cancer to facilitate the development of improved prevention and treatment approaches. In this study, we conducted pairwise case-case comparisons among five breast cancer subtypes by applying a case-case genome-wide association study (CC-GWAS) approach to summary statistics data of the Breast Cancer Association Consortium.
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- The study examined the relationship between reproductive factors and breast cancer risk across different subtypes, focusing on racial and ethnic groups that are often underrepresented in research.
- Data was collected from nearly 2,800 breast cancer cases and over 4,500 controls, predominantly from African American, Asian American, and Hispanic women, to analyze how reproductive characteristics like parity and breast-feeding impact breast cancer subtype risk.
- Findings indicated that reproductive factors influence breast cancer risk differently based on subtype, menopausal status, and race, with distinct patterns observed among premenopausal African American women compared to Asian American and Hispanic women regarding parity and breast-feeding effects.
Article Synopsis
- - The study analyzed genetic factors linked to breast cancer in a diverse sample of 18,034 African ancestry cases and 22,104 controls, identifying 12 genetic variants tied to increased risk.
- - Key findings included a rare variant (rs61751053) associated with overall breast cancer risk (odds ratio 1.48) and a common variant (rs76664032) connected to triple-negative breast cancer (odds ratio 1.30).
- - A polygenic risk score (PRS) showed a predictive capability (0.60 area under the curve) for breast cancer risk, illustrating improved accuracy compared to PRS based on European data and highlighting the significance of diversity in genetic research.
African-ancestry (AA) participants are underrepresented in genetics research. Here, we conducted a transcriptome-wide association study (TWAS) in AA female participants to identify putative breast cancer susceptibility genes. We built genetic models to predict levels of gene expression, exon junction, and 3' UTR alternative polyadenylation using genomic and transcriptomic data generated in normal breast tissues from 150 AA participants and then used these models to perform association analyses using genomic data from 18,034 cases and 22,104 controls.
View Article and Find Full Text PDFPurpose: Mammographic density phenotypes, adjusted for age and body mass index (BMI), are strong predictors of breast cancer risk. BMI is associated with mammographic density measures, but the role of circulating sex hormone concentrations is less clear. We investigated the relationship between BMI, circulating sex hormone concentrations, and mammographic density phenotypes using Mendelian randomization (MR).
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- Stromal tumor-infiltrating lymphocyte (sTIL) levels in breast tumors are linked to better responses to neoadjuvant treatment and improved survival rates.
- A study found no racial or ethnic differences in sTIL scores; however, higher sTIL scores were tied to lower breast cancer-specific mortality primarily in non-Hispanic White and Asian American women.
- The results indicate that sTIL enrichment does not provide the same survival benefits for African American and Hispanic women, highlighting the need for more research on treatment strategies that consider health disparities among different racial and ethnic groups.
Background: Nineteen genomic regions have been associated with high-grade serous ovarian cancer (HGSOC). We used data from the Ovarian Cancer Association Consortium (OCAC), Consortium of Investigators of Modifiers of (CIMBA), UK Biobank (UKBB), and FinnGen to identify novel HGSOC susceptibility loci and develop polygenic scores (PGS).
Methods: We analyzed >22 million variants for 398,238 women.