Timothy R Rebbeck

Timothy R Rebbeck
University of Pennsylvania | UP · Center for Genetics and Complex Traits

About

568
Publications
59,348
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37,969
Citations
Citations since 2017
153 Research Items
11974 Citations
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Publications

Publications (568)
Article
Full-text available
Background: Endometrial cancer risk stratification may help target interventions, screening, or prophylactic hysterectomy to mitigate the rising burden of this cancer. However, existing prediction models have been developed in select cohorts and have not considered genetic factors. Methods: We developed endometrial cancer risk prediction models...
Article
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Purpose The incidence of endometrial cancer (EC) has been increasing faster among Black women than among other racial/ethnic groups in the United States. Although the mortality rate is nearly twice as high among Black than White women, there is a paucity of literature on risk factors for EC among Black women, particularly regarding menopausal hormo...
Article
PURPOSE Cervical cancer is the leading cause of cancer death for women in Botswana. Barriers in access to cancer care can lead to later stages at diagnosis and increased mortality. This study evaluated access, defined as travel time from a patient's residential village to a multidisciplinary team clinic in Gaborone, with stage of cervical cancer at...
Article
Background: Both multiple myeloma and its precursor, monoclonal gammopathy of undetermined significance (MGUS), occur twice as often within Black compared to White populations, suggesting that racial disparities lie within the development of MGUS. Nonetheless, MGUS has been studied mainly in White cohorts; the study that first described the natura...
Article
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Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how...
Article
Background Personalized genomic classifiers have transformed the management of prostate cancer (PCa) by identifying the most aggressive subsets of PCa. Nevertheless, the performance of genomic classifiers to risk-classify African American men is thus far lacking in a prospective setting. Methods This is a prospective study of the Decipher genomic...
Article
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Background Emerging evidence suggests that a subset of Black men with National Comprehensive Cancer Network (NCCN) low-risk prostate cancer (PCa) may harbor high volume and genomically aggressive disease. However, limited, and ambiguous research exist to evaluate the risk of extreme Gleason reclassification in Black men with low-risk PCa. Methods...
Article
Over the past several decades, the incidence of early-onset cancers, often defined as cancers diagnosed in adults <50 years of age, in the breast, colorectum, endometrium, oesophagus, extrahepatic bile duct, gallbladder, head and neck, kidney, liver, bone marrow, pancreas, prostate, stomach and thyroid has increased in multiple countries. Increased...
Article
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Cancer heterogeneities hold the key to a deeper understanding of cancer etiology and progression and the discovery of more precise cancer therapy. Modern pathological and molecular technologies offer a powerful set of tools to profile tumor heterogeneities at multiple levels in large patient populations, from DNA to RNA, protein and epigenetics, an...
Article
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Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program (MVP) and additional independent studies. Methods: Within each ancestry population, the association of...
Article
e20032 Background: Monoclonal gammopathy of undetermined significance (MGUS) is the precursor to multiple myeloma (MM). MM disproportionately affects black individuals, but the cumulative risk of progression from MGUS to malignancy does not differ by race. Hence, the racial disparities in MM incidence appear to arise from differences in the occurre...
Article
5046 Background: Men in sub-Saharan Africa (SSA) are disproportionately affected by prostate cancer (PCa), and many have metastatic disease (mPCA) at presentation. In SSA, androgen deprivation therapy (ADT) is the first-line treatment for mPCa, and often the only available therapy. Treatment failure and death is common. We identified predictors of...
Article
6555 Background: Socioeconomic and racial disparities in prostate cancer (PCa) can be attributed to patient-level and physician-level factors. However, there is growing interest in investigating the role of the facility of care in driving cancer disparities. Therefore, we sought to examine receipt of guideline-concordant definitive treatment, time...
Article
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Carriers of germline BRCA2 pathogenic sequence variants have elevated aggressive prostate cancer risk and are candidates for precision oncology treatments. We examined whether BRCA2-deficient (BRCA2d) prostate tumors have distinct genomic alterations compared with BRCA2-intact (BRCA2i) tumors. Among 2536 primary and 899 metastatic prostate tumors f...
Preprint
Full-text available
Background: We recently developed a multi-ancestry polygenic risk score (PRS) that effectively stratifies prostate cancer risk across populations. In this study, we validated the performance of the PRS in the multi-ancestry Million Veteran Program (MVP) and additional independent studies. Methods: Within each ancestry population, the association of...
Article
In sub-Saharan Africa (SSA), urgent action is needed to curb a growing crisis in cancer incidence and mortality. Without rapid interventions, data estimates show a major increase in cancer mortality from 520 348 in 2020 to about 1 million deaths per year by 2030. Here, we detail the state of cancer in SSA, recommend key actions on the basis of anal...
Article
Genetic ancestry affects human health, but this is distinct from the impact of race, a social construct that has its foundations in systemic racism. These terms need to be better defined and understood in medical research to achieve health equity.
Article
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PURPOSE Geographic access to care is an important measure of health equity. In this study, we describe geographic access to cancer care centers (CCCs) in Rwanda with the current facilities providing care and examine how access could change with expanded care infrastructure. METHODS Health facilities included are public hospitals administered by th...
Article
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Background: There is substantial variability in prostate cancer (PCa) mortality rates across Caucasian American (CA), African American (AA), Asian, and Hispanic men; however, these estimates are unable to disentangle race or ethnicity from confounding factors. The current study explores survival differences in long-term PCa outcomes between self-r...
Article
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Background Socioeconomic and health care utilization factors are major drivers of prostate cancer (PC) mortality disparities in the USA; however, tumor molecular heterogeneity may also contribute to the higher mortality among Black men. Objective To compare differences in PC subtype frequency and genomic aggressiveness by self-identified race. De...
Article
Background: Prostate cancer is an important cause of death worldwide. The number of years of life lost (YLL) due to prostate cancer is a metric of the toll of prostate cancer and using projections of demographic changes, can be used to measure future burden. Methods: Prostate cancer mortality data by country and world region was retrieved from t...
Article
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Background Neighborhood deprivation is linked with inflammation, which may explain poorer health across populations. Behavioral risk factors are assumed to largely mediate these relationships, but few studies have examined this. We examined three neighborhood contextual factors that could exert direct effects on inflammation: (1) neighborhood socio...
Article
Survival improves when cancer is detected early. However, ~50% of cancers are at an advanced stage when diagnosed. Early detection of cancer or precancerous change allows early intervention to try to slow or prevent cancer development and lethality. To achieve early detection of all cancers, numerous challenges must be overcome. It is vital to bett...
Article
Background: Racial disparities in prostate cancer incidence and mortality rates are considerable. We previously found in the Health Professionals Follow-up Study (HPFS) that African American men had an 80% higher prostate cancer risk than white men. With 21 additional years of follow-up and four-fold increase in cases, we undertook a contemporary...
Article
Background Prevalence estimates for monoclonal gammopathy of undetermined significance (MGUS) are based on predominantly White study populations screened by serum protein electrophoresis supplemented with immunofixation electrophoresis. A prevalence of 3% is reported for MGUS in the general population of European ancestry aged 50 years or older. MG...
Article
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Purpose Prostate cancer mortality is predicted to nearly double by 2040 in Sub-Saharan Africa (SSA). The lack of prostate cancer screening in SSA contributes to late-stage diagnosis, treatment delays, and poor survival among patients. We analyzed the availability and use of prostate cancer screening, diagnostic and treatment guidelines, procedures,...
Article
281 Background: The COVID-19 pandemic has been associated with a significant disruption in healthcare services including cancer screening and diagnosis. Delays in cancer screening and treatment may lead to increased mortality. We aimed to analyze changes in screening, diagnosis and surgical treatment of common GU malignancies in relation to the COV...
Article
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Purpose African men are disproportionately affected by prostate cancer (PCa). Given the increasing prevalence of obesity in Africa, and its association with aggressive PCa in other populations, we examined the relationship of overall and central obesity with risks of total and aggressive PCa among African men. Methods Between 2016 and 2020, we rec...
Article
PURPOSE To provide precise age-specific risk estimates of cancers other than female breast and ovarian cancers associated with pathogenic variants (PVs) in BRCA1 and BRCA2 for effective cancer risk management. METHODS We used data from 3,184 BRCA1 and 2,157 BRCA2 families in the Consortium of Investigators of Modifiers of BRCA1/2 to estimate age-s...
Article
A rare African ancestry–specific germline deletion variant in HOXB13 (X285K, rs77179853) was recently reported in Martinican men with early-onset prostate cancer. Given the role of HOXB13 germline variation in prostate cancer, we investigated the association between HOXB13 X285K and prostate cancer risk in a large sample of 22 361 African ancestry...
Article
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Background Altered DNA damage response (DDR) has emerged as an important mechanism for the development of aggressive prostate cancer among men of European ancestry but not other ancestry groups. Since common mechanisms for aggressive disease are expected, we explored a large panel of DDR genes and pathways to demonstrate that DDR alterations contri...
Article
Background: Inflammation is important in multiple myeloma (MM) pathogenesis, and regular aspirin use has been shown to confer a reduced risk of MM. The influence of aspirin on survival after MM diagnosis is unknown. Methods: We identified 436 men and women diagnosed with MM between 1980 and 2016 in the Health Professionals Follow-up Study (HPFS)...
Article
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Existing tools for post-radical prostatectomy (RP) prostate cancer biochemical recurrence (BCR) prognosis rely on human pathologist-derived parameters such as tumor grade, with the resulting inter-reviewer variability. Genomic companion diagnostic tests such as Decipher tend to be tissue destructive, expensive, and not routinely available in most c...
Article
Background Multiple myeloma (MM) evolves from monoclonal gammopathy of undetermined significance (MGUS), a clinically detectable but asymptomatic premalignant phase seen in ~3% of the general population 50 years of age or older. The prevalence of MGUS has not been described in a population at high risk of developing MM, specifically Black/African A...
Article
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Background DNA methylation and gene expression are known to play important roles in the etiology of human diseases such as prostate cancer (PCa). However, it has not yet been possible to incorporate information of DNA methylation and gene expression into polygenic risk scores (PRSs). Here, we aimed to develop and validate an improved PRS for PCa ri...
Article
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Endometriosis, polycystic ovary syndrome (PCOS) and uterine fibroids have been proposed as endometrial cancer risk factors; however, disentangling their relationships with endometrial cancer is complicated due to shared risk factors and comorbidities. Using genome-wide association study (GWAS) data, we explored the relationships between these non-c...
Article
Background Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated wit...
Article
Background: High tumor mutation burden (TMB) and total mutation count (TMC) can be predictive of better response to immune checkpoint blockade (ICB). Nevertheless, TMB and TMC are limited by variation across cancers and inconsistent definitions due to different profiling methods (targeted vs whole genome sequencing. Our objective was to identify ge...
Article
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Background Cervical cancer is the leading cause of female cancer mortality in Botswana with the majority of cervical cancer patients presenting with late-stage disease. The identification of factors associated with late-stage disease could reduce the cervical cancer burden. This study aims to identify potential patient level clinical and sociodemog...
Conference Paper
Introduction: Prostate cancer (PCa) is the most common cancer diagnosis among men in the United States. However, a vast majority of patients with PCa die of causes other than PCa, the most common being cardiovascular disease (CVD). We hypothesize that CVD-related mortality in PCa patients is disproportionately higher among Blacks as compared to Whi...
Conference Paper
Background Genetic ancestry, a correlate of self-identified race/ethnicity, could be associated with mortality risk, allowing for more targeted treatments for cancer and other chronic diseases. However, associations may be confounded by neighborhood socioeconomic status (nSES). We investigated whether African ancestry and nSES were independently as...
Article
5005 Background: Risk stratification of prostate cancer (PC) using routine clinical variables remains suboptimal as they do not account for underlying tumor biology. The genomic classifier provides information on underlying biology and independently predicts an individual patient’s risk of metastasis. Although the performance of the genomic classif...
Article
Background: Massachusetts is a northeastern state with universally mandated health insurance since 2006. Although Black men have generally worse prostate cancer outcomes, emerging data suggest that they may experience equivalent outcomes within a fully insured system. In this setting, the authors analyzed treatments and outcomes of non-Hispanic Wh...
Article
Background: Inflammation and one of its mediators, NF-kappa B (NFκB), have been implicated in prostate cancer carcinogenesis. We assessed whether germline polymorphisms associated with NFκB are associated with the risk of developing lethal disease (metastases or death from prostate cancer). Methods: Using a Bayesian approach leveraging NFκB biol...
Article
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Background: The presence of invasive cribriform adenocarcinoma (ICC), an expanse of cells containing punched-out lumina uninterrupted by stroma, in radical prostatectomy (RP) specimens has been associated with biochemical recurrence (BCR). However, ICC identification has only moderate inter-reviewer agreement. Objective: To investigate quantitat...
Article
Background Reducing disparities in men with prostate cancer (PCa) that may be caused by racial and socioeconomic differences is a major public health priority. Few reports have studied whether these disparities have changed over time. Methods Men diagnosed with PCa from January 1, 2000 to December 31, 2015 were identified from the Massachusetts an...
Article
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Although American men of European ancestry represent the largest population of patients with prostate cancer, men of African ancestry are disproportionately affected by prostate cancer, with higher prevalence and worse outcomes. These racial disparities in prostate cancer are due to multiple factors, but variations in genomic susceptibility such as...
Article
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Liquid biopsy-based biomarkers have advantages in monitoring the dynamics of metastatic castration-resistant prostate cancer (mCRPC), a bone-predominant metastatic disease. Previous studies have demonstrated associations between circulating tumor cells (CTCs) and clinical outcomes of mCRPC patients, but little is known about the prognostic value of...
Article
Grade group 4 and 5 (GG-45) prostate cancer (PCa) patients are at the highest risk of lethal outcomes, yet lack genomic risk stratification for prognosis and treatment selection. Here, we assess whether transcriptomic interactions between tumor immune content score (ICS) and the Decipher genomic classifier can identify most lethal subsets of GG-45...
Article
A full‐term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy‐related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case‐cont...
Article
Background The 2012 US Preventive Services Task Force (USPSTF) recommendation against routine prostate-specific antigen (PSA) testing led to a decrease in prostate cancer screening, but the heterogeneity of its impact by race/ethnicity remains unclear. Methods The proportion of 40–74 year-old men who self-reported receiving a routine PSA test in t...
Article
Background In prostate cancer (PCa), lack of androgen receptor (AR) regulated TMPRSS2‐ETS‐related gene (ERG) gene fusion (ERGnegative) status has been associated with African American race; however, the implications of ERG status for the location of dominant tumors within the prostate remains understudied. Methods An African American‐enriched mult...
Article
Population growth, demographic transitions and urbanization in sub-Saharan Africa (SSA) will increase non-communicable disease (NCD) burden. We studied the association between neighborhood greenness and NCDs in a multi-country cross-sectional study. Among 1178 participants, in adjusted models, a 0.11 unit NDVI increase was associated with lower BMI...
Article
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Introduction: Decisions regarding the geographical placement of healthcare services require consideration of trade-offs between equity and efficiency, but few empirical assessments are available. We applied a novel geospatial framework to study these trade-offs in four African countries. Methods: Geolocation data on population density (a surroga...
Article
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Purpose: The role of immune-oncologic mechanisms of racial disparities in prostate cancer (PCa) remains understudied. Limited research exists to evaluate the molecular underpinnings of immune differences in African American (AAM) and European American (EAM) prostate tumor microenvironment (TME). Experimental Design: A total of 1,173 radiation naïve...
Conference Paper
Introduction Prognostic and therapeutic implications of the immunogenomic landscape in poorly differentiated Grade Group 5 (GG5) prostate cancer (PCa) remains largely unknown. While novel treatment strategies including immuno-radiotherapy have been hypothesized to attenuate disease progression in advanced PCa, limited data exist to show underlying...
Conference Paper
Introduction: Men of African descent have the highest burden of aggressive and lethal prostate cancer (PrCa). In Sub-Saharan Africa (SSA), PrCa accounts for 19% of all cancer-related deaths. However, there has been no large-scale PrCa survival studies in SSA. The objective of this study was to assess the feasibility of establishing a PrCa survival...
Conference Paper
Background: Socioeconomic, environmental, and healthcare utilization factors are likely drivers of the persistent prostate cancer disparities between African-American (AA) and European-American (EA) men. Tumor molecular heterogeneity may also contribute, and Eurocentric studies and initiatives have the potential to widen disparities through the dev...
Article
Full-text available
Blood lipids have been associated with the development of a range of cancers, including breast, lung and colorectal cancer. For endometrial cancer, observational studies have reported inconsistent associations between blood lipids and cancer risk. To reduce biases from unmeasured confounding, we performed a bidirectional, two‐sample Mendelian rando...
Article
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PURPOSE Germline testing (GT) is a central feature of prostate cancer (PCA) treatment, management, and hereditary cancer assessment. Critical needs include optimized multigene testing strategies that incorporate evolving genetic data, consistency in GT indications and management, and alternate genetic evaluation models that address the rising deman...
Article
Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine,...
Article
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Background: Use of risk-reducing Salpingo-oophorectomy (RRSO) substantially reduces the risk of ovarian and breast cancer for women who carry a BRCA1/2 mutation. It is important to adjust for RRSO use in the estimation of BRCA1/2 penetrance of breast and ovarian cancer. Methods: We searched PubMed for penetrance estimates of breast and ovarian c...
Article
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Background: Black men with prostate cancer (CaP) experience excess mortality compared with White men. Residential greenness, a health promoting contextual factor, could explain racial disparities in mortality among men with CaP. Methods: We identified Pennsylvania Cancer Registry cases diagnosed between January 2000 and December 2015. Totally, 1...
Article
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Background: Growing evidence suggests that neighborhood contextual environment could influence risk factors and, therefore, incidence of lethal prostate cancer. We studied the association between neighborhood greenness and lethal prostate cancer incidence and assessed mediation by vigorous physical activity. Methods: A total of 47,958 participan...