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Papers by Jennifer Hu

Research paper thumbnail of Genome-wide enriched pathway analysis of acute post-radiotherapy pain in breast cancer patients: a prospective cohort study

Human Genomics, 2019

Background: Adjuvant radiotherapy (RT) can increase the risk of developing pain; however, the mol... more Background: Adjuvant radiotherapy (RT) can increase the risk of developing pain; however, the molecular mechanisms of RT-related pain remain unclear. The current study aimed to identify susceptibility loci and enriched pathways for clinically relevant acute post-RT pain, defined as having moderate to severe pain (pain score ≥ 4) at the completion of RT. Methods: We conducted a genome-wide association study (GWAS) with 1,344,832 single-nucleotide polymorphisms (SNPs), a gene-based analysis using PLINK set-based tests of 19,621 genes, and a functional enrichment analysis of a gene list of 875 genes with p < 0.05 using NIH DAVID functional annotation module with KEGG pathways and GO terms (n = 380) among 1112 breast cancer patients. Results: About 29% of patients reported acute post-RT pain. None of SNPs nor genes reached genome-wide significant level. Four SNPs showed suggestive associations with post-RT pain; rs16970540 in RFFL or near the LIG3 gene (p = 1.7 × 10 −6), rs4584690, and rs7335912 in ABCC4/MPR4 gene (p = 5.5 × 10 −6 and p = 7.8 × 10 −6 , respectively), and rs73633565 in EGFL6 gene (p = 8.1 × 10 −6). Gene-based analysis suggested the potential involvement of neurotransmitters, olfactory receptors, and cytochrome P450 in post-RT pain, whereas functional analysis showed glucuronidation (FDR-adjusted p value = 9.46 × 10 −7) and olfactory receptor activities (FDR-adjusted p value = 0.032) as the most significantly enriched biological features. Conclusions: This is the first GWAS suggesting that post-RT pain is a complex polygenic trait influenced by many biological processes and functions such as glucuronidation and olfactory receptor activities. If validated in larger populations, the results can provide biological targets for pain management to improve cancer patients' quality of life. Additionally, these genes can be further tested as predictive biomarkers for personalized pain management.

Research paper thumbnail of Comparison of multivariate adaptive regression splines and logistic regression in detecting SNP–SNP interactions and their application in prostate cancer

Journal of Human Genetics, 2008

Single nucleotide polymorphism (SNP) interaction plays a critical role for complex diseases. The ... more Single nucleotide polymorphism (SNP) interaction plays a critical role for complex diseases. The primary limitation of logistic regressions (LR) in testing SNP-SNP interactions is that coefficient estimates may not be valid because of numerous terms in a model. Multivariate adaptive regression splines (MARS) have useful features to effectively reduce the number of terms in a model. To study how MARS can address these drawbacks possibly better than LR, the power of MARS and LR with SNPs using the reference-coding and additive-mode scheme was compared using simulated data of ten SNPs for 400 subjects based on 1,000 replications for five interaction models. In overall scenarios, MARS performed better than LR. In the model with a dominant two-way interaction, the power range was 76-96% for MARS and 1-8% for LR in both coding schemes. In the dominant three-way interaction model, the power was 57-85% for MARS and less than 4% for LR. In the prostate cancer example, we evaluated the association between ten SNPs and prostate cancer risk in 649 Caucasians. The best model with one two-way and one three-way interaction was selected using MARS. The findings supported that MARS may provide a useful tool for exploring SNP-SNP interactions.

Research paper thumbnail of Prospective evaluation of radiation-induced skin toxicity in a race/ethnically diverse breast cancer population

Cancer medicine, Jan 14, 2016

We evaluated predictors of radiation-induced skin toxicity in a prospective study of a tri-racial... more We evaluated predictors of radiation-induced skin toxicity in a prospective study of a tri-racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation-induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non-Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0-1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty-one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER-positive/PR-negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventional...

Research paper thumbnail of Ethnicity and Clinical Outcomes in Head and Neck Cancer: an Analysis of the SEER Database

Journal of Racial and Ethnic Health Disparities, 2014

Background We evaluated the differences within various ethnic groups diagnosed with head and neck... more Background We evaluated the differences within various ethnic groups diagnosed with head and neck cancer in the USA with a specific focus on the clinical outcomes of patients of Hispanic ethnicity. Material/Methods We used the Surveillance, Epidemiology, and End Results (SEER) database to examine the clinical outcomes of patients with head and neck cancer by ethnicity, region of origin, place of birth, treatment modality, primary location, age, gender, and SEER tumor stage. Results For all patients, African American race conferred the worst prognosis for head and neck cancer (1.41; CI 1.361-1.454), while non-US born Hispanics had the best prognosis (0.74; 0.684-0.804). US born Hispanics (0.86; CI 0.823-0.892) had a significantly better prognosis than Whites (ref.). Conclusion The Hispanic population appears to have a better prognosis compared to their Caucasian peers while both do better than Blacks across all stages and in local and regional disease subsets. Furthermore, non-US born Hispanics had a better prognosis than US born Hispanics. The cause of this disparity is unclear and warrants further investigation.

Research paper thumbnail of Complementary and alternative medicine in reducing radiation-induced skin toxicity

Radiation and Environmental Biophysics, 2014

The increasing prevalence of complementary and alternative medicine (CAM) use is a significant he... more The increasing prevalence of complementary and alternative medicine (CAM) use is a significant health care issue in contemporary societies and researchers have identified CAM as holding potential for treating and coping with chronic illness and other conditions experienced in later life. This paper focuses upon contemporary research literature to provide a critical review of the prevalence, correlates, conditions, perceptions and communication of CAM use in later life. Evidence from recent research illustrates the substantial prevalence and complexity of CAM use amongst older people and such 'community' use requires all providers, regardless of their experience or perception of the worth of CAM, to at least acknowledge and enquire with their older patients about the potential use of these other medicines.

Research paper thumbnail of African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer

IntroductionPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate ... more IntroductionPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46), showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify SNPs that might improve performance in this population.Material and MethodsAnonymized genotypic data were obtained from the PRACTICAL consortium for 6,253 men with African genetic ancestry. Ten iterations of a ten-fold cross-validation search were conducted, to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African were compared using the same cross-validated approach.ResultsThree SNPs (rs76229939, rs74421890, and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located...

Research paper thumbnail of Association between C-reactive protein and radiotherapy-related pain in a tri-racial/ethnic population of breast cancer patients: a prospective cohort study

Breast Cancer Research, 2019

Background: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in b... more Background: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in breast cancer patients; however, some patients develop cancer or treatment-related pain that negatively impacts quality of life. This study examined an inflammatory biomarker, C-reactive protein (CRP), in RT-related pain in breast cancer. Methods: During 2008 and 2014, breast cancer patients who underwent RT were prospectively evaluated for preand post-RT pain. Pre-and post-RT plasma CRP levels were measured using a highly sensitive CRP ELISA kit. Pain score was assessed as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were classified as clinically relevant pain. Multivariable logistic regression analyses were applied to ascertain the associations between CRP and RT-related pain. Results: In 366 breast cancer patients (235 Hispanic whites, 73 black/African Americans, and 58 non-Hispanic whites), 17% and 30% of patients reported pre-and post-RT pain, while 23% of patients had RT-related pain. Both pre-and post-RT pain scores differed significantly by race/ethnicity. In multivariable logistic regression analysis, RTrelated pain was significantly associated with elevated pre-RT CRP (≥ 10 mg/L) alone (odds ratio (OR) = 2.44; 95% confidence interval (CI) = 1.02, 5.85); or combined with obesity (OR = 4.73; 95% CI = 1.41, 15.81) after adjustment for age and race/ethnicity. Conclusions: This is the first pilot study of CRP in RT-related pain, particularly in obese breast cancer patients. Future larger studies are warranted to validate our findings and help guide RT decision-making processes and targeted interventions.

Research paper thumbnail of Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

JNCI: Journal of the National Cancer Institute, 2017

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The ... more Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency ¼ 2.2%, odds ratio [OR]

Research paper thumbnail of Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African ancestry anthropometry genetics consortium

PLoS genetics, Jan 21, 2017

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of a... more Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identi...

Research paper thumbnail of A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Dec 1, 2016

Genome-wide association studies (GWAS) in European populations have identified genetic risk varia... more Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM). We performed association testing of common variation in eight regions in 1,264 MM patients and 1,479 controls of European ancestry (EA) and 1,305 MM patients and 7,078 controls of African ancestry (AA) and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (p<0.05) associated with MM risk in AAs and EAs and the variant in 3p22.1 was associated in EAs only. In a combined AA-EA meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically signficantly associated with MM risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination s...

Research paper thumbnail of Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

Human genetics, Oct 5, 2016

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA de... more MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR...

Research paper thumbnail of Risk Stratification System for Oral Cancer Screening

Cancer prevention research (Philadelphia, Pa.), Jun 28, 2016

Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in inci... more Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in incidence. World-wide 5-year survival is only 50% due to delayed intervention with more than half of diagnoses at stage III and IV, whereas earlier detection (stage I and II) yields survival rates up to 80%-90%. Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels may facilitate oral cancer risk assessment and early intervention. This study used a hospital-based design with 150 cases and 150 frequency-matched controls to determine whether CD44 and total protein levels in oral rinses were associated with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol use, and socioeconomic status (SES). High-risk subjects receiving oral cancer prevention interventions as part of a community- based program (n=150) were followed over 1 year to determine marker specificity and variation. CD44 {greater than or equal to}5.33 ng/ml was highly associated wit...

Research paper thumbnail of Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

PloS one, 2015

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) ... more Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large num...

Research paper thumbnail of DNA-repair genetic polymorphisms and breast cancer risk

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2003

Mammalian cells are constantly exposed to genotoxic agents from both endogenous and exogenous sou... more Mammalian cells are constantly exposed to genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair contributes to deficient repair and breast cancer risk. Using samples collected in an ongoing, clinic-based, case-control study (253 cases and 268 controls), we tested whether breast cancer risk is associated with four amino acid substitution variants in three DNA repair genes, including XRCC1 Arg194Trp and XRCC1 Arg399Gln in base excision repair, XRCC3 Thr241Met in homologous recombination repair, and ERCC4/XPF Arg415Gln in nucleotide excision repair. Carriers of at least one variant allele of XRCC1 Arg194Trp [Arg/Trp and Trp/Trp versus Arg/Arg, odds ratio (OR) = 1.60, 95% confidence interval (CI) = 0.89-2.87] or two variant alleles of XRCC3 241Met/Metmay have an increased risk of breast cancer (Met/Met versus Thr/Thr and Thr/Met, OR = 1.54, 95% CI = 0.94-2.52). No association between XRCC1 Arg399Gln Dgenotype and breast cancer risk was observed. ...

Research paper thumbnail of A comprehensive examination of breast cancer risk loci in African American women

Human molecular genetics, Jan 15, 2014

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European... more Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive dis...

Research paper thumbnail of The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

PLoS Genetics, 2010

We consider the feasibility of reusing existing control data obtained in genetic association stud... more We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study.

Research paper thumbnail of Enhanced Statistical Tests for GWAS in Admixed Populations: Assessment using African Americans from CARe and a Breast Cancer Consortium

PLoS Genetics, 2011

While genome-wide association studies (GWAS) have primarily examined populations of European ance... more While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations.

Research paper thumbnail of Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

PLoS Genetics, 2011

Adult height is a classic polygenic trait of high heritability (h 2 ,0.8). More than 180 single n... more Adult height is a classic polygenic trait of high heritability (h 2 ,0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ,10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4610 212 and 2p14-rs4315565, P = 1.2610 28). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7610 24 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P,0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

Research paper thumbnail of Intake of Plant Foods and Associated Nutrients in Prostate Cancer Risk

Nutrition and Cancer, 2009

Plant foods and associated nutrients may impact prostate cancer (PC) risk and survival. Therefore... more Plant foods and associated nutrients may impact prostate cancer (PC) risk and survival. Therefore, we compared dietary intake, mainly plant food groups among 382 controls and 478 PC cases (373 incident and 105 prevalent cases). Caucasian controls had significantly higher daily servings of vegetables (3.4 vs. 2.5, P = 0.002) and fruits and/or fruit juices (1.6 vs. 1.3, P = 0.02) compared to African American controls. In Caucasians, incident cases reported lower intake of fiber, vitamin C, vitamin A, α-carotene, β-carotene, cryptoxanthin, folate, genistein, daidzein, and fruits and/or fruit juice than controls and/or prevalent cases. In African Americans, incident cases had lower intake of α-carotene compared to controls and prevalent cases. Reduced PC risk was associated with the highest tertile of cryptoxanthin (OR = 0.51; 95% CI = 0.35-0.75), fiber (OR = 0.56; 95% CI = 0.35-0.89), vitamin C (OR = 0.60; 95% CI = 0.41-0.88), and fruits and/or fruit juices (OR = 0.46; 95% CI = 0.31-0.68), with significant linear trends. Increased risk of PC was associated with the highest tertile of protein (OR = 1.99; 95% CI = 1.05-3.79) and daily servings of grains (OR = 1.99; 95% CI = 1.23-3.22) with significant linear trends. In summary, we demonstrate racial/ethnic differences in dietary intake of plant foods. The significantly higher consumption of protective dietary constituents among prevalent cases compared to incident cases suggests that PC survivors may be amenable to dietary change.

Research paper thumbnail of The landscape of recombination in African Americans

Nature, 2011

Recombination, together with mutation, is the ultimate source of genetic variation in populations... more Recombination, together with mutation, is the ultimate source of genetic variation in populations. We leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing-over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P<10 −245). We identify a 17 base pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of African-enriched alleles of PRDM9. In humans and many other species, recombination is not evenly distributed across the genome, but instead occurs in "hotspots": two kilobase (kb) segments where the crossover rate is far higher than in the flanking DNA sequence 1,2,3. The highest resolution genetic map in contemporary humans to date, the "deCODE Map", is based on about 500,000 crossovers identified in 15,000 Icelandic meioses 4. However, a limitation of maps built in people of European descent 4,5,6 is that they may not apply equally well in other populations, as suggested by comparisons of maps across ethnic groups 4,7,8,9 and patterns of linkage disequilibrium (LD) breakdown which suggest that more of the genome may be recombinationally active in West Africans 10. It is known that a major determinant of the positions of recombination hotspots is PRDM9, a meiosis-specific histone H3 methyltransferase whose zinc finger (ZF) domain binds DNA sequence motifs 11,12,13. In Europeans, PRDM9 ZF arrays are predominantly of two similar types, "A" and "B", both of which bind the 13-bp motif CCNCCNTNNCCNC 11. In contrast, 36% of West African Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Research paper thumbnail of Genome-wide enriched pathway analysis of acute post-radiotherapy pain in breast cancer patients: a prospective cohort study

Human Genomics, 2019

Background: Adjuvant radiotherapy (RT) can increase the risk of developing pain; however, the mol... more Background: Adjuvant radiotherapy (RT) can increase the risk of developing pain; however, the molecular mechanisms of RT-related pain remain unclear. The current study aimed to identify susceptibility loci and enriched pathways for clinically relevant acute post-RT pain, defined as having moderate to severe pain (pain score ≥ 4) at the completion of RT. Methods: We conducted a genome-wide association study (GWAS) with 1,344,832 single-nucleotide polymorphisms (SNPs), a gene-based analysis using PLINK set-based tests of 19,621 genes, and a functional enrichment analysis of a gene list of 875 genes with p < 0.05 using NIH DAVID functional annotation module with KEGG pathways and GO terms (n = 380) among 1112 breast cancer patients. Results: About 29% of patients reported acute post-RT pain. None of SNPs nor genes reached genome-wide significant level. Four SNPs showed suggestive associations with post-RT pain; rs16970540 in RFFL or near the LIG3 gene (p = 1.7 × 10 −6), rs4584690, and rs7335912 in ABCC4/MPR4 gene (p = 5.5 × 10 −6 and p = 7.8 × 10 −6 , respectively), and rs73633565 in EGFL6 gene (p = 8.1 × 10 −6). Gene-based analysis suggested the potential involvement of neurotransmitters, olfactory receptors, and cytochrome P450 in post-RT pain, whereas functional analysis showed glucuronidation (FDR-adjusted p value = 9.46 × 10 −7) and olfactory receptor activities (FDR-adjusted p value = 0.032) as the most significantly enriched biological features. Conclusions: This is the first GWAS suggesting that post-RT pain is a complex polygenic trait influenced by many biological processes and functions such as glucuronidation and olfactory receptor activities. If validated in larger populations, the results can provide biological targets for pain management to improve cancer patients' quality of life. Additionally, these genes can be further tested as predictive biomarkers for personalized pain management.

Research paper thumbnail of Comparison of multivariate adaptive regression splines and logistic regression in detecting SNP–SNP interactions and their application in prostate cancer

Journal of Human Genetics, 2008

Single nucleotide polymorphism (SNP) interaction plays a critical role for complex diseases. The ... more Single nucleotide polymorphism (SNP) interaction plays a critical role for complex diseases. The primary limitation of logistic regressions (LR) in testing SNP-SNP interactions is that coefficient estimates may not be valid because of numerous terms in a model. Multivariate adaptive regression splines (MARS) have useful features to effectively reduce the number of terms in a model. To study how MARS can address these drawbacks possibly better than LR, the power of MARS and LR with SNPs using the reference-coding and additive-mode scheme was compared using simulated data of ten SNPs for 400 subjects based on 1,000 replications for five interaction models. In overall scenarios, MARS performed better than LR. In the model with a dominant two-way interaction, the power range was 76-96% for MARS and 1-8% for LR in both coding schemes. In the dominant three-way interaction model, the power was 57-85% for MARS and less than 4% for LR. In the prostate cancer example, we evaluated the association between ten SNPs and prostate cancer risk in 649 Caucasians. The best model with one two-way and one three-way interaction was selected using MARS. The findings supported that MARS may provide a useful tool for exploring SNP-SNP interactions.

Research paper thumbnail of Prospective evaluation of radiation-induced skin toxicity in a race/ethnically diverse breast cancer population

Cancer medicine, Jan 14, 2016

We evaluated predictors of radiation-induced skin toxicity in a prospective study of a tri-racial... more We evaluated predictors of radiation-induced skin toxicity in a prospective study of a tri-racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation-induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non-Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0-1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty-one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER-positive/PR-negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventional...

Research paper thumbnail of Ethnicity and Clinical Outcomes in Head and Neck Cancer: an Analysis of the SEER Database

Journal of Racial and Ethnic Health Disparities, 2014

Background We evaluated the differences within various ethnic groups diagnosed with head and neck... more Background We evaluated the differences within various ethnic groups diagnosed with head and neck cancer in the USA with a specific focus on the clinical outcomes of patients of Hispanic ethnicity. Material/Methods We used the Surveillance, Epidemiology, and End Results (SEER) database to examine the clinical outcomes of patients with head and neck cancer by ethnicity, region of origin, place of birth, treatment modality, primary location, age, gender, and SEER tumor stage. Results For all patients, African American race conferred the worst prognosis for head and neck cancer (1.41; CI 1.361-1.454), while non-US born Hispanics had the best prognosis (0.74; 0.684-0.804). US born Hispanics (0.86; CI 0.823-0.892) had a significantly better prognosis than Whites (ref.). Conclusion The Hispanic population appears to have a better prognosis compared to their Caucasian peers while both do better than Blacks across all stages and in local and regional disease subsets. Furthermore, non-US born Hispanics had a better prognosis than US born Hispanics. The cause of this disparity is unclear and warrants further investigation.

Research paper thumbnail of Complementary and alternative medicine in reducing radiation-induced skin toxicity

Radiation and Environmental Biophysics, 2014

The increasing prevalence of complementary and alternative medicine (CAM) use is a significant he... more The increasing prevalence of complementary and alternative medicine (CAM) use is a significant health care issue in contemporary societies and researchers have identified CAM as holding potential for treating and coping with chronic illness and other conditions experienced in later life. This paper focuses upon contemporary research literature to provide a critical review of the prevalence, correlates, conditions, perceptions and communication of CAM use in later life. Evidence from recent research illustrates the substantial prevalence and complexity of CAM use amongst older people and such 'community' use requires all providers, regardless of their experience or perception of the worth of CAM, to at least acknowledge and enquire with their older patients about the potential use of these other medicines.

Research paper thumbnail of African-specific improvement of a polygenic hazard score for age at diagnosis of prostate cancer

IntroductionPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate ... more IntroductionPolygenic hazard score (PHS) models are associated with age at diagnosis of prostate cancer. Our model developed in Europeans (PHS46), showed reduced performance in men with African genetic ancestry. We used a cross-validated search to identify SNPs that might improve performance in this population.Material and MethodsAnonymized genotypic data were obtained from the PRACTICAL consortium for 6,253 men with African genetic ancestry. Ten iterations of a ten-fold cross-validation search were conducted, to select SNPs that would be included in the final PHS46+African model. The coefficients of PHS46+African were estimated in a Cox proportional hazards framework using age at diagnosis as the dependent variable and PHS46, and selected SNPs as predictors. The performance of PHS46 and PHS46+African were compared using the same cross-validated approach.ResultsThree SNPs (rs76229939, rs74421890, and rs5013678) were selected for inclusion in PHS46+African. All three SNPs are located...

Research paper thumbnail of Association between C-reactive protein and radiotherapy-related pain in a tri-racial/ethnic population of breast cancer patients: a prospective cohort study

Breast Cancer Research, 2019

Background: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in b... more Background: Post-surgery adjuvant radiotherapy (RT) significantly improves clinical outcomes in breast cancer patients; however, some patients develop cancer or treatment-related pain that negatively impacts quality of life. This study examined an inflammatory biomarker, C-reactive protein (CRP), in RT-related pain in breast cancer. Methods: During 2008 and 2014, breast cancer patients who underwent RT were prospectively evaluated for preand post-RT pain. Pre-and post-RT plasma CRP levels were measured using a highly sensitive CRP ELISA kit. Pain score was assessed as the mean of four pain severity items (i.e., pain at its worst, least, average, and now) from the Brief Pain Inventory. Pain scores of 4-10 were classified as clinically relevant pain. Multivariable logistic regression analyses were applied to ascertain the associations between CRP and RT-related pain. Results: In 366 breast cancer patients (235 Hispanic whites, 73 black/African Americans, and 58 non-Hispanic whites), 17% and 30% of patients reported pre-and post-RT pain, while 23% of patients had RT-related pain. Both pre-and post-RT pain scores differed significantly by race/ethnicity. In multivariable logistic regression analysis, RTrelated pain was significantly associated with elevated pre-RT CRP (≥ 10 mg/L) alone (odds ratio (OR) = 2.44; 95% confidence interval (CI) = 1.02, 5.85); or combined with obesity (OR = 4.73; 95% CI = 1.41, 15.81) after adjustment for age and race/ethnicity. Conclusions: This is the first pilot study of CRP in RT-related pain, particularly in obese breast cancer patients. Future larger studies are warranted to validate our findings and help guide RT decision-making processes and targeted interventions.

Research paper thumbnail of Two Novel Susceptibility Loci for Prostate Cancer in Men of African Ancestry

JNCI: Journal of the National Cancer Institute, 2017

Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The ... more Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency ¼ 2.2%, odds ratio [OR]

Research paper thumbnail of Discovery and fine-mapping of adiposity loci using high density imputation of genome-wide association studies in individuals of African ancestry: African ancestry anthropometry genetics consortium

PLoS genetics, Jan 21, 2017

Genome-wide association studies (GWAS) have identified >300 loci associated with measures of a... more Genome-wide association studies (GWAS) have identified >300 loci associated with measures of adiposity including body mass index (BMI) and waist-to-hip ratio (adjusted for BMI, WHRadjBMI), but few have been identified through screening of the African ancestry genomes. We performed large scale meta-analyses and replications in up to 52,895 individuals for BMI and up to 23,095 individuals for WHRadjBMI from the African Ancestry Anthropometry Genetics Consortium (AAAGC) using 1000 Genomes phase 1 imputed GWAS to improve coverage of both common and low frequency variants in the low linkage disequilibrium African ancestry genomes. In the sex-combined analyses, we identified one novel locus (TCF7L2/HABP2) for WHRadjBMI and eight previously established loci at P < 5×10-8: seven for BMI, and one for WHRadjBMI in African ancestry individuals. An additional novel locus (SPRYD7/DLEU2) was identified for WHRadjBMI when combined with European GWAS. In the sex-stratified analyses, we identi...

Research paper thumbnail of A meta-analysis of multiple myeloma risk regions in African and European ancestry populations identifies putatively functional loci

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Dec 1, 2016

Genome-wide association studies (GWAS) in European populations have identified genetic risk varia... more Genome-wide association studies (GWAS) in European populations have identified genetic risk variants associated with multiple myeloma (MM). We performed association testing of common variation in eight regions in 1,264 MM patients and 1,479 controls of European ancestry (EA) and 1,305 MM patients and 7,078 controls of African ancestry (AA) and conducted a meta-analysis to localize the signals, with epigenetic annotation used to predict functionality. We found that variants in 7p15.3, 17p11.2, 22q13.1 were statistically significantly (p<0.05) associated with MM risk in AAs and EAs and the variant in 3p22.1 was associated in EAs only. In a combined AA-EA meta-analysis, variation in five regions (2p23.3, 3p22.1, 7p15.3, 17p11.2, 22q13.1) was statistically signficantly associated with MM risk. In 3p22.1, the correlated variants clustered within the gene body of ULK4. Correlated variants in 7p15.3 clustered around an enhancer at the 3' end of the CDCA7L transcription termination s...

Research paper thumbnail of Genetic variants in microRNA and microRNA biogenesis pathway genes and breast cancer risk among women of African ancestry

Human genetics, Oct 5, 2016

MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA de... more MicroRNAs (miRNA) regulate breast biology by binding to specific RNA sequences, leading to RNA degradation and inhibition of translation of their target genes. While germline genetic variations may disrupt some of these interactions between miRNAs and their targets, studies assessing the relationship between genetic variations in the miRNA network and breast cancer risk are still limited, particularly among women of African ancestry. We systematically put together a list of 822 and 10,468 genetic variants among primary miRNA sequences and 38 genes in the miRNA biogenesis pathway, respectively; and examined their association with breast cancer risk in the ROOT consortium which includes women of African ancestry. Findings were replicated in an independent consortium. Logistic regression was used to estimate the odds ratio (OR) and 95 % confidence intervals (CI). For overall breast cancer risk, three single-nucleotide polymorphisms (SNPs) in miRNA biogenesis genes DROSHA rs78393591 (OR...

Research paper thumbnail of Risk Stratification System for Oral Cancer Screening

Cancer prevention research (Philadelphia, Pa.), Jun 28, 2016

Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in inci... more Oral cavity and oropharyngeal cancer (oral cancer) is a deadly disease that is increasing in incidence. World-wide 5-year survival is only 50% due to delayed intervention with more than half of diagnoses at stage III and IV, whereas earlier detection (stage I and II) yields survival rates up to 80%-90%. Salivary soluble CD44 (CD44), a tumor-initiating marker, and total protein levels may facilitate oral cancer risk assessment and early intervention. This study used a hospital-based design with 150 cases and 150 frequency-matched controls to determine whether CD44 and total protein levels in oral rinses were associated with oral cancer independent of age, gender, race, ethnicity, tobacco and alcohol use, and socioeconomic status (SES). High-risk subjects receiving oral cancer prevention interventions as part of a community- based program (n=150) were followed over 1 year to determine marker specificity and variation. CD44 {greater than or equal to}5.33 ng/ml was highly associated wit...

Research paper thumbnail of Methodological Considerations in Estimation of Phenotype Heritability Using Genome-Wide SNP Data, Illustrated by an Analysis of the Heritability of Height in a Large Sample of African Ancestry Adults

PloS one, 2015

Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) ... more Height has an extremely polygenic pattern of inheritance. Genome-wide association studies (GWAS) have revealed hundreds of common variants that are associated with human height at genome-wide levels of significance. However, only a small fraction of phenotypic variation can be explained by the aggregate of these common variants. In a large study of African-American men and women (n = 14,419), we genotyped and analyzed 966,578 autosomal SNPs across the entire genome using a linear mixed model variance components approach implemented in the program GCTA (Yang et al Nat Genet 2010), and estimated an additive heritability of 44.7% (se: 3.7%) for this phenotype in a sample of evidently unrelated individuals. While this estimated value is similar to that given by Yang et al in their analyses, we remain concerned about two related issues: (1) whether in the complete absence of hidden relatedness, variance components methods have adequate power to estimate heritability when a very large num...

Research paper thumbnail of DNA-repair genetic polymorphisms and breast cancer risk

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2003

Mammalian cells are constantly exposed to genotoxic agents from both endogenous and exogenous sou... more Mammalian cells are constantly exposed to genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair contributes to deficient repair and breast cancer risk. Using samples collected in an ongoing, clinic-based, case-control study (253 cases and 268 controls), we tested whether breast cancer risk is associated with four amino acid substitution variants in three DNA repair genes, including XRCC1 Arg194Trp and XRCC1 Arg399Gln in base excision repair, XRCC3 Thr241Met in homologous recombination repair, and ERCC4/XPF Arg415Gln in nucleotide excision repair. Carriers of at least one variant allele of XRCC1 Arg194Trp [Arg/Trp and Trp/Trp versus Arg/Arg, odds ratio (OR) = 1.60, 95% confidence interval (CI) = 0.89-2.87] or two variant alleles of XRCC3 241Met/Metmay have an increased risk of breast cancer (Met/Met versus Thr/Thr and Thr/Met, OR = 1.54, 95% CI = 0.94-2.52). No association between XRCC1 Arg399Gln Dgenotype and breast cancer risk was observed. ...

Research paper thumbnail of A comprehensive examination of breast cancer risk loci in African American women

Human molecular genetics, Jan 15, 2014

Genome-wide association studies have identified 73 breast cancer risk variants mainly in European... more Genome-wide association studies have identified 73 breast cancer risk variants mainly in European populations. Given considerable differences in linkage disequilibrium structure between populations of European and African ancestry, the known risk variants may not be informative for risk in African ancestry populations. In a previous fine-mapping investigation of 19 breast cancer loci, we were able to identify SNPs in four regions that better captured risk associations in African American women. In this study of breast cancer in African American women (3016 cases, 2745 controls), we tested an additional 54 novel breast cancer risk variants. Thirty-eight variants (70%) were found to have an association with breast cancer in the same direction as previously reported, with eight (15%) replicating at P < 0.05. Through fine-mapping, in three regions (1q32, 3p24, 10q25), we identified variants that better captured associations with overall breast cancer or estrogen receptor positive dis...

Research paper thumbnail of The Potential for Enhancing the Power of Genetic Association Studies in African Americans through the Reuse of Existing Genotype Data

PLoS Genetics, 2010

We consider the feasibility of reusing existing control data obtained in genetic association stud... more We consider the feasibility of reusing existing control data obtained in genetic association studies in order to reduce costs for new studies. We discuss controlling for the population differences between cases and controls that are implicit in studies utilizing external control data. We give theoretical calculations of the statistical power of a test due to Bourgain et al (Am J Human Genet 2003), applied to the problem of dealing with case-control differences in genetic ancestry related to population isolation or population admixture. Theoretical results show that there may exist bounds for the non-centrality parameter for a test of association that places limits on study power even if sample sizes can grow arbitrarily large. We apply this method to data from a multi-center, geographically-diverse, genome-wide association study of breast cancer in African-American women. Our analysis of these data shows that admixture proportions differ by center with the average fraction of European admixture ranging from approximately 20% for participants from study sites in the Eastern United States to 25% for participants from West Coast sites. However, these differences in average admixture fraction between sites are largely counterbalanced by considerable diversity in individual admixture proportion within each study site. Our results suggest that statistical correction for admixture differences is feasible for future studies of African-Americans, utilizing the existing controls from the African-American Breast Cancer study, even if case ascertainment for the future studies is not balanced over the same centers or regions that supplied the controls for the current study.

Research paper thumbnail of Enhanced Statistical Tests for GWAS in Admixed Populations: Assessment using African Americans from CARe and a Breast Cancer Consortium

PLoS Genetics, 2011

While genome-wide association studies (GWAS) have primarily examined populations of European ance... more While genome-wide association studies (GWAS) have primarily examined populations of European ancestry, more recent studies often involve additional populations, including admixed populations such as African Americans and Latinos. In admixed populations, linkage disequilibrium (LD) exists both at a fine scale in ancestral populations and at a coarse scale (admixture-LD) due to chromosomal segments of distinct ancestry. Disease association statistics in admixed populations have previously considered SNP association (LD mapping) or admixture association (mapping by admixture-LD), but not both. Here, we introduce a new statistical framework for combining SNP and admixture association in case-control studies, as well as methods for local ancestry-aware imputation. We illustrate the gain in statistical power achieved by these methods by analyzing data of 6,209 unrelated African Americans from the CARe project genotyped on the Affymetrix 6.0 chip, in conjunction with both simulated and real phenotypes, as well as by analyzing the FGFR2 locus using breast cancer GWAS data from 5,761 African-American women. We show that, at typed SNPs, our method yields an 8% increase in statistical power for finding disease risk loci compared to the power achieved by standard methods in case-control studies. At imputed SNPs, we observe an 11% increase in statistical power for mapping disease loci when our local ancestry-aware imputation framework and the new scoring statistic are jointly employed. Finally, we show that our method increases statistical power in regions harboring the causal SNP in the case when the causal SNP is untyped and cannot be imputed. Our methods and our publicly available software are broadly applicable to GWAS in admixed populations.

Research paper thumbnail of Identification, Replication, and Fine-Mapping of Loci Associated with Adult Height in Individuals of African Ancestry

PLoS Genetics, 2011

Adult height is a classic polygenic trait of high heritability (h 2 ,0.8). More than 180 single n... more Adult height is a classic polygenic trait of high heritability (h 2 ,0.8). More than 180 single nucleotide polymorphisms (SNPs), identified mostly in populations of European descent, are associated with height. These variants convey modest effects and explain ,10% of the variance in height. Discovery efforts in other populations, while limited, have revealed loci for height not previously implicated in individuals of European ancestry. Here, we performed a meta-analysis of genome-wide association (GWA) results for adult height in 20,427 individuals of African ancestry with replication in up to 16,436 African Americans. We found two novel height loci (Xp22-rs12393627, P = 3.4610 212 and 2p14-rs4315565, P = 1.2610 28). As a group, height associations discovered in European-ancestry samples replicate in individuals of African ancestry (P = 1.7610 24 for overall replication). Fine-mapping of the European height loci in African-ancestry individuals showed an enrichment of SNPs that are associated with expression of nearby genes when compared to the index European height SNPs (P,0.01). Our results highlight the utility of genetic studies in non-European populations to understand the etiology of complex human diseases and traits.

Research paper thumbnail of Intake of Plant Foods and Associated Nutrients in Prostate Cancer Risk

Nutrition and Cancer, 2009

Plant foods and associated nutrients may impact prostate cancer (PC) risk and survival. Therefore... more Plant foods and associated nutrients may impact prostate cancer (PC) risk and survival. Therefore, we compared dietary intake, mainly plant food groups among 382 controls and 478 PC cases (373 incident and 105 prevalent cases). Caucasian controls had significantly higher daily servings of vegetables (3.4 vs. 2.5, P = 0.002) and fruits and/or fruit juices (1.6 vs. 1.3, P = 0.02) compared to African American controls. In Caucasians, incident cases reported lower intake of fiber, vitamin C, vitamin A, α-carotene, β-carotene, cryptoxanthin, folate, genistein, daidzein, and fruits and/or fruit juice than controls and/or prevalent cases. In African Americans, incident cases had lower intake of α-carotene compared to controls and prevalent cases. Reduced PC risk was associated with the highest tertile of cryptoxanthin (OR = 0.51; 95% CI = 0.35-0.75), fiber (OR = 0.56; 95% CI = 0.35-0.89), vitamin C (OR = 0.60; 95% CI = 0.41-0.88), and fruits and/or fruit juices (OR = 0.46; 95% CI = 0.31-0.68), with significant linear trends. Increased risk of PC was associated with the highest tertile of protein (OR = 1.99; 95% CI = 1.05-3.79) and daily servings of grains (OR = 1.99; 95% CI = 1.23-3.22) with significant linear trends. In summary, we demonstrate racial/ethnic differences in dietary intake of plant foods. The significantly higher consumption of protective dietary constituents among prevalent cases compared to incident cases suggests that PC survivors may be amenable to dietary change.

Research paper thumbnail of The landscape of recombination in African Americans

Nature, 2011

Recombination, together with mutation, is the ultimate source of genetic variation in populations... more Recombination, together with mutation, is the ultimate source of genetic variation in populations. We leverage the recent mixture of people of African and European ancestry in the Americas to build a genetic map measuring the probability of crossing-over at each position in the genome, based on about 2.1 million crossovers in 30,000 unrelated African Americans. At intervals of more than three megabases it is nearly identical to a map built in Europeans. At finer scales it differs significantly, and we identify about 2,500 recombination hotspots that are active in people of West African ancestry but nearly inactive in Europeans. The probability of a crossover at these hotspots is almost fully controlled by the alleles an individual carries at PRDM9 (P<10 −245). We identify a 17 base pair DNA sequence motif that is enriched in these hotspots, and is an excellent match to the predicted binding target of African-enriched alleles of PRDM9. In humans and many other species, recombination is not evenly distributed across the genome, but instead occurs in "hotspots": two kilobase (kb) segments where the crossover rate is far higher than in the flanking DNA sequence 1,2,3. The highest resolution genetic map in contemporary humans to date, the "deCODE Map", is based on about 500,000 crossovers identified in 15,000 Icelandic meioses 4. However, a limitation of maps built in people of European descent 4,5,6 is that they may not apply equally well in other populations, as suggested by comparisons of maps across ethnic groups 4,7,8,9 and patterns of linkage disequilibrium (LD) breakdown which suggest that more of the genome may be recombinationally active in West Africans 10. It is known that a major determinant of the positions of recombination hotspots is PRDM9, a meiosis-specific histone H3 methyltransferase whose zinc finger (ZF) domain binds DNA sequence motifs 11,12,13. In Europeans, PRDM9 ZF arrays are predominantly of two similar types, "A" and "B", both of which bind the 13-bp motif CCNCCNTNNCCNC 11. In contrast, 36% of West African Users may view, print, copy, download and text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: