Victoria K Cortessis

University of Southern California, Los Angeles, California, United States

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Publications (58)354.84 Total impact

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    ABSTRACT: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) ≥ 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 × 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. ©2014 AACR.
    Cancer Research 10/2014; 74(20):5808-18. · 9.28 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
    Human Molecular Genetics 07/2014; · 7.69 Impact Factor
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    ABSTRACT: Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repair (BER), nucleotide excision repair (NER), non-homologous end-joining (NHEJ), and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT, and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (Smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2014; · 6.20 Impact Factor
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    ABSTRACT: Recent genome-wide association studies (GWAS) of Hodgkin lymphoma (HL) have identified associations with genetic variation at both HLA and non-HLA loci; however, much of heritable HL susceptibility remains unexplained. Here we perform a meta-analysis of three HL GWAS totaling 1,816 cases and 7,877 controls followed by replication in an independent set of 1,281 cases and 3,218 controls to find novel risk loci. We identify a novel variant at 19p13.3 associated with HL (rs1860661; odds ratio (OR)=0.81, 95% confidence interval (95% CI)=0.76–0.86, Pcombined=3.5 × 10^(−10)), located in intron 2 of TCF3 (also known as E2A), a regulator of B- and T-cell lineage commitment known to be involved in HL pathogenesis. This meta-analysis also notes associations between previously published loci at 2p16, 5q31, 6p31, 8q24 and 10p14 and HL subtypes. We conclude that our data suggest a link between the 19p13.3 locus, including TCF3, and HL risk.
    Nature Communications 06/2014; 5:3856. · 10.74 Impact Factor
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    ABSTRACT: To evaluate the accuracy of testicular germ cell tumor category in the Surveillance, Epidemiology, and End Results (SEER) database following the 2010 American Joint Committee of Cancer revision of the TNM staging criteria.
    Urologic oncology. 05/2014;
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    ABSTRACT: Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study of smoking and bladder cancer risk based on primary scan data from 3,002 cases and 4,411 controls from the NCI Bladder Cancer Genome- Wide Association Study (GWAS). Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P-values <5x10(-5) were evaluated further in an independent dataset of 2,422 bladder cancer cases and 5,751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial data set and in the combined data set, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers (combined OR=1.34, 95% CI=1.20-1.50, P-value=5.18x10(-7)); and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR=0.75, 95% CI=0.67-0.84, P-value=6.35x10(-7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, while the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer.
    Carcinogenesis 03/2014; · 5.64 Impact Factor
  • American journal of epidemiology 03/2014; · 5.59 Impact Factor
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    ABSTRACT: Objectives To evaluate the accuracy of testicular germ cell tumor category in the Surveillance, Epidemiology, and End Results (SEER) database following the 2010 American Joint Committee of Cancer revision of the TNM staging criteria. Methods We performed a retrospective review of our testicular cancer database from January 2010 to July 2011. Registrar extracted data on 76 patients were entered into the Cancer Surveillance Program database from 2 hospitals. We reviewed the SEER coding for each patient, including T, N, M, and S and overall stage group, as well as the range and S value given for tumor markers (lactate dehydrogenase, beta-human chorionic gonadotropin, and α-fetoprotein) both preorchiectomy and postorchiectomy. We then compared these values with the actual staging and tumor markers determined by patient medical record review by a single urologist. Results A high proportion of registry records were found to have inaccurate values of category: 71% of S category entries and 34% of N category entries, leading to an overall group stage inaccuracy of 77% in SEER data. Accuracy of overall combined stage group was significantly different between hospitals, with a higher percentage of errors at Hospital A (P< 0.05). Conclusion Despite improvements made to the SEER criteria for extracting data used to code testicular germ cell tumor TNM stage, considerable errors were identified, most notably in tumor marker and nodal status, resulting in an overwhelming number of errors in overall stage. Our findings suggest caution when utilizing SEER data for review of patients with testicular cancer and their staging.
    Urologic Oncology: Seminars and Original Investigations. 01/2014;
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    ABSTRACT: Candidate gene and genome-wide association studies (GWAS) have identified 11 independent susceptibility loci associated with bladder cancer risk. To discover additional risk variants, we conducted a new GWAS of 2,422 bladder cancer cases and 5,751 controls, followed by a meta-analysis with two independently published bladder cancer GWAS, resulting in a combined analysis of 6,911 cases and 11,814 controls of European descent. TaqMan genotyping of 13 promising SNPs with P< 1x10(-5) was pursued in a follow-up set of 801 cases and 1,307 controls. Two new loci achieved genome-wide statistical significance: rs10936599 on 3q26.2 (P=4.53×10(-9)) and rs907611 on 11p15.5 (P=4.11×10(-8)). Two notable loci were also identified that approached genome-wide statistical significance: rs6104690 on 20p12.2 (P=7.13×10(-7)) and rs4510656 on 6p22.3 (P=6.98×10(-7)); these require further studies for confirmation. In conclusion, our study has identified new susceptibility alleles for bladder cancer risk that require fine-mapping and laboratory investigation, which could further understanding into the biological underpinnings of bladder carcinogenesis.
    Human Molecular Genetics 10/2013; · 7.69 Impact Factor
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    ABSTRACT: Testicular germ cell tumors (TGCTs), the most common neoplasms of young men, are categorized histologically as either seminomas or nonseminomas/mixed germ cell tumors. These subtypes differ by age at diagnosis and clinical course, but little is known about etiological distinctions. To test the hypothesis that histological subtypes have distinct sets of unrecognized etiological factors, we used a recently described approach, estimating the association between histological types of first and second tumors of men with 2 primary TGCTs. The study population of 488 men each with 2 primary TGCTs was ascertained through population-based cancer registries in the United States between 1972 and 2006. Univariate logistic regression analysis revealed that the histology of second primary TGCTs was associated with the histology of first TGCTs (odds ratio = 1.70, 95% confidence interval: 1.14, 2.52); however, the association did not persist in analyses adjusted for age at diagnosis of first TGCT (odds ratio = 1.09, 95% confidence interval: 0.71, 1.70). These results would be expected if the subtypes share etiology but experience different rates of progression to diagnosis or if the histological fate of TGCTs is influenced by age-related processes. Men with 2 primary TGCTs provide novel opportunities to learn whether histological subtypes are likely to share etiology, so results may inform research designed to identify causes.
    American journal of epidemiology 08/2013; · 5.59 Impact Factor
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    ABSTRACT: N-Nitroso compounds (NOCs) have been proposed as possible bladder carcinogens. The main sources of exogenous exposure to NOCs are cigarette smoke and diet, particularly processed (i.e. nitrite-treated) meats. Perhaps more importantly, NOCs can be formed endogenously from dietary precursors such as nitrate, nitrite and amines. Heme has been shown to increase endogenous nitrosation. We examined the role of dietary sources of NOCs and NOC precursors as potential bladder cancer risk factors using data from the Los Angeles Bladder Cancer Study, a population-based case-control study. Dietary and demographic information was collected from 1660 bladder cancer cases and 1586 controls via a structured questionnaire. Intake of liver and of salami/pastrami/corned beef, were both statistically significantly associated with risk of bladder cancer in this study, particularly among non-smokers. Heme intake was also statistically significantly associated with risk of bladder cancer among non-smokers only. When considering NOC precursors, risk was consistently higher among subjects with concurrent high intake of nitrate and high intake of the different meats (sources of amines and nitrosamines). Results of this study are consistent with a role of dietary sources of NOC precursors from processed meats in bladder cancer risk, suggesting consumption of meats with high amine and heme content such as salami and liver as a risk factor for bladder cancer. In addition, any effect of consuming these meats may be greater when accompanied by high nitrate intake. © 2013 Wiley Periodicals, Inc.
    International Journal of Cancer 06/2013; · 6.20 Impact Factor
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    ABSTRACT: We conducted a meta-analysis to identify new susceptibility loci for testicular germ cell tumor (TGCT). In the discovery phase, we analyzed 931 affected individuals and 1,975 controls from 3 genome-wide association studies (GWAS). We conducted replication in 6 independent sample sets comprising 3,211 affected individuals and 7,591 controls. In the combined analysis, risk of TGCT was significantly associated with markers at four previously unreported loci: 4q22.2 in HPGDS (per-allele odds ratio (OR) = 1.19, 95% confidence interval (CI) = 1.12-1.26; P = 1.11 × 10(-8)), 7p22.3 in MAD1L1 (OR = 1.21, 95% CI = 1.14-1.29; P = 5.59 × 10(-9)), 16q22.3 in RFWD3 (OR = 1.26, 95% CI = 1.18-1.34; P = 5.15 × 10(-12)) and 17q22 (rs9905704: OR = 1.27, 95% CI = 1.18-1.33; P = 4.32 × 10(-13) and rs7221274: OR = 1.20, 95% CI = 1.12-1.28; P = 4.04 × 10(-9)), a locus that includes TEX14, RAD51C and PPM1E. These new TGCT susceptibility loci contain biologically plausible genes encoding proteins important for male germ cell development, chromosomal segregation and the DNA damage response.
    Nature Genetics 05/2013; · 35.21 Impact Factor
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    ABSTRACT: BACKGROUND: 4-Aminobiphenyl (ABP) is an established human bladder carcinogen, with tobacco smoke being a major source of human exposure. Other arylamine compounds, including 2,6-dimethylaniline (2,6-DMA), have been implicated as possible human bladder carcinogens. Hemoglobin adducts of 4-ABP and 2,6-DMA are validated biomarkers of exposure to those compounds in humans. METHODS: The Shanghai Bladder Cancer Study enrolled 581 incident bladder cancer cases and 604 population controls. Each participant was solicited for his/her history of tobacco use and other lifestyle factors, and donation of blood and urine specimens. Red blood cell lysates were used to quantify both hemoglobin adducts of 4-ABP and 2,6-DMA. Urine samples were used to quantify total cotinine. Odds ratios (ORs) and 95% confidence intervals (CIs) for bladder cancer were estimated using unconditional logistic regression methods. RESULTS: Among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for low (below median of positive values) and high versus undetectable levels of 2,6-DMA hemoglobin adducts were 3.87 (1.39-10.75) and 6.90 (3.17-15.02), respectively (Ptrend<0.001). Similarly, among lifelong nonsmokers, ORs (95% CIs) of bladder cancer for 3rd and 4th versus 1st/2nd quartiles of 4-ABP hemoglobin adducts was 1.30 (0.76-2.22) and 2.29 (1.23-4.24), respectively (Ptrend=0.00). The two associations were independent of each other. CONCLUSION: Hemoglobin adducts of 4-ABP and 2,6-DMA were significantly and independently associated with increased bladder cancer risk among lifelong nonsmokers in Shanghai, China. Impact: The findings of the present study in China with previous data in Los Angeles, California strongly implicate arylamines as potential causal agents of human bladder cancer.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2013; · 4.56 Impact Factor
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    ABSTRACT: Genome-wide association studies (GWAS) have identified multiple common genetic variants associated with an increased risk of testicular germ cell tumors (TGCT). A previous GWAS study reported a possible TGCT susceptibility locus on chromosome 1q23 in the UCK2 gene but failed to reach genome-wide significance following replication. We interrogated this region by conducting a meta-analysis of two independent GWAS including a total of 940 TGCT cases and 1,559 controls for 122 single nucleotide polymorphisms (SNP) on chromosome 1q23 and followed up the most significant SNPs in an additional 2,202 TGCT cases and 2,386 controls from four case-control studies. We observed genome-wide significant associations for several UCK2 markers, the most significant of which was for rs3790665 (PCombined=6.0x10-9). Additional support is provided from an independent familial study of TGCT where a significant over transmission for rs3790665 with TGCT risk was observed (PFBAT=2.3x10-3). Here, we provide substantial evidence for the association between UCK2 genetic variation and TGCT risk.
    Human Molecular Genetics 03/2013; · 7.69 Impact Factor
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    ABSTRACT: BACKGROUND: Traditional single-marker and multimarker molecular profiling approaches in bladder cancer do not account for major risk factors and their influence on clinical outcome. This study examined the prognostic value of molecular alterations across all disease stages after accounting for clinicopathological factors and smoking, the most common risk factor for bladder cancer in the developed world, in a population-based cohort. METHODS: Primary bladder tumors from 212 cancer registry patients (median follow-up, 13.2 years) were immunohistochemically profiled for Bax, caspase-3, apoptotic protease-activating factor 1 (Apaf-1), Bcl-2, p53, p21, cyclooxygenase-2, vascular endothelial growth factor, and E-cadherin alterations. "Smoking intensity" quantified the impact of duration and daily frequency of smoking. RESULTS: Age, pathological stage, surgical modality, and adjuvant therapy administration were significantly associated with survival. Increasing smoking intensity was independently associated with worse outcome (P < .001). Apaf-1, E-cadherin, and p53 were prognostic for outcome (P = .005, .014, and .032, respectively); E-cadherin remained prognostic following multivariable analysis (P = .040). Combined alterations in all 9 biomarkers were prognostic by univariable (P < .001) and multivariable (P = .006) analysis. A multivariable model that included all 9 biomarkers and smoking intensity had greater accuracy in predicting prognosis than models composed of standard clinicopathological covariates without or with smoking intensity (P < .001 and P = .018, respectively). CONCLUSIONS: Apaf-1, E-cadherin, and p53 alterations individually predicted survival in bladder cancer patients. Increasing number of biomarker alterations was significantly associated with worsening survival, although markers comprising the panel were not necessarily prognostic individually. Predictive value of the 9-biomarker panel with smoking intensity was significantly higher than that of routine clinicopathological parameters alone. Cancer 2013;. © 2013 American Cancer Society.
    Cancer 01/2013; · 5.20 Impact Factor
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    ABSTRACT: Although deaths from cervical cancer are declining, Latinas are not benefiting equally in this decline. Incidence of invasive cervical cancer among Los Angeles', California Latinas is much higher than among non-Latina Whites (14.7 versus 8.02 per 100,000). This paper examines cervical cancer screening among Latinas. Ninety-seven women of Mexican origin participated in 12 focus groups exploring barriers to screening. Saturation was reached. All participants knew what a Pap test was and most knew its purpose. More acculturated participants understood the link between HPV and cervical cancer. More recent immigrants did not. There was confusion whether women who were not sexually active need to be screened. Most frequently mentioned barriers were lack of time and concern over missing work. Lower income and less acculturated women were less likely to be aware of free/low-cost clinics. Older and less acculturated participants held more fatalistic beliefs, were more embarrassed about getting a Pap test, were more fearful of being perceived as sexually promiscuous, and were more fearful of receiving disapproval from their husbands. Latinas are informed regarding cervical cancer screening; rather they encounter barriers such as a lack of time, money and support. Health promotion interventions can be enhanced via peer-to-peer education, by addressing barriers to cervical cancer screening with in-language, culturally tailored interventions, and working with clinics on systemic changes, such as extended clinic hours.
    Californian journal of health promotion. 01/2013; 11(1):45-57.
  • John Charles A Lacson, Leslie Bernstein, Victoria K Cortessis
    Cancer 12/2012; · 5.20 Impact Factor
  • Victoria K Cortessis
    International Journal of Epidemiology 12/2012; 41(6):1761-3. · 6.98 Impact Factor
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    ABSTRACT: Testicular germ cell tumor (TGCT) incidence increased steadily in recent decades, but causes remain elusive. Germ cell function may be influenced by cannabinoids, and 2 prior epidemiologic studies reported that the use of marijuana may be associated with nonseminomatous TGCT. Here, the authors evaluate the relation between TGCTs and exposure to marijuana and other recreational drugs using a population-based case-control study. In total, 163 patients who were diagnosed with TGCT in Los Angeles County from December 1986 to April 1991 were enrolled, and 292 controls were matched on age, race/ethnicity, and neighborhood. Participants were asked about drug use by a structured, in-person interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression analysis adjusted for history of cryptorchidism; education; religiosity; and reported use of marijuana, cocaine, and amyl nitrite. Compared with never use, ever use of marijuana had a 2-fold increased risk (OR, 1.94; 95% CI, 1.02-3.68), whereas ever use of cocaine had a negative association with TGCT (OR, 0.54; 95% CI, 0.32-0.91). Stratification on tumor histology revealed a specific association of marijuana use with nonseminoma and mixed histology tumors (OR, 2.42; 95% CI, 1.08-5.42). A specific association was observed between marijuana use and the risk of nonseminoma and mixed tumors. To the authors' knowledge, this is the first report of a negative association between cocaine use and TGCT risk. The current results warrant mechanistic studies of marijuana's effect on the endocannabinoid system and TGCT risk and caution that recreational and therapeutic use of cannabinoids by young men may confer malignant potential to testicular germ cells. Cancer 2012. © 2012 American Cancer Society.
    Cancer 09/2012; 118(21):5374-83. · 5.20 Impact Factor
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    ABSTRACT: Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition, tobacco smoke, air pollutants, metals, organic chemicals, other sources of oxidative stress, and the microbiome, particularly if the exposure occurs during key periods of development. Thus, epigenetic changes could represent an important pathway by which environmental factors influence disease risks, both within individuals and across generations. We discuss some of the challenges in studying epigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.
    Human Genetics 06/2012; 131(10):1565-89. · 4.63 Impact Factor

Publication Stats

948 Citations
354.84 Total Impact Points

Institutions

  • 2001–2014
    • University of Southern California
      • Department of Preventive Medicine
      Los Angeles, California, United States
  • 2012
    • St. Joseph Hospital, Orange
      Orange, California, United States
    • Keck School of Medicine USC
      Los Angeles, California, United States
  • 2008
    • Institute of Cancer Research
      Londinium, England, United Kingdom
  • 1993–2008
    • University of California, Los Angeles
      • Department of Epidemiology
      Los Angeles, California, United States
  • 2006
    • University of Pennsylvania
      • Department of Medicine
      Philadelphia, PA, United States