Ilir Agalliu

Publications (28)122.84 Total impact

• Article: Preoperative statin therapy is not associated with biochemical recurrence after radical prostatectomy: our experience and meta-analysis.

  Alon Y Mass, Ilir Agalliu, Juliana Laze, Herbert Lepor
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  ABSTRACT: The effect of statins on prostate cancer recurrence has been investigated in several studies with inconsistent results. We investigated whether statins were associated with biochemical recurrence in a large cohort of men after radical prostatectomy. We also performed a meta-analysis of existing studies. A total of 1,446 patients who underwent radical prostatectomy at New York University were followed a median of 57 months for biochemical recurrence events. Baseline demographic and clinical characteristics were compared between 437 statin users and 1,009 nonusers. Kaplan-Meier curves and Cox models were used to examine biochemical recurrence-free survival by statin use. A meta-analysis was performed with data from our cohort and 5 published studies using the random effects model. Statin users were slightly older and more likely to have diabetes (p <0.01). They were similar to nonusers in race and body mass index. Although preoperative prostate specific antigen and tumor stage were similar between the 2 groups, the proportion of patients with pathological Gleason score 7-10 tumors was slightly higher among statin users (p = 0.03). The biochemical recurrence-free survival rate was 87.4% and 89.0% for statin users and nonusers, respectively, at the end of followup (log rank p = 0.26). Overall biochemical recurrence was not associated with statin use (HR 1.15, 95% CI 0.82-1.61). Results were similar when patients were stratified by D'Amico low and intermediate or high risk groups. Meta-analysis revealed no overall association between statins and biochemical recurrence (pooled HR 1.00, 95% CI 0.80-1.19). Our findings are consistent with the results of the meta-analysis, which indicated that preoperative statin use does not impact the overall risk of biochemical recurrence.
  The Journal of urology 07/2012; 188(3):786-91. · 4.02 Impact Factor
• Article: Comparison of health-related quality-of-life outcomes for African-American and Caucasian-American men after radical prostatectomy.

  Eugene W Lee, Tracy Marien, Juliana Laze, Ilir Agalliu, Herbert Lepor
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  ABSTRACT: Study Type - Therapy (outcomes) Level of Evidence 2c What's known on the subject? and What does the study add? In addition to a higher prevalence and biological aggressiveness of prostate cancer, African-Americans tend towards narrower pelvises than Caucasians resulting in a potentially more difficult surgical dissection doing radical prostatectomy and increased positive surgical margins. In this study, there was no difference in urinary or sexual HRQL or overall satisfaction between African-Americans and Caucasians 2 years after radical prostatectomy, suggesting that the potential technical challenges of a narrower pelvis do not translate into poorer outcomes for African-Americans. •  To determine if any differences exist in postoperative health-related quality-of-life (HRQL) outcomes, e.g. erectile function and continence, after radical prostatectomy (RP) in African-American (AA) vs Caucasian-American (CA) men. •  Between October 2000 and July 2008, 1338 CA and 56 AA men underwent open RP by a single surgeon and signed informed consent to participate in a prospective longitudinal outcomes study. •  The American Urological Association Symptom Score (AUA-SS) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and a global assessment of satisfaction were self-administered at baseline and after RP 24 months. •  Urinary, sexual, and satisfaction outcomes were compared at 24 months. •  AA men had significantly higher rates of hypertension and diabetes. •  There were no other significant baseline differences in age, co-morbidities, body mass index, phosphodiesterase type 5 inhibitor use, preoperative prostate-specific antigen level, AUA-SS, and UCLA-PCI scores. •  There were no differences in the percentage of men undergoing nerve-sparing procedures, estimated blood loss, transfusion rates, or complication rates between the groups. •  At 24 months after RP the mean UCLA-PCI urinary and sexual function and bother scores and global satisfaction scores were similar between the groups. •  AA and CA men experience no significant differences in urinary and sexual HRQL or overall satisfaction after open RP when performed by a single experienced surgeon.
  BJU International 03/2012; 110(8):1129-33. · 2.84 Impact Factor
• Article: Blood loss during radical prostatectomy: impact on clinical, oncological and functional outcomes and complication rates.

  Bob Djavan, Ilir Agalliu, Juliana Laze, Helen Sadri, Amir Kazzazi, Herbert Lepor
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  ABSTRACT: Study Type - Outcomes (cohort) Level of Evidence 2b What's known on the subject? and What does the study add? It is generally accepted in the medical community that total and intra-operative blood loss after RALP is significantly lower in comparison with ORRP. This has led to speculation that less bleeding results in better visualization of the operative field resulting in superior potency and continence. Blood loss (BL) during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with RALP would not be expected to improve functional or oncological outcomes. To determine the short- and long-term impact of blood loss (BL) on clinical, oncological and functional outcomes as well as complication rates after an open radical retropubic prostatectomy (ORRP). Between 2000 and 2008, 1567 men who underwent an ORRP participated in our prospective longitudinal outcomes study. Haematocrit (Hct) levels, transfusion rates, BL and complications were recorded prospectively. Validated, self-administered quality-of-life (QoL) questionnaires were completed at baseline, 3, 6 and 12 months and yearly thereafter. Urinary function and erectile dysfunction were assessed using AUA Symptom Score and the UCLA Prostate Cancer Index and analysis of variance (anova)/chi-square tests were used to compare clinical, BL, biochemical recurrence (BCR) and QoL outcomes amongst the three groups for continuous/categorical variables. The mean estimated BL was 742.7 (45 to 3500) mL and 5.4% and 3.8% received an autologous (AU) or allogeneic (AL) blood transfusions, respectively. The average baseline, induction, postoperative and discharge Hct was 43.8%, 48.3%, 35.7% and 34.1%, respectively. The estimated BL and the rate of change of Hct correlated moderately (r=0.41, P<0.0001). Tertiles of BL were based on the difference between induction and discharge Hct (Delta 1) and the average Delta 1 for Groups 1, 2 and 3 were 7.9%, 12.7% and 17.2%, respectively. Intra-operative, early/delayed complications, length of hospital stay (LoS), SM surgical margins status, anastomotic stricture and BCR were not statistically different (P<0.001) and the mean AUASS, UCLA Prostate Cancer urinary bother scores, urinary function scores, sexual bother/function scores at 24 months were similar amongst all tertiles (P>0.05). BL during ORRP does not adversely impact clinical and functional outcomes irrespective of how BL is defined. Thus, the lower BL associated with robotic-assisted laparoscopic prostatectomy (RALP) in and of itself would not be expected to improve functional or oncological outcomes.
  BJU International 12/2011; 110(1):69-75. · 2.84 Impact Factor
• Article: Risk of lung cancer in relation to contiguous windows of endotoxin exposure among female textile workers in Shanghai.

  Ilir Agalliu, Sadie Costello, Katie M Applebaum, Roberta M Ray, George Astrakianakis, Dao Li Gao, David B Thomas, Harvey Checkoway, Ellen A Eisen
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  ABSTRACT: Exposure to endotoxin has been consistently associated with a reduced risk of lung cancer. However, there is a paucity of information regarding temporal aspects of this relationship. The objective of this study was to investigate the associations between contiguous windows of endotoxin exposure and risk of lung cancer. Data were reanalyzed from a case-cohort study (602 cases, 3,038 subcohort) of female textile workers in Shanghai, China. Cumulative endotoxin exposure was partitioned into two windows: ≥20 and <20 years before risk. Exposure-response relations were examined using categorical and non-linear (semi-parametric) models, accounting for confounding by previous exposure windows. There was an inverse trend of decreasing risk of lung cancer associated with increasing levels of endotoxin exposure ≥20 years before risk (p trend = 0.02). Women in the highest two categories of cumulative exposures had hazard ratios of 0.78 (95% CI 0.60-1.03) and 0.77 (95% CI 0.58-1.02) for lung cancer, respectively, in comparison with unexposed textile workers. There was, however, a weaker association and not statistically significant between lung cancer and endotoxin exposure accumulated in the more recent window (<20 years before risk). Results provide further evidence that endotoxin exposure that occurred 20 years or more before risk confers the strongest protection against lung cancer, indicating a possible early anti-carcinogenic effect. Further studies are needed to better understand the underlying biological mechanisms for this effect.
  Cancer Causes and Control 07/2011; 22(10):1397-404. · 2.88 Impact Factor
• Article: Multi-institutional prostate cancer study of genetic susceptibility in populations of African descent.

  Emanuela Taioli, Rafael E Flores-Obando, Ilir Agalliu, Pascal Blanchet, Clareann H Bunker, Robert E Ferrell, Maria Jackson, La Creis R Kidd, Suzanne Kolb, Nicol A Lavender, [......], Jong Y Park, Alan L Patrick, Timothy R Rebbeck, Marc Romana, Janet L Stanford, Flora Ukoli, Tiva T Vancleave, Charnita M Zeigler-Johnson, Batsirai Mutetwa, Camille Ragin
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  ABSTRACT: Prostate cancer disparities have been reported in men of African descent who show the highest incidence, mortality, compared with other ethnic groups. Few studies have explored the genetic and environmental factors for prostate cancer in men of African ancestry. The glutathione-S-transferases family conjugates carcinogens before their excretion and is expressed in prostate tissue. This study addressed the role of GSTM1 and GSTT1 deletions on prostate cancer risk in populations of African descent. This multi-institutional case-control study gathered data from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database, the African-Caribbean Cancer Consortium (AC3) and Men of African Descent and Carcinoma of the Prostate Consortium (MADCaP). The analysis included 10 studies (1715 cases and 2363 controls), five in African-Americans, three in African-Caribbean and two in African men. Both the GSTM1 and the GSTT1 deletions showed significant inverse associations with prostate cancer [odds ratio (OR): 0.90, 95% confidence interval (CI) 0.83-0.97 and OR 0.88, 95% CI: 0.82-0.96, respectively]. The association was restricted to Caribbean and African populations. A significant positive association was observed between GSTM1 deletion and prostate cancer in smokers in African-American studies (OR: 1.28, 95% CI: 1.01-1.56), whereas a reduced risk was observed in never-smokers (OR: 0.66, 95% CI: 0.46-0.95). The risk of prostate cancer increased across quartiles of pack-years among subjects carrying the deletion of GSTM1 but not among subjects carrying a functional GSTM1. Gene-environment interaction between smoking and GSTM1 may be involved in the etiology of prostate cancer in populations of African descent.
  Carcinogenesis 06/2011; 32(9):1361-5. · 5.70 Impact Factor
• Article: The short-term use of erythropoetin-stimulating agents: impact on the biochemical recurrence of prostate cancer.

  Bob Djavan, Juliana Laze, Elisabeth Eckersberger, Julia Finkelstein, Ilir Agalliu, Herbert Lepor
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  ABSTRACT: To examine the impact of short-term preoperative utilization of erythropoietin-stimulating agents (ESAs) on biochemical recurrence (BCR)-free survival rates after open radical retropubic prostatectomy (ORRP) in light of the fact that the risk/benefit of ESAs has recently been questioned by the Food and Drug Administration (FDA) after reports showing a decreased survival. From 2000 to 2008, 1567 patients underwent ORRP and 97.5% of these signed informed consent to participate in the New York University Prospective and Longitudinal Outcomes Study. Of the remaining 1528 patients, 1317 (86%) received preoperative ESA (group 1) and 211 (14%) did not (group 2). Patients were also classified as having low-, intermediate- or high-risk disease based on D'Amico risk categories. Kaplan-Meier survival curves and Cox's proportional hazard models were used to estimate BCR-free survival by ESA treatment. A significant difference was observed for BCR-free survival between the low- and intermediate/high-risk groups. There were no statistically significant differences between groups 1 and 2 for BCR-free survival in the entire study populations and within risk groups. In addition, Cox regression models showed no statistically significant differences in BCR-free survival according to preoperative ESA administration in the entire cohort as well as among the low- and intermediate/high-risk groups. The short-term use of ESAs as a preoperative blood management strategy for patients undergoing ORRP has no clinically relevant adverse effects on the biology of prostate cancer. The present study supports the use of these agents before the procedure in patients undergoing surgery for localized disease.
  BJU International 03/2011; 108(10):1582-7. · 2.84 Impact Factor
• Article: Oxidative balance score and risk of prostate cancer: results from a case-cohort study.

  Ilir Agalliu, Victoria A Kirsh, Nancy Kreiger, Colin L Soskolne, Thomas E Rohan
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  ABSTRACT: Prostate cancer is a disease with a complex etiology. Oxidative stress has been implicated in its pathogenesis; however, few prospective studies have investigated the association between an oxidative stress/balance score and risk of prostate cancer. We investigated associations between an oxidative balance score, calculated as the summation of individual scores obtained from five pro-oxidative and eight anti-oxidative exposures, as well as each individual constituent of the score and risks of prostate cancer overall, and by clinical characteristics, in a case-cohort study (661 cases and 1864 subcohort) nested within the Canadian Study of Diet, Lifestyle, and Health cohort. Men in the lowest quintiles of each pro-oxidant exposure received a score of four (the highest score), while those in the highest quintile received a score of zero (the lowest score). In contrast, scoring for all anti-oxidants was performed in the opposite way. Total oxidative balance score was calculated by summating all individual scores of pro- and anti-oxidative variables, with higher values indicating a higher antioxidant status. The average oxidative balance score was similar between prostate cancer cases and men in the subcohort: 25.2 and 25.3, respectively. There was no association between oxidative balance score and overall risk of prostate cancer with hazard ratios (HRs) of 1.00, 1.02, 1.03, 0.97 and 1.01 for increasing quintiles of the score (p-trend=0.71). There were also no associations for non-advanced or advanced disease, or when analysis was restricted to incident cases that arose after two years of follow-up (n=508). In general constituents of the score were not associated with prostate cancer, except for red meat intake (HR=1.44; 95%CI 1.06-1.95 comparing Q5 vs. Q1) and lycopene (HRs of 0.7-0.8 for increasing quintiles). Our findings do not support an association between oxidative balance score and risks of overall prostate cancer or advanced disease.
  Cancer epidemiology. 12/2010; 35(4):353-61.
• Article: Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population.

  Ilir Agalliu, Suzanne M Leanza, Lorie Smith, Jeffrey M Trent, John D Carpten, Joan E Bailey-Wilson, Robert D Burk
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  ABSTRACT: Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain. Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. There was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P < 0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors. Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity.
  The Prostate 11/2010; 70(15):1716-27. · 3.48 Impact Factor
• Article: Contribution of HPC1 (RNASEL) and HPCX variants to prostate cancer in a founder population

  Ilir Agalliu, Suzanne M. Leanza, Lorie Smith, Jeffrey M. Trent, John D. Carpten, Joan E. Bailey-Wilson, Robert D. Burk MD
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  ABSTRACT: BACKGROUND Prostate cancer is a genetically complex disease with locus and disease heterogeneity. The RNASEL gene and HPCX locus have been implicated in hereditary prostate cancer; however, their contributions to sporadic forms of this malignancy remain uncertain.METHODS Associations of prostate cancer with two variants in the RNASEL gene (a founder mutation, 471delAAAG, and a non-synonymous SNP, rs486907), and with five microsatellite markers in the HPCX locus, were examined in 979 cases and 1,251 controls of Ashkenazi Jewish descent. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models.RESULTSThere was an inverse association between RNASEL rs486907 and prostate cancer in younger men (<65 years) and those with a first-degree relative with prostate cancer; men with AA genotype had ORs of 0.64 and 0.47 (both P < 0.05), respectively, in comparison to men with GG genotype. Within the HPCX region, there were positive associations for allele 135 of bG82i1.1 marker (OR = 1.77, P = 0.01) and allele 188 of DXS1205 (OR = 1.65, P = 0.02). In addition, allele 248 of marker D33 was inversely associated (OR = 0.65, P = 0.05) with Gleason score ≥7 tumors.CONCLUSIONS Results suggest that variants in RNASEL contribute to susceptibility to early onset and familial forms of prostate cancer, whereas HPCX variants are associated with prostate cancer risk and tumor aggressiveness. The observation that a mutation predicted to completely inactivate RNASEL protein was not associated with prostate cancer, but that a missense variant was associated, suggests that the effect is due to either partial inactivation of the protein, and/or acquisition of a new protein activity. Prostate 70: 1716–1727, 2010. © 2010 Wiley-Liss, Inc.
  The Prostate 06/2010; 70(15):1716 - 1727. · 3.48 Impact Factor
• Article: Genetic variation in DNA repair genes and prostate cancer risk: results from a population-based study.

  Ilir Agalliu, Erika M Kwon, Claudia A Salinas, Joseph S Koopmeiners, Elaine A Ostrander, Janet L Stanford
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  ABSTRACT: DNA repair pathways are crucial to prevent accumulation of DNA damage and maintain genomic stability. Alterations of this pathway have been reported in many cancers. An increase in oxidative DNA damage or decrease in DNA repair capacity with aging or due to germline genetic variation may affect prostate cancer risk. Pooled data from two population-based studies (1,457 cases and 1,351 controls) were analyzed to examine associations between 28 single-nucleotide polymorphisms (SNPs) in nine DNA repair genes (APEX1, BRCA2, ERCC2, ERCC4, MGMT, MUTYH, OGG1, XPC, and XRCC1) and prostate cancer risk. We also explored whether associations varied by smoking, by family history or clinical features of prostate cancer. There were no associations between these SNPs and overall risk of prostate cancer. Risks by genotype also did not vary by smoking or by family history of prostate cancer. Although two SNPs in BRCA2 (rs144848, rs1801406) and two SNPs in ERCC2 (rs1799793, rs13181) showed stronger associations with high Gleason score or advanced-stage tumors when comparing homozygous men carrying the minor versus major allele, results were not statistically significantly different between clinically aggressive and non-aggressive tumors. Overall, this study found no associations between prostate cancer and the SNPs in DNA repair genes. Given the complexity of this pathway and its crucial role in maintenance of genomic stability, a pathway-based analysis of all 150 genes in DNA repair pathways, as well as exploration of gene-environment interactions may be warranted.
  Cancer Causes and Control 11/2009; 21(2):289-300. · 2.88 Impact Factor
• Article: Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations.

  Ilir Agalliu, Robert Gern, Suzanne Leanza, Robert D Burk
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  ABSTRACT: Protein-truncating mutations in BRCA1 and in particular BRCA2 genes have been associated with prostate cancer. However, there is still uncertainty about the magnitude of association particularly with Gleason score, and family history of prostate, breast, and ovary cancers. To further examine associations between three founder mutations located in BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) genes and prostate cancer, we conducted a study of 979 prostate cancer cases and 1,251 controls among Ashkenazi Jewish men. Detailed information was obtained on prostate cancer pathology, age at diagnosis, and family history of all cancers. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression models. Prostate cancer risk was increased (OR, 1.9; 95% CI 0.9-4.1) for BRCA2 mutation carriers but not for BRCA1 mutation carriers. BRCA2 mutation carriers had an OR of 3.2 (95% CI, 1.4-7.3) for Gleason score of 7 to 10, but no association was observed for Gleason score of < 7. Carriers of BRCA1-185delAG mutation also had an OR of 3.5 (95% CI, 1.2-10.3) for Gleason score of > or =7 tumors; however, the association of either BRCA1-185delAG or 5382insC mutation was not statistically significant. Associations between founder mutations and prostate cancer were stronger in men with no first-degree family history of breast and/or ovarian cancers but were unaffected by family history of prostate cancer. These results indicate that the BRCA2 founder mutation confers a 3-fold elevated risk of high-grade prostate cancer. Although BRCA1 mutations were not associated with prostate cancer, the BRCA1-185delAG was associated with high Gleason score tumors. These findings should be carefully considered in genetic counseling and/or evaluating therapeutic options.
  Clinical Cancer Research 02/2009; 15(3):1112-20. · 7.74 Impact Factor
• Article: Illumina DNA test panel-based genotyping of whole genome amplified-DNA extracted from hair samples: performance and agreement with genotyping results from genomic DNA from buccal cells.

  Ilir Agalliu, Peter A Schweitzer, Suzanne M Leanza, Robert D Burk, Thomas E Rohan
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  ABSTRACT: Hair is a DNA source that can be collected easily and inexpensively from participants in epidemiological studies. However, there is concern about DNA quality and quantity. Therefore, we assessed genotyping performance of whole genome amplified (WGA)-DNA extracted from hair using the GenomePlex method and evaluated its agreement with genotyping results of buccal cell DNA from the same individuals, using the Illumina GoldenGate platform. The Illumina DNA test panel includes 360 highly validated single nucleotide polymorphisms (SNPs) selected from the Linkage IV Panel that are distributed across the entire genome. DNA was extracted from both archived hair and buccal cell samples obtained from 44 randomly selected subjects participating in a large cohort study in Canada. The genotyping success rate was 97.7% for 44 paired samples. However, WGA-DNA from hair failed more during genotyping in comparison to buccal cell DNA. Hair samples with a pre-WGA-DNA>or=1 ng/microL quantified using the PicoGreen assay (n=33) showed an average genotyping completion rate of 98.8% and SNP concordance of 91.2% with genotyping performance of buccal cell DNA. In contrast, samples with a pre-WGA-DNA<1 ng/microL had lower genotyping completion rate (94%) and poor SNP concordance (49%). Results suggest that WGA-DNA obtained from hair can produce excellent genotyping call rates and show relatively good SNP concordance with results from buccal cell DNA using high-throughput technology. DNA quantity obtained from hair samples is a crucial determinant of genotyping performance. Larger studies are needed to examine the utility of hair DNA with different genotyping platforms.
  Clinical Chemistry and Laboratory Medicine 01/2009; 47(5):516-22. · 2.15 Impact Factor
• Article: Statin use and risk of prostate cancer: results from a population-based epidemiologic study.

  Ilir Agalliu, Claudia A Salinas, Philip D Hansten, Elaine A Ostrander, Janet L Stanford
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  ABSTRACT: Epidemiologic studies of statin use in relation to prostate cancer risk have been inconclusive. Recent evidence, however, suggests that longer-term use may reduce risk of more advanced disease. The authors conducted a population-based study of 1,001 incident prostate cancer cases diagnosed in 2002-2005 and 942 age-matched controls from King County, Washington, to evaluate risk associated with statin use. Logistic regression was used to generate odds ratios for ever use, current use, and duration of use. No overall association was found between statin use and prostate cancer risk (odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2 for current use; OR = 1.1, 95% CI: 0.7, 1.8 for >10 years' use), even for cases with more advanced disease. Risk related to statin use, however, was modified by body mass index (interaction p = 0.04). Obese men (BMI > or =30 kg/m2) who used statins had an increased risk (OR = 1.5, 95% CI: 1.0, 2.2) relative to obese nonusers, with a stronger association for longer-term use (OR = 1.8, 95% CI: 1.1, 3.0 for > or =5 years' use). Although statin use was not associated with overall prostate cancer risk, the finding of an increased risk associated with statin use among obese men, particularly use for extended durations, warrants further investigation.
  American journal of epidemiology 08/2008; 168(3):250-60. · 5.59 Impact Factor
• Article: Evaluation of a variant in the transcription factor 7-like 2 (TCF7L2) gene and prostate cancer risk in a population-based study.

  Ilir Agalliu, Miia Suuriniemi, Ludmila Prokunina-Olsson, Bo Johanneson, Francis S Collins, Janet L Stanford, Elaine A Ostrander
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  ABSTRACT: Transcription factor 7-like 2 (TCF7L2) is a high mobility group-box containing protein that is a critical member of the Wnt/beta-catenin canonical signaling pathway. In addition to its recently recognized role in diabetes, aberrant TCF7L2 expression has been implicated in cancer through regulation of cell proliferation and apoptosis by c-MYC and cyclin D. It has been hypothesized that germline variants within the TCF7L2 gene previously associated with diabetes may affect cancer risk through the Wnt/beta-catenin signaling pathway. Specifically, the same risk allele of single nucleotide polymorphism (SNP) rs12255372 that is associated with diabetes (T allele) has recently been associated with an increased risk of breast cancer. Here, we investigated associations between rs12255372 and prostate cancer risk among 1,457 cases and 1,351 controls from a population-based study. The variant TT genotype was not associated with overall prostate cancer risk. However, there was evidence that men homozygous for the variant T allele had an elevated relative risk of more aggressive prostate cancer, as defined by high Gleason score (OR = 1.7, 95% CI = 1.0-2.8) or regional/distant stage (OR = 1.7, 95% CI = 1.1-2.6) disease. Our findings suggest that this variant in the TCF7L2 gene may be associated with risk of developing more clinically significant disease. These results need to be confirmed, but provide initial evidence that the TCF7L2 gene may alter risk of developing more aggressive prostate cancer.
  The Prostate 06/2008; 68(7):740-7. · 3.48 Impact Factor
• Article: Cigarette smoking and prostate cancer-specific mortality following diagnosis in middle-aged men.

  Zhihong Gong, Ilir Agalliu, Daniel W Lin, Janet L Stanford, Alan R Kristal
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  ABSTRACT: The aim of this study was to examine associations of smoking at the time of diagnosis with the risk of prostate cancer death in a population-based cohort of men with prostate cancer. Data were from 752 prostate cancer patients aged 40-64 years, who were enrolled in a case-control study and under long-term follow-up for mortality. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between smoking and prostate cancer-specific and other cause mortality. Compared to never smoking, smoking at the time of diagnosis was associated with a significant increase in risk of prostate cancer-specific mortality. After controlling for demographic characteristics, Gleason grade, stage at diagnosis, and primary treatment, the HR was 2.66 (95% CI: 1.10-6.43). Smoking at the time of diagnosis, independent of key clinical prognostic factors, is associated with an increased risk of prostate cancer death.
  Cancer Causes and Control 03/2008; 19(1):25-31. · 2.88 Impact Factor
• Source

  Available from: Antonio Hurtado-Coll

  Article: Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer.

  Liesel M FitzGerald, Ilir Agalliu, Karynn Johnson, Melinda A Miller, Erika M Kwon, Antonio Hurtado-Coll, Ladan Fazli, Ashish B Rajput, Martin E Gleave, Michael E Cox, Elaine A Ostrander, Janet L Stanford, David G Huntsman
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  ABSTRACT: The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22-3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23-3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45-3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
  BMC Cancer 02/2008; 8:230. · 3.01 Impact Factor
• Article: Association of TMPRSS2-ERG gene fusion with clinical characteristics and outcomes: results from a population-based study of prostate cancer

  Liesel FitzGerald, Ilir Agalliu, Karynn Johnson, Melinda Miller, Erika Kwon, Antonio Hurtado-Coll, Ladan Fazli, Ashish Rajput, Martin Gleave, Michael Cox, Elaine Ostrander, Janet Stanford, David Huntsman
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  ABSTRACT: Abstract Background The presence of the TMPRSS2-ERG fusion gene in prostate tumors has recently been associated with an aggressive phenotype, as well as recurrence and death from prostate cancer. These associations suggest the hypothesis that the gene fusion may be used as a prognostic indicator for prostate cancer. Methods In this study, fluorescent in situ hybridization (FISH) assays were used to assess TMPRSS2-ERG fusion status in a group of 214 prostate cancer cases from two population-based studies. The FISH assays were designed to detect both fusion type (deletion vs. translocation) and the number of fusion copies (single vs. multiple). Genotyping of four ERG and one TMPRSS2 SNPs using germline DNA was also performed in a sample of the cases (n = 127). Results Of the 214 tumors scored for the TMPRSS2-ERG fusion, 64.5% were negative and 35.5% were positive for the fusion. Cases with the TMPRSS2-ERG fusion did not exhibit reduced prostate cancer survival (HR = 0.92, 95% CI = 0.22–3.93), nor was there a significant difference in cause-specific survival when stratifying by translocation or deletion (HR = 0.84, 95% CI = 0.23–3.12) or by the number of retained fusion copies (HR = 1.22, 95% CI = 0.45–3.34). However, evidence for reduced prostate cancer-specific survival was apparent in those cases whose tumor had multiple copies of the fusion. The variant T allele of the TMPRSS2 SNP, rs12329760, was positively associated with TMPRSS2-ERG fusion by translocation (p = 0.05) and with multiple copies of the gene fusion (p = 0.03). Conclusion If replicated, the results presented here may provide insight into the mechanism by which the TMPRSS2-ERG gene fusion arises and also contribute to diagnostic evaluations for determining the subset of men who will go on to develop metastatic prostate cancer.
  BMC Cancer. 01/2008;
• Article: Prostate cancer mortality in relation to screening by prostate-specific antigen testing and digital rectal examination: a population-based study in middle-aged men.

  Ilir Agalliu, Noel S Weiss, Daniel W Lin, Janet L Stanford
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  ABSTRACT: Although prostate cancer screening by measurement of serum prostate-specific antigen (PSA) and digital rectal examination (DRE) is common in clinical practice, the impact of such screening on prostate cancer-specific mortality remains uncertain. Data from a population-based case-control study in King County, Washington, among men aged 50-64 years (706 cases, 645 controls) were used to examine the relationships between PSA and DRE screening and fatal prostate cancer and other-cause mortality. Incident cases were diagnosed in 1993-1996, identified via the Seattle-Puget Sound SEER cancer registry and followed for vital status through 1 June 2007. Controls were ascertained by random digit dialing and frequency age-matched to cases. The screening variable used in this analysis was self-reported receipt of one or more PSA and/or DRE tests performed as part of a routine checkup in the five-year period before diagnosis or reference date. A smaller proportion of men with fatal prostate cancer had one or more PSA and/or DRE screening tests compared to controls, resulting in an adjusted odds ratios (OR) of 0.38 (95% CI 0.19-0.77). There was no association, however, between PSA and/or DRE screening and other-cause mortality (OR = 1.02; 95% CI 0.51-2.02). Results of this study suggest a reduction in prostate cancer-specific mortality associated with PSA and/or DRE screening in middle-aged men. Findings should be interpreted cautiously, however, as results are based on observational data. Further, the study was not able to separate the relative efficacy of PSA versus DRE screening.
  Cancer Causes and Control 12/2007; 18(9):931-7. · 2.88 Impact Factor
• Article: Confirmation of a positive association between prostate cancer risk and a locus at chromosome 8q24.

  Miia Suuriniemi, Ilir Agalliu, Daniel J Schaid, Bo Johanneson, Shannon K McDonnell, Lori Iwasaki, Janet L Stanford, Elaine A Ostrander
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  ABSTRACT: Family-based linkage studies, association studies, and studies of tumors have highlighted human chromosome 8q as a genomic region of interest for prostate cancer susceptibility loci. Recently, a locus at 8q24, characterized by both a single nucleotide polymorphism (SNP) and a microsatellite marker, was shown to be associated with prostate cancer risk in Icelandic, Swedish, and U.S. samples. Although the data were provocative, the U.S. samples were not population based, which precludes assessment of the potential contribution of this locus to prostate cancer incidence in the United States. We analyzed both markers in a population-based, case-control study of middle-aged men from King County, Washington. Overall, there was a significant positive association between the A allele of the SNP rs1447295 and prostate cancer risk [odds ratio, 1.4; 95% confidence interval (95% CI), 1.1-2.0] but no significant association with the microsatellite DG8S737. However, significant associations were observed for both markers in men with high Gleason scores. Adjusting for age, first-degree family history of prostate cancer, and prostate cancer screening history, the adjusted odds ratios were 1.4 (95% CI, 1.1-1.8) for the A allele of the SNP and 1.9 (95% CI, 1.2-2.8) for the -10 allele of the microsatellite. These data suggest that the locus on chromosome 8q24 harbors a genetic variant associated with prostate cancer and that the microsatellite marker is a stronger risk factor for aggressive prostate cancers defined by poorly differentiated tumor morphology.
  Cancer Epidemiology Biomarkers &amp Prevention 05/2007; 16(4):809-14. · 4.12 Impact Factor
• Source

  Available from: Daniel Zadory

  Article: Germline mutations in the BRCA2 gene and susceptibility to hereditary prostate cancer.

  Ilir Agalliu, Erika M Kwon, Daniel Zadory, Laura McIntosh, Joseph Thompson, Janet L Stanford, Elaine A Ostrander
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  ABSTRACT: Several epidemiologic studies have reported that carriers of germline mutations in the BRCA2 gene have an increased risk of prostate cancer, with the highest risk observed in men diagnosed at earlier ages. However, studies of the contribution of BRCA2 mutations to the etiology of hereditary prostate cancer (HPC) have been inconsistent. To further address this issue, 266 subjects from 194 HPC families participating in the Seattle-based Prostate Cancer Genetic Research Study were screened for BRCA2 mutations by sequencing the coding regions, intron-exon boundaries, and suspected regulatory elements of this gene. Of selected HPC families, 32 had multiple breast or ovarian cancer cases, 16 were Jewish, 8 had a pancreatic cancer case, and 138 had at least one affected man diagnosed with prostate cancer at an early age (<60 years). No disease-associated protein truncating BRCA2 mutations were found in 266 subjects from HPC families. There were 61 DNA sequence variants, of which 31 (50.8%) changed the predicted amino acids. No associations were found between these missense changes and family characteristics. Among affected men with prostate cancer, there were no statistically significant differences between the genotype frequencies of DNA variants with a minor allele frequency of 1% or higher and between the strata defined by median age at diagnosis or by clinical features. No evidence was found in this study for an association between BRCA2 mutations and susceptibility to HPC in men selected from high-risk families.
  Clinical Cancer Research 03/2007; 13(3):839-43. · 7.74 Impact Factor