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  • American Association for Cancer Research (AACR)  (11)
  • 1
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 29, No. 5 ( 2020-05-01), p. 1074-1078
    Abstract: Lipid traits have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL). We examined the association of genetically predicted lipid traits with risk of diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic leukemia (CLL), follicular lymphoma (FL), and marginal zone lymphoma (MZL) using Mendelian randomization (MR) analysis. Methods: Genome-wide association study data from the InterLymph Consortium were available for 2,661 DLBCLs, 2,179 CLLs, 2,142 FLs, 824 MZLs, and 6,221 controls. SNPs associated (P & lt; 5 × 10−8) with high-density lipoprotein (HDL, n = 164), low-density lipoprotein (LDL, n = 137), total cholesterol (TC, n = 161), and triglycerides (TG, n = 123) were used as instrumental variables (IV), explaining 14.6%, 27.7%, 16.8%, and 12.8% of phenotypic variation, respectively. Associations between each lipid trait and NHL subtype were calculated using the MR inverse variance–weighted method, estimating odds ratios (OR) per standard deviation and 95% confidence intervals (CI). Results: HDL was positively associated with DLBCL (OR = 1.14; 95% CI, 1.00–1.30) and MZL (OR = 1.09; 95% CI, 1.01–1.18), while TG was inversely associated with MZL risk (OR = 0.90; 95% CI, 0.83–0.99), all at nominal significance (P & lt; 0.05). A positive trend was observed for HDL with FL risk (OR = 1.08; 95% CI, 0.99–1.19; P = 0.087). No associations were noteworthy after adjusting for multiple testing. Conclusions: We did not find evidence of a clear or strong association of these lipid traits with the most common NHL subtypes. While these IVs have been previously linked to other cancers, our findings do not support any causal associations with these NHL subtypes. Impact: Our results suggest that prior reported inverse associations of lipid traits are not likely to be causal and could represent reverse causality or confounding.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2020
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 14 ( 2018-07-15), p. 4086-4096
    Abstract: A growing number of loci within the human leukocyte antigen (HLA) region have been implicated in non-Hodgkin lymphoma (NHL) etiology. Here, we test a complementary hypothesis of “heterozygote advantage” regarding the role of HLA and NHL, whereby HLA diversity is beneficial and homozygous HLA loci are associated with increased disease risk. HLA alleles at class I and II loci were imputed from genome-wide association studies (GWAS) using SNP2HLA for 3,617 diffuse large B-cell lymphomas (DLBCL), 2,686 follicular lymphomas (FL), 2,878 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLL), 741 marginal zone lymphomas (MZL), and 8,753 controls of European descent. Both DLBCL and MZL risk were elevated with homozygosity at class I HLA-B and -C loci (OR DLBCL = 1.31, 95% CI = 1.06–1.60; OR MZL = 1.45, 95% CI = 1.12–1.89) and class II HLA-DRB1 locus (OR DLBCL = 2.10, 95% CI = 1.24–3.55; OR MZL = 2.10, 95% CI = 0.99–4.45). Increased FL risk was observed with the overall increase in number of homozygous HLA class II loci (P trend & lt; 0.0001, FDR = 0.0005). These results support a role for HLA zygosity in NHL etiology and suggests that distinct immune pathways may underly the etiology of the different NHL subtypes. Significance: HLA gene diversity reduces risk for non-Hodgkin lymphoma. Cancer Res; 78(14); 4086–96. ©2018 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 3
    In: Cancer Immunology Research, American Association for Cancer Research (AACR), Vol. 4, No. 11 ( 2016-11-01), p. 948-958
    Abstract: Granulocytic–macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 μg/m2/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6). Treatment was well tolerated with all grade 1 or 2 adverse events. Two patients had a decline in prostate-specific antigen (PSA) of more than 50%. GM-CSF treatment increased the numbers of circulating mature myeloid dendritic cells, proliferating conventional CD4 T cells, proliferating CD8 T cells, and to a lesser magnitude FoxP3+ regulatory CD4 T cells. Although GM-CSF treatment did not augment antigen-presenting cell localization to the prostate, treatment was associated with recruitment of CD8+ T cells to the tumor. These results suggest that systemic GM-CSF can modulate T-cell infiltration in the tumor microenvironment. Cancer Immunol Res; 4(11); 948–58. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 2326-6066 , 2326-6074
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
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  • 4
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 31, No. 5 ( 2022-05-04), p. 1103-1110
    Abstract: A previous International Lymphoma Epidemiology (InterLymph) Consortium evaluation of joint associations between five immune gene variants and autoimmune conditions reported interactions between B-cell response-mediated autoimmune conditions and the rs1800629 genotype on risk of B-cell non–Hodgkin lymphoma (NHL) subtypes. Here, we extend that evaluation using NHL subtype-specific polygenic risk scores (PRS) constructed from loci identified in genome-wide association studies of three common B-cell NHL subtypes. Methods: In a pooled analysis of NHL cases and controls of Caucasian descent from 14 participating InterLymph studies, we evaluated joint associations between B-cell–mediated autoimmune conditions and tertile (T) of PRS for risk of diffuse large B-cell lymphoma (DLBCL; n = 1,914), follicular lymphoma (n = 1,733), and marginal zone lymphoma (MZL; n = 407), using unconditional logistic regression. Results: We demonstrated a positive association of DLBCL PRS with DLBCL risk [T2 vs. T1: OR = 1.24; 95% confidence interval (CI), 1.08–1.43; T3 vs. T1: OR = 1.81; 95% CI, 1.59–2.07; P-trend (Ptrend) & lt; 0.0001]. DLBCL risk also increased with increasing PRS tertile among those with an autoimmune condition, being highest for those with a B-cell–mediated autoimmune condition and a T3 PRS [OR = 6.46 vs. no autoimmune condition and a T1 PRS, Ptrend & lt; 0.0001, P-interaction (Pinteraction) = 0.49]. Follicular lymphoma and MZL risk demonstrated no evidence of joint associations or significant Pinteraction. Conclusions: Our results suggest that PRS constructed from currently known subtype-specific loci may not necessarily capture biological pathways shared with autoimmune conditions. Impact: Targeted genetic (PRS) screening among population subsets with autoimmune conditions may offer opportunities for identifying those at highest risk for (and early detection from) DLBCL.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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  • 5
    In: Cancer Discovery, American Association for Cancer Research (AACR), Vol. 8, No. 12 ( 2018-12-01), p. 1548-1565
    Abstract: Malignant pleural mesothelioma (MPM) is a highly lethal cancer of the lining of the chest cavity. To expand our understanding of MPM, we conducted a comprehensive integrated genomic study, including the most detailed analysis of BAP1 alterations to date. We identified histology-independent molecular prognostic subsets, and defined a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity. We also report strong expression of the immune-checkpoint gene VISTA in epithelioid MPM, strikingly higher than in other solid cancers, with implications for the immune response to MPM and for its immunotherapy. Our findings highlight new avenues for further investigation of MPM biology and novel therapeutic options. Significance: Through a comprehensive integrated genomic study of 74 MPMs, we provide a deeper understanding of histology-independent determinants of aggressive behavior, define a novel genomic subtype with TP53 and SETDB1 mutations and extensive loss of heterozygosity, and discovered strong expression of the immune-checkpoint gene VISTA in epithelioid MPM. See related commentary by Aggarwal and Albelda, p. 1508. This article is highlighted in the In This Issue feature, p. 1494
    Type of Medium: Online Resource
    ISSN: 2159-8274 , 2159-8290
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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  • 6
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 5, No. 11_Supplement ( 2012-11-01), p. B72-B72
    Abstract: Introduction: Metformin is currently the drug of choice for management of type II diabetes mellitus. Recent epidemiological studies have reported that metformin use among diabetics decreases the risk of developing a variety of cancer types, including prostate cancer (PCa). However, the effect of metformin use on PCa outcome has yet to be clarified. The aim of this study was to investigate the association between pre-operative metformin use and biochemical recurrence (BCR) in a cohort of diabetic men who underwent radical prostatectomy (RP). Methods: We performed a retrospective analysis of 337 men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated for PCa with RP and with a diagnosis of diabetes prior to surgery. Cox proportional hazard models were used to assess time to BCR for diabetic men taking metformin in the year prior to RP compared to diabetic men not taking metformin. Models were adjusted for age, race, year of surgery, surgical center, pre-operative PSA and biopsy Gleason score. Results: Of 337 diabetic men, 173 (51%) were taking metformin in the year before RP. The median follow-up among men who did not recur was 49 months, during which 112 men (33%) experienced BCR. Metformin use was associated with more recent year of surgery (median 2005 vs. 2001; p & lt;0.001) but not with age, race, BMI or biopsy Gleason score (all p & gt;0.1). Diabetics taking metformin had lower pre-operative PSA (p=0.12) yet higher prostate volume (p=0.17), relative to diabetics not on metformin, though these associations did not reach statistical significance. On unadjusted analyses, metformin use was not significantly associated with BCR (log-rank, p=0.29). After adjusting for multiple pre-operative features, metformin use in the year before surgery remained not related to BCR (HR 0.97, 95% CI 0.59 to 1.60, p=0.912). Conclusion: In this cohort of diabetic men treated for PCa with RP, metformin use in the year prior to surgery was not significantly associated with time to BCR. Although this is the largest study to date to test the role of metformin among diabetics undergoing RP, larger studies with longer follow-up are needed to better assess whether metformin is associated with improved PCa outcomes, though the current study suggested no role for metformin for PCa control. Citation Format: Emma H. Allott, Michael R. Abern, Leah Gerber, Christopher J. Keto, William J. Aronson, Martha K. Terris, Joseph C. Presti, Christopher J. Kane, Christopher L. Amling, Stephen J. Freedland. Metformin use and risk of biochemical recurrence following radical prostatectomy: Results from the SEARCH database. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B72.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 880-880
    Abstract: INTRODUCTION: At the population level among otherwise “healthy” men, obesity is associated with prostate cancer mortality. However, few studies analyzed the associations between obesity and long-term progression after surgery, such as castration-resistant prostate cancer (CRPC) and prostate cancer-specific mortality (PCSM). We examined the effect of obesity at the time of radical prostatectomy (RP) on long-term prostate cancer-specific outcomes among men treated at Veterans Affairs Hospitals in the USA. METHODS: We combined data from patients undergoing RP at six Veterans Affairs Medical Centers (West Los Angeles, San Diego, and Palo Alto, CA; Augusta, GA; and Durham and Asheville, NC) into the SEARCH database. Our exposure, body mass index (BMI) was abstracted from the medical records at the time of but prior to RP and categorized as normal weight ( & lt;25 kg/m2), overweight (25-29.9kg/m2), and obese (≥30kg/m2). Crude and adjusted Cox models accounting for known risk cofactors were used to examine the associations between BMI and PCSM (primary outcome), biochemical recurrence (BCR) and CRPC. Hazard ratios for the risk of CRPC and PCSM were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk. RESULTS: Overall, 839 (23%) men had normal weight, 1,675 (45%) were overweight, and 1,184 (32%) were obese. A higher BMI was associated with younger age at surgery (p & lt;0.001), lower PSA (median 6.9 vs. 6.3 vs. 6.1; p & lt;0.001), and a shorter follow-up (p = 0.009). After adjusting for clinical and pathological features, both overweight (HR 2.85, p = 0.039) and obesity (HR 3.38, p = 0.017) were significantly associated with PCSM relative to normal weight. Obesity (vs. normal weight) was also associated with a higher risk of BCR (HR = 1.20, p = 0.026) and CRPC (HR = 2.12, p = 0.026), even after adjusting for clinical and pathological characteristics. Overweight was not associated with BCR (HR = 1.01, p = 0.948) or CRPC (HR = 1.44, p = 0.274) on multivariable analysis. CONCLUSIONS: Our study supports the hypothesis that obese men undergoing RP are at increased risk of worse long-term prostate cancer outcomes including PCSM. Our findings are consistent with a growing body of literature documenting that obesity in general is associated with more aggressive prostate cancer. Citation Format: Adriana C. Vidal, Lauren E. Howard, Matthew R Cooperberg, Christopher J. Kane, William J. Aronson, Martha K. Terris, Christopher L. Amling, Stephen J Freedland. Obesity predicts prostate cancer-specific mortality after radical prostatectomy: Results from the SEARCH database. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 880. doi:10.1158/1538-7445.AM2015-880
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
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    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
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  • 8
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 32, No. 9 ( 2023-09-01), p. 1208-1216
    Abstract: The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer–specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). Methods: Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values & gt; 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined]. Results: Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48–0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16–1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88–0.98). Conclusions: In men with late-stage prostate cancer, ICD-9/10 ‘code-identified’ diabetes is associated with better overall survival than ‘undiagnosed’ diabetes identified by high HbA1c values only. Impact: Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2023
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  • 9
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 25, No. 3 ( 2016-03-01), p. 547-554
    Abstract: Background: Black men are disproportionately affected by both cardiovascular disease and prostate cancer. Epidemiologic evidence linking dyslipidemia, an established cardiovascular risk factor, and prostate cancer progression is mixed. As existing studies were conducted in predominantly non-black populations, research on black men is lacking. Methods: We identified 628 black and 1,020 non-black men who underwent radical prostatectomy and never used statins before surgery in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Median follow-up was 2.9 years. The impact of preoperative hypercholesterolemia on risk of biochemical recurrence was examined using multivariable, race-stratified proportional hazards. In secondary analysis, we examined associations with low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, overall and among men with dyslipidemia. Results: High cholesterol was associated with increased risk of recurrence in black [HRper10 mg/dL 1.06; 95% confidence interval (CI), 1.02–1.11] but not non-black men (HRper10 mg/dL 0.99; 95% CI, 0.95–1.03; Pinteraction = 0.011). Elevated triglycerides were associated with increased risk in both black and non-black men (HRper10 mg/dL 1.02; 95% CI, 1.00–1.03 and 1.02; 95% CI, 1.00–1.02, respectively; Pinteraction = 0.458). There were no significant associations between LDL or HDL and recurrence risk in either race. Associations with cholesterol, LDL, and triglycerides were similar among men with dyslipidemia, but low HDL was associated with increased risk of recurrence in black, but not non-black men with dyslipidemia (Pinteraction = 0.047). Conclusion: Elevated cholesterol was a risk factor for recurrence in black but not non-black men, whereas high triglycerides were associated with increased risk regardless of race. Impact: Significantly contrasting associations by race may provide insight into prostate cancer racial disparities. Cancer Epidemiol Biomarkers Prev; 25(3); 547–54. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 10
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2014
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 23, No. 11 ( 2014-11-01), p. 2349-2356
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11 ( 2014-11-01), p. 2349-2356
    Abstract: Background: Evidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance. Methods: We conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines. Results: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10 mg/dl, 1.03; 95% confidence interval (CI), 1.01–1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01–1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41–0.91), respectively. Conclusions: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively. Impact: These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence. Cancer Epidemiol Biomarkers Prev; 23(11); 2349–56. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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