Neighborhood social vulnerability and disparities in time to kidney cancer surgical treatment and survival in Arizona.

BACKGROUND: Hispanics and American Indians (AI) have high kidney cancer incidence and mortality rates in Arizona. This study assessed: (1) whether racial and ethnic minority patients and patients from neighborhoods with high social vulnerability index (SVI) experience a longer time to surgery after clinical diagnosis, and (2) whether time to surgery, race and ethnicity, and SVI are associated with upstaging to pT3/pT4, disease-free survival (DFS), and overall survival (OS). METHODS: Arizona Cancer Registry (2009-2018) kidney and renal pelvis cases (n = 4592) were analyzed using logistic regression models to assess longer time to surgery and upstaging. Cox-regression hazard models were used to test DFS and OS. RESULTS: Hispanic and AI patients with T1 tumors had a longer time to surgery than non-Hispanic White patients (median time of 56, 55, and 45 days, respectively). Living in neighborhoods with high (≥75) overall SVI increased odds of a longer time to surgery for cT1a (OR 1.54, 95% CI: 1.02-2.31) and cT2 (OR 2.32, 95% CI: 1.13-4.73). Race and ethnicity were not associated with time to surgery. Among cT1a patients, a longer time to surgery increased odds of upstaging to pT3/pT4 (OR 1.95, 95% CI: 0.99-3.84). A longer time to surgery was associated with PFS (HR 1.52, 95% CI: 1.17-1.99) and OS (HR 1.63, 95% CI: 1.26-2.11). Among patients with cT2 tumor, living in high SVI neighborhoods was associated with worse OS (HR 1.66, 95% CI: 1.07-2.57). CONCLUSIONS: High social vulnerability was associated with increased time to surgery and poor survival after surgery.

Prostate Cancer Disparities in Metastatic and Treatment Status for Hispanic Americans Based on Country of Origin Compared to Non-Hispanic Whites Using the National Cancer Database.

INTRODUCTION: Among Hispanic-American (HA) men, prostatic cancer (PCa) accounts for nearly one-quarter of the total cancer burden. We sought to identify differences in PCa presentation and treatment status for HA subgroups based on country/region of origin. MATERIAL AND METHODS: Using the National Cancer Database, we identified patients with histologically confirmed prostate adenocarcinoma with reported race/ethnicity, clinical staging, Gleason score ≥ 6, and PSA level at diagnosis from 2010 to 2016. HAs were divided into 4 subgroups: Mexican, Puerto Ricans, Cubans, and Central/South Americans. Non-Hispanic White (NHW) men were used as a reference group. Statistical analysis was derived from the Kruskal-Wallis test for continuous variables and χ2 test for categorical variables. Models were constructed to evaluate the association of Hispanic country of origin with metastatic presentation and treatment status. RESULTS: A total of 428,829 patients were included, with 5625 (1.3%) classified as HA. Within the Hispanic group, 2880 (51.2%) were Mexican, 999 (17.8%) Puerto Rican, 477 (8.5%) Cuban, and 1269 (22.6%) South/Central American. Mexican men presented with higher median PSA, more Gleason 8 to 10 disease, and higher rates of metastatic presentation compared to NHW and other HA subgroups (all, p < .01). Metastatic rates over the study period for Mexican, Puerto Rican, Cuban, and South/Central Americans were 6.4 (±1.2), 5.3 (±3.0), 3.2 (±2.0), and 4.6% (±1.7), respectively (p = .01). Treatment rates were 89.1, 89.6, 92.4, and 89.3% for Mexican, Puerto Rican, Cuban, and South/Central Americans, respectively (p = .19). Mexican men had higher odds of initial metastatic presentation (OR: 1.32; 95%CI: 1.07-1.63, p = .01) but lower odds of receiving treatment (0.68; 0.55-0.85, p < .01). CONCLUSION: Men of Mexican origin presented with more advanced PCa when compared to NHW and other Hispanic subgroups. Our results warrant further investigation into potential biological factors affecting Hispanic patients as well as the identification of treatment barriers for this vulnerable population.

Clear cell renal cell carcinoma molecular variations in non-Hispanic White and Hispanic patients.

BACKGROUND: The United States is becoming increasingly diverse, but few molecular studies have assessed the progression of clear cell renal cell carcinoma (ccRCC) in diverse patient populations. This study examined ccRCC molecular variations in non-Hispanic White (NHW) and Hispanic patients and their effect on the association of gene expression with high-grade (Grade 3 or 4) ccRCC and overall mortality. METHODS: A total of 156 patients were included in VHL sequencing and/or TempO-Seq analysis. DESeq2 was used to identify the genes associated with high-grade ccRCC. Logistic regression analysis was performed to assess whether race and ethnicity was associated with high/moderate impact VHL somatic mutations and the ccA/ccB subtype. Cox regression analysis was performed to assess association of molecular subtype and gene expression with overall mortality. RESULTS: NHWs had moderate or high impact mutations in the VHL gene at a higher frequency than Hispanics (40.2% vs. 27.4%), while Hispanics had a higher frequency of the ccA subtype than NHWs (61.9% vs. 45.8%). ccA was more common in patients with BMI≥35 (65.2%) than in those with BMI < 25 (45.0%). There were 11 differentially expressed genes between high- and low-grade tumors. The Haptoglobin (HP) gene was most significantly overexpressed in high- compared to low-grade ccRCC in all samples (p-adj = 1.7 × 10-12 ). When stratified by subtype, the 11 genes were significantly differentially expressed in the ccB subtype, but none of them were significant after adjusting for multiple testing in ccA. Finally, patients with the ccB subtype had a significantly increased risk of overall mortality (HR 4.87; p = 0.01) compared to patients with ccA, and patients with high HP expression and ccB, had a significantly increased risk of mortality compared to those with low HP expression and ccA (HR 6.45, p = 0.04). CONCLUSION: This study reports ccRCC molecular variations in Hispanic patients who were previously underrepresented.

Genome-Wide Association Study of Metachronous Colorectal Adenoma Risk among Participants in the Selenium Trial.

Genetic variants related to colorectal adenoma may help identify those who are at highest risk of colorectal cancer development or illuminate potential chemopreventive strategies. The purpose of this genome-wide association study was to identify genetic variants that are associated with risk of developing a metachronous colorectal adenoma among 1,215 study participants of European descent from the Selenium Trial. Associations of variants were assessed with logistic regression analyses and validated in an independent case-control study population of 1,491 participants from the Colorectal Cancer Study of Austria (CORSA). No statistically significant genome-wide associations between any variant and metachronous adenoma were identified after correction for multiple comparisons. However, an intron variant of FAT3 gene, rs61901554, showed a suggestive association (P = 1.10 × 10-6) and was associated with advanced adenomas in CORSA (P = 0.04). Two intronic variants, rs12728998 and rs6699944 in NLRP3 were also observed to have suggestive associations with metachronous lesions (P = 2.00 × 10-6) in the Selenium Trial and were associated with advanced adenoma in CORSA (P = 0.03). Our results provide new areas of investigation for the genetic basis of the development of metachronous colorectal adenoma and support a role for FAT3 involvement in the Wnt/ß-catenin pathway leading to colorectal neoplasia.Trial Registration number: NCT00078897 (ClinicalTrials.gov).

Effect Modification of Selenium Supplementation by Intake and Serum Concentrations of Antioxidants on the Development of Metachronous Colorectal Adenoma.

BACKGROUND: Selenium (Se) is a trace element that has been investigated as a potential chemopreventive agent for colorectal cancer. Dietary intake of other antioxidant nutrients may modify the effect of Se. OBJECTIVE: We examined the association between intake and serum concentrations of retinol, ß-carotene, ß-cryptoxanthin, lycopene, lutein/zeaxanthin, and α- and γ-tocopherol and the development of metachronous colorectal adenoma, and if these nutrients modified the effect of Se. METHODS: We conducted a prospective study of 1874 participants from the Se Trial with data for antioxidant intake, as well as a subcohort of 508 participants with serum biomarker concentrations. RESULTS: Statistically significantly lower odds for the development of metachronous adenoma were observed for those participants in the highest tertile of intake for lutein/zeaxanthin compared to the lowest, with an OR (95% CI) of 0.72 (0.56-0.94). No effect modification for intake of any nutrient was observed. However, circulating concentrations of lycopene exhibited statistically significant effect modification of selenium supplementation (p < 0.06). CONCLUSION: These findings show that intake and circulating concentrations of antioxidant nutrients were not consistently associated with reduced odds for the development of metachronous lesions, although blood concentrations of lycopene may modify the effect of selenium supplementation.

Examination of eQTL Polymorphisms Associated with Increased Risk of Progressive Complicated Sarcoidosis in European and African Descent Subjects.

Background: A limited pool of SNPs are linked to the development and severity of sarcoidosis, a systemic granulomatous inflammatory disease. By integrating genome-wide association studies (GWAS) data and expression quantitative trait loci (eQTL) single nuclear polymorphisms (SNPs), we aimed to identify novel sarcoidosis SNPs potentially influencing the development of complicated sarcoidosis. Methods: A GWAS (Affymetrix 6.0) involving 209 African-American (AA) and 193 European-American (EA, 75 and 51 complicated cases respectively) and publicly-available GWAS controls (GAIN) was utilized. Annotation of multi-tissue eQTL SNPs present on the GWAS created a pool of ~46,000 eQTL SNPs examined for association with sarcoidosis risk and severity (Logistic Model, Plink). The most significant EA/AA eQTL SNPs were genotyped in a sarcoidosis validation cohort (n=1034) and cross-validated in two independent GWAS cohorts. Results: No single GWAS SNP achieved significance (p<1x10-8), however, analysis of the eQTL/GWAS SNP pool yielded 621 eQTL SNPs (p<10-4) associated with 730 genes that highlighted innate immunity, MHC Class II, and allograft rejection pathways with multiple SNPs validated in an independent sarcoidosis cohort (105 SNPs analyzed) (NOTCH4, IL27RA, BTNL2, ANXA11, HLA-DRB1). These studies confirm significant association of eQTL/GWAS SNPs in EAs and AAs with sarcoidosis risk and severity (complicated sarcoidosis) involving HLA region and innate immunity. Conclusion: Despite the challenge of deciphering the genetic basis for sarcoidosis risk/severity, these results suggest that integrated eQTL/GWAS approaches may identify novel variants/genes and support the contribution of dysregulated innate immune responses to sarcoidosis severity.

Formative Assessment to Improve Cancer Screenings in American Indian Men: Native Patient Navigator and mHealth Texting.

Cancer screening rates among American Indian men remain low, without programs specifically designed for men. This paper describes the Community-Based Participatory Research processes and assessment of cancer screening behavior and the appropriateness of the mHealth approach for Hopi men's promotion of cancer screenings. This Community-Based Participatory Research included a partnership with H.O.P.I. (Hopi Office of Prevention and Intervention) Cancer Support Services and the Hopi Community Advisory Committee. Cellular phone usage was assessed among male participants in a wellness program utilizing text messaging. Community surveys were conducted with Hopi men (50 years of age or older). The survey revealed colorectal cancer screening rate increased from 51% in 2012 to 71% in 2018, while prostate cancer screening rate had not changed (35% in 2012 and 37% in 2018). Past cancer screening was associated with having additional cancer screening. A cellular phone was commonly used by Hopi men, but not for healthcare or wellness. Cellular phone ownership increased odds of prostate cancer screening in the unadjusted model (OR 9.00, 95% CI: 1.11-73.07), but not in the adjusted model. Cellular phones may be applied for health promotion among Hopi men, but use of cellular phones to improve cancer screening participation needs further investigation.

Renal Cell Carcinoma Surgical Treatment Disparities in American Indian/Alaska Natives and Hispanic Americans in Arizona.

American Indians/Alaska Natives (AI/AN) and Hispanic Americans (HA) have higher kidney cancer incidence and mortality rates compared to non-Hispanic Whites (NHW). Herein, we describe the disparity in renal cell carcinoma (RCC) surgical treatment for AI/AN and HA and the potential association with mortality in Arizona. A total of 5111 stage I RCC cases diagnosed between 2007 and 2016 from the Arizona Cancer Registry were included. Statistical analyses were performed to test the association of race/ethnicity with surgical treatment pattern and overall mortality, adjusting for patients' demographic, healthcare access, and socioeconomic factors. AI/AN were diagnosed 6 years younger than NHW and were more likely to receive radical rather than partial nephrectomy (OR 1.49 95% CI: 1.07-2.07) compared to NHW. Mexican Americans had increased odds of not undergoing surgical treatment (OR 1.66, 95% CI: 1.08-2.53). Analysis showed that not undergoing surgical treatment and undergoing radical nephrectomy were statistically significantly associated with higher overall mortality (HR 1.82 95% CI: 1.21-2.76 and HR 1.59 95% CI: 1.30-1.95 respectively). Mexican Americans, particularly U.S.-born Mexican Americans, had an increased risk for overall mortality and RCC-specific mortality even after adjusting for neighborhood socioeconomic factors and surgical treatment patterns. Although statistically not significant after adjusting for neighborhood-level socioeconomic factors and surgical treatment patterns, AI/AN had an elevated risk of mortality.

Impacts of Neighborhood Characteristics and Surgical Treatment Disparities on Overall Mortality in Stage I Renal Cell Carcinoma Patients.

Racial/ethnic minority groups in the United States have high renal cell carcinoma (RCC) mortality rates. This study assessed surgical treatment disparities across racial/ethnic groups and impacts of neighborhood socioeconomic characteristics on surgical treatments and overall mortality. Stage I RCC patients diagnosed between 2004 and 2016 from National Cancer Database were included (n = 238,141). We assessed differences in associations between race/ethnicity and treatment patterns using logistic regression and between race/ethnicity and overall mortality using Cox regression with and without neighborhood characteristics in the regression models. When compared to non-Hispanic Whites (NHWs), American Indians/Alaska Natives and non-Hispanic Blacks (NHBs) were more likely not to receive surgical care and all racial/ethnic minority groups had significantly increased odds of undergoing radical rather than partial nephrectomy, even after adjusting for neighborhood characteristics. Including surgical treatment and neighborhood factors in the models slightly attenuated the association, but NHBs had a significantly increased risk of overall mortality. NHBs who underwent radical nephrectomy had an increased risk of mortality (HR 1.15, 95% CI: 1.08-1.23), but not for NHBs who underwent partial nephrectomy (HR 0.92, 95% CI: 0.84-1.02). Neighborhood factors were associated with surgical treatment patterns and overall mortality in both NHBs and NHWs. Neighborhood socioeconomic factors may only partly explain RCC disparities.

Interrogating Patterns of Cancer Disparities by Expanding the Social Determinants of Health Framework to Include Biological Pathways of Social Experiences.

The objective of this article is to call for integrating biological pathways of social experiences in the concept model of cancer disparities and social determinants of health (SDH) fields. Black, Indigenous, and People of Color (BIPOC) populations experience more negative outcomes across the cancer continuum. Social conditions are instrumental in better understanding the contemporary and historical constructs that create these patterns of disparities. There is an equally important body of evidence that points to the ways that social conditions shape biological pathways. To date, these areas of research are, for the most part, separate. This paper calls for a bridging of these two areas of research to create new directions for the field of cancer disparities. We discuss inflammation, epigenetic changes, co-morbidities, and early onset as examples of the biological consequences of social conditions that BIPOC populations experience throughout their lifespan that may contribute to disproportionate tumorigenesis and tumor progression.

Digital image analysis using video microscopy of human-derived prostate cancer vs normal prostate organoids to assess migratory behavior on extracellular matrix proteins.

The advent of perpetuating living organoids derived from patient tissue is a promising avenue for cancer research but is limited by difficulties with precise characterization. In this brief communication, we demonstrate via time-lapse imaging distinct phenotypes of prostate organoids derived from patient material- without confirmation of cellular identity. We show that organoids derived from histologically normal tissue more readily spread on a physiologic extracellular matrix (ECM) than on pathologic ECM (p<0.0001), while tumor-derived organoids spread equally on either substrate (p=0.2406). This study is an important proof-of-concept to defer precise characterization of organoids and still glean information into disease pathology.

Factors Associated with Cancer Screening Among Hopi Men.

Cancer screening rates remain low among American Indian men, and cancer screening behaviors and barriers to cancer screening among American Indian men are not well understood. This study evaluated cancer screening behaviors in 102 Hopi men who were 50 years of age or older from the Hopi Survey of Cancer and Chronic Disease. Reported cancer screening frequencies were 15.7%, 45.1%, and 35.3% for fecal occult blood test (FOBT), colonoscopy, and prostate-specific antigen (PSA) test, respectively. Among men who reported having had a FOBT, 81.2% had the test more than 1 year ago. Among men who reported a colonoscopy, 60.8% had colonoscopy within the past 3 years. Similarly, among men who reported having had PSA, 72.3% had PSA within the past 3 years. "No one told me" was the most common answer for not undergoing FOBT (33.7%), colonoscopy (48.2%), and PSA (39.4%). Men who reported having had a PSA or digital rectal exam were three times as likely to also report having a FOBT or colonoscopy (odds ratio [OR] 3.19, 95% confidence interval [CI]: 1.21-8.46). Younger age (< 65) was associated with reduced odds of ever having prostate cancer screening (OR 0.28, 95% CI: 0.10-0.77). Ever having colorectal cancer screening and previous diagnosis of cancer increased odds of ever having prostate cancer screening (OR 3.15, 95% CI: 1.13-8.81 and OR 5.28, 95% CI: 1.15-24.18 respectively). This study illustrates the importance of community cancer education for men to improve cancer screening participation.

Mendelian randomisation and experimental medicine approaches to interleukin-6 as a drug target in pulmonary arterial hypertension.

BACKGROUND: Inflammation and dysregulated immunity are important in the development of pulmonary arterial hypertension (PAH). Compelling preclinical data supports the therapeutic blockade of interleukin-6 (IL-6) signalling. METHODS: We conducted a phase 2 open-label study of intravenous tocilizumab (8 mg·kg-1) over 6 months in patients with group 1 PAH. Co-primary end-points were safety, defined by incidence and severity of adverse events, and change in pulmonary vascular resistance. Separately, a mendelian randomisation study was undertaken on 11 744 individuals with European ancestry including 2085 patients with idiopathic/heritable disease for the IL-6 receptor (IL6R) variant (rs7529229), known to associate with circulating IL-6R levels. RESULTS: We recruited 29 patients (male/female 10/19; mean±sd age 54.9±11.4 years). Of these, 19 had heritable/idiopathic PAH and 10 had connective tissue disease-associated PAH. Six were withdrawn prior to drug administration; 23 patients received at least one dose of tocilizumab. Tocilizumab was discontinued in four patients owing to serious adverse events. There were no deaths. Despite evidence of target engagement in plasma IL-6 and C-reactive protein levels, both intention-to-treat and modified intention-to-treat analyses demonstrated no change in pulmonary vascular resistance. Inflammatory markers did not predict treatment response. Mendelian randomisation did not support an effect of the lead IL6R variant on risk of PAH (OR 0.99, p=0.88). CONCLUSION: Adverse events were consistent with the known safety profile of tocilizumab. Tocilizumab did not show any consistent treatment effect.

Genetic Contributions to Prostate Cancer Disparities in Men of West African Descent.

Prostate cancer (PCa) is the second most frequently diagnosed malignancy and the second leading cause of death in men worldwide, after adjusting for age. According to the International Agency for Research on Cancer, continents such as North America and Europe report higher incidence of PCa; however, mortality rates are highest among men of African ancestry in the western, southern, and central regions of Africa and the Caribbean. The American Cancer Society reports, African Americans (AAs), in the United States, have a 1.7 increased incidence and 2.4 times higher mortality rate, compared to European American's (EAs). Hence, early population history in west Africa and the subsequent African Diaspora may play an important role in understanding the global disproportionate burden of PCa shared among Africans and other men of African descent. Nonetheless, disparities involved in diagnosis, treatment, and survival of PCa patients has also been correlated to socioeconomic status, education and access to healthcare. Although recent studies suggest equal PCa treatments yield equal outcomes among patients, data illuminates an unsettling reality of disparities in treatment and care in both, developed and developing countries, especially for men of African descent. Yet, even after adjusting for the effects of the aforementioned factors; racial disparities in mortality rates remain significant. This suggests that molecular and genomic factors may account for much of PCa disparities.

National trends and survival outcomes of penile squamous cell carcinoma based on human papillomavirus status.

BACKGROUND: There are no series evaluating penile squamous cell carcinoma (pSCC) based on human papillomavirus (HPV) infection. Herein, we present national registry data on clinical and survival outcomes for pSCC based on HPV status. METHODS: We performed a retrospective review of 1224 pSCC patients with known HPV staining from the National Cancer Database. Patients with cM1 disease, those who did not receive treatment, or had missing follow-up data were excluded. Logistic regression identified factors associated with locally aggressive disease. Univariable, multivariable, and inverse probability of treatment weighting (IPTW)-Cox proportional hazard modeling were used to assess hazard ratios (HR) associated with overall survival (OS). RESULTS: After exclusion criteria, we identified 825 cases of which 321 (38.9%) were HPV positive. The HPV-positivity rate did not significantly change by year. HPV-positive patients were younger, had lower Charlson-Deyo performance score, and resided in areas with both lower median household income and lower school education completion. HPV-positive tumors presented with lower American Joint Committee on Cancer clinical T-stage (cT), poorer differentiation, lower rates of lymphovascular invasion (LVI), but more node-positive disease (cN+). For those who underwent lymph node surgery, there were no differences in final pathologic stage, upstaging, or presence of extranodal extension. Only tumor differentiation, LVI, and performance score were independent predictors for locally aggressive disease. HPV status was not a predictor of OS (IPTW-HR:0.89, p = 0.13). CONCLUSIONS: In the largest series evaluating pSCC based on HPV status, HPV-positive tumors were associated with lower cT stages, less LVI, but more cN + disease. More studies on prognostic factors are needed, and time may still be immature to use HPV information for risk stratification.

Racial and Ethnic Disparities in Preoperative Surgical Wait Time and Renal Cell Carcinoma Tumor Characteristics.

Racial/ethnic minority groups have a disproportionate burden of kidney cancer. The objective of this study was to assess if race/ethnicity was associated with a longer surgical wait time (SWT) and upstaging in the pre-COVID-19 pandemic time with a special focus on Hispanic Americans (HAs) and American Indian/Alaska Natives (AIs/ANs). Medical records of renal cell carcinoma (RCC) patients who underwent nephrectomy between 2010 and 2020 were retrospectively reviewed (n = 489). Patients with a prior cancer diagnosis were excluded. SWT was defined as the date of diagnostic imaging examination to date of nephrectomy. Out of a total of 363 patients included, 34.2% were HAs and 8.3% were AIs/ANs. While 49.2% of HA patients experienced a longer SWT (≥90 days), 36.1% of Non-Hispanic White (NHW) patients experienced a longer SWT. Longer SWT had no statistically significant impact on tumor characteristics. Patients with public insurance coverage had increased odds of longer SWT (OR 2.89, 95% CI: 1.53-5.45). Public insurance coverage represented 66.1% HA and 70.0% AIs/ANs compared to 56.7% in NHWs. Compared to NHWs, HAs had higher odds for longer SWT in patients with early-stage RCC (OR, 2.38; 95% CI: 1.25-4.53). HAs (OR 2.24, 95% CI: 1.07-4.66) and AIs/ANs (OR 3.79, 95% CI: 1.32-10.88) had greater odds of upstaging compared to NHWs. While a delay in surgical care for early-stage RCC is safe in a general population, it may negatively impact high-risk populations, such as HAs who have a prolonged SWT or choose active surveillance.

Nephrectomy Delay of More than 10 Weeks from Diagnosis Is Associated with Decreased Overall Survival in pT3 RCC.

In this study, we aimed to evaluate the impact of surgical wait time (SWT) on outcomes of patients with renal cell carcinoma (RCC), and to investigate risk factors associated with prolonged SWT. Using the National Cancer Database, we retrospectively reviewed the records of patients with pT3 RCC treated with radical or partial nephrectomy between 2004 and 2014. The cohort was divided based on SWT. The primary outcome was 5-year overall survival (OS). Logistic regression analysis was used to investigate the risk factors associated with delayed surgery. Cox proportional hazards models were fitted to assess relations between SWT and 5-year OS after adjusting for confounding factors. A total of 22,653 patients were included in the analysis. Patients with SWT > 10 weeks had higher occurrence of upstaging. Using logistic regression, we found that female patients, African-American or Spanish origin patients, treatment in academic or integrated network cancer center, lack of insurance, median household income of <$38,000, and the Charlson-Deyo score of ≥1 were more likely to have prolonged SWT. SWT > 10 weeks was associated with decreased 5-year OS (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.15-1.33). This risk was not markedly attenuated after adjusting for confounding variables, including age, gender, race, insurance status, Charlson-Deyo score, tumor size, and surgical margin status (adjusted HR, 1.13; 95% CI, 1.04-1.24). In conclusion, the vast majority of patients underwent surgery within 10 weeks. There is a statistically significant trend of increasing SWT over the study period. SWT > 10 weeks is associated with decreased 5-year OS.

Genetic Variation and Immunohistochemical Localization of the Glucocorticoid Receptor in Breast Cancer Cases from the Breast Cancer Care in Chicago Cohort.

BACKGROUND: Glucocorticoid, one of the primary mediators of stress, acts via its receptor, the glucocorticoid receptor (GCR/NR3C1), to regulate a myriad of physiological processes. We measured the genetic variation and protein expression of GCR, and the genes that regulate GCR function or response and examined whether these alterations were associated with breast cancer clinicopathological characteristics. METHOD: We used samples from a multiracial cohort of breast cancer patients to assess the association between breast cancer characteristics and the genetic variants of single nucleotide polymorphisms (SNPs) in GCR/NR3C1, FKBP5, Sgk1, IL-6, ADIPOQ, LEPR, SOD2, CAT, and BCL2. RESULTS: Several SNPs were associated with breast cancer characteristics, but statistical significance was lost after adjustment for multiple comparisons. GCR was detected in all normal breast tissues and was predominantly located in the nuclei of the myoepithelial cell layer, whereas the luminal layer was negative for GCR. GCR expression was significantly decreased in all breast cancer tissue types, compared to nontumor tissue, but was not associated with breast cancer characteristics. We found that high nuclear GCR expression was associated with basal cell marker cytokeratin 5/6 positivity. CONCLUSION: GCR expression is reduced in breast cancer tissue and correlates with the basal cell marker CK5/6.

Correlation between body mass index and prostate volume in benign prostatic hyperplasia patients undergoing holmium enucleation of the prostate surgery.

BACKGROUND: Benign prostatic obstruction (BPO) due to benign prostatic hyperplasia (BPH) is a leading cause of morbidity in men over the age of 40. This study examined whether there was an association between body mass index (BMI) and pre-operative prostate volume and whether expression of two genes, alpha-2-macroglobulin (A2M) and transforming growth factor beta 3 (TGFB3), was correlated with BMI, pre-operative prostate volume, and age at surgery. METHODS: Medical records of patients who underwent holmium enucleation of the prostate surgery for treatment of BPO were retrospectively reviewed. Surgical specimens were obtained from formalin-fixed paraffin-embedded blocks, and expression of the targeted genes was quantified using a real time PCR approach. Linear regression analysis was performed to assess association between BMI and prostate volume adjusting for demographic characteristics and co-morbidity. Spearman's correlation was used to examine whether gene expression was correlated with BMI, prostate volume, and age at surgery. RESULTS: A total of 278 patients were identified, including 62.9% European Americans (n = 175) and 27.7% Hispanic Americans (n = 77). BMI was significantly correlated with prostate volume (Spearman's rho = 0.123, P = 0.045). In linear regression analysis, BMI was positively associated with prostate volume (ß = 0.01, P = 0.004), while hyperlipidemia was negatively associated with prostate volume (ß = -0.08, P = 0.02). A trend for a positive association was also observed for diabetes (ß = 0.07, P = 0.099). In the race/ethnicity stratified analysis, age at surgery showed a trend for significantly positive association with prostate volume in European Americans (ß = 0.005, P = 0.08), but not in Hispanic Americans. Expression of the A2M gene in the stroma was negatively correlated with age at surgery (P = 0.006). A2M expression in the gland was positively correlated with prostate volume among older men (Age ≥ 70, P = 0.01) and overweight men (BMI 25-30, P = 0.04). TGFB3 expression in the gland was positively correlated with BMI (P = 0.007) among older men. CONCLUSIONS: This study demonstrated the positive correlation between BMI and prostate volume. Expression of TGFB3 and A2M was correlated with BMI, prostate volume, and age at surgery.