Julie J. Ruterbusch

Evidence Supports a Faster Growth Rate and/or Earlier Transformation to Clinically Significant Prostate Cancer in Black Than in White American Men, and Influences Racial Progression and Mortality Disparity

PURPOSE The incidence of prostate cancer is approximately 60% higher and the mortality rate is 2 to 3 times greater in black than in white American men. We propose that a more rapid prostate cancer growth rate and/or earlier transformation from latent to aggressive prostate cancer in black than in white men contribute to this disparity. MATERIALS AND METHODS We evaluated entirely embedded prostate glands on autopsy from 1,056 black and white men who died of causes other than prostate cancer. We also reviewed data from our radical prostatectomy database and from the Detroit Surveillance, Epidemiology and End Results database. RESULTS Autopsy data indicated that subclinical prostate cancer in black and white men starts at early age and clinical characteristics do not differ by race at early ages. Radical prostatectomy specimen data revealed that prostate cancer volume and Gleason grade were greater in black than in white men. Advanced or metastatic prostate cancer occurred at a 4:1 ratio in black and white men, respectively, in the Detroit Surveillance, Epidemiology and End Results registry database. CONCLUSIONS Results showed that age at prostate cancer initiation and clinical characteristics did not differ by race in our autopsy series, prostate cancer volume after radical prostatectomy was greater in black than in white men and disease became distant disease at a ratio of 4 black men to 1 white man in the Detroit Surveillance, Epidemiology and End Results population. These findings support the concept that prostate cancer grows more rapidly in black than in white men and/or earlier transformation from latent to aggressive prostate cancer occurs in black than in white men.

Hypertension and risk of renal cell carcinoma among white and black Americans.

Background: Renal cell carcinoma and hypertension (a well-established renal cancer risk factor) are both more frequent among blacks than whites in the United States. The association between hypertension and renal cell carcinoma has not been examined in black Americans. We investigated the hypertension–renal cancer association by race, and we assessed the role of hypertension in the racial disparity of renal cancer incidence. Methods: Participants were enrolled in a population-based case-control study in Detroit and Chicago during 2002–2007 (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519 blacks). Participants reported their history of hypertension and antihypertensive drug use. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic characteristics, smoking, body mass index, and family history of cancer. Results: Hypertension doubled renal cancer risk (OR = 2.0 [CI = 1.7–2.5]) overall. For whites, the OR was 1.9 (CI = 1.5–2.4), whereas for blacks it was 2.8 (2.1–3.8) (P for interaction = 0.11). ORs increased with time after hypertension diagnosis (P for trend <0.001), reaching 4.1 (CI = 2.3–7.4) for blacks and 2.6 (CI = 1.7–4.1) for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI = 2.3–8.8) for blacks and 2.1 (CI = 1.2–3.8) for whites. If these estimates correctly represent causal effects and if, hypothetically, hypertension could be prevented entirely among persons aged 50–79 years, the black/white disparity in renal cancer could be reversed among women and reduced by two-thirds among men. Conclusions: Hypertension is a risk factor for renal cancer among both blacks and whites, and might explain a substantial portion of the racial disparity in renal cancer incidence. Preventing and controlling hypertension might reduce renal cancer incidence, adding to the known benefits of blood pressure control for heart disease and stroke reduction, particularly among blacks.

Contemporary Clinical Epidemiology of Renal Cell Carcinoma: Insight From a Population Based Case-Control Study

PURPOSE To clarify the contemporary clinical epidemiology of renal cell carcinoma we present trends in clinical presentation and treatment in patients enrolled in a population based case-control study. MATERIALS AND METHODS The National Cancer Institute performed a population based case-control study in metropolitan Detroit and Chicago from 2002 through 2007. In 1,136 patients with renal cell carcinoma who consented to an epidemiological interview and medical record review we ascertained detailed information on social and medical history, methods of renal cell carcinoma detection and diagnosis, cancer severity and treatment(s) received. From these data we assessed the demographic and cancer specific characteristics of study cases, and trends in clinical presentation, diagnosis and treatment. RESULTS Most patients with renal cell carcinoma had localized or regional tumors, including 52% with tumors 4 cm or less. The proportion of asymptomatic cases increased from 35% in 2002 to 50% in 2007 (p<0.001). Hypertension and diabetes were common in patients (58% and 17%, respectively) and 24% had at least 2 significant comorbid conditions at cancer diagnosis. While the use of laparoscopic surgery increased with time (p<0.001), fewer than 1/5 patients underwent nephron sparing surgery. CONCLUSIONS The proportion of patients presenting with small, asymptomatic renal cell carcinoma continues to increase. Most of these cases are still treated with radical nephrectomy, although increasingly via a laparoscopic approach. Since most patients with small renal cell carcinomas have 1 or more renal function relevant comorbidities, there is an imperative to increase the use of nephron sparing surgery.

Genes Associated with Prostate Cancer Are Differentially Expressed in African American and European American Men

Background: Despite more aggressive screening across all demographics and gradual declines in mortality related to prostate cancer (PCa) in the United States, disparities among populations persist. A substantial proportion of African American men (AAM) have a higher overall incidence, earlier age of onset, increased proportion of clinically advanced disease, and increased bone metastases and mortality from PCa compared to European American men (EAM). Limited early evidence indicates that underlying causes for disparities may be observed in tumor-specific gene expression programs. Methods: This study used microarray-based methods to measure expression levels for 517 genes that were previously associated with PCa in archived formalin-fixed paraffin embedded (FFPE) specimens; testing the hypothesis that gene expression features of functional consequence to cancer distinguish PCa from AAM and EAM. A t test was conducted comparing AAM to EAM expression levels for each probe on the array. Results: Analysis of 639 tumor samples (270 AAM, 369 EAM) showed that 95 genes were overexpressed specifically in PCa from AAM relative to EAM and 132 were overexpressed in PCa from EAM relative to AAM. Furthermore, systems-level analyses highlight the relevant signaling pathways and functions associated with the EAM- or AAM-specific overexpressed gene sets, for example, inflammation and lipid metabolism. Conclusions: Results here bring further understanding to the potential for molecular differences for PCa in AAM versus EAM. Impact: The results support the notion that therapeutic benefits will be realized when targeted treatments are designed to acknowledge and address a greater spectrum of PCa subtypes and molecular distinctions. Cancer Epidemiol Biomarkers Prev; 22(5); 891–7. ©2013 AACR.

An investigation of risk factors for renal cell carcinoma by histologic subtype in two case-control studies

To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case‐control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case‐only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case‐control analyses were performed to compute subtype‐specific ORs for other risk factors using polytomous regression. In case‐only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1–1.4 per 10‐year increase), less likely to be female (OR = 0.5, 95% CI = 0.4–0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8–3.9) as compared to clear cell cases (N = 1,524). In case‐control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1–1.3 per 5 kg/m2 increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1–1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0–1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity‐RCC association differs by histology.

A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma.

Background Low mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U.S. population-based case-control study of RCC. Methodology/Principal Findings Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay using DNA extracted from peripheral whole blood. Cases (n = 603) had significantly lower mtDNA copy number than controls (n = 603; medians 0.85, 0.91 respectively; P = 0.0001). In multiple logistic regression analyses, the lowest quartile of mtDNA copy number was associated with a 60% increase in RCC risk relative to the highest quartile (OR = 1.6, 95% CI = 1.1–2.2; P trend = 0.009). This association remained in analyses restricted to cases treated by surgery alone (OR Q1 = 1.4, 95% CI = 1.0–2.1) and to localized tumors (2.0, 1.3–2.8). Conclusions/Significance Our findings from this investigation, to our knowledge the largest of its kind, offer important confirmatory evidence that low mtDNA copy number is associated with increased RCC risk. Additional research is needed to assess whether the association is replicable in prospective studies.

The Growing Burden of Endometrial Cancer: A Major Racial Disparity Affecting Black Women

Background: In contrast with the decreasing incidence seen for most cancers, endometrial cancer has been increasing in the United States. We examined whether the increasing incidence and mortality from endometrial cancer are equally distributed by race/ethnicity and tumor histologic subtype. Methods: Surveillance, Epidemiology, and End Results (SEER) endometrial cancer incidence and mortality data were obtained from 2000 to 2011. Age-adjusted incidence and incidence-based mortality rates, 95% confidence intervals, and annual percent changes (APC) were calculated. Rate ratios were calculated to compare racial/ethnic groups. Five-year relative survival rates were presented to explore survival by stage at diagnosis. Results: Incidence rates for endometrial cancers are rising across all racial/ethnic groups, with the greatest APC seen among non-Hispanic black (NHB) and Asian women (APC, 2.5 for both). NHB women have significantly higher incidence rates of aggressive endometrial cancers (clear cell, serous, high-grade endometrioid, and malignant mixed Mullerian tumors) compared with non-Hispanic white (NHW) women. Hispanic and Asian women have incidence rates equal to or lower than NHW women for all tumor subtypes. For nearly every stage and subtype, the 5-year relative survival for NHB women is significantly less than NHW women, whereas Hispanic and Asian women have the same or better survival. Conclusions: Endometrial cancer incidence is increasing for all women, particularly the aggressive subtypes. The disparity associated with excess incidence for these aggressive histologic subtypes and poorer survival is limited to NHB women. Impact: Increasing rates of aggressive endometrial cancers may widen the survival disparity between NHW and NHB women. Cancer Epidemiol Biomarkers Prev; 24(9); 1407–15. ©2015 AACR.

Serum leptin and adiponectin levels and risk of renal cell carcinoma

The incidence of renal cell carcinoma (RCC) has increased rapidly in the U.S., particularly among African Americans. Despite a well‐established link between obesity and RCC, the mechanism through which obesity increases cancer risk has yet to be established. Adipokines, such as leptin and adiponectin, may link obesity and cancer, with different quantitative effects by race.

Reducing Prostate Cancer Racial Disparity: Evidence for Aggressive Early Prostate Cancer PSA Testing of African American Men

Background: There is continuing controversy about prostate cancer testing and the recent American Urological Association guidelines. We hypothesize that the reduction and elimination of racial survival disparity among African American men (AAM; high-risk group) compared with European American men (EAM; intermediate-risk group) during the PSA testing era compared with the pre-PSA era strongly supports the use of PSA testing in AAM. Methods: We used Surveillance, Epidemiology, and End Results (SEER) data to investigate relative survival disparities between AAM and EAM. To evaluate pre-PSA testing era, we selected malignant first primary prostate cancer in AAM and EAM, all stages, diagnosed during 1973–1994. To evaluate relative survival disparities in the current PSA testing era, we selected malignant first primary local, regional, and distant stage prostate cancers diagnosed during 1998–2005 to calculate 5-year relative survival rates. Results: Age-adjusted 5-year relative survival of prostate cancer diagnosed during 1973–1994 in the national SEER data revealed significantly shorter survival for AAM compared with EAM (P < 0.0001). The SEER-based survival analysis from 1995 to 2005 indicated no statistical difference in relative survival rates between AAM and EAM by year of diagnosis of local, regional, or distant stage prostate cancer. Conclusion: We conclude that the elimination of prostate cancer racial disparity of local, regional, and metastatic prostate cancer relative survival in the current PSA testing era compared with pre-PSA era as an endpoint to test PSA efficacy as a marker for prostate cancer diagnosis is evidence for aggressive testing of AAM. Impact: Evidence for screening AAM. Cancer Epidemiol Biomarkers Prev; 23(8); 1505–11. ©2014 AACR.

Quality of life and self-esteem of long-term survivors of invasive and noninvasive cervical cancer.

OBJECTIVE We compared long-term survivors of invasive and noninvasive cervical cancer (1) to determine if there are differences in the quality of life (QOL) and (2) to assess the association between self-esteem and QOL. METHODS A sample of cervical cancer survivors diagnosed with invasive and noninvasive cervical cancer during 1995-1996 was drawn from the metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) cancer registry. There were 145 participating survivors, 42 with invasive and 103 with noninvasive cervical cancer. Data were collected using a structured interview, conducted primarily over the telephone. The outcome measures were the QOL (measured by the Medical Outcomes Study Short Form-36 [SF-36]) summary scales, the Physical Component Summary (PCS) score and the Mental Component Summary (MCS) score. Differences in MCS and PCS between women with invasive and noninvasive cancer were determined using analysis of covariance (ANCOVA). Multivariate analysis was performed to determine the association between self-esteem and MCS and PCS. RESULTS There were no differences in either PCS or MCS scores between long-term survivors of invasive and noninvasive cervical cancer. Self-esteem was associated with MCS but not with PCS in women with invasive cancer as well as in women with noninvasive cancer. CONCLUSIONS The distinctive association of self-esteem with MCS but not PCS indicates that interventions for supporting and improving self-esteem may be more effective by promoting psychological well-being rather than physical well-being. Moreover, women with noninvasive cervical cancer, a group often neglected in cervical cancer studies, should also be targeted for these interventions.