Prostate Cancer Research
Distribution and Determinants of Prostate and Genitourinary Cancer Risk, Survival and Outcomes
Racial Disparities & Prostate Cancer
Prostate cancer incidence and mortality rates continue to be higher in the Detroit area than elsewhere in the country and remain a focus of the research being conducted in this program. African American men have higher overall prostate cancer incidence, present with more clinically advanced disease and are more likely to have bone metastases and higher mortality than white men. Tumor-specific gene expression differences may contribute to these disparities. Measuring gene expression levels for 517 genes in 639 tumor samples demonstrated variation by race in gene expression patterns, with inflammation pathways dominating the profiles for white men and lipid metabolism pathways dominating the profiles for African American men. This work was conducted in the Genomics Core and Biostatistics Core. Program Members established a cohort of men with prostate cancer to follow-up on these findings. Program members are continuing cohort recruitment with a DOD racial disparities grant and will examine the roles of plasma microRNA levels and polymorphisms in genes in the microRNA biosynthesis pathway in prostate cancer aggressiveness, PSA relapse,and racial disparities.
- Lead Researchers: Drs. Beebe-Dimmer, Bock, Powell, Podgorski and Schwartz
- Grants: W81XH-06-1-0091; W81XWH-09-1-0203; Fund for Cancer Research; W81XWH-13-1-0477’
Metabolic Syndrome & Prostate Cancer
Metabolic syndrome refers to a cluster of conditions including hypertension, abdominal obesity, impaired glucose tolerance/elevated fasting glucose or diabetes, low HDL cholesterol, and hypertriglyceridemia, with increasing prevalence in the U.S. The frequency of these characteristics varies by race and the syndrome has been linked to prostate cancer. Hypertension, a feature of metabolic syndrome, was significantly associated with biochemical recurrence in both African American and white men suggesting that lifestyle interventions are a viable strategy in reducing risk of biochemical recurrence. Genetic variation in ADIPOQ, the gene coding for adiponectin, and ADIPOR1, its type 1 receptor, has been linked to both breast and colorectal cancer. Program members, in collaboration with the University of Michigan, showed that variation in these genes did not predict prostate cancer risk in African American men, but rs1501299 was associated with obesity in this population. Obesity is also a feature of metabolic syndrome that is open to intervention.
- Lead Researcher: Dr. Beebe-Dimmer
Genetics & Prostate Cancer
Family history of the disease is one of the strongest risk factors for prostate cancer. In addition to prostate-specific family history, program members identified gene regions associated with familial clustering of breast and prostate cancer among first-degree family members in a set of 50 families participating in a large study of hereditary prostate cancer. A genome-wide multipoint nonparametric linkage analyses was conducted among these families with the strongest evidence for linkage detected at 16q22 (LOD=3.07 at rs722579), a region very close to another previously reported to be in linked to prostate cancer in a set of 317 families from the same study. In collaboration with the University of Michigan and Johns Hopkins University, Dr. Beebe-Dimmer also reported that carriers of a rare G84E variant in HOXB13 had a younger age at diagnosis and were more likely to have a family history of prostate cancer than non-carriers of the variant. The variant was not associated with high grade or advanced stage tumors.
- Lead Researcher: Dr. Beebe-Dimmer
- Grant: K07 CA127214
Androgen Deprivation Therapy & Prostate Cancer
Negative side effects for men treated with Androgen Deprivation Therapy (ADT) were evaluated using SEER-Medicare data. Duration of ADT use was associated with increased risk of fracture irrespective of the timing of use, however, risk declined over time among those patients who stopped treatment. Other side effects of ADT use included a modest increase in cataract incidence (HR=1.09, 95% CI 1.06-1.12).
- Lead Researcher: Dr. Beebe-Dimmer
Racial Disparities & Renal Cell Carcinoma
Relatively little is known about the underlying contributors to racial disparities in renal cell carcinoma. In a large, multi-center case-control study, several novel observations have been made. Karmanos led projects included the discovery of differential smoking associated risks by race and obesity and a stronger role for obesity in renal cancer risk in whites as compared to African Americans. The proportion of patients presenting with small, asymptomatic renal cell carcinoma increased across the study period, with 24% of patients overall having at least 2 significant comorbidities at the time of diagnosis, suggesting the need for increased use of nephron sparing surgery.
- Lead Researchers: Drs. Cote & Beebe-Dimmer
Intervention Research with African Americans to Reduce and Eliminate Disparities
Prostate Cancer
Program members are using daily patient reports of quality of life (QOL) as an intervention to improve physicians’ clinical decisions about how well patients are responding to treatment. Daily diaries can provide physicians with clinically relevant information that may not otherwise be available during routine follow-up (e.g., test results, adverse effects), and as a result, can provide a more comprehensive picture of how patients physical and psychosocial treatment responses. Traditionally QOL information has been acquired either by informal and subjective queries of the patient by a physician or nurse. However, asking patients to retrospectively remember and summarize their QOL since the previous visit can adversely affect the accuracy of recall, thereby leading to an incomplete or erroneous report of symptoms. Using iPads provided to patients, daily diary technology can increase the accuracy of symptom reports and capture daily changes in symptoms that fluctuate and impact patient quality of life (e.g., pain, mood, fatigue). This information has application in monitoring adverse events in clinical trial protocols, improving patient adherence to medication, identifying the need for medication changes, and provide patient feedback to physicians outside of clinical appointment. Thus, daily diary information can improve patient-provider communication and medical management including treatment decision-making.
- Lead Researchers: Drs. Harper and Penner
- Grant: R21 CA152347