Androgenetic alopecia at various ages and prostate cancer risk in an equal-access multiethnic case-control series of veterans.

PURPOSE: Epidemiological data are conflicting regarding the association between androgenetic alopecia (AA) and prostate cancer (CaP). We examined the relationship between these two conditions. MATERIALS AND METHODS: We performed a case-control study at a Veterans Affairs Hospital among 708 men: 312 healthy controls, 167 men with CaP, and 229 men without CaP on prostate biopsy. Participants were asked to self-describe hair patterns at ages 30 and 40 and at study enrollment. We tested the association between hair pattern (overall, vertex, or frontal) and CaP status using logistic regression analysis adjusting for multiple clinical features. Disease grade was similarly examined as a secondary outcome. RESULTS: Relative to healthy controls, younger age of AA onset was significantly associated with increased CaP risk (p = 0.008). Similar patterns were noted for frontal (p = 0.005) and not vertex balding (p = 0.22). When compared with biopsy-negative men, a similar pattern was seen with younger age of AA onset having higher risk of CaP, though this was not significant (p = 0.07). A suggestion for younger age of AA onset for frontal (p = 0.07) being associated with CaP versus biopsy-negative men was also observed. Overall balding (yes/no) was associated with greater than twofold increase in high-grade disease (p = 0.02). CONCLUSIONS: Men reporting earlier AA onset were at increased CaP risk and suggestively had more aggressive disease. Contrary to other studies, frontal balding was the predominant pattern associated with elevated CaP risk. Further study is required to confirm these findings in a larger sample and to better understand the role of AA, androgens, and CaP biology.

Association of prostate-specific antigen doubling time and cancer in men undergoing repeat prostate biopsy.

OBJECTIVES: To analyze the association between prostate-specific antigen doubling time with prostate cancer risk and grade among men with prostate-specific antigen levels ≥4.0 ng/mL undergoing repeat prostate biopsy. METHODS: A total of 286 patients with prostate-specific antigen ≥4 ng/mL and available prostate-specific antigen doubling time data, who underwent repeat prostate biopsy from 1996-2009, were included in this analysis. Prostate-specific antigen doubling time was divided into three groups: >9 years, 3-9 years and <3 years. Multivariate analyses of prostate-specific antigen doubling time with cancer risk and grade (≤3 + 4 vs ≥4 + 3) were carried out using logistic regression adjusting for prebiopsy prostate-specific antigen, race, age, digital rectal examination, year of biopsy and number of prior negative biopsies. RESULTS: The median prostate-specific antigen doubling time before biopsy was 4.5 years (interquartile range = 2.5-10). Shorter prostate-specific antigen doubling time was associated with higher prostate-specific antigen (P < 0.001), but it was unrelated to age, digital rectal examination or race. Shorter prostate-specific antigen doubling time as a continuous variable was associated with greater prostate cancer risk in both uni- (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.001) and multivariate analysis (hazard ratio = 0.99, 95% confidence interval = 0.98-0.99, P = 0.004). The prevalence of cancer among prostate-specific antigen doubling time groups (>9, 3-9, <3 years) was 17%, 37% and 40%, respectively. Shorter prostate-specific antigen doubling time groups were associated with higher cancer risk (P = 0.001). Stratified by grade, short prostate-specific antigen doubling time as a continuous variable significantly predicted both low- (P = 0.010) and high-grade disease (P = 0.049). The inclusion of prostate-specific antigen doubling time groups in a multivariate model to predict biopsy positivity increased its accuracy from 0.69 to 0.74. CONCLUSION: Prostate-specific antigen doubling time seems to provide further cancer risk assessment in men undergoing repeat biopsy for prostate-specific antigen ≥4.0 ng/mL. If validated in future studies, the present findings support the use of prostate-specific antigen doubling time in the risk stratification of this patient population.

The association of diabetes mellitus and high-grade prostate cancer in a multiethnic biopsy series.

OBJECTIVE: To analyze the association of diabetes mellitus (DM) with risk of prostate cancer and cancer grade among men undergoing prostate biopsy and to analyze how obesity and race modify these associations. MATERIALS AND METHODS: Retrospective analysis of 998 men from the Durham VA undergoing first prostate biopsy between 2001 and 2009 with complete data available. History of DM was determined by chart review. Patients' characteristics at biopsy were analyzed with chi-square and ranksum. Multivariable analyses of DM and risk of cancer and cancer grade were done using logistic regression adjusting for PSA, body mass index, race, age, year, and digital rectal exam. RESULTS: At biopsy, 284 (28%) men had DM. DM was associated with African American (AAM; p = 0.010) and higher BMI (p < 0.001). DM was not associated with prostate cancer risk on either bivariate (p = 0.600) or multivariate analysis (p = 0.485). Similar results were found after stratification by race and obesity. In multivariable analysis, DM was associated with greater risk of high-grade disease (RR = 2.13, p = 0.024). The association was stronger among obese men (RR = 3.84, p = 0.020) and null in non-obese subjects (RR = 1.39, p = 0.460). After further stratification by race, DM was associated with high-grade disease only in obese Caucasian men (CM; RR = 5.81, p = 0.025) but not in obese AAM. DM was not associated with risk of low-grade disease in all men together or after stratification by obesity or race. CONCLUSION: History of DM was associated with greater risk of high-grade disease. The association was strongest among obese CM suggesting the effect of DM on high-grade prostate cancer is modified by race and obesity.

Effect of isocaloric low fat diet on prostate cancer xenograft progression in a hormone deprivation model.

PURPOSE: Previous mouse studies suggesting that low fat diets slow prostate cancer growth often used corn oil (omega-6), which enhances prostate cancer growth, as the primary fat. Using a saturated fat based diet we previously found no significant difference in tumor growth between low and high fat fed SCID mice (Taconic Farms, Hudson, New York) xenografted with LAPC-4 cells. Whether similar results would hold in a castration model is unclear. MATERIALS AND METHODS: A total of 80 male SCID mice were fed a Western diet (40% fat and 44% carbohydrate) and injected with LAPC-4 human prostate cancer cells. When tumors were 200 mm(3), the mice were castrated and randomized to an isocaloric Western or a low fat diet (12% fat and 72% carbohydrate). Animals were sacrificed when tumors were 1,000 mm(3). Serum was collected and assayed for prostate specific antigen, insulin, insulin-like growth factor 1 and insulin-like growth factor binding protein 3. Tumors were assayed for total and phosphorylated Akt. RESULTS: Mouse weight was equivalent in the 2 groups. Overall dietary group was not significantly associated with survival (log rank p = 0.32). There were no statistically significant differences in prostate specific antigen (p = 0.53), insulin-like growth factor axis parameters (each p >0.05) or p-Akt-to-t-Akt ratios (p = 0.22) between the groups at sacrifice. CONCLUSIONS: In this xenograft model we found no difference in tumor growth or survival between low fat vs Western fed mice when the fat source was saturated fat. These results conflict with those of other studies in which corn oil was used to show that low fat diets delay prostate cancer growth, suggesting that fat type may be as important as fat amount in the prostate cancer setting.

Exercise and prostate cancer risk in a cohort of veterans undergoing prostate needle biopsy.

PURPOSE: Epidemiological and molecular evidence suggest potential associations between exercise and prostate cancer risk reduction. We further characterized this relationship by examining exercise and cancer risk among men undergoing prostate needle biopsy. MATERIALS AND METHODS: A total of 190 men who underwent prostate biopsy at the Durham Veterans Affairs Medical Center completed a questionnaire on current exercise behavior. Participants were asked average frequency of mild, moderate and strenuous intensity exercise in a typical week, as well as average duration as assessed by the Godin Leisure Time Exercise Questionnaire. Total current exercise was calculated in terms of metabolic equivalent task hours per week. Primary outcome measures were prostate biopsy result and Gleason sum. RESULTS: After adjusting for age, race, body mass index, prostate specific antigen, digital rectal examination, family history, previous prostate biopsy and comorbidity score, men who reported 9 or more metabolic equivalent task hours per week of exercise were significantly less likely to have cancer on biopsy (OR 0.35, CI 0.17-0.75, p = 0.007). Furthermore, among men with malignant biopsy results, reporting moderate exercise (3 to 8.9 metabolic equivalent task hours weekly) was associated with a lower risk of high grade disease (Gleason 7 or greater, OR 0.14, CI 0.02-0.94, p = 0.04). CONCLUSIONS: To our knowledge these results provide the first evidence of an association between exercise and prostate cancer risk as well as grade at diagnosis in men scheduled to undergo prostate biopsy. Specifically moderate exercise was associated with a lower risk of prostate cancer and in men with cancer, lower grade disease. Further investigation using an objective measure of exercise in a larger sample size is required to confirm these findings.

Prostate cancer risk in men with baseline history of coronary artery disease: results from the REDUCE Study.

BACKGROUND: Coronary artery disease (CAD) and prostate cancer (PCa) are not only common diseases, but share many risk factors. To date, only a few studies have explored the relationship between CAD and PCa risk, with conflicting results. METHODS: The four-year REDUCE study tested dutasteride 0.5 mg daily for PCa risk reduction in men with prostate specific antigen (PSA) of 2.5 to 10.0 ng/mL and a negative biopsy. Among men who underwent at least one on-study biopsy (n = 6,729; 82.8%), the association between CAD and overall PCa risk and disease grade was examined with logistic and multinomial logistic regression adjusting for clinicopathologic features, respectively. RESULTS: Overall, 547 men (8.6%) had a history of CAD. Men with CAD were significantly older and had higher body mass index, PSA, and larger prostate volumes and were more likely to have diabetes, hypertension, and hypercholesterolemia and take aspirin and statins. On multivariate analysis, CAD was associated with a 35% increased risk of PCa diagnosis (OR = 1.35, 95% CI: 1.08-1.67, P = 0.007), while elevating risk of both low- (OR = 1.34, 95% CI: 1.05-1.73, P = 0.02) and high-grade disease (OR = 1.34, 95% CI: 0.95-1.88, P = 0.09). CONCLUSIONS: In a post hoc hypothesis developing secondary analysis of the REDUCE study, CAD was significantly associated with increased PCa diagnosis. IMPACT: If confirmed in other studies, this suggests CAD may be a novel PCa risk factor and suggests common shared etiologies. Whether lifestyle changes shown to reduce CAD risk (i.e., weight loss, exercise, cholesterol reduction, etc.) can reduce PCa risk, warrants further study.

Obesity and prostate cancer: collateral damage in the battle of the bulge.

Prostate cancer is the most common non-cutaneous malignancy diagnosed in US men. With the increasing prevalence of obesity, it is of interest how this condition impacts prostate cancer. However, only recently has the relationship between obesity and prostate cancer been earnestly studied by investigators. Indeed, the relationship between obesity and prostate cancer appears to be complex one. Therefore, we sought to review the most recent and relevant epidemiological data discussing the link between prostate cancer and obesity. In this review, we will discuss both "biological" and "non-biological" means by which obesity may potentially impact prostate cancer.