Risk Of Fatal Prostate Cancer Research Articles

Body mass index trajectories across adulthood and smoking in relation to prostate cancer risks: the NIH-AARP Diet and Health Study.

Previously we showed that adulthood body mass index (BMI) trajectories that result in obesity were associated with elevated risks of fatal prostate cancer (PCA). To further explore this relationship, we conducted a study within the NIH-AARP Diet and Health Study. Among 153730 eligible men enrolled in the NIH-AARP cohort from 1995 to 1996 (median follow-up = 15.1 years), we identified 630 fatal PCA cases and 16896 incident cases. BMI was assessed for ages 18, 35 and 50 and at study entry, enabling examination of latent class-identified BMI trajectories. Hazard ratios (HRs) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. BMI at study entry (mean age = 63, HR = 1.12; 95% CI = 1.01, 1.24, per 5-unit increase) and maximum BMI during adulthood (HR = 1.12; 95% CI = 1.02, 1.24, per 5-unit increase) shared modest associations with increased risk of fatal PCA. Smoking status likely modified the relationship between BMI trajectories and fatal PCA (Pinteraction = 0.035 via change-in-estimate variable section, P = 0.065 via full a priori model). Among never-smokers, BMI trajectory of normal weight to obesity was associated with increased risk of fatal disease (HR = 2.37; 95% CI = 1.38, 4.09), compared with the maintained normal weight trajectory, whereas there was no association among former or current-smokers. Total and non-aggressive PCA exhibited modest inverse associations with BMI at all ages, whereas no association was observed for aggressive PCA. Increased BMI was positively associated with fatal PCA, especially among never-smokers. Future studies that examine PCA survival will provide additional insight as to whether these associations are the result of biology or confounding.

Abstract 3224: Prospective serum metabolomic profiling of fatal prostate cancer

Abstract Metabolic dysregulation may play a role in the etiology of fatal prostate cancer, yet the association with pre-diagnostic serum metabolites has not been elucidated. We conducted a prospective serum metabolomic analysis of fatal prostate cancer risk in 523 cases and 523 matched controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Median time from baseline fasting serum collection to prostate cancer death was 18 years (interdecile range 10-26 years). We profiled 860 known metabolites through an ultrahigh-performance LC-MS/MS platform, and conditional logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals of risk associated with 1-standard deviation increases in the log-metabolite signals. Based on a false discovery rate (FDR) of 0.15 or lower, 34 metabolites are identified as being associated with fatal prostate cancer. Notably, increased serum thioproline and the three cysteine-related amino acids combined (thioproline, cysteine and cystine) are associated with lower odds of fatal disease (OR=0.75 and 0.71, respectively; P≤8.2×10-5). In contrast, the serum dipeptide leucylglycine (OR=1.36, P=8.2×10-5), and three gamma-glutamyl amino acids, including gamma-glutamylvaline, gamma-glutamylglycine and gamma-glutamylleucine (OR=1.28-1.30, P≤4.6×10-4), are associated with increased fatal disease risk. Several other dipeptides including histidylalanine, valylglycine and leucylglutamine, as well as the nucleotides dihydroorotate, pseudouridine, 2'-O-methyluridine, 5,6-dihydrouridine and 5-methyluridine (ribothymidine), also have significant positive associations with fatal disease risk. Findings are not materially altered by adjustment for body mass index, smoking, serum total and HDL cholesterol, serum alpha-tocopherol and retinol, or the ATBC trial supplementation. Our results are also similar across strata of time from blood collection to prostate cancer death and age at blood collection. Gene-set analysis (GSA) reveals a significant peptide super-metabolic pathway association with lethal disease (P<0.0001), and the sub-pathways of dipeptides, pyrimidines (uracil containing), gamma-glutamyl amino acids, glycine/serine/threonine, n3 and n6 polyunsaturated fatty acids, amino-sugars, androgenic steroids, dicarboxylate fatty acids, and endocannabinoids are similarly associated with fatal prostate cancer (FDRs ≤ 0.1). Our study demonstrates a serum risk profile up to two decades prior to death of prostate cancer that is characterized by multiple dysregulated biochemical metabolites of redox status and dipeptide, pyrimidine (uracil), and gamma-glutamyl amino acid metabolism. The findings represent novel leads related to the molecular basis of the etiology or subclinical course of fatal prostate cancer that warrant examination in other populations. Citation Format: Jiaqi Huang, Alison M. Mondul, Stephanie J. Weinstein, Andriy Derkach, Steven C. Moore, Joshua N. Sampson, Demetrius Albanes. Prospective serum metabolomic profiling of fatal prostate cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3224.

Midlife metabolic factors and prostate cancer risk in later life.

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967-1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high-grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0-4) combining the risk factors: BMI ≥30 kg/m2 ; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mmHg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self-reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high-grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3-4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.

Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers.

Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (<7 vs ≥7) and race (European American vs. African American). We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ-specific sex hormone metabolism, implying that other sex steroid hormone-related factors (eg, androgen receptor) play important roles in organ-specific androgenic actions, and that other overlapping pathways may be involved in associations between the two complex conditions.

Abstract 3009: Lipid-lowering drug use and risk of fatal prostate cancer in the Atherosclerosis Risk in Communities (ARIC) Study

Abstract Background: Studies show that lipid-lowering medications, particularly statins, may be protective for more aggressive prostate cancer. Lethal prostate cancer is often considered an optimal outcome in epidemiologic studies when the aim is to identify modifiable risk factors with the potential to reduce morbidity and mortality from this disease, yet this outcome remains understudied. Further, lipid drug use and prostate cancer risk is understudied in black men, whose risk of fatal prostate cancer is 2-3 times higher than that of white men. Thus, we studied lipid medication use and fatal prostate cancer risk in the ARIC Study, which includes ~25% black participants. Methods: The ARIC Study is a prospective cohort that included 15,792 participants (7,082 men) recruited from four US communities. We conducted a prospective cohort analysis of 6,547 men who attended visit 2 (1990-1992, the start of the statin era) and were followed for cancer death through 12/31/2012. Death from prostate cancer (n=90) as the underlying cause was obtained from death certificates supplemented with medical records. Updated information on medication use was collected throughout the study follow-up during study visits and annual telephone calls. Lipid medication use was modeled as a time-dependent variable in two ways: 1) current use (yes/no), and 2) duration of use (&amp;lt;10, ≥10 years). Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of prostate cancer death overall and by race. All models were adjusted for age (years), race, and study center. Additional models were further adjusted for height, BMI, smoking, diabetes, and education. Results: The prevalence of lipid medication use was 17% by visit 4, partway into the statin drug era, and 76% of those medications were statins. After adjustment for age, race, and study center, men who used lipid medications were statistically significantly less likely to die from prostate cancer than men who did not use lipid medications (HR=0.56, 95% CI=0.33-0.95). This finding was slightly attenuated after further mutlivariable adjustment (HR=0.62, 0.36-1.08). The statistically significant inverse association appeared to be restricted to men who used lipid medications for ≥10 years (vs. never use: HR=0.39, 95% CI=0.19-0.82, p-trend=0.02). Lipid medication use was inversely associated with a reduced risk of prostate cancer death in both white and black men. Conclusions: Use of lipid medications was associated with a lower risk of fatal prostate cancer in both black and white men. Whether the fact that black men are less likely to receive/take lipid medications could partly explain the black-white disparity in prostate cancer in the US requires further study. Support: NHLBI contracts, NCI grant, NPCR Citation Format: Alison M. Mondul, Corinne E. Joshu, John Barber, Anna Prizment, Nrupen Bahvsar, Josef Coresh, Elizabeth Selvin, Aaron Folsom, Elizabeth A. Platz. Lipid-lowering drug use and risk of fatal prostate cancer in the Atherosclerosis Risk in Communities (ARIC) Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3009. doi:10.1158/1538-7445.AM2017-3009

Abstract 2306: Sleep duration and risk of fatal prostate cancer in CPS-I and CPS-II

Abstract There is growing evidence that factors associated with circadian rhythm disruption may be associated with prostate cancer risk. In a previous analysis focusing on shift-work in the Cancer Prevention Study (CPS)-II that included only employed men, we observed an association between short sleep duration and higher risk of prostate cancer death that was limited to the first eight years of follow-up of the cohort. To corroborate and expand on these results, we examined the association between sleep duration and death from prostate cancer in a combined analysis of men in CPS-II and men enrolled in an earlier cohort study, CPS-I, regardless of employment status. After excluding men with uninterpretable sleep information, prevalent cancer and prevalent prostate disease at baseline, the analysis included 407,649 men from CPS-I followed from 1950 through 1972, and 416,040 men from CPS-II followed from 1982 through 2012. During follow-up, 1,546 men in CPS-I and 8,704 men in CPS-II died of prostate cancer. Cox proportional hazards regression was used to estimate multivariable-adjusted relative risks (RR) and 95% confidence intervals (CI) and estimates were meta-analyzed using a fixed-effects model because the design and population of CPS-I and CPS-II were similar. Among men aged 65 years and younger, short sleep duration was associated with higher risk of death from prostate cancer during the first eight years of follow-up; compared to 7 hours/night, the RRs (95% CIs) for 3-5, and 6 hours/night were 1.61 (1.10-2.37), and 1.25 (0.99-1.58), respectively. Among men older than age 65 years, the corresponding RRs (95% CIs) were 0.97 (0.68, 1.38), and 1.02 (0.82, 1.27), respectively. There was no association between sleep duration and fatal prostate cancer during later follow-up. These findings support evidence that factors related to circadian rhythms may increase fatal prostate cancer risk. The observed association between short sleep duration and higher risk of fatal prostate cancer only during the first 8-years of follow-up suggests that short sleep duration could affect later stages of prostate carcinogenesis. Reasons for lack of an association in older men are unclear but may include the marked decline in nocturnal melatonin levels with age, which could reduce the relative biologic impact of melatonin inhibition by sleep-deprivation. Citation Format: Susan M. Gapstur, Victoria L. Stevens, Brian D. Carter, Ying Wang, Eric J. Jacobs. Sleep duration and risk of fatal prostate cancer in CPS-I and CPS-II [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2306. doi:10.1158/1538-7445.AM2017-2306

Weight change, obesity and risk of prostate cancer progression among men with clinically localized prostate cancer.

Obesity is associated with an increased risk of fatal prostate cancer. We aimed to elucidate the importance and relevant timing of obesity and weight change for prostate cancer progression. We identified 5,158 men diagnosed with localized prostate cancer (clinical stage T1/T2) from 1986 to 2012 in the Health Professionals Follow-up Study. Men were followed for biochemical recurrence and lethal prostate cancer (development of distant metastasis or prostate cancer-specific mortality) until 2012. Cox regression estimated hazard ratios (HRs) for body mass index (BMI) at age 21, BMI at diagnosis, "long-term" weight change from age 21 to diagnosis and "short-term" weight change over spans of 4 and 8 years preceding diagnosis. Because weight, weight change and mortality are strongly associated with smoking, we repeated analyses among never smokers only (N = 2,559). Among all patients, neither weight change nor BMI (at age 21 or at diagnosis) was associated with lethal prostate cancer. Among never smokers, long-term weight gain was associated with an increased risk of lethal disease (HR for gaining >30 pounds vs. stable weight [±10 pounds] 1.59, 95% CI, 1.01-2.50, p-trend = 0.06). Associations between weight change, BMI and lethal prostate cancer were stronger for men with BMI ≥ 25 at age 21 compared to those with BMI < 25. Weight change and obesity were not associated with an increased risk of biochemical recurrence. Our findings among never smoker men diagnosed with localized prostate cancer suggest a positive association between long-term weight gain and risk of lethal prostate cancer. Metabolic changes associated with weight gain may promote prostate cancer progression.

Prediagnostic Body Mass Index Trajectories in Relation to Prostate Cancer Incidence and Mortality in the PLCO Cancer Screening Trial.

Evidence suggests that obesity in adulthood is associated with increased risk of "clinically significant" prostate cancer. However, studies of body mass index (BMI) across the adult life course and prostate cancer risks remain limited. In a prospective cohort of 69 873 men in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, we examined associations of prediagnostic BMI across the adult life course with risk of incident prostate cancer and fatal prostate cancer (prostate cancer-specific mortality). At 13 years of follow-up, we identified 7822 incident prostate cancer cases, of which 3078 were aggressive and 255 fatal. BMI trajectories were determined using latent-class trajectory modeling. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). BMI at age 20 years, 50 years, and baseline questionnaire (mean age = 63 years) were associated with increased risks of fatal prostate cancer (HRs = 1.27-1.32 per five-unit increase). In five BMI trajectories identified, fatal prostate cancer risk was increased in men who had a normal BMI (HR = 1.95, 95% CI = 1.21 to 3.12) or who were overweight (HR = 2.65, 95% CI = 1.35 to 5.18) at age 20 years and developed obesity by baseline compared with men who maintained a normal BMI. Aggressive and nonaggressive prostate cancer were not associated with BMI, and modest inverse associations were seen for total prostate cancer. Our results suggest that BMI trajectories during adulthood that result in obesity lead to an elevated risk of fatal prostate cancer.

Metformin for Reducing Racial/Ethnic Difference in Prostate Cancer Incidence for Men with Type II Diabetes.

Racial/ethnic disparity in prostate cancer is under studied in men with diabetes who are at a higher risk of aggressive prostate cancer. This study assessed the race/ethnic disparity in prostate cancer incidence for men with type II diabetes (T2D) and whether the impact of metformin on prostate cancer incidence varied by race/ethnicity. We conducted a retrospective study in 76,733 male veterans with T2D during 2003 to 2012. Cox proportional hazards model adjusting for covariates and propensity scores of metformin use and race/ethnic group membership was utilized to compute the HR of prostate cancer incidence associated with race/ethnicity and compare HR associated with metformin use between race/ethnic groups. Mean follow-up was 6.4 ± 2.8 years; 7% were Hispanics; 17% were African Americans (AA); mean age was 67.8 ± 9.8 years; 5.2% developed prostate cancer; and 38.9% used metformin. Among these diabetic men without metformin use, prostate cancer incidence was higher in Hispanics and AA than in non-Hispanic White (NHW). Use of metformin alone or metformin + statins was associated with a greater prostate cancer incidence reduction in Hispanics compared with NHW, but not between AA and NHW. Use of metformin + finasteride was associated with a greater prostate cancer incidence reduction in Hispanics and AA compared with NHW. Our results suggested that metformin treatment could be a potential strategy to reduce prostate cancer incidence in the minority populations who are at high risk for fatal prostate cancer. It will be important to further examine the pleiotropic effects of metformin in multi-race/ethnic prospective studies to better inform clinical management and potentially reduce racial/ethnic disparity in prostate cancer incidence among diabetic men. Cancer Prev Res; 9(10); 779-87. ©2016 AACR.

Higher BMI, waist circumference associated with increased risk of prostate cancer

Ahigher body mass index (BMI) and waist circumference are associated with an increased risk of aggressive prostate cancer, according to a study of nearly 150,000 men from 8 European countries. This analysis of the European Prospective Investigation Into Cancer and Nutrition (EPIC) was performed by Aurora Pérez-Cornago, PhD, a nutritional epidemiologist in the cancer epidemiology unit at the University of Oxford in England, and her colleagues. They presented their findings at the 2016 European Obesity Summit, which was held June 1–4 in Gothenburg, Sweden. To date, evidence for the association of body size and obesity with prostate cancer risk has been unclear. Dr. Pérez-Cornago and her team investigated the associations between various body measurements at baseline and risk of prostate cancer incidence. They focused on tumor stage and grade as well as mortality. The participants included 141,896 men with a mean age of 52 years from Italy, Spain, the United Kingdom, the Netherlands, Greece, Germany, Sweden, and Denmark. Data were adjusted for education level, smoking, marital status, diabetes, and physical activity. Specifically, investigators focused on high-grade cancers and those that resulted in death. Men with a higher BMI and waist circumference had an increased risk of more aggressive, high-grade prostate cancer (10% increased risk for every 5 kg/m2 increase in BMI and 13% increased risk for every 10-cm increase in waist circumference). Moreover, a 14% higher risk for fatal prostate cancer was observed for every 5 kg/m2 increase in BMI along with an 18% increased risk for every 10 cm of additional waist circumference.

Abstract 1755: Weight change, prostate cancer-specific mortality, and biochemical recurrence in a prospective cohort study of U.S. men

Abstract Obesity is associated with an increased risk of fatal prostate cancer. However, the relevant timing of obesity for risk has not been established, and the impact of weight change on prognosis has been understudied. We prospectively investigated the association between weight change and obesity with prostate cancer outcomes among 5,173 men diagnosed with prostate cancer (clinical TNM-stage &amp;lt;T3b) from 1986 to 2012 in the Health Professionals Follow-up Study. Men were followed for biochemical recurrence, development of distant metastasis, and mortality until 2014. Cox proportional hazards models were used to estimate hazard ratios for change in weight from age 21 to diagnosis and in the 4 years prior to diagnosis, adjusting for potential confounding by lifestyle and clinical factors. Because weight, weight change, and mortality are strongly associated with smoking, we conducted the analysis among all prostate cancer patients and among never smokers only (N = 2,554). Among all patients, weight gain from age 21 to the time of diagnosis was associated with risk of lethal prostate cancer (distant metastases or prostate cancer death). Compared to those with stable weight (±10 lbs) from age 21 to diagnosis, those who gained &amp;gt;30 lbs had a 1.44-fold higher risk of lethal cancer (95% CI 1.03-2.01, p-trend = 0.06, adjusting for lifestyle factors, stage, grade, PSA at diagnosis, and weight at age 21). Among never smokers, this association was stronger (HR 2.19, 95% CI 1.31-3.68, p-trend = 0.005). Weight gain in the 4 years preceding diagnosis was suggestively, but not significantly, associated with lethal cancer among never smokers (HR for &amp;gt;5 lbs gain vs stable weight [±5 lbs] 1.48, 95% CI, 0.96, 2.28). No significant associations were found between weight change and biochemical recurrence. Our findings suggest a positive association between adult weight gain and risk of lethal prostate cancer. Metabolic changes associated with weight gain may promote prostate cancer progression. Citation Format: Barbra Dickerman, Thomas Ahearn, Edward Giovannucci, Lorelei Mucci, Kathryn Wilson. Weight change, prostate cancer-specific mortality, and biochemical recurrence in a prospective cohort study of U.S. men. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1755.

Male Pattern Baldness in Relation to Prostate Cancer-Specific Mortality: A Prospective Analysis in the NHANES I Epidemiologic Follow-up Study.

We used male pattern baldness as a proxy for long-term androgen exposure and investigated the association of dermatologist-assessed hair loss with prostate cancer-specific mortality in the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. From the baseline survey (1971-1974), we included 4,316 men who were 25-74 years of age and had no prior cancer diagnosis. We estimated hazard ratios and used Cox proportional hazards regressions with age as the time metric and baseline hazard stratified by baseline age. A hybrid framework was used to account for stratification and clustering of the sample design, with adjustment for the variables used to calculate sample weights. During follow-up (median, 21 years), 3,284 deaths occurred; prostate cancer was the underlying cause of 107. In multivariable models, compared with no balding, any baldness was associated with a 56% higher risk of fatal prostate cancer (hazard ratio = 1.56; 95% confidence interval: 1.02, 2.37), and moderate balding specifically was associated with an 83% higher risk (hazard ratio = 1.83; 95% confidence interval: 1.15, 2.92). Conversely, patterned hair loss was not statistically significantly associated with all-cause mortality. Our analysis suggests that patterned hair loss is associated with a higher risk of fatal prostate cancer and supports the hypothesis of overlapping pathophysiological mechanisms.

Body mass index at mCRPC, weight change, and survival in advanced prostate cancer.

270 Background: Body mass index (BMI) at diagnosis is associated with increased risk of fatal prostate cancer, but the link between BMI at mCRPC and cancer progression is less clear. Cachexia, often defined as involuntary weight loss &gt; 5% over 6 months, is common in advanced cancers. The goal of this study was to examine the link between BMI at mCRPC and weight change as it relates to cancer progression, the outcomes of survival, and treatment use in a single-institution setting. Methods: 58 mCRPC patients treated at Tulane Hospital were identified, 41 of whom had an overweight BMI at mCRPC (BMI &gt; 25) and 17 with normal BMI at mCRPC (BMI &lt; 25). All patients had a confirmed prostate cancer death. Survival, treatment history, and percent weight change were compared according to BMI status. Rate of percent weight change was defined as the change in weight per day, from date of mCRPC diagnosis to the last treatment stop date or death date (“mCRPC days”). Linear regression, overall survival (OS), and nonparametric analyses were performed. Results: There was no significant difference between the normal and overweight BMI groups in overall survival, from date of diagnosis to death (median = 1835 days vs. 2710 days respectively). Additionally, the difference in survival from mCRPC to death was not statistically significant (median = 630 days vs. 799 days, p = 0.115). Use of Taxotere was not significantly different (47% vs. 68% respectively); however, overweight patients (n = 28) more likely received Abiraterone than normal BMI patients (n = 2) (p-value = 0.0001). The rate of percent weight change was significantly different for normal and overweight patients (mean = –0.050%/day vs. –0.019%/day, p = 0.003). Linear regression analysis showed that mCRPC days had a significant effect on percent weight change (p = 0.0109), and this effect was not significantly different between BMI groups (p = 0.6991). Conclusions: Survival after mCRPC was not significantly different between BMI groups. We observed a significant effect of mCRPC days on percent weight change, with a similar effect for both BMI groups. This outcome is expected, as more time would allow for greater weight changes to occur. Larger studies are needed to fully evaluate these observations.

Body Mass Index and Weight Change in Men with Prostate Cancer: Progression and Mortality.

Body mass index (BMI) is a modifiable lifestyle factor that has been associated with an increased risk of fatal prostate cancer and biochemical recurrence. The main purpose of the present study was ...

Associations of body mass index, smoking, and alcohol consumption with prostate cancer mortality in the Asia Cohort Consortium.

Many potentially modifiable risk factors for prostate cancer are also associated with prostate cancer screening, which may induce a bias in epidemiologic studies. We investigated the associations of body mass index (weight (kg)/height (m)(2)), smoking, and alcohol consumption with risk of fatal prostate cancer in Asian countries where prostate cancer screening is not widely utilized. Analysis included 18 prospective cohort studies conducted during 1963-2006 across 6 countries in southern and eastern Asia that are part of the Asia Cohort Consortium. Body mass index, smoking, and alcohol intake were determined by questionnaire at baseline, and cause of death was ascertained through death certificates. Analysis included 522,736 men aged 54 years, on average, at baseline. During 4.8 million person-years of follow-up, there were 634 prostate cancer deaths (367 prostate cancer deaths across the 11 cohorts with alcohol data). In Cox proportional hazards analyses of all cohorts in the Asia Cohort Consortium, prostate cancer mortality was not significantly associated with obesity (body mass index >25: hazard ratio (HR) = 1.08, 95% confidence interval (CI): 0.85, 1.36), ever smoking (HR = 1.00, 95% CI: 0.84, 1.21), or heavy alcohol intake (HR = 1.00, 95% CI: 0.74, 1.35). Differences in prostate cancer screening and detection probably contribute to differences in the association of obesity, smoking, or alcohol intake with prostate cancer risk and mortality between Asian and Western populations and thus require further investigation.

Abstract 4603: Male pattern baldness in relation to prostate cancer-specific mortality: A prospective analysis in the NHANES I Epidemiologic Followup Study (NHEFS)

Abstract Background: Androgenic action underlies prostate gland development and prostate cancer progression. However, the role of such in prostate carcinogenesis remains unclear. Results from studies that have quantitated pre-diagnostic, circulating androgens at a single time-point in relation to prostate cancer are inconsistent, possibly due to the failure to capture cumulative or relevant age-specific hormone exposure. Therefore, we used male pattern baldness as a proxy of long-term androgen exposure, and investigated the association between dermatologist-assessed male pattern baldness and prostate cancer-specific mortality in the NHANES-I Epidemiologic Followup Study (NHEFS). Methods: We included 4,316 men from NHEFS, who were 25-74 years, received dermatologic exams, and had no prior cancer diagnosis at baseline. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated using Cox proportional hazards regression with age as the time-metric and baseline hazard stratified by age at baseline. A hybrid model was used to account for stratification and clustering of the survey design, while adjusting for variables used to calculate sample weights. Results: During follow-up (median = 21 years), 3,284 deaths occurred, 107 of which had the underlying cause of prostate cancer. Any degree of baldness was associated with a 56% increased risk of prostate cancer-specific mortality (HR = 1.56; 95%CI = 1.02, 2.37) and, specifically, moderate balding was associated with an 83% increased risk of the outcome (HR = 1.83; 95%CI = 1.15, 2.92), each compared with no balding. Conversely, male pattern baldness was not statistically significantly associated with all-cause mortality. Conclusion: Our analysis suggests that male pattern baldness is associated with an increased risk of fatal prostate cancer, and supports the hypothesis of overlapping pathophysiological mechanisms. Impact: If the association between male pattern baldness and fatal prostate cancer is substantiated in future studies, male pattern baldness may contribute to predictive algorithms of prostate cancer risk, helping guide individuals as to whether they should opt to undergo cancer screening. Citation Format: Cindy Ke Zhou, Paul H. Levine, Sean D. Cleary, Heather J. Hoffman, Barry I. Graubard, Michael B. Cook. Male pattern baldness in relation to prostate cancer-specific mortality: A prospective analysis in the NHANES I Epidemiologic Followup Study (NHEFS). [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 4603. doi:10.1158/1538-7445.AM2015-4603

Circulating vitamin D, vitamin D-related genetic variation, and risk of fatal prostate cancer in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium.

Evidence from experimental animal and cell line studies supports a beneficial role for vitamin D in prostate cancer (PCa). Although the results from human studies have been mainly null for overall PCa risk, there may be a benefit for survival. This study assessed the associations of circulating 25-hydroxyvitamin D (25(OH)D) and common variations in key vitamin D-related genes with fatal PCa. In a large cohort consortium, 518 fatal cases and 2986 controls with 25(OH)D data were identified. Genotyping information for 91 single-nucleotide polymorphisms (SNPs) in 7 vitamin D-related genes (vitamin D receptor, group-specific component, cytochrome P450 27A1 [CYP27A1], CYP27B1, CYP24A1, CYP2R1, and retinoid X receptor α) was available for 496 fatal cases and 3577 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the associations of 25(OH)D and SNPs with fatal PCa. The study also tested for 25(OH)D-SNP interactions among 264 fatal cases and 1169 controls. No statistically significant relationship was observed between 25(OH)D and fatal PCa (OR for extreme quartiles, 0.86; 95% CI, 0.65-1.14; P for trend = .22) or the main effects of the SNPs and fatal PCa. There was evidence suggesting that associations of several SNPs, including 5 related to circulating 25(OH)D, with fatal PCa were modified by 25(OH)D. Individually, these associations did not remain significant after multiple testing; however, the P value for the set-based test for CYP2R1 was .002. Statistically significant associations were not observed for either 25(OH)D or vitamin D-related SNPs with fatal PCa. The effect modification of 25(OH)D associations by biologically plausible genetic variation may deserve further exploration.

Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies

Dairy product and calcium intakes have been associated with increased prostate cancer risk, but whether specific dairy products or calcium sources are associated with risk is unclear. In the Continuous Update Project, we conducted a meta-analysis of prospective studies on intakes of dairy products and calcium and prostate cancer risk. PubMed and several other databases were searched up to April 2013. Summary RRs were estimated by using a random-effects model. Thirty-two studies were included. Intakes of total dairy products [summary RR: 1.07 (95% CI: 1.02, 1.12; n = 15) per 400 g/d], total milk [summary RR: 1.03 (95% CI: 1.00, 1.07; n = 14) per 200 g/d], low-fat milk [summary RR: 1.06 (95% CI: 1.01, 1.11; n = 6) per 200 g/d], cheese [summary RR: 1.09 (95% CI: 1.02, 1.18; n = 11) per 50 g/d], and dietary calcium [summary RR: 1.05 (95% CI: 1.02, 1.09; n = 15) per 400 mg/d] were associated with increased total prostate cancer risk. Total calcium and dairy calcium intakes, but not nondairy calcium or supplemental calcium intakes, were also positively associated with total prostate cancer risk. Supplemental calcium was associated with increased risk of fatal prostate cancer. High intakes of dairy products, milk, low-fat milk, cheese, and total, dietary, and dairy calcium, but not supplemental or nondairy calcium, may increase total prostate cancer risk. The diverging results for types of dairy products and sources of calcium suggest that other components of dairy rather than fat and calcium may increase prostate cancer risk. Any additional studies should report detailed results for subtypes of prostate cancer.

Circadian clock genes and risk of fatal prostate cancer.

Circadian genes may be involved in regulating cancer-related pathways, including cell proliferation, DNA damage response, and apoptosis. We aimed to assess the role of genetic variation in core circadian rhythm genes with the risk of fatal prostate cancer and first morning void urinary 6-sulfatoxymelatonin levels. We used unconditional logistic regression to evaluate the association of 96 single-nucleotide polymorphisms (SNPs) across 12 circadian-related genes with fatal prostate cancer in the AGES-Reykjavik cohort (n = 24 cases), the Health Professionals Follow-Up Study (HPFS) (n = 40 cases), and the Physicians' Health Study (PHS) (n = 105 cases). We used linear regression to evaluate the association between SNPs and first morning void urinary 6-sulfatoxymelatonin levels in AGES-Reykjavik. We used a kernel machine test to evaluate whether multimarker SNP sets in the pathway (gene based) were associated with our outcomes. None of the individual SNPs were consistently associated with fatal prostate cancer across the three cohorts. In each cohort, gene-based analyses showed that variation in the CRY1 gene was nominally associated with fatal prostate cancer (p values = 0.01, 0.01, and 0.05 for AGES-Reykjavik, HPFS, and PHS, respectively). In AGES-Reykjavik, SNPs in TIMELESS (four SNPs), NPAS2 (six SNPs), PER3 (two SNPs) and CSNK1E (one SNP) were nominally associated with 6-sulfatoxymelatonin levels. We did not find a strong and consistent association between variation in core circadian clock genes and fatal prostate cancer risk, but observed nominally significant gene-based associations with fatal prostate cancer and 6-sulfatoxymelatonin levels.

Confirmation of genetic variants associated with lethal prostate cancer in a cohort of men from hereditary prostate cancer families.

Germline genetic variants have been suggested as prognostic biomarkers for identifying patients at high risk for lethal prostate cancer (PCa). Validation studies have confirmed the association of several single nucleotide polymorphisms (SNPs) with fatal PCa, but whether these variants affect PCa-specific mortality (PCSM) in patients with an inherited predisposition to PCa, based on familial history, is unknown. For this study, a cohort of 957 PCa patients from 270 hereditary prostate cancer families of European ancestry was genotyped for a panel of 22 PCSM-associated SNPs. Death certificates were reviewed to confirm cause of death. Mixed-effect Cox proportional hazards models were used to assess survival according to genotypes, accounting for relatedness and clinicopathological factors. Within this cohort, 98 PCa deaths were confirmed over an average follow-up period of 12.7 years after diagnosis. Variant allele carriers for three SNPs had significantly altered risk for PCSM [rs635261 at RNASEL, hazard ratio (HR), 0.35, 95% CI, 0.18-0.66; p = 0.002; rs915927 in XRCC1, HR, 1.91, 95% CI, 1.21-3.02; p = 0.009; and rs2494750 at AKT1, HR, 0.45, 95% CI, 0.23-0.90; p = 0.016). These results confirm the association of genetic variation in three genes with PCa lethality in a cohort of men with an inherited susceptibility to the disease and provide validation evidence that germline SNPs provide prognostic information for PCa patients. Development of a panel of germline biomarkers with clinical utility for distinguishing patients at detection who have an increased risk for fatal PCa is warranted.