Meng Yang

Dietary Patterns after Prostate Cancer Diagnosis in Relation to Disease-Specific and Total Mortality

Men diagnosed with nonmetastatic prostate cancer have a long life expectancy, and many die of unrelated causes. It is therefore important to know to what extent post-diagnostic diet may affect disease-specific and overall mortality. A total of 926 men participating in the Physicians Health Study diagnosed with nonmetastatic prostate cancer completed diet questionnaires for a median of 5.1 years after diagnosis, and were followed thereafter to assess mortality for a median of 9.9 years since questionnaire completion. Two post-diagnostic dietary patterns were identified: a Prudent pattern, characterized by higher intake of vegetables, fruits, fish, legumes, and whole grains; and a Western pattern, characterized by higher intake of processed and red meats, high-fat dairy and refined grains. Cox regression was used to estimate multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI). During 8,093 person-years of follow-up, 333 men died, 56 (17%) of prostate cancer. The Western pattern was significantly related to a higher risk of prostate cancer–specific and all-cause mortality. Comparing men in the highest versus the lowest quartile of the Western pattern, the HRs were 2.53 (95% CI, 1.00–6.42; Ptrend = 0.02) for prostate cancer–specific mortality and 1.67 (95% CI, 1.16–2.42; Ptrend = 0.01) for all-cause mortality. The Prudent pattern was associated with a significantly lower all-cause mortality (HRQuartile 4 vs. Quartile 1: 0.64; 95% CI, 0.44–0.93; Ptrend = 0.02); the relationship with prostate cancer–specific mortality was inverse but not statistically significant. A post-diagnostic Western dietary pattern was associated with higher prostate cancer–specific and all-cause mortality, whereas a Prudent dietary pattern was related to lower all-cause mortality after prostate cancer diagnosis. Cancer Prev Res; 8(6); 545–51. ©2015 AACR.

Dairy intake after prostate cancer diagnosis in relation to disease-specific and total mortality

Information regarding postdiagnostic dairy intake and prostate cancer survival is limited. We evaluated intake of total, high‐fat and low‐fat dairy after prostate cancer diagnosis in relation to disease‐specific and total mortality. We included 926 men from the Physicians’ Health Study diagnosed with non‐metastatic prostate cancer between 1982 and 2000 who completed a diet questionnaire a median of 5 years after diagnosis and were followed thereafter for a median of 10 years to assess mortality. Cox proportional hazards regression was used to estimate associations between dairy intake and prostate cancer specific and all‐cause mortality. During 8,903 person‐years of follow‐up, 333 men died, 56 due to prostate cancer. Men consuming ≥3 servings/day of total dairy products had a 76% higher risk of total mortality and a 141% higher risk of prostate cancer‐specific mortality compared to men who consumed less than 1 dairy product/day (hazard ratio (HR)u2009=u20091.76, 95% confidence interval (CI): 1.21, 2.55, ptrendu2009<u20090.001 for total mortality; HRu2009=u20092.41, 95% CI: 0.96, 6.02, ptrendu2009=u20090.04 for prostate cancer‐specific mortality). The association between high‐fat dairy and mortality risk appeared to be stronger than that of low‐fat dairy, but the difference between them was not statistically significant (p for differenceu2009=u20090.57 for prostate cancer‐specific mortality and 0.56 for total mortality). Among men without metastases when diagnosed, higher intake of dairy foods after prostate cancer diagnosis may be associated with increased prostate cancer‐specific and all‐cause mortality.

Fat intake after prostate cancer diagnosis and mortality in the Physicians' Health Study.

AbstractPurposeDiet after prostate cancer diagnosis may impact disease progression. We hypothesized that consuming saturated fat after prostate cancer diagnosis would increase risk of mortality, and consuming vegetable fat after diagnosis would lower the risk of mortality.nMethodsThis was a prospective study among 926 men with non-metastatic prostate cancer in the Physicians’ Health Study who completed a food frequency questionnaire a median of 5xa0years after diagnosis and were followed for a median of 10xa0years after the questionnaire. We examined post-diagnostic saturated, monounsaturated, polyunsaturated, and trans fat, as well as animal and vegetable fat, intake in relation to all-cause and prostate cancer-specific mortality. Hazard ratios (HR) and 95xa0% confidence intervals (CI) were estimated using multivariate Cox proportional hazards regression.ResultsWe observed 333 deaths (56 prostate cancer deaths) during follow-up. Men who obtained 5xa0% more of their daily calories from saturated fat and 5xa0% less of their daily calories from carbohydrate after diagnosis had a 1.8-fold increased risk of all-cause mortality (HR 1.81; 95xa0% CI 1.20, 2.74; p value 0.005) and a 2.8-fold increased risk of prostate cancer-specific mortality (HR 2.78; 95xa0% CI 1.01, 7.64; p value 0.05). Men who obtained 10xa0% more of their daily calories from vegetable fats and 10xa0% less of their daily calories from carbohydrates had a 33xa0% lower risk of all-cause mortality (HR 0.67; 95xa0% CI 0.47, 0.96; p value 0.03).ConclusionsAmong men with non-metastatic prostate cancer, saturated fat intake may increase risk of death and vegetable fat intake may lower risk of death.

Nut consumption and risk of colorectal cancer in women

Background/Objectives:Increasing nut consumption has been associated with reduced risk of obesity and type II diabetes, the risk factors for colorectal cancer. However, the association between nut consumption and colorectal cancer risk is unclear. We aimed to examine the association of long-term nut consumption with risk of colorectal cancer.Subjects/Methods:We prospectively followed 75u2009680 women who were free of cancer at baseline in the Nurses’ Health Study, and examined the association between nut consumption and colorectal cancer risk. Nut consumption was assessed at baseline and updated every 2–4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.Results:During 2u2009103u2009037 person-years of follow-up, we identified 1503 colorectal cancer cases. After adjustment for other known or suspected risk factors, women who consumed nuts 2 or more times per week (that is, ⩾56u2009g per week) had a 13% lower risk of colorectal cancer compared with those who rarely consumed nuts, but the association was not statistically significant (RR: 0.87; 95% CI: 0.72–1.05; P-trend: 0.06). No association was observed for peanut butter.Conclusions:In this large prospective cohort of women, frequent nut consumption was not significantly associated with colorectal cancer risk after adjusting for other risk factors.

Nut consumption and prostate cancer risk and mortality

Background:Little is known of the association between nut consumption, and prostate cancer (PCa) incidence and survivorship.Methods:We conducted an incidence analysis and a case-only survival analysis in the Health Professionals Follow-up Study on the associations of nut consumption (updated every 4 years) with PCa diagnosis, and PCa-specific and overall mortality.Results:In 26 years, 6810 incident PCa cases were identified from 47u2009299 men. There was no association between nut consumption and being diagnosed with PCa or PCa-specific mortality. However, patients who consumed nuts five or more times per week after diagnosis had a significant 34% lower rate of overall mortality than those who consumed nuts less than once per month (HR=0.66, 95% CI: 0.52–0.83, P-trend=0.0005).Conclusions:There were no statistically significant associations between nut consumption, and PCa incidence or PCa-specific mortality. Frequent nut consumption after diagnosis was associated with significantly reduced overall mortality.

Effect Modification by Time Since Blood Draw on the Association Between Circulating Fatty Acids and Prostate Cancer Risk

A recent meta-analysis suggested that circulating fatty acids do not play an important role in prostate carcinogenesis. We hypothesized that the relation between circulating fatty acids and prostate cancer (PCa) risk is modified by time between blood draw and diagnosis. We tested this hypothesis in a prospective case-control study of 476 PCa cases and matched control subjects nested in the Physicians Health Study. The previously reported associations between fatty acids and PCa in this cohort were dramatically stronger among men diagnosed 10 or more years after blood collection. Statistically significant effect modification by time since blood collection was identified for mono-unsaturated and poly-unsaturated fatty acids and was more pronounced for aggressive tumors. Among men diagnosed fewer than 10 years since blood collection, the relative risks per interquartile range were 1.03 (95% confidence interval [CI] = 0.86 to 1.25) for total mono-unsaturated fatty acids (MUFA) and 0.95 (95% CIu2009=u20090.78 to 1.15) for total poly-unsaturated fatty acids (PUFA) whereas among men diagnosed 10 or more years after blood draw the relative risks per interquartile range were 1.69 (95% CIu2009=u20091.21 to 2.34) for MUFA (Pheterogeneity = .01) and 0.59 (95% CIu2009=u20090.42 to 0.83) for PUFA (Pheterogeneity = .02). These data suggest that the results of the meta-analysis may be partly explained by insufficient follow-up time. Furthermore, they suggest that some environmental and metabolic factors may play a role in prostate carcinogenesis decades before clinical identification of this disease.

Blood fatty acid patterns are associated with prostate cancer risk in a prospective nested case–control study

AbstractBackgroundCirculating fatty acids are highly correlated with each other, and analyzing fatty acid patterns could better capture their interactions and their relation to prostate cancer. We aimed to assess the associations between data-derived blood fatty acid patterns and prostate cancer risk.MethodsnWe conducted a nested case–control study in the Physicians’ Health Study. Fatty acids levels were measured in whole blood samples of 476 cases and their matched controls by age and smoking status. Fatty acid patterns were identified using principal component analysis. Conditional logistic regression was used to estimate odds ratio (OR) and 95xa0% confidence interval (CI).ResultsTwo patterns explaining 40.9xa0% of total variation in blood fatty acid levels were identified. Pattern 1, which mainly reflects polyunsaturated fatty acid metabolism, was suggestively positively related to prostate cancer risk (ORquintile 5 vs. quintile 1xa0=xa01.37, 95xa0% CIxa0=xa00.91–2.05, Ptrendxa0=xa00.07). Pattern 2, which largely reflects de novo lipogenesis, was significantly associated with higher prostate cancer risk (ORquintile5 vs. quintile1xa0=xa01.63, 95xa0% CIxa0=xa01.04–2.55, Ptrendxa0=xa00.02). This association was similar across tumor stage, grade, clinical aggressiveness categories and follow-up time.ConclusionThe two patterns of fatty acids we identified were consistent with known interactions between fatty acid intake and metabolism. A pattern suggestive of higher activity in the de novo lipogenesis pathway was related to higher risk of prostate cancer.

Abstract 2674: High fat diet accelerates MYC-driven prostate cancer through metabolic and epigenomic rewiring

Introduction: The mechanisms underlying the association between high dietary fat intake and prostate cancer (PCa) are unknown. Using a MYC-driven PCa mouse model, we sought to identify metabolic and epigenomic alterations driven by high fat diet (HFD) that facilitate PCa progression. Additionally, we investigated whether these alterations were relevant to PCa progression and lethality in humans. Material and Methods: Wild-type (WT) and transgenic Hi-MYC (MYC) mice were assigned either a HFD or control diet and were sacrificed at 12, 24, and 36 weeks of age for histologic and phenotypic characterization. Metabolic and epigenomic analyses were carried on the ventral prostates of 12-week old mice. Human PCa gene expression profiling data were obtained from 319 men with PCa and well-annotated post-diagnostic saturated fat intake (SFI) data from the Physicians’ Health Study and Health Professionals Follow-up Study prospective cohorts. Results: HFD does not affect the incidence of MYC-induced murine prostate intraepithelial neoplasia (mPIN) at 12 weeks, but increases mPIN proliferative index (Ki-67) at 24 weeks and tumor burden at 36 weeks. MYC overexpression, as expected, induces a significant metabolic reprogramming and HFD further enhances this rewiring to provide additional anabolic metabolites to sustain the increased proliferation of MYC prostate while having little effect on the WT prostate. Moreover, MYC altered key metabolites of the methionine cycle in a direction suggestive of a global hypomethylation, again amplified by HFD. Targeted quantitative histone mass spectrometry revealed a robust MYC-driven signature, including a global demethylation of H3K27 and H4K20 marks, the latter enhanced by HFD. Moreover, ChIP-seq revealed an intricate crosstalk between MYC and the H4K20me1 demethylase PHF8, resulting in enhanced genomic instability in the context of HFD. Finally, RNA-seq and ATAC-seq analyses showed that HFD rewires MYC-driven PCa through the alteration of genes implicated in chromatin function and remodeling. In humans, SFI was associated with enrichment in genes associated with increased MYC transcriptional activity in the prostate. Furthermore, this MYC transcriptional signature was associated with PCa lethality overall (OR = 3.21; 95% CI = 1.47, 7.35 comparing extreme score tertiles), and the association was stronger among men with high post-diagnostic SFI (OR = 1.32; 95%CI = 1.11, 1.66) than those with low SFI (OR = 1.05; 95%CI = 0.98, 1.12). Conclusions: HFD supports a coordinated metabolomic and epigenomic rewiring to increase epigenomic plasticity and MYC transcriptional activity prior to the appearance of phenotypic alterations in the prostate. Importantly, HFD requires MYC-mediated transformation to trigger its deleterious effects. In humans, SFI also enhances MYC transcriptional activity, which is associated with increased PCa lethality. Citation Format: David P. Labbe’, Giorgia Zadra, Meng Yang, Charles Y. Lin, Jaime M. Reyes, Stefano Cacciatore, Ericka M. Ebot, Maura B. Cotter, Amanda L. Creech, Jacob D. Jaffe, Philip W. Kantoff, James E. Bradner, Lorelei A. Mucci, Jorge E. Chavarro, Massimo Loda, Myles Brown. High fat diet accelerates MYC-driven prostate cancer through metabolic and epigenomic rewiring. [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 2674.

Abstract 1263: Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality

Objective: We investigated the relation of post-diagnostic dietary patterns with prostate cancer-specific and all-cause mortality. Methods: 926 men participating in the Physicians9 Healthy Study diagnosed with non-metastatic prostate cancer completed a food frequency questionnaire (FFQ) a median of 5.1 years after diagnosis, and were followed thereafter to assess mortality for a median of 9.9 years. Two dietary patterns, a Prudent and a Western pattern, were identified using principal component analysis. Multivariate Cox proportional hazards regression was used to estimate the relative hazard of prostate cancer-specific and all-cause mortality in relation to post-diagnostic dietary pattern scores. Models were adjusted for age at diagnosis, time between diagnosis and FFQ completion, energy intake, vigorous exercise, BMI, smoking status, and a modified D9Amico risk score. Results: We identified 333 deaths, 56 due to prostate cancer, during 8,093 person-years of follow-up. The Prudent pattern was characterized by higher intake of vegetables, fruits, fish, legumes and whole grains, while the Western pattern was characterized by higher intake of processed and red meats, potatoes, high-fat dairy and refined grains. Men in the highest quartile (Q4) of the Western pattern had a higher risk of prostate cancer-specific death than men in the lowest quartile (Q1) (Hazard ratio [HR]: 2.39; 95% Confidence Interval [CI]: 0.95, 6.00; P for linear trend=0.03). The association between the Western pattern and prostate cancer-specific mortality appeared to be driven by intake of potatoes (HR[Q4 vs Q1]: 2.85; 95% CI: 1.06, 7.62; P for linear trend=0.01). In addition, the Western pattern was associated with higher all-cause mortality (HR[Q4 vs Q1]: 1.73; 95% CI: 1.20, 2.49; P for linear trend=0.005). A Prudent pattern after diagnosis was unrelated to prostate cancer-specific mortality but was associated with lower all-cause mortality (HR[Q4 vs Q1]: 0.60; 95% CI: 0.42, 0.88; P for linear trend=0.007). Conclusions: A Western dietary pattern may increase risk of prostate cancer-specific and all-cause mortality, whereas a Prudent dietary pattern may decrease the risk of all-cause mortality, all among men diagnosed with localized prostate cancer. Citation Format: Meng Yang, Stacey A. Kenfield, Erin L. Van Blarigan, Julie L. Kasperzyk, Howard D. Sesso, Jing Ma, Meir Stampfer, Jorge E. Chavarro. Dietary patterns after prostate cancer diagnosis in relation to disease-specific and total mortality. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1263. doi:10.1158/1538-7445.AM2014-1263

Vascular morphology differentiates prostate cancer mortality risk among men with higher Gleason grade

BackgroundHigher Gleason grade is associated with prostate cancer mortality; however, there is significant heterogeneity in this association. We evaluated whether vessel morphology, a biomarker of angiogenesis, aided in distinguishing mortality risks among men with high Gleason grading.MethodsWe characterized vessel morphology (area and irregularity) among 511 patients diagnosed with prostate cancer during 1986 to 2000, re-reviewed Gleason grade, and followed men through 2012. Men were grouped according to integrated vessel lumen irregularity and vessel area across Gleason grade. The more angiogenic group was identified as those with more irregular vessel lumen and smaller vessel area. Crude rates (95xa0% confidence intervals) and survival probability were estimated across Gleason grade and vessel morphology.ResultsDuring a median 14-year follow-up, 62 men developed bone metastases or died of prostate cancer. Lethality rates were uniformly low within Gleason grade categories 6 and 7(3xa0+xa04), regardless of vessel morphology. However, among men with Gleason grades of 7(4xa0+xa03) or 8–10, the more angiogenic group was associated with fourfold higher risk of lethal outcomes compared to those with less angiogenic potential. Ten-year survival probability ranged from 95 to 74xa0% according to the extent of vessel morphology (pxa0<xa00.0001, log-rank test).ConclusionsVessel morphology may aid Gleason grading in predicting prostate cancer mortality risks among men diagnosed with high-grade Gleason cancers.