Accumulating evidence supports green tea catechins (GTCs) in chemoprevention for prostate cancer (PCa), a leading cause of cancer morbidity and mortality among men. GTCs include (−)-epigallocatechin-3-gallate, which may modulate the molecular pathways implicated in prostate carcinogenesis. Prior studies of GTCs suggested that they are bioavailable, safe, and effective for modulating clinical and biological markers implicated in prostate carcinogenesis. GTCs may be of particular benefit to those with low-grade PCas typically managed with careful monitoring via active surveillance (AS). Though AS is recommended, it has limitations including potential under-grading, variations in eligibility, and anxiety reported by men while on AS. Secondary chemoprevention of low-grade PCas using GTCs may help address these limitations. When administrated orally, the gut microbiome enzymatically transforms GTC structure, altering its bioavailability, bioactivity, and toxicity. In addition to xenobiotic metabolism, the gut microbiome has multiple other physiological effects potentially involved in PCa progression, including regulating inflammation, hormones, and other known/unknown pathways. Therefore, it is important to consider not only the independent roles of GTCs and the gut microbiome in the context of PCa chemoprevention, but how gut microbes may relate to individual responses to GTCs, which, in turn, can enhance clinical decision-making.

INTRODUCTION: Diet may affect bile acid (BA) metabolism and signaling. In turn, BA concentrations may be associated with cancer risk. We investigated (i) associations of BA concentrations with adenoma recurrence and (ii) the effect of a high-fiber, high-fruit and vegetable, and low-fat dietary intervention on serum BA concentrations. METHODS: The Polyp Prevention Trial is a 4-year randomized, controlled trial that investigated the effect of a high-fiber, high-fruit and vegetable, and low-fat diet on colorectal adenoma recurrence. Among 170 participants who reported adhering to the intervention and 198 comparable control arm participants, we measured 15 BAs in baseline, year 2, and year 3 serum using targeted, quantitative liquid chromatography-tandem mass spectrometry. We estimated associations of BAs with adenoma recurrence using multivariable logistic regression and the effect of the dietary intervention on BA concentrations using repeated-measures linear mixed-effects models. In a subset (N = 65), we investigated associations of BAs with 16S rRNA gene sequenced rectal tissue microbiome characteristics. RESULTS: Baseline total BA concentrations were positively associated with adenoma recurrence (odds ratio_{Q3 vs Q1} = 2.17; 95% confidence interval = 1.19–4.04; P _trend = 0.03). Although we found no effect of the dietary intervention on BA concentrations, pretrial dietary fiber intake was inversely associated with total baseline BAs (Spearman = −0.15; P _FDR = 0.02). BA concentrations were associated with potential colorectal neoplasm-related microbiome features (lower alpha diversity and higher Bacteroides abundance). DISCUSSION: Baseline circulating BAs were positively associated with adenoma recurrence. Although the dietary intervention did not modify BA concentrations, long-term fiber intake may be associated with lower concentrations of BAs that are associated with higher risk of adenoma recurrence.

Background: Emerging evidence suggests that bacteria residing in colorectal tissue are plausibly associated with colorectal cancer. Prior studies investigated the effects of dietary interventions on the fecal microbiome, but few assessed colorectal tissue microbiome endpoints. We investigated the effects of a high-fiber, high-fruit, high-vegetable, and low-fat dietary intervention on the rectal tissue microbiome in the Polyp Prevention Trial (PPT). Methods: PPT is a 4-year randomized clinical trial with intervention goals of consuming (1) at least 18 g of fiber per 1000 kcal/day; (2) at least 3.5 servings of fruits and vegetables per 1000 kcal/day; and (3) no more than 20% of kcal/day from fat. Using 16S ribosomal RNA gene sequencing, we characterized bacteria in rectal biopsies collected at baseline and the end of years 1 and 4 (n = 233 in intervention arm and n = 222 in control arm). We estimated effects of the intervention on alpha and beta diversity and relative abundance of a priori–selected bacteria using repeated-measures linear mixed-effects models. Results: The intervention did not statistically significantly modify rectal tissue alpha diversity. Compared with the control arm, relative abundance of a priori–selected Porphyromonas (absolute intervention effects [standard errors] at T1 vs T0 = –0.24 [0.07] and T4 vs T0 = –0.12 [0.07]; P = .004) and Prevotella (absolute intervention effects at T1 vs T0 = –0.40 [0.14] and at T4 vs T0 = –0.32 [0.15]; P = .01) were more strongly decreased in the intervention arm. Conclusion: The PPT intervention did not influence rectal tissue microbiome diversity or the relative abundance of most bacteria, except for 2 oral-originating bacteria that were previously associated with colorectal cancer presence.

Background: Sex difference in the immune response may influence patients’ response to immune checkpoint inhibitors (ICIs). We conducted a prospective observation study to determine the correlation between pretreatment sex hormone levels and response to ICIs in metastatic non-small cell lung cancer (NSCLC). Method: Pretreatment plasma samples from 61 patients with newly diagnosed NSCLC prior to ICI therapy were collected. Six sex hormone levels [pyrazole triol, 17 β-estradiol, 5-androstenediol, 3β-androstenediol, dehydroepiandrosterone (DHEA), and S-equol] were measured using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). Overall survival (OS) and progression-free survival (PFS) were compared between the high- and low-level groups in the whole cohort. Result: Among the six sex hormones measured, DHEA levels were significantly higher among patients without clinical benefits in the discovery cohort; the remaining sex hormones did not differ significantly. In the whole cohort, median PFS was 22 months for patients with low DHEA levels vs. 3.8 months for those with high DHEA [hazard ratio, 14.23 (95% CI, 4.7–43); p < 0.001]. A significant association was also observed for OS [hazard ratio, 8.2 (95% CI, 2.89–23.35); p < 0.0001]. Conclusions: High pretreatment plasma DHEA levels were associated with poor clinical outcomes for patients with metastatic NSCLC treated with ICIs.

Background: The gut microbiome is plausibly associated with colorectal cancer risk; however, previous studies mostly investigated this association cross-sectionally. We investigated cross-sectional and prospective associations of the rectal tissue microbiome with adenoma recurrence in the Polyp Prevention Trial (PPT). Methods: PPT is a 4-year randomized clinical trial of the effect of a dietary intervention on adenoma recurrence among community members. We extracted DNA from rectal biopsies at baseline, end of year 1, and end of year 4 among 455 individuals and sequenced the V4 region of the 16S rRNA gene. At each timepoint, we investigated associations of alpha diversity, beta diversity, and presence and relative abundance of select taxa with adenoma recurrence using multivariable logistic regression. Results: Variation in beta diversity was primarily explained by subject and minimally by year of collection or time between biopsy and colonoscopy. Cross-sectionally, year 4 alpha diversity was strongly, inversely associated with adenoma prevalence [ORQ3 vs. Q1 Shannon index = 0.40 (95% confidence interval, CI: 0.21–0.76)]. Prospective alpha diversity associations (i.e., baseline/year 1 alpha diversity with adenoma recurrence 3–4 years later) were weak or null, as were cross-sectional and prospective beta diversity–adenoma associations. Bacteroides abundance was more strongly, positively associated with adenoma prevalence cross-sectionally than prospectively. Conclusions: Rectal tissue microbiome profiles may be associated with prevalent adenomas, with little evidence supporting prospective associations. Impact: Additional prospective studies, with serial fecal and tissue samples, to explore microbiome-colorectal cancer associations are needed. Eventually, it may be possible to use microbiome characteristics as intervenable risk factors or screening tools.