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IMPORTANCE: The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota profiles in individuals without melanoma and those with early-stage and late-stage melanoma may reveal features associated with disease progression. OBJECTIVE: To characterize and compare gut microbiota profiles between healthy volunteers and patients with melanoma and between patients with early-stage and late-stage melanoma. DESIGN, SETTING, AND PARTICIPANTS: This single-site case-control study took place at an academic comprehensive cancer center. Fecal samples were collected from systemic treatment−naive patients with stage I to IV melanoma from June 1, 2015, to January 31, 2019, and from healthy volunteers from June 1, 2021, to January 31, 2022. Patients were followed up for disease recurrence until November 30, 2021. MAIN OUTCOMES AND MEASURES: Fecal microbiota was profiled by 16S ribosomal RNA sequencing. Clinical and pathologic characteristics, treatment, and disease recurrence were extracted from electronic medical records. Fecal microbiome diversity, taxonomic profiles and inferred functional profiles were compared between groups. RESULTS: A total of 228 participants were enrolled (126 men [55.3%]; median age, 59 [range, 21-90] years), including 49 volunteers without melanoma, 38 patients with early-stage melanoma (29 with stage I or melanoma in situ and 9 with stage II), and 141 with late-stage melanoma (66 with stage III and 75 with stage IV). Community differences were observed between patients with melanoma and volunteers. Patients with melanoma had a higher relative abundance of Fusobacterium compared with controls on univariate analysis (0.19% vs 0.003%; P < .001), but this association was attenuated when adjusted for covariates (log2 fold change of 5.18 vs controls; P = .09). Microbiomes were distinct between patients with early-stage and late-stage melanoma. Early-stage melanoma had a higher alpha diversity (Inverse Simpson Index 14.6 [IQR, 9.8-23.0] vs 10.8 [IQR, 7.2-16.8]; P = .003), and a higher abundance of the genus Roseburia on univariate analysis (2.4% vs 1.2%; P < .001) though statistical significance was lost with covariate adjustment (log2 fold change of 0.86 vs controls; P = .13). Multiple functional pathways were differentially enriched between groups. No associations were observed between the microbial taxa and disease recurrence in patients with stage III melanoma treated with adjuvant immunotherapy. CONCLUSIONS AND RELEVANCE: The findings of this case-control study suggest that fecal microbiota profiles were significantly different among patients with melanoma and controls and between patients with early-stage and late-stage melanoma. Prospective investigations of the gut microbiome and changes that occur with disease progression may identify future microbial targets for intervention.

Coffee intake in a large cohort of men with prostate cancer was nominally associated with longer prostate cancer–specific survival among men with the CYP1A2−163AA (*1F/*1F) caffeine metabolism genotype.

Popular views of what constitutes a healthy diet may shift, but the professional consensus is comparatively static and largely supported by our growing understanding of diet–microbiota interactions. The gut microbiome’s responsiveness to diet and ability to calibrate immune and metabolic function shape new research opportunities across the cancer continuum.

AbstractCancer is a major public health problem and is the second leading cause of death in the United States and worldwide; nearly one in six deaths are attributable to cancer. Approximately 20% of all cancers diagnosed in the United States are attributable to unhealthy diet, excessive alcohol consumption, physical inactivity, and body fatness. Individual cancers are distinct disease states that are multifactorial in their causation, making them exceedingly cumbersome to study from a nutrition standpoint. Genetic influences are a major piece of the puzzle and personalized nutrition is likely to be most effective in disrupting cancer during all stages. Increasing evidence shows that after a cancer diagnosis, continuing standard dietary recommendations may not be appropriate. This is because powerful dietary interventions such as short-term fasting and carbohydrate restriction can disrupt tumor metabolism, synergizing with standard therapies such as radiation and drug therapy to improve efficacy and ultimately, cancer survival. The importance of identifying dietary interventions cannot be overstated, and the American College of Nutrition’s commitment to advancing knowledge and research is evidenced by dedication of the 2017 ACN Annual Meeting to “Disrupting Cancer: The Role of Personalized Nutrition” and this resulting proceedings manuscript, which summarizes the meeting’s findings.

BACKGROUND:CpG island methylator phenotype (CIMP) tumors, comprising 20% of colorectal cancers, are associated with female sex, age, right-sided location, and BRAF mutations. However, other factors potentially associated with CIMP have not been robustly examined. This meta-analysis provides a comprehensive assessment of the clinical, pathologic, and molecular characteristics that define CIMP tumors. METHODS:We conducted a comprehensive search of the literature from January 1999 through April 2018 and identified 122 articles, on which comprehensive data abstraction was performed on the clinical, pathologic, molecular, and mutational characteristics of CIMP subgroups, classified based on the extent of DNA methylation of tumor suppressor genes assessed using a variety of laboratory methods. Associations of CIMP with outcome parameters were estimated using pooled odds ratio or standardized mean differences using random-effects model. RESULTS:We confirmed prior associations including female sex, older age, right-sided tumor location, poor differentiation, and microsatellite instability. In addition to the recognized association with BRAF mutations, CIMP was also associated with PIK3CA mutations and lack of mutations in KRAS and TP53. Evidence of an activated immune response was seen with high rates of tumor-infiltrating lymphocytes (but not peritumoral lymphocytes), Crohn-like infiltrates, and infiltration with Fusobacterium nucleatumbacteria. Additionally, CIMP tumors were associated with advance T-stage and presence of perineural and lymphovascular invasion. CONCLUSION:The meta-analysis highlights key features distinguishing CIMP in colorectal cancer, including molecular characteristics of an active immune response. Improved understanding of this unique molecular subtype of colorectal cancer may provide insights into prevention and treatment.

Objective: Vitamin D supplementation may be required for certain subgroups in the United States in whom status and intake are inadequate, but the impact of various doses, and whether calcium administration jointly or independently influences vitamin D metabolite levels, is unclear.Methods: In a pilot chemoprevention trial of biomarkers of risk for colorectal adenoma, we measured the impact of vitamin D supplementation and/or calcium supplementation on plasma vitamin D metabolite concentrations. Ninety-two adult men and women living in the southeastern United States were randomized to 800 IU vitamin D3, 2000 mg elemental calcium, both, or placebo daily for 6 months. We examined vitamin D status at baseline and postintervention and compared the change in plasma 25-hydroxyvitamin D (25(OH)D) and 1,25(OH)2D levels by intervention group using general linear models.Results: Eighty-two percent of the study population had insufficient plasma 25(OH)D concentrations (<75 nmol/L) at baseline, with the lowest levels observed among African American participants. Vitamin D supplements, with or without calcium supplementation, raised plasma 25(OH)D concentrations, on average, by 25 to 26 nmol/L. Half of the study participants were classified as having sufficient 25(OH)D status after 6 months of 800 IU of vitamin D3daily. Calcium alone did not influence 25(OH)D concentrations.Conclusion: In this southeastern U.S. population, half of the study participants receiving 800 IU vitamin D3daily had blood 25(OH)D concentrations of ≤75 nmol/L after a 6-month intervention period, supporting higher vitamin D dose requirements estimated by some groups. More research is needed to identify the optimal vitamin D dose to improve 25(OH)D status in various at-risk populations.