Intratumoral vitamin D signaling and lethal prostate cancer.

High circulating vitamin D levels and supplementation may lower prostate cancer mortality. To probe for direct effects of vitamin D signaling in the primary tumor, we assessed how activation of intratumoral vitamin D signaling in prostate cancer is associated with lethal prostate cancer during long-term follow-up. Among 404 participants with primary prostate cancer in the Health Professionals Follow-up Study and the Physicians' Health Study, we defined a gene score of expected activated intratumoral vitamin D signaling consisting of transcriptionally upregulated (CYP27A1, CYP2R1, RXRA, RXRB, VDR) and downregulated genes (CYP24A1, DHCR7). We contrasted vitamin D signaling in tumors that progressed to lethal disease (metastases/prostate cancer-specific death, n = 119) over up to three decades of follow-up with indolent tumors that remained nonmetastatic for >8 years post-diagnosis (n = 285). The gene score was downregulated in tumor tissue compared to tumor-adjacent histologically normal tissue of the same men. Higher vitamin D gene scores were inversely associated with lethal prostate cancer (odds ratio for highest vs. lowest quartile: 0.46, 95% CI: 0.21 to 0.99) in a dose-response fashion and after adjusting for clinical and pathologic factors. This association appeared strongest among men with high predicted plasma 25-hydroxyvitamin D3 and men with body mass index ≥25 kg/m2. Findings were replicated with broader gene sets. These data support the hypothesis that active intratumoral vitamin D signaling is associated with better prostate cancer outcomes and provide further rationale for testing how vitamin D-related interventions after diagnosis could improve prostate cancer survival through effects on the tumor.

Marital Status, Living Arrangement, and Survival among Individuals with Advanced Prostate Cancer in the International Registry for Men with Advanced Prostate Cancer.

BACKGROUND: Studies have shown improved survival among individuals with cancer with higher levels of social support. Few studies have investigated social support and overall survival (OS) in individuals with advanced prostate cancer in an international cohort. We investigated the associations of marital status and living arrangements with OS among individuals with advanced prostate cancer in the International Registry for Men with Advanced Prostate Cancer (IRONMAN). METHODS: IRONMAN is enrolling participants diagnosed with advanced prostate cancer (metastatic hormone-sensitive prostate cancer, mHSPC; castration-resistant prostate cancer, CRPC) from 16 countries. Participants in this analysis were recruited between July 2017 and January 2023. Adjusting for demographics and tumor characteristics, the associations were estimated using Cox regression and stratified by disease state (mHSPC, CRPC), age (<70, ≥70 years), and continent of enrollment (North America, Europe, Other). RESULTS: We included 2,119 participants with advanced prostate cancer, of whom 427 died during up to 5 years of follow-up (median 6 months). Two-thirds had mHSPC. Most were married/in a civil partnership (79%) and 6% were widowed. Very few married participants were living alone (1%), while most unmarried participants were living alone (70%). Married participants had better OS than unmarried participants [adjusted HR: 1.44; 95% confidence interval (CI): 1.02-2.02]. Widowed participants had the worst survival compared with married individuals (adjusted HR: 1.89; 95% CI: 1.22-2.94). CONCLUSIONS: Among those with advanced prostate cancer, unmarried and widowed participants had worse OS compared with married participants. IMPACT: This research highlighted the importance of social support in OS within this vulnerable population.

Prospective Study of Avocado Consumption and Cancer Risk in U.S. Men and Women.

Avocados contain nutrients and phytochemicals that make it promising for cancer prevention, and chemopreventive properties have been demonstrated in prior studies. Prospective studies on avocado consumption and cancer risk have yet to be conducted. This study included data from 45,289 men in the Health Professionals Follow-Up Study (HPFS, 1986-2016) and 67,039 women in the Nurses' Health Study (NHS, 1986-2014). Avocado consumption was assessed using validated food frequency questionnaires every 4 years. Cox proportional hazards models calculated multivariable HRs and 95% confidence intervals (CI) for associations between avocado consumption and risk of total and site-specific cancers in each cohort. In HPFS, consumption of ≥1 weekly serving of avocados was associated with decreased risk of total (HR, 0.85; 95% CI, 0.80-0.91), colorectal (HR, 0.71; 95% CI, 0.59-0.85), lung (HR, 0.71; 95% CI, 0.57-0.90), and bladder cancer (HR, 0.72; 95% CI, 0.57-0.90). In NHS, avocado consumption was associated with increased risk of breast cancer (HR, 1.21; 95% CI, 1.07-1.37). No associations were observed between avocado consumption and risk of total cancer (HR, 1.06; 95% CI, 0.98-1.14) or other site-specific cancers in NHS. Considering the surprising breast cancer finding, analyses were repeated using data from 93,230 younger women in the parallel NHSII (1991-2017). In NHSII, avocado consumption was not associated with breast cancer risk (HR, 0.93; 95% CI, 0.76-1.13). Overall, avocado consumption may be associated with reduced risk of total and some site-specific cancers in men. The positive association with breast cancer risk in NHS was not seen in the younger NHSII. PREVENTION RELEVANCE: The results of this prospective study suggest that avocado consumption may be associated with decreased risk of total and some site-specific cancers in men. See related Spotlight, p. 187.