Developing Policy Infrastructure to Guide Genomics-Informed Oncology Nursing in Canada: An Interpretive Descriptive Study.

BACKGROUND: Genomic technologies such as genetic testing and precision treatments are rapidly becoming routine in oncology care, and nurses play an increasingly important role in supporting the growing demands for genomics-informed healthcare. Policy infrastructure such as competencies, standards, scope of practice statements, and education and curriculum frameworks are urgently needed to guide these practice and education changes. PURPOSE: This study is part of a larger three-phase project to develop recommendations and catalyze action for genomics-informed oncology nursing education and practice for the Canadian Association of Nurses in Oncology and the Canadian Association of Schools of Nursing. This phase aimed to enhance understanding of policy needs and action drivers for genomics-informed oncology nursing education and practice through the perspectives of Canadian oncology nurses and patient partners. METHODS: Interpretive description methodology guided the study. Twenty semi-structured virtual interviews were conducted; 17 with oncology nurses in various domains of practice, and three with patient partner representatives. Data collection and analysis occurred concurrently. RESULTS: Our analysis identified three themes: 1) nurses and patients recognize that it is time for action, 2) nurses and patients see advantages to executing intentional, strategic, and collaborative policy development, and 3) leadership and advocacy are required to drive action. CONCLUSION: Nursing policy infrastructure is required to increase genomic literacy, support nurses in providing safe patient care, and establish clear roles, responsibilities, and accountabilities within the interdisciplinary team. Strong leadership and advocacy at the practice, organizational, and systems levels are vital to accelerating action.

The influence of obesity on folate status, DNA methylation and cancer-related gene expression in normal breast tissues from premenopausal women.

Epidemiological studies have established obesity as a critical risk factor for postmenopausal breast cancer (post-BC), whereas a reverse association holds prior to menopause. A significant scientific gap exists in understanding the mechanism(s) underpinning this epidemiological phenomenon, particularly the reverse association between obesity and premenopausal breast cancer (pre-BC). This study aimed to understand how folate metabolism and DNA methylation inform the association between obesity and pre-BC. Fifty normal breast tissue samples were collected from premenopausal women who underwent reduction mammoplasty. We modified the Lactobacillus Casei microbiological folate assay and measured folate levels in our breast tissue samples. The DNA methylation of LINE-1, a biomarker of genome-wide methylation, and the expression of a panel of breast cancer-related genes was measured by pyrosequencing and real-time PCR. We found that a high BMI is associated with an increase of folate levels in mammary tissue, with an increase of 2.65 ng/g of folate per every 5-unit increase of BMI (p < 0.05). LINE-1 DNA methylation was significantly associated with BMI (p < 0.05), and marginally associated with folate concentration (p = 0.087). A high expression of SFRP1 was observed in subjects with high BMI or high folate status (p < 0.05). This study demonstrated that, in premenopausal women, obesity is associated with increased mammary folate status, genome-wide DNA methylation and SFRP1 gene expression. Our findings indicated that the improved folate and epigenetic status represents a novel mechanism responsible for the reverse association between obesity and pre-BC.

MYC DNA Methylation in Prostate Tumor Tissue Is Associated with Gleason Score.

Increasing evidence suggests a role of epigenetic mechanisms at chromosome 8q24, an important cancer genetic susceptibility region, in prostate cancer. We investigated whether MYC DNA methylation at 8q24 (six CpG sites from exon 3 to the 3' UTR) in prostate tumor was associated with tumor aggressiveness (based on Gleason score, GS), and we incorporated RNA expression data to investigate the function. We accessed radical prostatectomy tissue for 50 Caucasian and 50 African American prostate cancer patients at the University of Maryland Medical Center, selecting an equal number of GS 6 and GS 7 cases per group. MYC DNA methylation was lower in tumor than paired normal prostate tissue for all six CpG sites (median difference: -14.74 to -0.20 percentage points), and we observed similar results for two nearby sites in The Cancer Genome Atlas (p < 0.0001). We observed significantly lower methylation for more aggressive (GS 7) than less aggressive (GS 6) tumors for three exon 3 sites (for CpG 212 (chr8:128753145), GS 6 median = 89.7%; GS 7 median = 85.8%; p-value = 9.4 × 10-4). MYC DNA methylation was not associated with MYC expression, but was inversely associated with PRNCR1 expression after multiple comparison adjustment (q-value = 0.04). Findings suggest that prostate tumor MYC exon 3 hypomethylation is associated with increased aggressiveness.

Prospective study of DNA methylation at chromosome 8q24 in peripheral blood and prostate cancer risk.

BACKGROUND: Chromosome 8q24 has emerged as an important genetic susceptibility region for several cancers, including prostate cancer; however, little is known about the contribution of DNA methylation in this region to risk. METHODS: We prospectively evaluated DNA methylation at 8q24 in relation to prostate cancer using pre-diagnostic blood samples from 694 prostate cancer cases (including 172 aggressive cases) and 703 controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used logistic regression to estimate odds ratios and 95% confidence intervals. RESULTS: Although none remained significant after adjustment for multiple testing (q>0.05), of the 50 CpG sites meeting quality control, we identified 8 sites that were nominally associated with prostate cancer (Ptrend<0.05), including 6 correlated (Spearman ρ: 0.20-0.52) sites in POU5F1B and 2 intergenic sites (most significant site: Chr8:128428897 in POU5F1B, Ptrend=0.01). We also identified two correlated (ρ=0.39) sites in MYC (Chr8:128753187 and Chr8:128753154) that were associated with aggressive (Ptrend=0.02 and 0.03), but not non-aggressive disease (Ptrend=0.70 and 0.20; Pheterogeneity=0.01 and 4.6 × 10-3). These findings persisted after adjustment for the top 8q24 prostate cancer variants in our study. CONCLUSIONS: Although requiring replication, our findings provide some evidence that 8q24 DNA methylation levels may be associated with prostate cancer risk.

DNA methylation levels at chromosome 8q24 in peripheral blood are associated with 8q24 cancer susceptibility loci.

Chromosome 8q24 has emerged as an important region for genetic susceptibility to various cancers, but little is known about the contribution of DNA methylation at 8q24. To evaluate variability in DNA methylation levels at 8q24 and the relationship with cancer susceptibility single nucleotide polymorphisms (SNPs) in this region, we quantified DNA methylation levels in peripheral blood at 145 CpG sites nearby 8q24 cancer susceptibility SNPs or MYC using pyrosequencing among 80 Caucasian men in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. For the 60 CpG sites meeting quality control, which also demonstrated temporal stability over a 5-year period, we calculated pairwise Spearman correlations for DNA methylation levels at each CpG site with 42 8q24 cancer susceptibility SNPs. To account for multiple testing, we adjusted P values into q values reflecting the false discovery rate (FDR). In contrast to the MYC CpG sites, most sites nearby the SNPs demonstrated good reproducibility, high methylation levels, and moderate-high between-individual variation. We observed 10 statistically significant (FDR < 0.05) CpG site-SNP correlations. These included correlations between an intergenic CpG site at Chr8:128393157 and the prostate cancer SNP rs16902094 (ρ = -0.54; P = 9.7 × 10(-7); q = 0.002), a PRNCR1 CpG site at Chr8:128167809 and the prostate cancer SNP rs1456315 (ρ = 0.52; P = 1.4 × 10(-6); q = 0.002), and two POU5F1B CpG sites and several prostate/colorectal cancer SNPs (for Chr8:128498051 and rs6983267, ρ = 0.46; P = 2.0 × 10(-5); q = 0.01). This is the first report of correlations between blood DNA methylation levels and cancer susceptibility SNPs at 8q24, suggesting that DNA methylation at this important susceptibility locus may contribute to cancer risk.

A Swedish telephone help-line for sexual problems: a 5-year survey.

INTRODUCTION: Telephone help-lines for people with sexual problems have been established in many European countries during the late decade. They, however, have very different modes of operation, and very few reports focusing on the way they function have been published internationally. AIM: To describe the methods and activities of a Swedish help-line for sexual problems. METHODS: In the 5 years, from 1999 to 2003, 27,387 persons called the Swedish toll-free help-line for "impotence and sexual problems" that operates around the clock. The majority of callers appeared to be looking for information on erectile dysfunction. A counseling option staffed by experts in sexual medicine counseled 2,817 (men 73%, women 27%). A further 478 callers were professionals wanting information or advice. RESULTS: Among a wide spectrum of problems associated with the callers' sexual life, sexual dysfunctions were the most frequent. Calls about sexual abuse, sexual preference, paraphilias, and other subjects were also received. Among those with sexual dysfunction, 33% of men and 41% of women had more than one sexual dysfunction. These were often concomitant with a frequently drug-treated, medical condition. In addition to counseling, the majority of callers were advised to contact physicians or specialists in sexology/sexual medicine for further help. CONCLUSION: Competent person-to-person telephone counseling in the multifaceted bio-psycho-social field of sexual problems requires broad knowledge on sexual medicine.