Perceptions of Prostate MRI and Fusion Biopsy of Radiation Oncologists and Urologists for Patients Diagnosed with Prostate Cancer: Results from a National Survey.

BACKGROUND: Magnetic resonance imaging (MRI) of the prostate and fusion biopsy have been advanced to improve the detection of clinically significant prostate cancer (PCa). Yet, frequency of their use and contemporary attitudes among radiation oncologists (ROs) and urologists (UROs) remain largely unknown. OBJECTIVE: We performed a national survey of UROs and ROs to assess the perceived attitudes towards and frequency of prostate MRI and fusion biopsy. DESIGN, SETTING, AND PARTICIPANTS: We conducted a national survey of 915 ROs and 940 UROs about prostate MRI and fusion biopsy in 2017. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The survey queried respondents about perceptions of prostate MRI and fusion biopsy and inquired about self-reported utilization. Pearson chi-square test and multivariable logistic regression were used to identify physician characteristics associated with survey responses. RESULTS AND LIMITATIONS: The overall response rate was 37% (n=691). Both UROs and ROs demonstrated similar positive views that MRI with fusion biopsy improves PCa risk stratification (67% vs 71%; p=0.19) and fusion biopsy increases the confidence recommending active surveillance (55% vs 60%; p=0.18). Yet, only a quarter of both specialties reported frequent use of prostate MRI for treatment decisions for low- and intermediate-risk PCa. Compared with respondents practicing in community practices, those in academic practices were more likely to report using prostate MRI for low- (44% vs 19%; adjusted odds ratio [OR]: 3.96; p<0.001) and intermediate-risk PCa (42% vs 24%; adjusted OR: 2.49; p<0.001). Our study was limited by a modestly lower response rate. CONCLUSIONS: While both specialties have perceived value in favor of prostate MRI and fusion biopsy, only a quarter of respondents report their use in clinical practice. Physicians practicing in academic medical centers had greater self-reported use. PATIENT SUMMARY: Magnetic resonance imaging of the prostate and targeted biopsies have growing evidence of their use as a superior diagnostic methodology for prostate cancer diagnosis and treatment decisions. Our survey study found that a majority of radiation oncologists and urologists view both favorably in improving prostate cancer detection and treatment decisions. Yet, only a quarter report using it in routine clinical practice for men diagnosed with prostate cancer.

seXY: a tool for sex inference from genotype arrays.

Motivation: Checking concordance between reported sex and genotype-inferred sex is a crucial quality control measure in genome-wide association studies (GWAS). However, limited insights exist regarding the true accuracy of software that infer sex from genotype array data. Results: We present seXY, a logistic regression model trained on both X chromosome heterozygosity and Y chromosome missingness, that consistently demonstrated >99.5% sex inference accuracy in cross-validation for 889 males and 5,361 females enrolled in prostate cancer and ovarian cancer GWAS. Compared to PLINK, one of the most popular tools for sex inference in GWAS that assesses only X chromosome heterozygosity, seXY achieved marginally better male classification and 3% more accurate female classification. Availability and Implementation: https://github.com/Christopher-Amos-Lab/seXY. Contact: Christopher.I.Amos@dartmouth.edu. Supplementary information: Supplementary data are available at Bioinformatics online.

GWAS meta-analysis of 16 852 women identifies new susceptibility locus for endometrial cancer.

Endometrial cancer is the most common gynecological malignancy in the developed world. Although there is evidence of genetic predisposition to the disease, most of the genetic risk remains unexplained. We present the meta-analysis results of four genome-wide association studies (4907 cases and 11 945 controls total) in women of European ancestry. We describe one new locus reaching genome-wide significance (P < 5 × 10 -8) at 6p22.3 (rs1740828; P = 2.29 × 10 -8, OR = 1.20), providing evidence of an additional region of interest for genetic susceptibility to endometrial cancer.

Common germline polymorphisms associated with breast cancer-specific survival.

INTRODUCTION: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. METHODS: A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. RESULTS: Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. CONCLUSIONS: Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.

Exome-wide association study of endometrial cancer in a multiethnic population.

Endometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.

Pleiotropic associations of risk variants identified for other cancers with lung cancer risk: the PAGE and TRICL consortia.

BACKGROUND: Genome-wide association studies have identified hundreds of genetic variants associated with specific cancers. A few of these risk regions have been associated with more than one cancer site; however, a systematic evaluation of the associations between risk variants for other cancers and lung cancer risk has yet to be performed. METHODS: We included 18023 patients with lung cancer and 60543 control subjects from two consortia, Population Architecture using Genomics and Epidemiology (PAGE) and Transdisciplinary Research in Cancer of the Lung (TRICL). We examined 165 single-nucleotide polymorphisms (SNPs) that were previously associated with at least one of 16 non-lung cancer sites. Study-specific logistic regression results underwent meta-analysis, and associations were also examined by race/ethnicity, histological cell type, sex, and smoking status. A Bonferroni-corrected P value of 2.5×10(-5) was used to assign statistical significance. RESULTS: The breast cancer SNP LSP1 rs3817198 was associated with an increased risk of lung cancer (odds ratio [OR] = 1.10; 95% confidence interval [CI] = 1.05 to 1.14; P = 2.8×10(-6)). This association was strongest for women with adenocarcinoma (P = 1.2×10(-4)) and not statistically significant in men (P = .14) with this cell type (P het by sex = .10). Two glioma risk variants, TERT rs2853676 and CDKN2BAS1 rs4977756, which are located in regions previously associated with lung cancer, were associated with increased risk of adenocarcinoma (OR = 1.16; 95% CI = 1.10 to 1.22; P = 1.1×10(-8)) and squamous cell carcinoma (OR = 1.13; CI = 1.07 to 1.19; P = 2.5×10(-5)), respectively. CONCLUSIONS: Our findings demonstrate a novel pleiotropic association between the breast cancer LSP1 risk region marked by variant rs3817198 and lung cancer risk.

Patient satisfaction with the endoscopy experience and willingness to return in a central Canadian health region.

OBJECTIVE: Patient experiences with endoscopy visits within a large central Canadian health region were evaluated to determine the relationship between the visit experience and the patients' willingness to return for future endoscopy, and to identify the factors associated with patients' willingness to return. METHODS: A self-report survey was distributed to 1200 consecutive individuals undergoing an upper and/or lower gastrointestinal endoscopy at any one of the six hospital-based endoscopy facilities in the region. The Spearman correlation coefficient was used to assess the association between the patients' overall rating of the visits and willingness to return for repeat procedures under similar medical circumstances. Logistic regression analyses were performed to identify the factors associated with willingness to return for repeat endoscopy and overall satisfaction (rating) of the visit. RESULTS: A total of 529 (44%) individuals returned the questionnaire, with 45% rating the visit as excellent and 56% indicating they were extremely likely to return for repeat endoscopy. There was a low moderate correlation between overall rating of the visit and patients' willingness to return for repeat endoscopy (r=0.30). The factors independently associated with patient willingness to return for repeat endoscopy included perceived technical skills of the endoscopists (OR 2.7 [95% CI 1.3 to 5.5]), absence of pain during the procedure (OR 2.2 [95% CI 1.3 to 3.6]) and history of previous endoscopy (OR 2.4 [95% CI 1.4 to 4.1]). In contrast, the independent factors associated with the overall rating of the visit included information provided pre- and postprocedure, wait time before and on the day of the visit, and the physical environment. CONCLUSIONS: To facilitate patient return for needed endoscopy, it is important to assess patients' willingness to return because positive behavioural intent is not simply a function of satisfaction with the visit.

Genetic variation in the vitamin d pathway in relation to risk of prostate cancer--results from the breast and prostate cancer cohort consortium.

BACKGROUND: Studies suggest that vitamin D status may be associated with prostate cancer risk although the direction and strength of this association differs between experimental and observational studies. Genome-wide association studies have identified genetic variants associated with 25-hydroxyvitamin D [25(OH)D] status. We examined prostate cancer risk in relation to single-nucleotide polymorphisms (SNP) in four genes shown to predict circulating levels of 25(OH)D. METHODS: SNP markers localized to each of four genes (GC, CYP24A1, CYP2R1, and DHCR7) previously associated with 25(OH)D were genotyped in 10,018 cases and 11,052 controls from the National Cancer Institute (NCI) Breast and Prostate Cancer Cohort Consortium. Logistic regression was used to estimate the individual and cumulative association between genetic variants and risk of overall and aggressive prostate cancer. RESULTS: We observed a decreased risk of aggressive prostate cancer among men with the allele in rs6013897 near CYP24A1 associated with lower serum 25(OH)D [per A allele, OR, 0.86; 95% confidence interval (CI), 0.80-0.93; Ptrend = 0.0002) but an increased risk for nonaggressive disease (per A allele: OR, 1.10; 95% CI, 1.04-1.17; Ptrend = 0.002). Examination of a polygenic score of the four SNPs revealed statistically significantly lower risk of aggressive prostate cancer among men with a greater number of low vitamin D alleles (OR for 6-8 vs. 0-1 alleles, 0.66; 95% CI, 0.44-0.98; Ptrend = 0.003). CONCLUSIONS: In this large, pooled analysis, genetic variants related to lower 25(OH)D levels were associated with a decreased risk of aggressive prostate cancer. IMPACT: Our genetic findings do not support a protective association between loci known to influence vitamin D levels and prostate cancer risk.