Cancer Risk Score Research Articles

Oncological Outcome of Primary and Secondary Muscle-Invasive Bladder Cancer: A Systematic Review and Meta-analysis

Conflicting results of survival outcomes for primary and secondary muscle-invasive bladder cancer (MIBC) have been reported in previous studies. Primary MIBC is defined as presentation of muscle-invasive disease at initial diagnosis while secondary MIBC presumes that non-muscle invasive disease later progressed to MIBC. Due to the varying reports, we conducted a systematic review and meta-analysis to compare survival outcomes between the two groups. Relevant studies were retrieved from Medline, Embase, the Cochrane Library, and Scopus using a comprehensive search approach. Cancer-specific survival (CSS) was the outcome measure. A total of 14 studies involving 4,075 cases were included. Patients with secondary MIBC were significantly correlated with worse CSS in model I (pooled HR: 1.29, 95% CI: 1.07–1.56, P = 0.008). The results of sensitivity analyses indicated that the omission of any single study each time did not have a significant impact on the combined risk estimates. Egger’s test suggested no publication bias among these studies. The European Organization for Research and Treatment of Cancer (EORTC) risk score offers the possibility of stratifying the secondary MIBC patients into different risk groups. In high-risk NMIBC, timely radical cystectomy should be considered. Further study is required to assess the multimodal therapy in both high-risk NMIBC and secondary MIBC patients as well as to evaluate genetic and molecular drivers of tumor induction, promotion, and progression.

MP82-15 HYPOGONADISM IS ASSOCIATED WITH A REDUCED RISK OF HIGH GRADE PROSTATE CANCER

You have accessJournal of UrologyProstate Cancer: Detection & Screening VII1 Apr 2018MP82-15 HYPOGONADISM IS ASSOCIATED WITH A REDUCED RISK OF HIGH GRADE PROSTATE CANCER Cosimo De Nunzio, Francesco Esperto, Riccardo Lombardo, Mariangela Bellangino, Antonio Nacchia, Angela Sica, Fabiana Cancrini, and Andrea Tubaro Cosimo De NunzioCosimo De Nunzio More articles by this author , Francesco EspertoFrancesco Esperto More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Mariangela BellanginoMariangela Bellangino More articles by this author , Antonio NacchiaAntonio Nacchia More articles by this author , Angela SicaAngela Sica More articles by this author , Fabiana CancriniFabiana Cancrini More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2743AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Aim of our study was to explore the risk of prostate cancer and poorly differentiated prostate cancer (PCa) in hypogonadal men undergoing prostate biopsies. METHODS From 2008 onwards, a consecutive series of men undergoing 12-core prostate biopsy at one center in Italy were enrolled into a prospective database. Indications for prostatic biopsy were PSA value = 4 ng/ml and/or a positive digital rectal examination (DRE). Blood samples were collected before biopsy and tested for: total PSA levels, SHBG, serum testosterone level. Hypogonadism was defined as serum Testosterone levels < 2.3 ng/ml.We evaluated the association between hypogonadism status and prostate cancer risk and biopsy Gleason score using logistic regression analyses. RESULTS Overall 1124 patients were enrolled. Median age was 68 years (IQR: 62/63), median BMI was 27 kg/m2 (IQR: 25/29); median PSA 6.2 ng/ml (IQR: 4.4/9.0); median testosterone level was 3.8 ng/ml (IQR: 3.0/4.8), median SHBG 40 mmol/l (IQR 30/53). Overall 460/1124 (40.9%) had cancer on biopsy and out of them 126/460 presented a high grade disease (Gleason score =4+3).185/1124 (16%) of patients were hypogonadal. Prostate cancer detection was 380/939 (40.5%) in eugonadal patients and 80/185 (43.2%) in hypogonadal men (p=0.267). High grade prostate cancer was observed in 111/380 (29.2%) in eugonadal men and 15/80 (19%) in hypogonadal men (p=0.002). On multivariate analysis age (OR: 1.046 95%CI: 1.030-1.063; p= 0.000) and PSA (OR: 1.068 95%CI: 1.046-1.091; p= 0.000) were the only independent parameters associated with prostate cancer diagnosis while no difference was observed regarding the hypogonadal state. On multivariate analysis age (OR: 1.044 95%CI: 1.017-1.072; p= 0.000) and PSA (OR: 1.030 95%CI: 1.015-1.045; p= 0.000) were associated with high grade prostate cancer diagnosis while the presence of hypogonadal state reduced the risk of high grade PCa by 60% (OR: 0.40, IC 0.25-0.84, p=0.012). CONCLUSIONS In our study about 16% of patients at risk of PCa were hypogonadal. Hypogonadism was associated with a reduced risk of high grade prostate cancer. Although further studies should evaluate the pathophysiology behind this association, we support that hormonal status should be evaluated in patients at risk of PCa. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1112 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Cosimo De Nunzio More articles by this author Francesco Esperto More articles by this author Riccardo Lombardo More articles by this author Mariangela Bellangino More articles by this author Antonio Nacchia More articles by this author Angela Sica More articles by this author Fabiana Cancrini More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Abstract P3-10-05: Normal breast biopsies reveal an "active" transcriptome associating with higher breast cancer risk (Gail) scores and increased IGF-1 growth factor expression

Abstract Background: Recent studies have identified at least two different transcriptional subtypes of benign human breast tissue (Haakensen et al., 2011), including an “active” subtype associated with increased risk of later life mortality from breast cancer (Troester et al., 2016). However, previous studies used "normal" breast samples from cosmetic surgery, biopsies from abnormal mammograms, or cancer-adjacent tissue. The present study evaluates normal breast transcriptome phenotypes from healthy women who donated for this study purpose only. Methods: 200 formalin-fixed paraffin-embedded (FFPE) breast tissue biopsy samples were analyzed from healthy, parous non-Hispanic white women ranging in age from 27–66 (median = 45) with no prior history of breast cancer (&amp;lt;16% had prior breast biopsies), who donated to the Komen Tissue Bank (KTB) and provided questionnaire data enabling calculation of breast cancer risk (Gail) scores. Extractable RNA from FFPE sections sufficient for RNA sequencing (˜100ng) was obtained from 145/200 donor samples; digitized H&amp;E analysis confirmed normal breast histology. Transcript levels were quantified using RSEM and normalized; 2558 genes were used for unsupervised hierarchical clustering to identify “active” vs. “inactive” normal transcriptome subtypes as previously described (Roman-Perez et al., 2012), and these subtypes were compared for risk scores and IGF1R and IGF-1 gene expression levels and their respective signatures (Creighton et al., 2008; Mu et al., 2012). Results: As expected, the normal histologic composition of these KTB samples varied considerably with mean % adipose area twice that of fibrous area, and epithelial content averaging &amp;lt;5%. Unsupervised gene expression analysis produced two primary clusters, with 31% of donor samples showing the “active” transcriptome phenotype. These “active” breast samples came from women with significantly higher Gail scores (Wilcoxon rank sum p=0.007) and showed significantly different expression levels in 12 of 17 IGF-1/IGF1R pathway genes (FDR-corrected p values) including higher IGF-1, IGF-2, IRS1, IRS2, IGF2R, IGFBP3, IGFBP5, IGFBP6, and IGF2BP3 levels, and lower IGF1R, IGFBP2, and IGFBP3 transcript levels. A multigene signature associated with IGF-1 induction was consistent with the 2-fold significant increase in mean IGF-1 mRNA levels seen in this “active” subset; likewise, an independent multigene signature associated with IGF1R activation was consistent with the 0.84-fold significant reduction in mean IGF1R mRNA levels observed in this same subset. Conclusion: Over 30% of healthy adult women with histologically normal breast tissue carry an “active” breast transcriptome phenotype previously linked to co-existent breast cancer and now shown to be associated with increased future risk of developing breast cancer assessed by Gail score. This “active” transcriptome phenotype is characterized by increased endogenous IGF-1 activity, a known breast cancer promoting growth factor, along with an inverse reduction in IGF1R expression and activity as previously seen in some breast cancers. Further morphologic and molecular characterization of this risk-associated subset of normal breast tissues is underway. Citation Format: Benz C, Yau C, Benz S, Krings G, Powell M. Normal breast biopsies reveal an "active" transcriptome associating with higher breast cancer risk (Gail) scores and increased IGF-1 growth factor expression [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-05.

Abstract P3-09-07: Breast cancer risk assessment in a multiethnic patient population

Abstract The United States Preventive Services Task Force recommends that women who are at increased risk for breast cancer and at low risk for adverse medication effects should be offered risk-reducing medications, such as tamoxifen or raloxifene, by their clinicians. In addition, the National Comprehensive Cancer Network recommends risk counseling for women with a 5-year risk of ≥1.7% as calculated by the NCI-developed Breast Cancer Risk Assessment Tool (BCRAT, based on the Gail model) or other risk model. Thus, breast cancer risk assessment is important for the identification of women at "high risk" who should be offered risk counseling and potentially intervention. The Athena Breast Health Network, which has served &amp;gt;120,000 breast screening patients across California and the midwest, has integrated breast cancer risk assessment into its clinical breast screening programs. The goal of our study was to characterize breast cancer risk for &amp;gt;10,000 mammography patients in the University of California Irvine Athena Breast Health Network, overall and by race/ethnicity, using several different risk models, including the BCRAT, BCSC, and IBIS models. Our cohort was comprised of 47% non-Hispanic White, 13% non-Hispanic Asian, 38% Hispanic, and 2% women of other race/ethnicities. Using data collected from electronic medical records and self-completed questionnaires, we determined that, as expected, non-Hispanic White and Asian women had higher breast cancer risk scores than Hispanic women for all risk models (5-year risks = 1.51-1.68% and 1.22-1.40% vs. 0.95-1.05%, respectively). In addition, when women were categorized as "increased risk" according to a given risk model if their 5-year risk score was ≥1.7%, the percentages of women at "increased risk" were higher in White women (26.5–42.2%) than in Asian (15.8–28.6%) and Hispanic (6.2–10.7%) women. However, the correlations between risk models were low to moderate in our cohort, overall (Pearson's r = 0.47-0.62) and especially for Asian women (Pearson's r = 0.29-0.49). Our results indicate that using only one risk model in a clinical breast cancer risk assessment program to identify "high risk" women would miss a significant proportion of women who would have been considered "high risk" according to another risk model. Conversely, some women who are identified as "high risk" according to one model may not need risk counseling and intervention since they are not considered "high risk" according to two other models. As our cohort expands and incident breast cancers occur, we will be able to determine which risk model or combination of risk models will have the highest discriminatory accuracy for predicting breast cancer risk in women of different race/ethnicities, which will enable our risk assessment programs to have a more targeted approach to risk counseling and intervention. Citation Format: Park HL, Columbus A, Athena Breast Health Network Investigators and Advocate Partners, Kelly R, Alvarez A, Goodman D, Larsen K, Ziogas A, Anton-Culver H. Breast cancer risk assessment in a multiethnic patient population [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-09-07.

Assessment of Results of the Mammography Screenings among Women Older than 40 Years in a Residential Area

Objective: This study was conducted in order to determine the breast cancer risk levels among women older than 40, gain the habit of having a mammography which is one of the early screening programs, direct women to mammography, and assess the mammography results. Methods: The study was conducted on female patients older than 40, who were hospitalized in the services of a research and training hospital between 1 February and 1 June 2014, and their relatives (n=409). Appointments were received from Kirsehir Early Diagnosis, Screening, and Training Center for women who completed the data collection form and breast cancer risk assessment form and they were guided in having mammography. Results: As a result of the mammography screening; while normal breast tissues were determined in 42.5% of the women, nodular lumps were determined in 21.8%. Breast cancer risk scores were observed to be higher in women who had personal history of breast cancer and a history of breast cancer in their mothers, had no children, menstruated before the age of 11, had a fat body structure, were in the high risk group according to the breast cancer risk. Discussion: Early diagnosis in breast cancer could be possible through training and informing women on this issue and applying the screening programs. In this study, many women were screened by using mammography, which is a cheap, easily applicable, and easily accessible screening method, and the risk factors were determined.

Using a genetic/clinical risk score to stop smoking (GeTSS): randomised controlled trial

BackgroundAs genetic tests become cheaper, the possibility of their widespread availability must be considered. This study involves a risk score for lung cancer in smokers that is roughly 50% genetic (50% clinical criteria). The risk score has been shown to be effective as a smoking cessation motivator in hospital recruited subjects (not actively seeking cessation services).MethodsThis was an RCT set in a United Kingdom National Health Service (NHS) smoking cessation clinic. Smokers were identified from medical records. Subjects that wanted to participate were randomised to a test group that was administered a gene-based risk test and given a lung cancer risk score, or a control group where no risk score was performed. Each group had 8 weeks of weekly smoking cessation sessions involving group therapy and advice on smoking cessation pharmacotherapy and follow-up at 6 months. The primary endpoint was smoking cessation at 6 months. Secondary outcomes included ranking of the risk score and other motivators.Results67 subjects attended the smoking cessation clinic. The 6 months quit rates were 29.4%, (10/34; 95% CI 14.1–44.7%) for the test group and 42.9% (12/28; 95% CI 24.6–61.2%) for the controls. The difference is not significant. However, the quit rate for test group subjects with a “very high” risk score was 89% (8/9; 95% CI 68.4–100%) which was significant when compared with the control group (p = 0.023) and test group subjects with moderate risk scores had a 9.5% quit rate (2/21; 95% CI 2.7–28.9%) which was significantly lower than for above moderate risk score 61.5% (8/13; 95% CI 35.5–82.3; p = 0.03).ConclusionsOnly the sub-group with the highest risk score showed an increased quit rate. Controls and test group subjects with a moderate risk score were relatively unlikely to have achieved and maintained non-smoker status at 6 months.ClinicalTrials.gov ID NCT01176383 (date of registration: 3 August 2010)

Clinical Decision-Making in Patients with Variant of Uncertain Significance in BRCA1 or BRCA2 Genes.

How diagnosis with a variant of uncertain significance (VUS) in a BRCA gene impacts clinical decision-making is not well known. We queried for all patients attending Mayo Clinic Rochester from 2004 to 2016 who tested positive for BRCA1 or BRCA2 VUS and reviewed patient management choices. Groups were compared by using Wilcoxon rank-sum and Chi-square tests. We identified 97 patients (95 females, 2 males) with BRCA VUS. For patients without cancer history (n=20), 80% had a mother or sister with breast cancer, and median Tyrer-Cuzick (IBIS) lifetime breast cancer risk score was 27% (range 16-62%). Management included bilateral prophylactic mastectomy (BPM) in 39%, where choice for BPM was significantly associated with IBIS score (median 32 vs. 24%, p=0.02) and first-degree family history of breast cancer (100 vs. 64%, p=0.03) but not Gail score or total number of family members with cancer. For patients with breast cancer who had known VUS statusprior to surgery (n=9), the rate of contralateral prophylactic mastectomy (CPM) was 22% compared with 25% without known VUS and 83% with known BRCA pathogenic mutation. In 21 of 97 (22%) patients, the BRCA VUS has been reclassified (95% benign, 5% deleterious). BRCA VUS carriers with cancer elected surgical choices similar to average-risk breast cancer patients. However, VUS carriers without cancer had high rates of BPM, associated with first-degree family history and IBIS score. Over time, a significant proportion of BRCA VUS were reclassified, illustrating the importance of appropriate counseling regarding VUS.

Prognostic Impact of a 12-gene Progression Score in Non–muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study

BackgroundProgression of non–muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed. ObjectiveTo validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study. Design, setting, and participantsWe enrolled 1224 patients in ten European centres between 2008 and 2012. A total of 750 patients (851 tumours) fulfilled the inclusion and sample quality criteria for testing. Patients were followed for an average of 28 mo (range 0–76). A 12-gene real-time qualitative polymerase chain reaction assay was performed for all tumours and progression scores were calculated using a predefined formula and cut-off values. Outcome measurements and statistical analysisWe measured progression to MIBC using Cox regression analysis and log-rank tests for comparing survival distributions. Results and limitationsThe progression score was significantly (p<0.001) associated with age, stage, grade, carcinoma in situ, bacillus Calmette-Guérin treatment, European Organisation for Research and Treatment of Cancer risk score, and disease progression. Univariate Cox regression analysis showed that patients molecularly classified as high risk experienced more frequent disease progression (hazard ratio 5.08, 95% confidence interval 2.2–11.6; p<0.001). Multivariable Cox regression models showed that the progression score added independent prognostic information beyond clinical and histopathological risk factors (p<0.001), with an increase in concordance statistic from 0.82 to 0.86. The progression score showed high correlation (R2=0.85) between paired fresh-frozen and formalin-fixed paraffin-embedded tumour specimens, supporting translation potential in the standard clinical setting. A limitation was the relatively low progression rate (5%, 37/750 patients). ConclusionsThe 12-gene progression score had independent prognostic power beyond clinical and histopathological risk factors, and may help in stratifying NMIBC patients to optimise treatment and follow-up regimens. Patient summaryClinical use of a 12-gene molecular test for disease aggressiveness may help in stratifying patients with non–muscle-invasive bladder cancer to optimal treatment regimens.

Association of Smoking in the Home With Lung Cancer Worry, Perceived Risk, and Synergistic Risk.

To examine the association of smoking in the home with lung cancer worry, perceived risk, and synergistic risk, controlling for sociodemographics, family history of lung cancer, and health-related self-concept. The hypothesis is that participants with smoking in the home would have higher scores for lung cancer worry, perceived risk, and synergistic risk. . Cross-sectional baseline survey. . Participants recruited from an outpatient clinic and pharmacy at University of Kentucky HealthCare, an academic medical center. . 515 homeowners from a larger randomized, controlled trial aimed at reducing exposure to radon and secondhand smoke (SHS). . Homeowners were selected via quota sampling so that about half would have a smoker or smokers in the home. . Lung cancer worry and perceived risk; perception of synergistic risk of radon and SHS exposure; demographics. . Participants with smoking in the home had higher rates of lung cancer worry and perceived risk. In addition, those with less education and a family history of lung cancer and who were current smokers had higher lung cancer worry and perceived lung cancer risk scores. Predictors of perception of synergistic risk were marital status and health-related self-concept. . Homeowners with smoking in the home, less education, and a family history of lung cancer had greater lung cancer worry and perceived lung cancer risk. Lung cancer risk reduction interventions with vulnerable populations are needed. . Nurses are in a unique position to target high-risk populations and identify opportunities to create teachable moments to reduce environmental risks of radon and tobacco smoke exposure.

Non-invasive optical spectroscopic monitoring of breast development during puberty

BackgroundTanner staging (TS), a five-stage classification indicating no breast tissue (TS1) to full breast development (TS5), is used both in health research and clinical care to assess the onset of breast development (TS2) and duration in each stage. Currently, TS is measured both visually and through palpation but non-invasive methods will improve comparisons across settings.MethodsWe used optical spectroscopy (OS) measures from 102 girls at the Ontario site of the LEGACY girls study (average age 12 years, range 10.0–15.4 years) to determine whether breast tissue optical properties map to each TS. We further examined whether these properties differed by age, body mass index (BMI), and breast cancer risk score (BCRS) by examining the major principal components (PC).ResultsAge and BMI increased linearly with increasing TS. Eight PCs explained 99.9% of the variation in OS data. Unlike the linear increase with age and BMI, OS components had distinct patterns by TS: the onset of breast development (TS1 to TS2) was marked by elevation of PC3 scores indicating an increase in adipose tissue and decrease in signal from the pectoral muscle; transition to TS3 was marked by elevation of PC6 and PC7 and decline of PC2 scores indicating an increase in glandular or dense tissue; and transition to TS4+ by decline of PC2 scores representing a further increase in glandular tissue relative to adipose tissue. Of the eight PCs, three component scores (PC4, PC5, and PC8) remained in the best-fitting model of BCRS, suggesting different levels of collagen in the breast tissue by BCRS.ConclusionsOur results suggest that serial measures of OS, a non-invasive assessment of breast tissue characteristics, can be used as an objective outcome that does not rely on visual inspection or palpation, for studying drivers of breast development.

Circulating microRNAs Predict the Initiation of NHL in a Novel In Vivo Model: Impact of Age and Sex Via a Systems Biology Approach

Background: Extensive epidemiological data have demonstrated an exponential rise in the incidence of NHL associated with increasing age. The molecular etiology of this remains largely unknown. Additionally, recent data have suggested that older females with diffuse large B cell lymphoma (DLBCL) have improved survival when treated with rituximab-based therapy. We recently reported that there were significant global transcriptomic differences in DLBCL cases in the TCGA based on patient age and sex (Beheshti et al Cancer Inform. 2015). The hypotheses of the current studies were that age and sex-dependent circulating microRNA (miRNA) signatures exist and predict NHL initiation and progression. Leveraging a comprehensive systems biology approach in combination with a novel in vivo spontaneous DLBCL model, we sought to identify circulating miRNA signatures that drive initiation and progression.Methods: We utilized a novel murine model for spontaneous DLBCL initiation (Smurf2-deficient mice with C57BL/6 background, Nat Commun. 2013) at two age groups: 2 and 15 months old. All Smurf2-deficient mice develop visible DLBCL starting at 15 months of age. Total miRNA was isolated from serum collected for all age groups for both Smurf2-deficient mice and wild-type C57BL/6 mice as controls. Using innovative technology with Droplet Digital and real time PCR (ddPCR), we quantified the 10 circulated miRNAs in the serum. Predictions on how miRNA signature impacts cancer risk were obtained using previously established methods (Beheshti et al. Cancer Res. 2015) by relating impact of miRNA on DLBCL and determined a cancer risk score based on fold-change differences compared with control. Additional effect of how miRNAs impact the transcriptome globally was completed via CluePedia Cytoscape plugin and functional significance on cancer was determined through Ingenuity Pathway Analysis (IPA).Results: Using systems biology techniques, we identified 10 common circulating miRNAs that were significantly expressed in the spleen and bone marrow of Smurf2-deficient male and female mice at 2 months of age compared with wild-type mice. Furthermore, we predicted the impact it had on DLBCL initiation and progression from this miRNA signature (see Figure). For young Smurf2-deficient mice compared with wild-type mice, there was a predicted risk of cancer promotion due to the miRNA signature detection at 12 months prior to tumor formation. This miRNA signature was further modulated at older ages associated with the beginning of DLBCL formation. Additionally, this miRNA signature was more prominent in males and ongoing work is examining distinct miRNA associated with females. When determining the impact of the miRNA signature on DLBCL biology, we identified that these miRNAs have the most prominent impact on oncogenes, MYC and JUN with global impact on cancer related functions starting several months before actual histologic DLBCL formation.Conclusions: It was determined that there is a key miRNA signature circulating throughout a host prior to the formation of a tumor starting at 2 months old which becomes modulated by age and tumor formation. This age based circulating miRNA signature can be used to predict DLBCL development at a young age before actual tumor formation. Furthermore, this can potentially be used as a simple biomarker at a young age to predict future lymphoma development and allow for advanced novel therapeutic strategies to prevent lymphomagenesis. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Residential Radon: The Neglected Risk Factor in Lung Cancer Risk Scores

There are some published scores to estimate lung cancer risk of mortality or incidence. Nevertheless, no score has included residential radon as a variable to be considered when estimating lung cancer risk. In this commentary we discuss the importance of including residential radon as a factor to be taken into account when calculating lung cancer risk.

Genotyping to identify cancer risk

Cancer Genetics Certain genetic variants can increase a person's risk of developing cancer. For breast cancer, the link between BRCA1/2 variants and increased cancer risk is well established; however, the risk conferred by other breast cancer–associated genetic variants is not as well understood. To gain more insight, Li et al. combined family history with 24 previously identified cancer-associated single-nucleotide variants (excluding the BRCA1/2 genes) to develop a breast cancer risk score. Applying these risk scores prospectively to 2599 women revealed that this method was more accurate than familial history alone in determining the risk of developing breast cancer. Genet. Med. 10.1038/gim.2016.43 (2016).

Alteration of Leptin and Adiponectin in Multistep Colorectal Tumorigenesis

There is an established link between obesity related metabolic derangement and colorectal cancer development. Recently, we developed a metabolic-colorectal cancer risk score. In this follow-up study, we studied its association with colorectal neoplasm by measuring two major metabolic syndrome biomarkers, leptin and adiponectin. To evaluate the serum levels of leptin and adiponectin in patients with colorectal polyps and colorectal cancer and to determine any correlation with metabolic risk score. In total, 130 individuals were studied: 30 controls without colonic pathology, 18 with colonic adenoma (CAP), and 82 with colorectal adenocarcinoma (CRC, 17 cases of T1-2 and 65 cases of T3-4). The metabolic risk scores in CAP and T1-2 CRC were higher than those in the controls and T3-4 CRC cases. There were no statistically significant differences in leptin levels among CAPs, CRCs, and controls. Both leptin and adiponectin levels reflected differences in body mass index and metabolic risk scores. Cases in the CAP group and early T-stage CRC groups had lower adiponectin levels (14.03 and 13.01 mg/ml, respectively) than the no polyps group (19.5mg/ml, p = 0.03). The average serum adiponectin level in the invasive cancer group (18.5 ng/ml) was comparable with that of the control group. The level of serum adiponectin was positively correlated with the metabolic risk score. Decreased serum adiponectin was significantly associated with the development of colorectal adenoma and early stage colorectal carcinoma.

Lung cancer screening in patients with chronic obstructive pulmonary disease.

Lung cancer and chronic obstructive pulmonary disease (COPD) are two intimately related diseases, with great impact on public health. Annual screening using low-dose computed tomography (LDCT) of the chest significantly reduces mortality due to lung cancer, and several scientific societies now recommend this technique. COPD, defined by the presence of airflow obstruction [forced expiratory volume and forced vital capacity (FVC) ratio less than 0.70], and their clinical phenotypes, namely emphysema and chronic bronchitis, have been associated with increased lung cancer risk. Several epidemiological studies, including lung cancer screening trials, have found a 2- to 4-fold increase in lung cancer risk in patients with COPD when compared to individuals without airflow obstruction. Part of the risk attributed to airflow obstruction appears to be derived from the presence of radiographic emphysema. The latter has proven to be an important lung cancer risk factor in smokers without airflow obstruction and even in never smokers. This evidence supports the idea of including patients with COPD and/or emphysema in lung cancer screening programs. There is evidence that lung cancer screening in this population is effective and can potentially reduce mortality. Specific lung cancer risk scores have been developed for patients with COPD [COPD lung cancer screening score (LUCSS) and COPD-LUCSS-diffusing capacity for carbon monoxide (DLCO)] to identify those at high risk. A multidisciplinary approach for an adequate patient selection, especially of patients with severe disease, is key to maximize benefits and reduce harms from lung cancer screening in this population. Patients with COPD included in lung cancer screening programs could also benefit from other interventions, such as smoking cessation and adequate treatment.

Associations of Breast Cancer Risk Prediction Tools With Tumor Characteristics and Metastasis.

The association between established risk factors for breast cancer and subtypes or prognosis of the disease is not well known. We analyzed whether the Tyrer-Cuzick-predicted 10-year breast cancer risk score (TCRS), mammographic density (MD), and a 77-single nucleotide polymorphism polygenic risk score (PRS) were associated with breast cancer tumor prognosticators and risk of distant metastasis. We used a case-only design in a population-based cohort of 5,500 Swedish patients with breast cancer. Logistic and multinomial logistic regression of outcomes, estrogen receptor (ER) status, lymph node involvement, tumor size, and grade was performed with TCRS, PRS, and percent MD as exposures. Cox proportional hazard models were used to estimate hazard ratios (HRs) of distant metastasis. Women at high risk for breast cancer based on PRS and/or TCRS were significantly more likely to be diagnosed with favorable prognosticators, such as ER-positive and low-grade tumors. In contrast, PRS weighted on ER-negative disease was associated with ER-negative tumors. When stratifying by age, the associations of TCRS with favorable prognosticators were restricted to women younger than age 50. Women scoring high in both TCRS and PRS had a lower risk of distant metastasis (HR, 0.69; 95% CI, 0.49 to 0.98). MD was not associated with any of the examined prognosticators. Women at high risk for breast cancer based on genetic and lifestyle factors were significantly more likely to be diagnosed with breast cancers with a favorable prognosis. Better knowledge of subtype-specific risk factors could be vital for the success of prevention programs aimed at lowering mortality.

A meta-analysis-derived proposal for a clinical, ultrasonographic, and cytological scoring system to evaluate thyroid nodules: the "CUT" score.

The purpose of this study is to develop a new cancer risk score for preoperative assessment of thyroid nodules (TN) trying to reduce unnecessary thyroidectomies. On the basis of a recent meta-analysis of published literature, we assigned a matching value to the clinical (C) and ultrasonographic (U) features of TN with increased malignancy risk (MR). The created "CUT" score derived from "C+U" score, (CU[1-10] ), along with the five-tiered "T" (T[1-5] ), represents the cytologic result of the fine-needle aspiration. The C+U score was prospectively applied to 683 consecutive patients with 705 TN and validated through a ROC curve analysis. The CUT score was correlated with the histopathological diagnoses of 110 surgically resected TN. Fifty-five histologically benign TN had a mean C+U score of 2.4 versus 5.7 of 55 malignant TN (p < 0.001). Three categories were identified: low risk for C+U score ≤2.5 (MR: 9 %), intermediate risk for C+U score ≥2.75 and ≤5 (MR: 38 %), and high risk for C+U score ≥5.25 (MR: 95 %). Sensitivity and specificity were, respectively, 95 and 60 % for a cut-off value >2.5, and 69 and 96 % for >5. The "CUT" score can be easily applied, aiding clinicians in the evaluation of TN, especially in cases with indeterminate or repeated non-diagnostic FNA.

Abstract 4602: Exome sequencing of UKLS lung cancer CT screened early stage cancers

Abstract INTRODUCTION Developments in both low-dose CT-screening within populations at high risk of lung cancer and sequencing analysis of lung tumours have improved the prospects for early detection and clinical management of lung cancer. Such approaches potentially could provide biological insight into the early stages of lung cancer development, which until now have been refractory to genomic analysis, since lung tumours are rarely identified at a presymptomatic timepoint. BRIEF DESCRIPTION OF PERTINENT EXPERIMENTAL PROCEDURES Individuals with at least a 5% risk of developing lung cancer within 5 years (according to the LLPv2 lung cancer risk score) were recruited to the UK Lung low dose CT Screening (UKLS) trial. Ten of the early stage NSCLC UKLS tumours were prepared for exome sequencing. Tumour DNA was extracted from FFPE material and DNA was also extracted from matched blood samples. Tumour and blood libraries were prepared using an Agilent SureSelect exome-capture kit and sequenced to 100x and 50x, depth respectively, on the Illumina HiSeq platform (Oxford Gene Technology, UK). Sequence data were aligned against the GRCh37 human reference and matched samples were subject to local realignment in pairs. Somatic variants were identified using a combination of EBCall, MuTect and VarScan2 and were post-filtered to remove false positive variants (alignment artifacts and FFPE-hypersensitive sites) by comparison between samples. TCGA (The Cancer Genome Atlas) lung adenocarcinoma and squamous cell carcinoma samples from smokers and former smokers (who had complete data for a minimal set of clinical and epidemiological variables) were compared to the UKLS samples described above. To ensure comparable genomic regions were studied, both the UKLS and TCGA somatic variants were restricted to protein-coding regions covered by the Agilent SureSelect array but disjoint from simple-repetitive regions. SUMMARY OF THE NEW, UNPUBLISHED DATA Despite detection at an early stage, somatic mutations were identified in all CT-detected tumours, including non-synonymous variants in known driver genes. Between 71 and 471 variants were detected within non-repetitive protein-coding regions, which is comparable to, if somewhat lower than, the number of variants in the same regions in the TCGA ever-smoker samples (p = 0.17; Kruskal-Wallis). The results suggest that the majority of somatic variants exist in lung tumours prior to the evolution of symptoms and are consistent with recent studies of lung cancer heterogeneity wherein the majority of mutations occur prior to subclonal branching. STATEMENT OF CONCLUSIONS Somatic variations in the host genome are readily detected in FFPE material from pre-symptomatic lung tumours. Mutational burden is comparable to lung adenocarcinoma and squamous carcinoma from mature symptomatic individuals providing further evidence for the long latency of lung tumour development. Citation Format: Russell Hyde, Michael Davies, Martin Ledson, John A. Holemans, Richard D. Page, John Gosney, David R. Baldwin, Anand Devaraj, David M. Hansell, Stephen W. Duffy, John K. Field. Exome sequencing of UKLS lung cancer CT screened early stage cancers. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4602. doi:10.1158/1538-7445.AM2015-4602

A comparison of ED and direct admission care of cancer patients with febrile neutropenia

ObjectiveWe compared the quality of care in admitted febrile neutropenic cancer patients presenting through the emergency department (ED) vs those directly admitted (DA) from the clinic or infusion center. We hypothesized that the quality of care would be comparable between these 2 pathways. MethodsWe conducted a retrospective, observational cohort study of all adult cancer patients hospitalized with subjective or objective fever (≥100.4°F) and documented neutropenia (absolute neutrophil count ≤1000/mm3) from January 1, 2011 to June 30, 2013, at 2 hospitals. Two investigators retrieved data including patient age, sex, race, tumor type, blood culture growth, temperature (actual or reported), pathway to admission (ED or DA), time to antibiotic administration, length of stay, and the Multinational Association for Supportive Care in Cancer (MASCC) risk score. The primary outcome measures were time to antibiotic administration, appropriateness of antibiotic(s) administered based on published guidelines, length of stay, and MASCC score–based risk assessment. We used the t test for the difference between 2 means with unequal population variances to compare these outcome measures between ED and DA patients. ResultsOne hundred twenty-seven visits met inclusion criteria (42 [33%] ED visits, 85 [67%] DA visits). Mean time to antibiotic administration, mean length of stay, appropriateness of antibiotics, and MASCC score–based risk assessment were comparable between ED and DA visits (P>.05 for all comparisons). ConclusionThe quality of care for febrile neutropenia in patients presenting through the ED was comparable to those directly admitted to the hospital in this 2-center study.

Association of Nonsteroidal Anti-Inflammatory Drugs with Colorectal Cancer by Subgroups in the VITamins and Lifestyle (VITAL) Study.

There is substantial evidence that use of NSAIDs reduces the risk of colorectal cancer, but no subgroup has been identified for which the chemoprevention effect outweighs the risk of side effects. We tested the interaction between NSAID use and multiple risk factors on colorectal cancer risk in the VITAL cohort. A total of 73,458 individuals ages 50 to 76 years completed a questionnaire between 2000 and 2002, and 674 incidental colorectal cancer cases were identified through 2010. In stratified analysis, high use of any type of NSAIDs (4+ days/week for 4+ years) was statistically significantly associated with a lower risk of colorectal cancer across all subgroups stratified by sex, body mass index, physical activity, smoking, alcohol intake, screening, and dietary factors. There was a suggestion of stronger associations among men, obese individuals, and heavier drinkers; however, none of these tests for interaction reached statistical significance. The associations were almost identical for subjects with higher overall colorectal cancer risk scores [HR, 0.62; 95% confidence interval (CI), 0.49-0.79] and those with lower risk scores (HR, 0.61; 95% CI, 0.42-0.88). Differential effects by cancer subsites and stages were tested. NSAID use was associated with a greater risk reduction of proximal colon cancer versus distal (P for difference = 0.06) and distant stage versus local (P for difference = 0.04). The association between high use of NSAIDs and colorectal cancer risk does not differ significantly among subgroups. Our results suggest that NSAIDs have a generally beneficial role in colorectal cancer prevention, largely unmodified by other exposures.