Modifiable risk factors for cancer among people with lynch syndrome: an international, cross-sectional survey.

Background: Lynch syndrome is the most common cause of hereditary colorectal and endometrial cancer. Lifestyle modification may provide an opportunity for adjunctive cancer prevention. In this study, we aimed to characterise modifiable risk factors in people with Lynch syndrome and compare this with international guidelines for cancer prevention.

Modifiable Risk Factors and Risk of Colorectal and Endometrial Cancers in Lynch Syndrome: A Systematic Review and Meta-Analysis.

Purpose: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancers. Modifiable risk factors, including obesity, physical activity, alcohol intake, and smoking, are well-established in sporadic cancers but are less studied in Lynch syndrome.

Methods: Searches were conducted on MEDLINE, Embase, and Web of Science for cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome.

Aqueous Photoelectrochemical CO Reduction to CO and Methanol over a Silicon Photocathode Functionalized with a Cobalt Phthalocyanine Molecular Catalyst.

We report a precious-metal-free molecular catalyst-based photocathode that is active for aqueous CO reduction to CO and methanol. The photoelectrode is composed of cobalt phthalocyanine molecules anchored on graphene oxide which is integrated via a (3-aminopropyl)triethoxysilane linker to p-type silicon protected by a thin film of titanium dioxide. The photocathode reduces CO to CO with high selectivity at potentials as mild as 0 V versus the reversible hydrogen electrode (vs RHE).

Uptake of BRCA1/BRCA2 predictive genetic testing in an Irish population is low: a missed opportunity.

Introduction: Predictive testing for BRCA1 or BRCA2 allows at-risk individuals to engage with appropriate screening and treatment services if a pathogenic mutation is identified. Previous studies have shown uptake of predictive testing to most commonly range between 20% and 40% (Table 2). This represents a missed cancer prevention opportunity.

A pilot study investigating feasibility of mainstreaming germline BRCA1 and BRCA2 testing in high-risk patients with breast and/or ovarian cancer in three tertiary Cancer Centres in Ireland.

In the Republic of Ireland (ROI), BRCA1/BRCA2 genetic testing has been traditionally undertaken in eligible individuals, after pre-test counselling by a Clinical Geneticist/Genetic Counsellor. Clinical Genetics services in ROI are poorly resourced, with routine waiting times for appointments at the time of this pilot often extending beyond a year. The consequent prolonged waiting times are unacceptable where therapeutic decision-making depends on the patient's BRCA status.

Extramural venous invasion (EMVI) in colorectal cancer is associated with increased cancer recurrence and cancer-related death.

Introduction: Colorectal cancer (CRC) outcomes vary depending on tumour biology, with several features used to predict disease behaviour. Extramural venous invasion (EMVI) is associated with negative outcomes and its presence has been established as an indicator of more aggressive disease in CRC.

Methods: A prospectively maintained database was examined for patients undergoing curative resection for non-metastatic CRC between 2012 and 2018 in a tertiary institution.

Insertion of an SVA element in MSH2 as a novel cause of Lynch syndrome.

Germline mutations in the DNA mismatch repair (MMR) genes cause Lynch syndrome (LS). In this study, we identified and characterized a novel SINE-VNTR-Alu (SVA) insertion in exon 12 of MSH2 in an individual with early-onset colorectal cancer and a very strong LS family history. RT-PCR analysis indicated a larger aberrant MSH2 transcript in one of the family members.

Prevalence of pancreaticobiliary cancers in Irish families with pathogenic BRCA1 and BRCA2 variants.

Pathogenic variants (PVs) in the BRCA1 and BRCA2 genes are associated with an increased lifetime risk of pancreatic ductal adenocarcinoma (PDAC), and more recently have been associated with increased risk of biliary tract cancers (BTC). This study assessed the prevalence, age and gender distribution of PDAC/BTC cases in families known to carry a BRCA1/2 PV compared to those of the Irish population. A review of all families referred to a national genetics clinic from 09/11/1997 to 01/06/2018 was performed.

High-risk family colorectal cancer screening service in Ireland: Critical review of clinical outcomes.

Background: We present the 15-year experience of a family colorectal cancer screening service in Ireland with emphasis on real life experience and outcomes.

Methods: Questionnaires were used to assess family cancer history and assign patients to risk categories; 'Moderate Risk', HNPCC, (suspected) genetic syndrome (non-HNPCC), 'Low Risk'. Screening was by full colonoscopy.

Screening for mismatch repair deficiency in colorectal cancer: data from three academic medical centers.

Reflex immunohistochemistry (rIHC) for mismatch repair (MMR) protein expression can be used as a screening tool to detect Lynch Syndrome (LS). Increasingly the mismatch repair-deficient (dMMR) phenotype has therapeutic implications. We investigated the pattern and consequence of testing for dMMR in three Irish Cancer Centres (CCs).

Young patients with synchronous colorectal liver metastases.

Background: An increasing proportion of patients are presenting with colorectal cancer at an early age. A proportion of these occur with genetic syndromes; however the majority present as sporadic. The purpose of this study is to investigate the prognosis and treatment of young patients with sporadic metastatic colorectal cancer.

An overview of triple negative breast cancer for surgical oncologists.

Triple negative breast cancers (TNBCs) represent a distinct subgroup of breast cancers with an immunohistochemical phenotype that is negative for oestrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). The aim of this article is to provide a broad overview of recent developments in the diagnosis and management of TNBC for surgical oncologists. This overview discusses the subtypes of TNBC and the relationship between this type of breast cancer and the BRCA1 gene.

Phase II study of gemcitabine, carboplatin, and bevacizumab in patients with advanced unresectable or metastatic urothelial cancer.

Purpose: Although gemcitabine and carboplatin (GCa) is a standard option for patients with advanced urothelial cancer (UC) who are ineligible for cisplatin, outcomes remain poor. This trial evaluated the efficacy and safety of bevacizumab with GCa in advanced UC.

Patients And Methods: Patients with Karnofsky performance status of 60% to 70%, creatinine clearance less than 60 mL/min, visceral metastasis, or solitary kidney were eligible and received a lead-in dose of bevacizumab 10 mg/kg followed 2 weeks later by gemcitabine 1,000 mg/m(2) on days 1 and 8 and carboplatin at area under the [concentration-time] curve (AUC) 5.

Prostate cancer: germline prediction for a commonly variable malignancy.

Unlabelled: What's known on the subject? and What does the study add? Prostate cancer is a heterogeneous disease and biomarkers to predict its incidence and subsequent clinical behaviour are needed to tailor screening, prevention and therapeutic strategies. Rare mutations in genes such as BRCA1, BRCA2 and HOXB13 can affect prostate cancer incidence and/or clinical behaviour. Genome wide association studies (GWAS) have identified more common genetic variations that explain an estimated 20% of familial prostate cancer risk.

Clinical correlation and molecular evaluation confirm that the MLH1 p.Arg182Gly (c.544A>G) mutation is pathogenic and causes Lynch syndrome.

Approximately 25 % of mismatch repair (MMR) variants are exonic nucleotide substitutions. Some result in the substitution of one amino acid for another in the protein sequence, so-called missense variants, while others are silent. The interpretation of the effect of missense and silent variants as deleterious or neutral is challenging.

Germline BRCA mutation does not prevent response to taxane-based therapy for the treatment of castration-resistant prostate cancer.

Objective: • To investigate the relationship between BRCA mutation status and response to taxane-based chemotherapy, since BRCA mutation carriers with prostate cancer appear to have worse survival than non-carriers and docetaxel improves survival in patients with castration-resistant prostate cancer.

Patients And Methods: • We determined BRCA mutation prevalence in 158 Ashkenazi Jewish (AJ) men with castration-resistant prostate cancer. Clinical data were collected as part of an institutional prostate cancer research database and through additional medical record review.

Sunitinib in urothelial cancer: clinical, pharmacokinetic, and immunohistochemical study of predictors of response.

Background: Sunitinib has activity in patients with metastatic urothelial cancer (UC), but most patients do not respond.

Objective: To identify predictors of response to sunitinib.

Design, Setting, And Participants: Seventy-seven patients with advanced UC received sunitinib on one of two schedules at a single institution.

Diagnosing hereditary colorectal cancer.

Although progress in the treatment of patients with colorectal cancer (CRC) has resulted in improved median survival, most patients with metastatic CRC still die of their disease, and essentially all patients with early-stage disease must undergo surgical resection and subsequently face the possibility of adjuvant chemotherapy. As effective screening and prevention strategies for CRC have been developed, identification of individuals with a hereditary predisposition to developing CRC is especially important and provides the opportunity to reduce disease burden in this high-risk population. Increased awareness and improved diagnostic techniques for hereditary CRC syndromes have facilitated more frequent diagnosis and management of a small number of highly penetrant syndromes within families.

Genitourinary cancer predisposition syndromes.

Despite epidemiologic data supporting a significant genetic contribution to the cause of genitourinary malignancies, their diagnosis rarely results in clinical genetics referral and the heritability of prostate, bladder, kidney, and testicular cancer remains poorly understood. Little of this inheritance has been explained by rare, high-penetrance predisposition syndromes and, although rare genetic variation may explain some of the remaining familial predisposition, recent genome-wide association studies support an important causal role for more common genomic variation and other structural variants. Susceptibility loci associated with risk of prostate, bladder, and testicular cancer have been identified that may improve our understanding of the cause and natural history of these malignancies.

Hypoxia-inducible factor and mammalian target of rapamycin pathway markers in urothelial carcinoma of the bladder: possible therapeutic implications.

Objective: To investigate the rationale for using targeted therapies against hypoxia-inducible factor (HIF) and mammalian target of rapamycin (mTOR) pathways in urothelial carcinoma of the bladder, by studying the immunohistochemical expression of molecules of these pathways in urothelial carcinoma, as recent pre-clinical studies and clinical trials have shown the potential utility of such targeted therapies.

Patients And Methods: Immunohistochemical stains were performed on a tissue microarray prepared from 92 cases of ≥ pT2 urothelial (transitional cell) carcinoma of bladder, using antibodies against HIF-1α and VEGF-R2, and phospho-S6 and phospho-4E BP1, molecules of HIF and activated mTOR pathways, respectively. Immunoreactivity was graded from 0 to 3+ (0, 0-5%; 1+, 6-25%; 2+, 26-50%; 3+, > 50% tumour cells positive).

Genome-wide association studies of cancer: principles and potential utility.

Genome-wide association studies (GWAS) have emerged as a new approach for investigating the genetic basis of complex diseases. In oncology, genome-wide studies of nearly all common malignancies have been performed and more than 100 genetic variants associated with increased risks have been identified. GWAS approaches are powerful research tools that are revealing novel pathways important in carcinogenesis and promise to further enhance our understanding of the basis of inherited cancer susceptibility.

Improving response and outcomes for patients with liver-limited metastatic colorectal cancer.

Long-term survival with colorectal liver metastases (CLM) usually requires surgical resection, despite considerable improvements in systemic chemotherapy that have extended median survival with metastatic colorectal cancer from 6 months to in excess of 2 years. Multidisciplinary management is now the norm in the perioperative setting, and chemotherapy has become part of an accepted treatment paradigm. Systemic and intrahepatic chemotherapy can shrink inoperable disease to the point of resection, and a combination of neoadjuvant and adjuvant chemotherapy improves disease-free survival for patients with operable CLM.

Metastatic colorectal cancer: from improved survival to potential cure.

Context: The treatment of colorectal cancer has improved considerably in recent years, but it remains the second commonest cause of cancer deaths in men and women in the United States. Better therapies have resulted in prolonged median survival for patients with metastatic disease and a select number of patients can now be cured.

Evidence Acquisition: We conducted a computerized search using PubMed and Google Scholar for reports published between January 1993 and August 2009 using mesh headings and key words relating to the treatment of colorectal cancer.

Susceptibility loci associated with prostate cancer progression and mortality.

Purpose: Prostate cancer is a heterogeneous disease with a variable natural history that is not accurately predicted by currently used prognostic tools.

Experimental Design: We genotyped 798 prostate cancer cases of Ashkenazi Jewish ancestry treated for localized prostate cancer between June 1988 and December 2007. Blood samples were prospectively collected and de-identified before being genotyped and matched to clinical data.

False elevation of human chorionic gonadotropin in a patient with testicular cancer.

Background: A 44-year-old, HIV-positive man presented with a painless swelling of his left testicle. He underwent left radical orchiectomy for a pathological stage T1 nonseminomatous germ cell tumor (NSGCT). A persistently elevated postoperative human chorionic gonadotropin (hCG) level resulted in the patient being diagnosed as having low-risk, stage 1S disseminated NSGCT.