Using urine as a biomarker in human exposure risk associated with arsenic and other heavy metals contaminating drinking groundwater in intensively agricultural areas of Thailand.

Urine used as a biomarker was collected and compared between two groups of participants: (1) a groundwater-drinking group and (2) a non-groundwater-drinking group in intensively agricultural areas in Ubon Ratchathani province, Thailand. The statistical relationship with the metal concentration in shallow groundwater wells was established with urine data. According to the groundwater data, the health risk assessment results for four metals appeared to be higher for participants who drank groundwater than for the other group.

Psychosocial factors associated with the uptake of contralateral prophylactic mastectomy among BRCA1/2 mutation noncarriers with newly diagnosed breast cancer.

Purpose: Women who are newly diagnosed with breast cancer may consider contralateral prophylactic mastectomy (CPM) to reduce their future risk of cancer in their unaffected breast. Pre-surgical BRCA1/2 genetic testing can provide valuable risk information to guide this choice. However, little is understood about why BRCA1/2 mutation noncarriers, who are generally not at substantially elevated risk of contralateral disease, select CPM.

Decision-Making Preferences About Secondary Germline Findings That Arise From Tumor Genomic Profiling Among Patients With Advanced Cancers.

Purpose: In patients with advanced cancers, tumor genomic profiling (TGP) can reveal secondary germline findings (SGFs) regarding inherited disease risks. This study examines the process by which patients with advanced cancers would make the decision about whether or not to learn these SGFs, and their preferences regarding specific challenging decision scenarios including whether patients should be required to receive SGFs and whether SGFs should be returned to family after a patient's death.

Patients And Methods: We conducted qualitative semi-structured interviews with 40 patients with advanced breast, bladder, colorectal, or lung cancer who had TGP.

ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016.

The European Society for Medical Oncology (ESMO) and the American Society of Clinical Oncology (ASCO) are publishing a new edition of the ESMO/ASCO Global Curriculum (GC) thanks to contribution of 64 ESMO-appointed and 32 ASCO-appointed authors. First published in 2004 and updated in 2010, the GC edition 2016 answers to the need for updated recommendations for the training of physicians in medical oncology by defining the standard to be fulfilled to qualify as medical oncologists. At times of internationalisation of healthcare and increased mobility of patients and physicians, the GC aims to provide state-of-the-art cancer care to all patients wherever they live.

A Recurrent ERCC3 Truncating Mutation Confers Moderate Risk for Breast Cancer.

Unlabelled: Known gene mutations account for approximately 50% of the hereditary risk for breast cancer. Moderate and low penetrance variants, discovered by genomic approaches, account for an as-yet-unknown proportion of the remaining heritability. A truncating mutation c.

Characterization of a novel germline PALB2 duplication in a hereditary breast and ovarian cancer family.

Purpose: Mutations in PALB2 have been associated with a predisposition to breast and pancreatic cancers. This study aims to characterize a novel PALB2 exon 13 duplication in a hereditary breast and ovarian cancer family.

Methods: The PALB2 exon 13 duplication in this family was evaluated using Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT™) and confirmed by multiplex ligation-dependent probe amplification (MLPA).

Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression: identification of a modifier of breast cancer risk at locus 11q22.3.

Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways.

Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2.

A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale.

Veliparib is an orally administered poly(ADP-ribose) polymerase inhibitor that is being studied in Phase I-III clinical trials, including Phase III studies in non-small-cell lung cancer, ovarian cancer and breast cancer. Tumor cells with deleterious BRCA1 or BRCA2 mutations are deficient in homologous recombination DNA repair and are intrinsically sensitive to platinum therapy and poly(ADP-ribose) polymerase inhibitors. We describe herein the design and rationale of a Phase II trial investigating whether the addition of veliparib to temozolomide or carboplatin/paclitaxel provides clinical benefit over carboplatin/paclitaxel with placebo in patients with locally recurrent or metastatic breast cancer harboring a deleterious BRCA1 or BRCA2 germline mutation (Trial registration: EudraCT 2011-002913-12, NCT01506609).

Educational and Psychosocial Support Needs in Lynch Syndrome: Implementation and Assessment of an Educational Workshop and Support Group.

Few reports of educational and counseling support resources exist for Lynch syndrome (LS), a disorder requiring multi-organ cancer screening and specialized medical care throughout adult life. Here we describe the development and efficacy of two resources designed to address this need, the Memorial Sloan Kettering Cancer Center Clinical Genetics Service annual Lynch Syndrome Educational Workshop (LSEW), and a quarterly Lynch Syndrome Patient Advocacy Network (LSPAN) support group. The LSEW and LSPAN were implemented beginning in 2012.

Conflicting Interpretation of Genetic Variants and Cancer Risk by Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing.

Purpose Massively parallel sequencing allows simultaneous testing of multiple genes associated with cancer susceptibility. Guidelines are available for variant classification; however, interpretation of these guidelines by laboratories and providers may differ and lead to conflicting reporting and, potentially, to inappropriate medical management. We describe conflicting variant interpretations between Clinical Laboratory Improvement Amendments-approved commercial clinical laboratories, as reported to the Prospective Registry of Multiplex Testing (PROMPT), an online genetic registry.

Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress.

Using data collected before, during, and after the 2008 Summer Olympic Games in Beijing, this study examines associations between biomarkers of blood coagulation (vWF, sCD62P and sCD40L), pulmonary inflammation (EBC pH, EBC nitrite, and eNO), and systemic oxidative stress (urinary 8-OHdG) with sources of air pollution identified utilizing principal component analysis and with concentrations of three aldehydes of health concern. Associations between the biomarkers and the air pollution source types and aldehydes were examined using a linear mixed effects model, regressing through seven lag days and controlling for ambient temperature, relative humidity, gender, and day of week for the biomarker measurements. The biomarkers for pulmonary inflammation, particularly EBC pH and eNO, were most consistently associated with vehicle and industrial combustion, oil combustion, and vegetative burning.

Inherited DNA-Repair Gene Mutations in Men with Metastatic Prostate Cancer.

Background: Inherited mutations in DNA-repair genes such as BRCA2 are associated with increased risks of lethal prostate cancer. Although the prevalence of germline mutations in DNA-repair genes among men with localized prostate cancer who are unselected for family predisposition is insufficient to warrant routine testing, the frequency of such mutations in patients with metastatic prostate cancer has not been established.

Methods: We recruited 692 men with documented metastatic prostate cancer who were unselected for family history of cancer or age at diagnosis.

Uterine Cancer After Risk-Reducing Salpingo-oophorectomy Without Hysterectomy in Women With BRCA Mutations.

Importance: The link between BRCA mutations and uterine cancer is unclear. Therefore, although risk-reducing salpingo-oophorectomy (RRSO) is standard treatment among women with BRCA mutations (BRCA+ women), the role of concomitant hysterectomy is controversial.

Objective: To determine the risk for uterine cancer and distribution of specific histologic subtypes in BRCA+ women after RRSO without hysterectomy.

Counselling framework for moderate-penetrance cancer-susceptibility mutations.

The use of multigene panels for the assessment of cancer susceptibility is expanding rapidly in clinical practice, particularly in the USA, despite concerns regarding the uncertain clinical validity for some gene variants and the uncertain clinical utility of most multigene panels. So-called 'moderate-penetrance' gene mutations associated with cancer susceptibility are identified in approximately 2-5% of individuals referred for clinical testing; some of these mutations are potentially actionable. Nevertheless, the appropriate management of individuals harbouring such moderate-penetrance genetic variants is unclear.

Salivary cotinine levels as a biomarker for green tobacco sickness in dry tobacco production among Thai traditional tobacco farmers.

Background: Dry Thai traditional tobacco (Nicotiana Tabacum L.) production involves a unique process: (a) picking tobacco leaves, (b) curing tobacco leaves, (c) removing stems of tobacco leaves, cutting leaves and putting on a bamboo rack, (d) drying in the sun, reversing a rack, spraying a tobacco extract to adjust the tobacco's color, storing dried tobacco and packaging. These processes may lead to adverse health effects caused by dermal absorption of nicotine such as Green Tobacco Sickness (GTS).

Age- and Tumor Subtype-Specific Breast Cancer Risk Estimates for CHEK2*1100delC Carriers.

Purpose: CHEK2*1100delC is a well-established breast cancer risk variant that is most prevalent in European populations; however, there are limited data on risk of breast cancer by age and tumor subtype, which limits its usefulness in breast cancer risk prediction. We aimed to generate tumor subtype- and age-specific risk estimates by using data from the Breast Cancer Association Consortium, including 44,777 patients with breast cancer and 42,997 controls from 33 studies genotyped for CHEK2*1100delC.

Patients And Methods: CHEK2*1100delC genotyping was mostly done by a custom Taqman assay.

A single method for detecting 11 organophosphate pesticides in human plasma and breastmilk using GC-FPD.

Organophosphate (OP) pesticides are widely used for crop protection in many countries including Thailand. Aside from causing environmental contamination, they affect human health especially by over-stimulating of the neurotransmission system. OP pesticides, as with other non-persistent pesticides, degrade quickly in the environment as well as are metabolized quite rapidly in humans.

Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.

Sequencing tests assaying panels of genes or whole exomes are widely available for cancer risk evaluation. However, methods for classification of variants resulting from this testing are not well studied. We evaluated the ability of a variant-classification methodology based on American College of Medical Genetics and Genomics (ACMG) guidelines to define the rate of mutations and variants of uncertain significance (VUS) in 180 medically relevant genes, including all ACMG-designated reportable cancer and non-cancer-associated genes, in individuals who met guidelines for hereditary cancer risk evaluation.

The Impact of an Ergonomics Intervention on Psychosocial Factors and Musculoskeletal Symptoms among Thai Hospital Orderlies.

(1) BACKGROUND: Musculoskeletal disorders have a multifactorial etiology that is not only associated with physical risk factors, but also psychosocial risk factors; (2) OBJECTIVE: This study evaluated the effects of an ergonomic intervention on musculoskeletal disorders and psychosocial risk factors; (3) MATERIAL AND METHODS: This study took a participatory ergonomic (PE) approach with a randomized controlled trial (RCT) conducted at tertiary care hospitals during July to December 2014. A group of hospital orderlies in Thailand were randomly selected for examination. Fifty orderlies were placed in a case group and another 50 orderlies were placed in the control group.

Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer.

Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 × 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.

An international survey of surveillance schemes for unaffected BRCA1 and BRCA2 mutation carriers.

Female BRCA1/BRCA2 mutation carriers are at substantially increased risk for developing breast and/or ovarian cancer, and are offered enhanced surveillance including screening from a young age and risk-reducing surgery (RRS)-mastectomy (RRM) and/or salpingo-oophorectomy (RRSO). While there are established guidelines for early detection of breast cancer in high-risk women who have not undergone RRM, there are less developed guidelines after RRM. We evaluated the schemes offered before and after RRS in internationally diverse high-risk clinics.

Reliable Detection of Mismatch Repair Deficiency in Colorectal Cancers Using Mutational Load in Next-Generation Sequencing Panels.

Purpose: Tumor screening for Lynch syndrome is recommended in all or most patients with colorectal cancer (CRC). In metastatic CRC, sequencing of RAS/BRAF is necessary to guide clinical management. We hypothesized that a next-generation sequencing (NGS) panel that identifies RAS/BRAF and other actionable mutations could also reliably identify tumors with DNA mismatch repair protein deficiency (MMR-D) on the basis of increased mutational load.