Genetic variants for head size share genes and pathways with cancer.

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer.

Visible Pulsed Laser-Assisted Selective Killing of Cancer Cells with PVP-Capped Plasmonic Gold Nanostars.

A new generation of nanoscale photosensitizer agents has improved photothermal capabilities, which has increased the impact of photothermal treatments (PTTs) in cancer therapy. Gold nanostars (GNS) are promising for more efficient and less invasive PTTs than gold nanoparticles. However, the combination of GNS and visible pulsed lasers remains unexplored. This article reports the use of a 532 nm nanosecond pulse laser and polyvinylpyrrolidone (PVP)-capped GNS to kill cancer cells with location-specific exposure. Biocompatible GNS were synthesized via a simple method and were characterized under FESEM, UV-visible spectroscopy, XRD analysis, and particle size analysis. GNS were incubated over a layer of cancer cells that were grown in a glass Petri dish. A nanosecond pulsed laser was irradiated on the cell layer, and cell death was verified via propidium iodide (PI) staining. We assessed the effectiveness of single-pulse spot irradiation and multiple-pulse laser scanning irradiation in inducing cell death. Since the site of cell killing can be accurately chosen with a nanosecond pulse laser, this technique will help minimize damage to the cells around the target cells.

Large multi-ethnic genetic analyses of amyloid imaging identify new genes for Alzheimer disease.

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aß) deposits in the brain and to study Alzheimer's disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associated with brain amyloidosis and AD risk. We found a strong APOE signal on chr19q.13.32 (top SNP: APOE ɛ4; rs429358; ß = 0.35, SE = 0.01, P = 6.2 × 10-311, MAF = 0.19), driven by APOE ɛ4, and five additional novel associations (APOE ε2/rs7412; rs73052335/rs5117, rs1081105, rs438811, and rs4420638) independent of APOE ɛ4. APOE ɛ4 and ε2 showed race specific effect with stronger association in Non-Hispanic Whites, with the lowest association in Asians. Besides the APOE, we also identified three other genome-wide loci: ABCA7 (rs12151021/chr19p.13.3; ß = 0.07, SE = 0.01, P = 9.2 × 10-09, MAF = 0.32), CR1 (rs6656401/chr1q.32.2; ß = 0.1, SE = 0.02, P = 2.4 × 10-10, MAF = 0.18) and FERMT2 locus (rs117834516/chr14q.22.1; ß = 0.16, SE = 0.03, P = 1.1 × 10-09, MAF = 0.06) that all colocalized with AD risk. Sex-stratified analyses identified two novel female-specific signals on chr5p.14.1 (rs529007143, ß = 0.79, SE = 0.14, P = 1.4 × 10-08, MAF = 0.006, sex-interaction P = 9.8 × 10-07) and chr11p.15.2 (rs192346166, ß = 0.94, SE = 0.17, P = 3.7 × 10-08, MAF = 0.004, sex-interaction P = 1.3 × 10-03). We also demonstrated that the overall genetic architecture of brain amyloidosis overlaps with that of AD, Frontotemporal Dementia, stroke, and brain structure-related complex human traits. Overall, our results have important implications when estimating the individual risk to a population level, as race and sex will needed to be taken into account. This may affect participant selection for future clinical trials and therapies.

Breaking bad news: Awareness and practice of the SPIKES protocol among general surgery residents at a tertiary care institute in northern India.

Background In general surgery, a clinician is commonly required to break bad news. However, training in communication is not a part of the formal curriculum either in medical school or in surgical residency and there is a paucity of data on awareness of the SPIKES (Setting up the interview, Perception, Invitation, Knowledge sharing, Emotion, Strategy and Summary) protocol among practising surgeons and residents in India. Methods We did a cross-sectional study in the Department of General Surgery at our institution. Junior residents were invited to take part in a one-on-one interview. Descriptive statistics were used to describe the findings of the study. Comparison for categorical data was done using Fisher exact test or chi-square test (whichever was applicable). Results A total of 82 residents with mean (SD) age of 27 (2.5) years (range 23-37 years) participated in the study. Only 31 (37.8%) had ever received training for breaking bad news, though 80 (97.6%) had broken bad news at least once. Twenty-one (26.3%) participants had a bad experience while breaking bad news. Seventy-seven (93.9%) participants felt the need for training in breaking bad news and 76 of them were willing to attend the same. Although the complete SPIKES protocol was followed only by 25 (31.3%) residents, 46 (56.1%) felt that it was practically possible to follow the SPIKES protocol. Conclusion Resident doctors in general surgery face situations of breaking bad news and adherence to the SPIKES protocol is poor. Formal training at every level may enhance their communication skills and enable better healthcare delivery.

Awareness about breast cancer in first-year junior residents at a tertiary care institute in India: A cross-sectional study.

BACKGROUND: Primary physicians have a very important role in identifying early breast cancer, as well as promotion of awareness about breast cancer to general public. However, there is insufficient data about the knowledge of doctors, who have just finished their basic medical training, on breast cancer. METHODS: All the postgraduate residents who had joined within the last 3 months, irrespective of the department, were invited to take part in the study. After explaining the aims of the study telephonically, consent was taken through online signatures and the participants were asked to fill online proformas. Descriptive statistics were used, and chi-square test was used to compare groups. P value of less than 0.05 was considered as significant. RESULTS: A total of 106 participants took part in the study. Only 63 (59.4%) participants had satisfactory knowledge about the warning signs of breast cancer. Apart from question of ideal frequency of breast examination, which was answered by 59 (55.7%) participants, the rest of the questions were answered correctly by less than 50% of participants. On the questions on risk factors, 102 (96.5%) of the participants were assessed to have adequate knowledge. Overall only 51 (48.1%) participants were assessed to have satisfactory knowledge about warning signs, screening and risk factors related to breast cancer. CONCLUSIONS: The awareness about warning signs, risk factors and screening practices of breast cancer in newly joined residents was less than satisfactory. To improve this level of awareness, significant steps are needed at the level of undergraduate teaching.

A Novel Approach for Pathway Analysis of GWAS Data Highlights Role of BMP Signaling and Muscle Cell Differentiation in Colorectal Cancer Susceptibility - Erratum.

The publishers regret to announce that the affiliation for the above paper was incorrectly inserted. The correct affiliation is below: Aniket Mishra1, Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO) and the Colorectal Cancer Family Registry (CCFR), and Stuart MacGregor1 1 Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

A Novel Approach for Pathway Analysis of GWAS Data Highlights Role of BMP Signaling and Muscle Cell Differentiation in Colorectal Cancer Susceptibility.

Genome-wide association studies (GWAS) have revolutionized the field of gene mapping. As the GWAS field matures, it is becoming clear that for many complex traits, a proportion of the missing heritability is attributable to common variants of individually small effect. Detecting these small effects individually can be difficult, and statistical power would be increased if relevant variants could be grouped together for testing. Here, we propose a VEGAS2Pathway approach that aggregates association strength of individual markers into pre-specified biological pathways. It accounts for gene size and linkage disequilibrium between markers using simulations from the multivariate normal distribution. Pathway size is taken into account via a resampling approach. Importantly, since the approach only requires summary data, the method can easily be applied in all GWASs, including meta-analysis, singleton-based, family-based, and DNA-pooling-based designs. This approach is implemented in a user-friendly web page https://vegas2.qimrberghofer.edu.au and a command line tool. The web implementation uses gene-sets from the gene ontology (GO), curated gene-sets from MSigDB (containing canonical pathways and gene-sets from BIOCARTA, REACTOME, KEGG databases), PANTHER, and pathway commons databases, enabling analysis of a wide range of complex traits. We applied this method on a colorectal cancer GWAS meta-analysis data set (10,934 cases, 12,328 controls) from the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). We report statistically significant enrichment of association signal for the 'BMP signaling' and 'muscle cell differentiation' pathways, suggesting a possible role for these pathways onto the risk of colorectal cancer.

Chronic gastroesophageal reflux disease shares genetic background with esophageal adenocarcinoma and Barrett's esophagus.

Esophageal adenocarcinoma (EA) is a rapidly fatal cancer with rising incidence in the developed world. Most EAs arise in a metaplastic epithelium, Barrett's esophagus (BE), which is associated with greatly increased risk of EA. One of the key risk factors for both BE and EA is chronic gastroesophageal reflux disease (GERD). This study used the linkage disequilibrium (LD) score regression and genomic profile risk scoring approaches to investigate the contribution of multiple common single-nucleotide polymorphisms (SNPs) to the risk of GERD, and the extent of genetic overlap between GERD and BE or EA. Using LD score regression, we estimated an overall phenotypic variance of 7% (95% CI 3-11%) for GERD explained by all the genotyped SNPs. A genetic correlation of 77% (s.e. = 24%, P = 0.0012) between GERD and BE and 88% between GERD and EA (s.e. = 25%, P = 0.0004) was estimated using the LD score regression approach. Results from the genomic profile risk scoring approach, as a robustness check, were broadly similar to those from the LD score regression. This study provides the first evidence for a polygenic basis for GERD and supports for a polygenic overlap between GERD and BE, and GERD and EA.