This article provides an update on the global cancer burden using the GLOBOCAN 2020 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer. Worldwide, an estimated 19.3 million new cancer cases (18.1 million excluding nonmelanoma skin cancer) and almost 10.0 million cancer deaths (9.9 million excluding nonmelanoma skin cancer) occurred in 2020. Female breast cancer has surpassed lung cancer as the most commonly diagnosed cancer, with an estimated 2.3 million new cases (11.7%), followed by lung (11.4%), colorectal (10.0 %), prostate (7.3%), and stomach (5.6%) cancers. Lung cancer remained the leading cause of cancer death, with an estimated 1.8 million deaths (18%), followed by colorectal (9.4%), liver (8.3%), stomach (7.7%), and female breast (6.9%) cancers. Overall incidence was from 2-fold to 3-fold higher in transitioned versus transitioning countries for both sexes, whereas mortality varied <2-fold for men and little for women. Death rates for female breast and cervical cancers, however, were considerably higher in transitioning versus transitioned countries (15.0 vs 12.8 per 100,000 and 12.4 vs 5.2 per 100,000, respectively). The global cancer burden is expected to be 28.4 million cases in 2040, a 47% rise from 2020, with a larger increase in transitioning (64% to 95%) versus transitioned (32% to 56%) countries due to demographic changes, although this may be further exacerbated by increasing risk factors associated with globalization and a growing economy. Efforts to build a sustainable infrastructure for the dissemination of cancer prevention measures and provision of cancer care in transitioning countries is critical for global cancer control.

https://acsjournals.onlinelibrary.wiley.com/doi/pdf/10.3322/caac.21660

Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries.

Next-generation DNA sequencing (NGS) projects, such as the 1000 Genomes Project, are already revolutionizing our understanding of genetic variation among individuals. However, the massive data sets generated by NGS—the 1000 Genome pilot alone includes nearly five terabases—make writing feature-rich, efficient, and robust analysis tools difficult for even computationally sophisticated individuals. Indeed, many professionals are limited in the scope and the ease with which they can answer scientific questions by the complexity of accessing and manipulating the data produced by these machines. Here, we discuss our Genome Analysis Toolkit (GATK), a structured programming framework designed to ease the development of efficient and robust analysis tools for next-generation DNA sequencers using the functional programming philosophy of MapReduce. The GATK provides a small but rich set of data access patterns that encompass the majority of analysis tool needs. Separating specific analysis calculations from common data management infrastructure enables us to optimize the GATK framework for correctness, stability, and CPU and memory efficiency and to enable distributed and shared memory parallelization. We highlight the capabilities of the GATK by describing the implementation and application of robust, scale-tolerant tools like coverage calculators and single nucleotide polymorphism (SNP) calling. We conclude that the GATK programming framework enables developers and analysts to quickly and easily write efficient and robust NGS tools, many of which have already been incorporated into large-scale sequencing projects like the 1000 Genomes Project and The Cancer Genome Atlas.

/pdf/the-genome-analysis-toolkit-a-mapreduce-framework-for-4aygfa9b66.pdf

The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data

Summary: Research over the last few years has revealed significant haplotype structure in the human genome. The characterization of these patterns, particularly in the context of medical genetic association studies, is becoming a routine research activity. Haploview is a software package that provides computation of linkage disequilibrium statistics and population haplotype patterns from primary genotype data in a visually appealing and interactive interface.

Availability: http://www.broad.mit.edu/mpg/haploview/

Contact: jcbarret@broad.mit.edu

/pdf/haploview-analysis-and-visualization-of-ld-and-haplotype-1p9iyir38a.pdf

Haploview: analysis and visualization of LD and haplotype maps

Motivation: DnaSP is a software package for a comprehensive analysis of DNA polymorphism data. Version 5 implements a number of new features and analytical methods allowing extensive DNA polymorphism analyses on large datasets. Among other features, the newly implemented methods allow for: (i) analyses on multiple data files; (ii) haplotype phasing; (iii) analyses on insertion/deletion polymorphism data; (iv) visualizing sliding window results integrated with available genome annotations in the UCSC browser.

Availability: Freely available to academic users from: http://www.ub.edu/dnasp

Contact: [email protected]

DnaSP v5

The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations. Here we report completion of the project, having reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-genome sequencing, deep exome sequencing, and dense microarray genotyping. We characterized a broad spectrum of genetic variation, in total over 88 million variants (84.7 million single nucleotide polymorphisms (SNPs), 3.6 million short insertions/deletions (indels), and 60,000 structural variants), all phased onto high-quality haplotypes. This resource includes >99% of SNP variants with a frequency of >1% for a variety of ancestries. We describe the distribution of genetic variation across the global sample, and discuss the implications for common disease studies.

https://cdr.lib.unc.edu/downloads/v692t8920

A global reference for human genetic variation.

We thank Kranendonk and colleagues for their interest in the treatment of facial flushing. It is unfortunate that their patient experienced muscle paralysis after treatment with 8 U of botulinum toxin given in 2 U increments in four injections 1 cm apart on the right midcheek. On examination of the photograph, it appears that the levator labii superioris muscle is involved because their patient is unable to raise the middle third of the right side of the lip (above the canine) and the zygomatic muscles (seen by blunting of the modiolus). The levator labii superioris muscle is located in the right midcheek, medial to the zygomaticus minor muscle. Their patient may have developed the paralysis if the injections were placed deeper than anticipated, or the paralysis may be due to the fact that 2 U were placed in each site. In our patient, 10 injection sites were performed of 0.05 cc (1 U each) distributed evenly over the cheek extending from the malar prominence, down to the midcheek (but above the modiolus), and lateral to cover the area of prominent flushing. Our patient has had the procedure repeated four times, with no loss of muscle function. In addition, I have treated five other patients in a similar manner, on one side of the cheek only, and none have experienced any facial muscle weakness. These patients were followed every 4 weeks for 14 to 22 weeks. The authors who treated Frey’s syndrome likely stayed within the borders of the parotid gland because Frey’s syndrome is due to damage to parasympathetic salivary nerve fibers of the auriculotemporal nerve located at the parotid gland.1 In this syndrome, the regenerating cholinergic nerve fibers make contact with the sweat glands on the cheek, causing paradoxical sweating on the cheek when eating. The efficacy of this treatment for facial flushing has yet to be determined in a large-scale study. The mechanisms by which it may occur are speculative but have been partially elucidated. The vasoconstriction may be related to inhibition of release of vasoactive intestinal peptide (VIP), calcitonin gene–related peptide (CGRP), or other neuropeptides contained in presynaptic vesicles. Acetylcholine, catecholamine, VIP, atrial natriuretic peptide, CGRP, galanin, and adenosine triphosphate have been localized in the periglandular nerves. Their significance on sweat gland function is not known. CGRP, VIP, and substance P are all potent vasodilators. CGRP and substance P increase nitrite formation through increasing nitric oxide synthase (constitutively expressed on endothelial cells in the microvasculature of the human dermis).2 Nitric oxide is a potent mediator of endothelium-dependent vasodilation. CGRP and VIP (but not substance P) are cotransmitters in the sudomotor nerve terminals.3 When the release of acetylcholine is blocked from the sudomotor nerve terminals by botulinum toxin, the release of CGRP and VIP is blocked as well.4 Therefore, blockage of release of vasodilators may lead to a comparative vasoconstriction. These clinical results have been noted by experts in the field of botulinum. Carruthers and Carruthers noted that patients treated with both broadband light treatments and botulinum toxin A (BTX-A) chemodenervation had greater improvement in telangiectasias than those with broadband light treatments alone.5 Makowichuk and Carruthers noted this phenomenon when BTX-A injections were used in the treatment of facial hyperkinetic lines (personal communication, July 2001). In addition, Carl Swartling, MD, noted that his patients treated with BTXA for palmar hyperhidrosis experienced mild blanching of the treated palm (personal communication, August 2003). Dr. Andrew Roberts has noted that BTX-A is suitable for emotional blushing (personal communication, July 2003). Whether these clinical phenomena are consistently reproducible remains to be seen. It may be that the patients with severe telangiectasia at rest are better candidates for KTP or broadband light therapy to reduce the permanently dilated vessels, followed by botulinum toxin for the reduction of further facial flushing.

/pdf/reply-to-kranendonk-et-al-1mowhv3e14.pdf

Reply to Kranendonk et al.

Individuals with proven hereditary cancer syndrome (HCS) such as BRCA1 and BRCA2 have elevated rates of ovarian, breast, and other cancers. If these high-risk people can be identified before a cancer is diagnosed, risk-reducing interventions are highly effective and can be lifesaving. Despite this evidence, the vast majority of Canadians with HCS are unaware of their risk. In response to this unmet opportunity for prevention, the British Columbia Gynecologic Cancer Initiative convened a research summit “Gynecologic Cancer Prevention: Thinking Big, Thinking Differently” in Vancouver, Canada on 26 November 2021. The aim of the conference was to explore how hereditary cancer prevention via population-based genetic testing could decrease morbidity and mortality from gynecologic cancer. The summit invited local, national, and international experts to (1) discuss how genetic testing could be more broadly implemented in a Canadian system, (2) identify key research priorities in this topic and (3) outline the core essential elements required for such a program to be successful. This report summarizes the findings from this research summit, describes the current state of hereditary genetic programs in Canada, and outlines incremental steps that can be taken to improve prevention for high-risk Canadians now while developing an organized population-based hereditary cancer strategy.

/pdf/gynecologic-cancer-risk-and-genetics-informing-an-ideal-26268e0e.pdf

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention

Prenatal and Preimplantation Diagnosis: International Policy Perspectives

éthique Et juridique spécifique nécessaire

We appreciate the comments provided by C Harling on our published article1 describing the existing legal approaches regarding the rights of minors to consent to healthcare interventions, including how laws in the 28 member states of the European Union and in Canada consider competent minors We agree with the nuances provided by C Harling We understand that England and Wales have a mixed approach, where the age for capacity to consent to healthcare interventions is fixed at 16, but younger patients who, in the view of the treating physician, have sufficient maturity and intelligence to understand fully what is proposed can also provide consent (Gillick competence) As a matter of fact, this nuance was clearly included in the Supplementary Information that accompanies our manuscript, and is available online at http://wwwnaturecom/ejhg/journal/v24/n11/suppinfo/ejhg201661s1html

Bartha Maria Knoppers

Papers

Reply to Kranendonk et al.

Gynecologic Cancer Risk and Genetics: Informing an Ideal Model of Gynecologic Cancer Prevention

Prenatal and Preimplantation Diagnosis: International Policy Perspectives

éthique Et juridique spécifique nécessaire

Reply to C Harling.