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.

Stem cell banks are increasingly recognized as an essential resource of biological materials for both basic and translational stem cell research. By providing transnational access to quality controlled and ethically sourced stem cell lines, stem cell banks seek to foster international collaboration and innovation. However, given that national stem cell banks operate under different policy, regulatory and commercial frameworks, the transnational sharing of stem cell materials and data can be complicating. This paper will provide an overview of the most pressing challenges regarding the governance of stem cell banks, and the difficulties in designing regulatory and commercial frameworks that foster stem cell research. Moreover, the paper will shed light on the numerous international initiatives that have arisen to help harmonize and standardize stem cell banking and research processes to overcome such challenges.

/pdf/from-banking-to-international-governance-fostering-4i0j4abq82.pdf

From Banking to International Governance: Fostering Innovation in Stem Cell Research

Laws in the 20 jurisdictions studied for this project display many similar approaches to protecting privacy in biobank research. Although few have enacted biobank-specific legislation, many countries address biobanking within other laws. All provide for some oversight mechanisms for biobank research, even though the nature of that oversight varies between jurisdictions. Most have some sort of controlled access system in place for research with biobank specimens. While broad consent models facilitate biobanking, countries without national or federated biobanks have been slow to adopt broad consent. International guidelines have facilitated sharing and generally take a proportional risk approach, but many countries have provisions guiding international sharing and a few even limit international sharing. Although privacy laws may not prohibit international collaborations, the multi-prong approach to privacy unique to each jurisdiction can complicate international sharing. These symposium issues can serve as a resource for explaining the sometimes intricate privacy laws in each studied jurisdiction, outlining the key issues with regards to privacy and biobanking, and serving to describe a framework for the process of harmonization of privacy laws.

Comparative Approaches to Biobanks and Privacy.

Whole-genome sequencing (WGS) technologies analyze genetic variation across the entire range of human genetic material (1–4). With rapidly decreasing costs, WGS may be used for both targeted diagnostic testing (5) and genome-wide searches for the mutations that underlie unexplained disorders (3, 6, 7). It is currently recommended that genetic testing should be as targeted as possible to solve a particular clinical problem (8). If targeted testing fails however, physicians may justifiably ‘trawl’ through the genome for mutations that underlie complex cases of multiple congenital malformation or unexplained intellectual disability (3). The introduction of untargeted WGS for diagnostic testing in the clinic has great potential to improve the range and efficacy of genetic testing. With reference to international ethical guidelines, this article explores how WGS impacts four traditional obligations of physicians: the duty to obtain informed consent, the duty to treat, the duty to follow-up and the duty of professional secrecy.

/pdf/whole-genome-sequencing-and-the-physician-24002fp3ch.pdf

Whole‐genome sequencing and the physician

1. Background Information derived from the Human Genome Project (HGP) promises to inspire an array of future innovations with profound societal benefits. (1) Population genetic research is now viewed as a necessary next step in the evolution of research based on the human genome. (2) It is anticipated that projects will be developed in which the DNA from thousands of research subjects will be linked to medical records and to genealogical data; these complex databases will provide much needed insight into the etiology and prevention of many complex human diseases. Analyses of data procured in large-scale population genetic studies will enable researchers to gain a better understanding of the gene-environment interactions that are now implicated in cardiovascular diseases, metabolic disorders, musculoskeletal diseases, neuropsychiatric diseases and cancer. The completion of the sequencing phase of the HGP provides researchers: with an unparalleled opportunity to advance our understanding of the role of genetic factors in human health and disease, to allow more precise definition of the non-genetic factors involved, and to apply this insight rapidly into the prevention, diagnosis and treatment of disease.... [T]he time is right to develop and apply large-scale genomic strategies to empower improvements in human health, while anticipating and avoiding potential harm. (3) The challenge remains to justly translate the potential of the HGP into improved human health and well-being. (4) To facilitate the understanding of gene-environment interactions, numerous large-scale population genetic research studies have been commenced or are in the process of being developed. (5) Prospectively gathered and appropriately stored biological materials coupled with comprehensive measures of environmental exposure, phenotype and genotype will help researchers to confirm or refute existing assumptions about the interrelatedness of these factors. It is hoped that such new knowledge will facilitate the planning of health promotion and disease prevention at the level of populations as well as render adverse drug reactions predictable and avoidable based on an individual's genotype. (6) 1(a) The general concerns However, with this optimism about the long-term potential of population genetic research come numerous ethical, legal and social issues; concerns regarding individual and group consent, (7) ownership of human biologic materials (8), privacy and confidentiality, (9) genetic discrimination and stigmatization (10) and eugenics (11) have been repeatedly raised. Academic researchers focussing on the "ethical, legal and social issues" (ELSI) of the HGP have initiated much debate on these topics. It has been noted that failure to apply the highest ethical standards to population genetic studies could undermine public trust and confidence in scientific development and the products of medical research. (12) Moreover, the increased involvement of the private sector in human genetic and genomic research may promote secrecy amongst researchers, inhibit academic freedom, diminish the collaborative will of researchers and inappropriately shift the focus of research from basic discovery to commercializable end products. (13) 1(b) The particular problem of property Concepts of ownership, values, rights and sharing of knowledge vary from one culture to another, between political systems and between legal systems. These differences have particular relevance to the collection and banking of human biological samples: should they be characterized "person", "property", "sui-generis"--or not at all; should human genes be patentable; what is the legal status of linked and linkable databases? These questions have been imperfectly addressed. For example, no consensus exists as to who owns donated DNA samples. In the present age of globalization, it is important that these fundamental conceptual differences not be ignored. …

Beyond the rhetoric: population genetics and benefit-sharing.

Background: Genomics research is becoming increasingly globally connected and collaborative, contesting traditional ethical and legal boundaries between global and local research practice. As well, global data-driven genomics research holds great promise for health discoveries. Yet, paradoxically, current research ethics review systems around the world challenge potential improvements in human health from such research and thus undermine respect for research participants. Case reports illustrate that the current system is costly, fragmented, inefficient, inadequate, and inconsistent. There is an urgent need to improve the governance system of ethics review to enable secure and seamless genomic and clinical data sharing across jurisdictions. Discussion: Building on the international privacy ‘safe harbor’ model that was developed following the adoption of the European Privacy Directive, we propose an international infrastructure. The goal is to create a streamlined and harmonized ethics governance system for international, data-driven genomics research projects. The proposed ‘Safe Harbor Framework for International Ethics Equivalency’ would consist in part of an agency supporting an International Federation for Ethics Review (IFER), formed by a voluntary agreement among countries, granting agencies, philanthropies, institutions, and healthcare, patient advocacy, and research organizations. IFER would be both a central ethics review body and also a forum for review and follow-up of policies concerning ethics norms for international genomics research projects. It would be built on five principle elements: (1) registration; (2) compliance review; (3) recognition; (4) monitoring and enforcement; and (5) public participation. Summary: A Safe Harbor Framework for International Ethics Equivalency would create many benefits for researchers, countries, and the general public, and may eventually have application beyond genomics to other areas of biomedical research that increasingly engage in secondary use of data and present only negligible risks. Among the benefits, research participants and patients would have uniform adequate protection, while researchers would be ensured expert ethics review with a reduction in cost, time, administrative hassle, and redundant regulatory hurdles. Most importantly, society would enjoy the maximization of the potential benefits of genomics research.

/pdf/an-ethics-safe-harbor-for-international-genomics-research-3qcjv65xs0.pdf

Bartha Maria Knoppers

Papers

From Banking to International Governance: Fostering Innovation in Stem Cell Research

Comparative Approaches to Biobanks and Privacy.

Whole‐genome sequencing and the physician

Beyond the rhetoric: population genetics and benefit-sharing.

An ethics safe harbor for international genomics research