General lessons from large-scale studies to identify human cancer predisposition genes

The Journal of Pathology
Jean-Baptiste Cazier, Ian Tomlinson

Abstract

There are now about 100 genes known to cause Mendelian inherited cancer syndromes, but these only explain a minor part of the familial clustering of the common cancers. The increased familial relative risk of cancer in the general population must largely involve genes of low- or moderate-penetrance. Until recently, attempts to identify cancer predisposition genes with low penetrance had proved similarly unrewarding. However, in the past 2 years, developments in this area have been rapid. In particular, the 'common disease-common variant' model of predisposition has come to the fore. In this model, alleles of high frequency (typically > 10%) and low penetrance (typically < two-fold increased lifetime risk) contribute substantially to susceptibility to the common human diseases, including cancers. Many common risk alleles for cancer have been found by genome-wide association studies (GWASs) in the form of tagging SNPs, although identification of the disease-causing variants generally remains a difficult problem. The 'common disease-common variant' model has recently been criticized by proponents of a 'common disease-rare variant' model. In fact, the conflict between the models is false and a more continuous approach, bounded only...Continue Reading

References

Sep 1, 1997·Nature Genetics·S J LakenB Vogelstein
Aug 7, 2001·Gastroenterology·R S Houlston, I P Tomlinson
Apr 23, 2002·Nature Genetics·Hanne Meijers-HeijboerUNKNOWN CHEK2-Breast Cancer Consortium
Mar 15, 2003·Science·Hengmi CuiAndrew P Feinberg
Dec 19, 2003·American Journal of Human Genetics·Christopher S CarlsonDeborah A Nickerson
Aug 23, 2006·Human Molecular Genetics·Zoe KempUNKNOWN ColoRectal tumour Gene Identification (CoRGI) Study Consortium
Jan 4, 2007·Nature Genetics·Nazneen RahmanMichael R Stratton
Feb 16, 2007·The New England Journal of Medicine·Megan P HitchinsRobyn L Ward
May 30, 2008·Nature Genetics·Walter Bodmer, Carolina Bonilla
Aug 13, 2008·Diabetologia·T M FraylingJ C Florez
Oct 15, 2008·Human Molecular Genetics·Douglas F Easton, Rosalind A Eeles
Oct 15, 2008·Human Molecular Genetics·Steven A McCarroll
Dec 3, 2008·Cancer Research·Dominika WokolorczykCezary Cybulski
Jan 24, 2009·Nature Genetics·Augustine KongKari Stefansson
Apr 17, 2009·The New England Journal of Medicine·David B Goldstein
Apr 17, 2009·The New England Journal of Medicine·Joel N Hirschhorn
Apr 28, 2009·Genome Research·Alan M PittmanRichard S Houlston
Sep 22, 2009·Nature Genetics·Ali Amin Al OlamaDouglas F Easton

❮ Previous
Next ❯

Citations

Dec 14, 2011·BMC Medical Genetics·Ashley J R Carter, Andrew Q Nguyen
Sep 17, 2010·PloS One·Ceres Fernández-RozadillaUNKNOWN Gastrointestinal Oncology Group of the Spanish Gastroenterological Association
Dec 5, 2009·The Journal of Pathology·Peter A HallRichard Poulsom
Jun 14, 2013·BioMed Research International·Francesco Baudi
Feb 12, 2010·Annals of the New York Academy of Sciences·Peter A Victor
Nov 18, 2009·The Journal of Pathology·Daphne W Bell
Sep 27, 2016·European Journal of Endocrinology·Garcilaso Riesco-Eizaguirre, Pilar Santisteban
Feb 28, 2019·Frontiers in Endocrinology·Jeff M P HollyClaire M Perks
Mar 1, 2011·Evolutionary Applications·Bernard J Crespi
Aug 10, 2019·Stress and Health : Journal of the International Society for the Investigation of Stress·Alberto Recio
Dec 2, 2010·Current Opinion in Oncology·Gerd P Pfeifer, Pierre Hainaut
Jun 16, 2010·Journal of the National Cancer Institute·Adi F Gazdar, Paolo Boffetta

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.