Age-specific incidence of cancer: Phases, transitions, and biological implications.

Abstract:

:The observation that the age-specific incidence curve of many carcinomas is approximately linear on a double logarithmic plot has led to much speculation regarding the number and nature of the critical events involved in carcinogenesis. By a consideration of colorectal and pancreatic cancers in the Surveillance Epidemiology and End Results (SEER) registry we show that the log-log model provides a poor description of the data, and that a much better description is provided by a multistage model that predicts two basic phases in the age-specific incidence curves, a first exponential phase until the age of approximately 60 followed by a linear phase after that age. These two phases in the incidence curve reflect two phases in the process of carcinogenesis. Paradoxically, the early-exponential phase reflects events between the formation (initiation) of premalignant clones in a tissue and the clinical detection of a malignant tumor, whereas the linear phase reflects events leading to initiated cells that give rise to premalignant lesions because of abrogated growth/differentiation control. This model is consistent with Knudson's idea that renewal tissue, such as the colon, is converted into growing tissue before malignant transformation. The linear phase of the age-specific incidence curve represents this conversion, which is the result of recessive inactivation of a gatekeeper gene, such as the APC gene in the colon and the CDKN2A gene in the pancreas.

authors

Meza R,Jeon J,Moolgavkar SH,Luebeck EG

doi

10.1073/pnas.0801151105

subject

Has Abstract

pub_date

2008-10-21 00:00:00

pages

16284-9

issue

42

eissn

0027-8424

issn

1091-6490

pii

0801151105

journal_volume

105

pub_type

杂志文章
  • Active contractility in actomyosin networks.

    abstract::Contractile forces are essential for many developmental processes involving cell shape change and tissue deformation. Recent experiments on reconstituted actomyosin networks, the major component of the contractile machinery, have shown that active contractility occurs above a threshold motor concentration and within a...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1204205109

    authors: Wang S,Wolynes PG

    更新日期:2012-04-24 00:00:00

  • Noncanonical Wnt signaling mediates androgen-dependent tumor growth in a mouse model of prostate cancer.

    abstract::Prostate cancer development is associated with hyperactive androgen signaling. However, the molecular link between androgen receptor (AR) function and humoral factors remains elusive. A prostate cancer mouse model was generated by selectively mutating the AR threonine 877 into alanine in prostatic epithelial cells thr...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1014850108

    authors: Takahashi S,Watanabe T,Okada M,Inoue K,Ueda T,Takada I,Watabe T,Yamamoto Y,Fukuda T,Nakamura T,Akimoto C,Fujimura T,Hoshino M,Imai Y,Metzger D,Miyazono K,Minami Y,Chambon P,Kitamura T,Matsumoto T,Kato S

    更新日期:2011-03-22 00:00:00

  • Scale-free, programmable design of morphable chain loops of kilobots and colloidal motors.

    abstract::Micron-scale robots require systems that can morph into arbitrary target configurations controlled by external agents such as heat, light, electricity, and chemical environment. Achieving this behavior using conventional approaches is challenging because the available materials at these scales are not programmable lik...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1922635117

    authors: Agrawal M,Glotzer SC

    更新日期:2020-04-21 00:00:00

  • 3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase.

    abstract::We have shown that 3-nitropropionate, an isoelectronic analogue of succinate, is a suicide inactivator of succinate dehydrogenase [succinate:(acceptor) oxidoreductase, EC 1.3.99.1] as follows. (i) When rat liver mitochondria oxidize succinate in the presence of 3-nitropropionate carbanion, the rate of O(2) consumption...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.74.9.3767

    authors: Alston TA,Mela L,Bright HJ

    更新日期:1977-09-01 00:00:00

  • Interaction of the yeast Swi4 and Swi6 cell cycle regulatory proteins in vitro.

    abstract::In budding yeast, two transcription factors, Swi4 and Swi6, control the expression of important cell cycle regulatory proteins (the G1 cyclins, Cln1 and Cln2, and the cyclin-like Hcs26) as well as the HO gene, whose product initiates mating-type switching. Both Swi4 and Swi6 are components of a protein complex that fo...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.89.24.11852

    authors: Andrews BJ,Moore LA

    更新日期:1992-12-15 00:00:00

  • Structure and assembly of an augmented Sm-like archaeal protein 14-mer.

    abstract::To better understand the roles of Sm proteins in forming the cores of many RNA-processing ribonucleoproteins, we determined the crystal structure of an atypical Sm-like archaeal protein (SmAP3) in which the conserved Sm domain is augmented by a previously uncharacterized, mixed alpha/beta C-terminal domain. The struct...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0538042100

    authors: Mura C,Phillips M,Kozhukhovsky A,Eisenberg D

    更新日期:2003-04-15 00:00:00

  • The karrikin signaling regulator SMAX1 controls Lotus japonicus root and root hair development by suppressing ethylene biosynthesis.

    abstract::An evolutionarily ancient plant hormone receptor complex comprising the α/β-fold hydrolase receptor KARRIKIN INSENSITIVE 2 (KAI2) and the F-box protein MORE AXILLARY GROWTH 2 (MAX2) mediates a range of developmental responses to smoke-derived butenolides called karrikins (KARs) and to yet elusive endogenous KAI2 ligan...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2006111117

    authors: Carbonnel S,Das D,Varshney K,Kolodziej MC,Villaécija-Aguilar JA,Gutjahr C

    更新日期:2020-09-01 00:00:00

  • Direct and adaptor-mediated substrate recognition by an essential AAA+ protease.

    abstract::Regulated proteolysis is required to execute many cellular programs. In Caulobacter crescentus, timely degradation of the master regulator CtrA by ClpXP protease is essential for cell-cycle progression and requires the colocalization of CtrA and RcdA. Here, we establish a biochemical framework to understand regulated ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0701776104

    authors: Chien P,Perchuk BS,Laub MT,Sauer RT,Baker TA

    更新日期:2007-04-17 00:00:00

  • Molecular evidence for ecological speciation in tropical habitats.

    abstract::Recent research on rainforest speciation has highlighted the importance of habitat variation in generating population diversification but lacks evidence of an associated reduction in gene flow. This paper describes a study in which molecular markers were used to examine the effects of allopatric divergence and habitat...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.212248499

    authors: Ogden R,Thorpe RS

    更新日期:2002-10-15 00:00:00

  • Rapid elimination of mature autoreactive B cells demonstrated by Cre-induced change in B cell antigen receptor specificity in vivo.

    abstract::Developing autoreactive B cells edit their B cell antigen receptor (BCR) in the bone marrow and are clonally deleted when they fail to reexpress an innocent BCR. Here, inducible Cre-loxP-mediated gene inversion is used to change the specificity of the BCR on mature IgM+ IgD+ B cells in vivo to address the fate of lymp...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.95.22.13171

    authors: Lam KP,Rajewsky K

    更新日期:1998-10-27 00:00:00

  • Adenovirus-vectored vaccine containing multidimensionally conserved parts of the HIV proteome is immunogenic in rhesus macaques.

    abstract::An effective vaccine that can protect against HIV infection does not exist. A major reason why a vaccine is not available is the high mutability of the virus, which enables it to evolve mutations that can evade human immune responses. This challenge is exacerbated by the ability of the virus to evolve compensatory mut...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2022496118

    authors: Murakowski DK,Barton JP,Peter L,Chandrashekar A,Bondzie E,Gao A,Barouch DH,Chakraborty AK

    更新日期:2021-02-02 00:00:00

  • Multiple functional variants in long-range enhancer elements contribute to the risk of SNP rs965513 in thyroid cancer.

    abstract::The [A] allele of SNP rs965513 in 9q22 has been consistently shown to be highly associated with increased papillary thyroid cancer (PTC) risk with an odds ratio of ∼1.8 as determined by genome-wide association studies, yet the molecular mechanisms remain poorly understood. Previously, we noted that the expression of t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1506255112

    authors: He H,Li W,Liyanarachchi S,Srinivas M,Wang Y,Akagi K,Wang Y,Wu D,Wang Q,Jin V,Symer DE,Shen R,Phay J,Nagy R,de la Chapelle A

    更新日期:2015-05-12 00:00:00

  • Insertion site preferences of the P transposable element in Drosophila melanogaster.

    abstract::We determined the genomic sequence at the site of insertion in 2,266 unselected P element insertion events. Estimating physical properties of the genomic DNA at these insertion sites-such as base composition, bendability, A-philicity, protein-induced deformability, and B-DNA twist-revealed that they differ significant...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.050017397

    authors: Liao GC,Rehm EJ,Rubin GM

    更新日期:2000-03-28 00:00:00

  • Control of A-system amino acid transport by a second regulatory gene R2 in Chinese hamster ovary cells CHO-K1 and the possible connection of this gene with insulin activity.

    abstract::Evidence based on a study of alanine-resistant (Alar), constitutive mutants of CHO-K1 cells and the conditions that favor stimulation of the A system of amino acid activity supports the model that the A system of amino acid transport in these cells is repressible and under negative control of regulatory gene R1. In th...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.22.8040

    authors: Moffett J,Périer F,Jones M,Englesberg E

    更新日期:1987-11-01 00:00:00

  • Acquired copy number alterations in adult acute myeloid leukemia genomes.

    abstract::Cytogenetic analysis of acute myeloid leukemia (AML) cells has accelerated the identification of genes important for AML pathogenesis. To complement cytogenetic studies and to identify genes altered in AML genomes, we performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult pa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0903091106

    authors: Walter MJ,Payton JE,Ries RE,Shannon WD,Deshmukh H,Zhao Y,Baty J,Heath S,Westervelt P,Watson MA,Tomasson MH,Nagarajan R,O'Gara BP,Bloomfield CD,Mrózek K,Selzer RR,Richmond TA,Kitzman J,Geoghegan J,Eis PS,Maupin R,

    更新日期:2009-08-04 00:00:00

  • New forms of bovine carboxypeptidase B and their homologous relationships to carboxypeptidase A.

    abstract::Two new forms of carboxypeptidase B have been isolated from spontaneously activated bovine pancreatic juice. The fully active enzymes contain an internal split at residues 92-93 and 95-96, respectively. Sequenator analysis of the amino terminal segments of the two chains of the enzyme has extended the sequence informa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.68.6.1226

    authors: Reeck GR,Walsh KA,Hermodson MA,Neurath H

    更新日期:1971-06-01 00:00:00

  • Impaired attentional selection following lesions to human pulvinar: evidence for homology between human and monkey.

    abstract::We examined the contributions of the human pulvinar to goal directed selection of visual targets in 3 patients with chronic, unilateral lesions involving topographic maps in the ventral pulvinar. Observers completed 2 psychophysical tasks in which they discriminated the orientation of a lateralized target grating in t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.0810086106

    authors: Snow JC,Allen HA,Rafal RD,Humphreys GW

    更新日期:2009-03-10 00:00:00

  • A quantitative analysis of the kinetics of the G(2) DNA damage checkpoint system.

    abstract::A detailed model of the G(2) DNA damage checkpoint (G2DDC) system is presented that includes complex regulatory networks of the mitotic kinase Cdc2, phosphatase Cdc25, Wee1 kinase, and damage signal transduction pathways involving Chk1 and p53. Assumptions on the kinetic equations of the G2DDC are made, and computer s...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.20.11352

    authors: Aguda BD

    更新日期:1999-09-28 00:00:00

  • Physical interaction between VIVID and white collar complex regulates photoadaptation in Neurospora.

    abstract::Photoadaptation, the ability to attenuate a light response on prolonged light exposure while remaining sensitive to escalating changes in light intensity, is essential for organisms to decipher time information appropriately, yet the underlying molecular mechanisms are poorly understood. In Neurospora crassa, VIVID (V...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1011190107

    authors: Chen CH,DeMay BS,Gladfelter AS,Dunlap JC,Loros JJ

    更新日期:2010-09-21 00:00:00

  • ATRIP associates with replication protein A-coated ssDNA through multiple interactions.

    abstract::The ATR (ATM- and rad3-related)-mediated checkpoint pathway has a crucial role in regulating the cellular responses to DNA damage and DNA-replication stress. ATRIP (ATR-interacting protein), the regulatory partner of ATR, binds directly to replication protein A (RPA)-coated ssDNA and enables the ATR-ATRIP complex to r...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0510223103

    authors: Namiki Y,Zou L

    更新日期:2006-01-17 00:00:00

  • Influence of general anesthetics on a specific neural pathway in Drosophila melanogaster.

    abstract::The neural pathway that governs an escape response of Drosophila to sudden changes in light intensity can be artificially induced by electrical stimulation of the brain and monitored by electrical recording from the effector muscles. We have refined previous work in this system to permit reliable ascertainment of two ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.19.10446

    authors: Lin M,Nash HA

    更新日期:1996-09-17 00:00:00

  • Loss of Arc attenuates the behavioral and molecular responses for sleep homeostasis in mice.

    abstract::The activity-regulated cytoskeleton-associated protein (Arc) gene is a neural immediate early gene that is involved in synaptic downscaling and is robustly induced by prolonged wakefulness in rodent brains. Converging evidence has led to the hypothesis that wakefulness potentiates, and sleep reduces, synaptic strength...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1906840117

    authors: Suzuki A,Yanagisawa M,Greene RW

    更新日期:2020-05-12 00:00:00

  • Neural correlates of the psychedelic state as determined by fMRI studies with psilocybin.

    abstract::Psychedelic drugs have a long history of use in healing ceremonies, but despite renewed interest in their therapeutic potential, we continue to know very little about how they work in the brain. Here we used psilocybin, a classic psychedelic found in magic mushrooms, and a task-free functional MRI (fMRI) protocol desi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 临床试验,杂志文章

    doi:10.1073/pnas.1119598109

    authors: Carhart-Harris RL,Erritzoe D,Williams T,Stone JM,Reed LJ,Colasanti A,Tyacke RJ,Leech R,Malizia AL,Murphy K,Hobden P,Evans J,Feilding A,Wise RG,Nutt DJ

    更新日期:2012-02-07 00:00:00

  • Linkage disequilibrium matches forensic genetic records to disjoint genomic marker sets.

    abstract::Combining genotypes across datasets is central in facilitating advances in genetics. Data aggregation efforts often face the challenge of record matching-the identification of dataset entries that represent the same individual. We show that records can be matched across genotype datasets that have no shared markers ba...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1619944114

    authors: Edge MD,Algee-Hewitt BFB,Pemberton TJ,Li JZ,Rosenberg NA

    更新日期:2017-05-30 00:00:00

  • Analysis of barotactic and chemotactic guidance cues on directional decision-making of Dictyostelium discoideum cells in confined environments.

    abstract::Neutrophils and dendritic cells when migrating in confined environments have been shown to actuate a directional choice toward paths of least hydraulic resistance (barotaxis), in some cases overriding chemotactic responses. Here, we investigate whether this barotactic response is conserved in the more primitive model ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.2000686117

    authors: Belotti Y,McGloin D,Weijer CJ

    更新日期:2020-10-13 00:00:00

  • Brain G protein gamma subunits contain an all-trans-geranylgeranylcysteine methyl ester at their carboxyl termini.

    abstract::We have shown previously that guanine nucleotide-binding protein (G protein) beta gamma complexes purified from bovine brain membranes are methyl esterified on a C-terminal cysteine residue of the gamma polypeptide. In the present study, 3H-methylated G beta gamma complexes cleaved to their constituent amino acids by ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.15.5868

    authors: Yamane HK,Farnsworth CC,Xie HY,Howald W,Fung BK,Clarke S,Gelb MH,Glomset JA

    更新日期:1990-08-01 00:00:00

  • Serum half-life and tumor localization of a chimeric antibody deleted of the CH2 domain and directed against the disialoganglioside GD2.

    abstract::Recombinant techniques allow one to engineer an antibody molecule and, in this way, manipulate its properties and functions. We engineered a chimeric human/mouse antibody to the tumor-associated antigen ganglioside GD2, with the aim of decreasing its serum half-life, maintaining its full antigen-binding capacity, and ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.87.15.5702

    authors: Mueller BM,Reisfeld RA,Gillies SD

    更新日期:1990-08-01 00:00:00

  • Pre-steady-state DNA unwinding by bacteriophage T4 Dda helicase reveals a monomeric molecular motor.

    abstract::Helicases are molecular motor enzymes that unwind and translocate nucleic acids. One of the central questions regarding helicase activity is whether the process of coupling ATP hydrolysis to DNA unwinding requires an oligomeric form of the enzyme. We have applied a pre-steady-state kinetics approach to address this qu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.232401899

    authors: Nanduri B,Byrd AK,Eoff RL,Tackett AJ,Raney KD

    更新日期:2002-11-12 00:00:00

  • Herpes simplex virus 1 infected cell protein 0 forms a complex with CIN85 and Cbl and mediates the degradation of EGF receptor from cell surfaces.

    abstract::Infected cell protein 0 (ICP0) is a 775-residue multifunctional herpes simplex virus protein associated with numerous functions related to transactivation of gene expression and repression of host defenses to infection. We report that an uncharted domain of ICP0 located between residues 245 and 510 contains multiple S...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0501253102

    authors: Liang Y,Kurakin A,Roizman B

    更新日期:2005-04-19 00:00:00

  • Cardioprotection from ischemia by a brief exposure to physiological levels of ethanol: role of epsilon protein kinase C.

    abstract::Recent epidemiological studies indicate beneficial effects of moderate ethanol consumption in ischemic heart disease. Most studies, however, focus on the effect of long-term consumption of ethanol. In this study, we determined whether brief exposure to ethanol immediately before ischemia also produces cardioprotection...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.22.12784

    authors: Chen CH,Gray MO,Mochly-Rosen D

    更新日期:1999-10-26 00:00:00