Telomerase reverse transcriptase locus polymorphisms and cancer risk: a field synopsis and meta-analysis
Simone Mocellin1, Daunia Verdi, Karen A Pooley
1Department of Oncological and Surgical Sciences, Meta-analysis Unit, University of Padova, Padova, Italy. simone.mocellin@unipd.it
Journal of the National Cancer Institute
|April 24, 2012
Summary
Genetic variations in the telomerase reverse transcriptase (TERT) gene locus are linked to cancer risk. This large-scale meta-analysis confirms TERT polymorphisms significantly influence human cancer susceptibility.
Area of Science:
- Molecular epidemiology
- Genetics of cancer
Background:
- Polymorphisms in the telomerase reverse transcriptase (TERT) gene are implicated in cancer development.
- A comprehensive overview of these associations is lacking.
Purpose of the Study:
- To systematically review and meta-analyze molecular epidemiology data on TERT locus polymorphisms and cancer predisposition.
- To assess the strength of evidence for these associations.
Main Methods:
- Systematic literature search of multiple databases (PubMed, Embase, etc.).
- Random-effects meta-analysis of TERT and CLPTM1L polymorphisms and cancer risk.
- Assessment of heterogeneity, bias, and cumulative evidence using Venice criteria.
Main Results:
- Analysis of 85 studies with 490,901 subjects and 494 allelic contrasts.
- Statistically significant associations found for 22 TERT locus polymorphisms across 24 tumor types.
- Strong evidence for association with lung cancer risk for TERT rs2736100, rs4635969, and CLPTM1L rs402710 (41% joint population attributable risk).
Conclusions:
- This is the most extensive data compilation on TERT locus polymorphisms and cancer risk to date.
- Genetic variability within the TERT locus significantly modulates human cancer susceptibility.
Related Concept Videos
03:18Non-LTR Retrotransposons
As the name suggests, non-LTR retrotransposons lack the long terminal repeats characteristic of the LTR retrotransposons. Additionally, both LTR and non-LTR retrotransposons use distinct mechanisms of mobilization. Non-LTR retrotransposons are further divided into two classes - Long interspersed nuclear elements (LINEs) and short interspersed nuclear elements (SINEs), both of which occur abundantly in most mammals, including humans. Some of the active non-LTR retrotransposons in humans are L1...
02:41Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
02:41Telomeres and Telomerase
In eukaryotic DNA replication, a single-stranded DNA fragment remains at the end of a chromosome after the removal of the final primer. This section of DNA cannot be replicated in the same manner as the rest of the strand because there is no 3’ end to which the newly synthesized DNA can attach. This non-replicated fragment results in gradual loss of the chromosomal DNA during each cell duplication. Additionally, it can induce a DNA damage response by enzymes that recognize single-stranded DNA.
02:15Replicative Cell Senescence
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds the telomeric...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:33Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...