MLH1 polymorphisms and cancer risk: a meta-analysis based on 33 case-control studies
Jia-Li Xu1, Zhi-Qiang Yin, Ming-De Huang
1Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Asian Pacific Journal of Cancer Prevention : APJCP
|May 29, 2012
Summary
The MLH1 -93G>A gene variant is linked to increased cancer risk, particularly in non-Asian populations. The MLH1 I219V polymorphism showed no significant association with overall cancer risk in this meta-analysis.
Area of Science:
- Genetics and Oncology
- Molecular Biology
- Cancer Research
Background:
- The MLH1 gene is crucial for DNA mismatch repair, a pathway significant in human cancers.
- Two MLH1 gene polymorphisms, -93G>A and I219V, have been investigated for their potential roles in cancer susceptibility.
Purpose of the Study:
- To conduct a meta-analysis summarizing the evidence on the association between MLH1 polymorphisms (-93G>A and I219V) and cancer risk.
- To evaluate the strength of these associations using quantitative genetic models.
Main Methods:
- A systematic literature search was performed across PubMed, ScienceDirect, and Embase databases.
- Included studies were case-control in design, focusing on MLH1 polymorphisms and cancer risk.
- Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to assess the strength of associations.
Main Results:
- The meta-analysis of 33 studies indicated that the variant A allele of the MLH1 -93G>A polymorphism is associated with an increased cancer risk across all genetic models (AA vs. GG: OR = 1.22, 95% CI: 1.03-1.44).
- This association was particularly pronounced in non-Asian populations (AA vs. GG: OR = 1.28, 95% CI: 1.04-1.58).
- No significant association was found for the MLH1 I219V polymorphism with overall cancer risk in any genetic model.
Conclusions:
- The MLH1 -93G>A polymorphism may serve as a biomarker for cancer susceptibility.
- Further large-scale association studies are needed to confirm these findings.
- Investigating gene-to-gene and gene-to-environment interactions is recommended for a comprehensive understanding.
Related Concept Videos
01:12Hazard Ratio
The hazard ratio (HR) is a widely used measure in clinical trials to compare the risk of events, such as death or disease recurrence, between two groups over time. It reflects the ratio of hazard rates—the instantaneous risk of the event occurring—between a treatment group and a control group. This measure provides valuable insights into the relative effectiveness of a treatment by assessing how the risk of an event differs between the two groups.
For example, in a clinical trial evaluating a...
For example, in a clinical trial evaluating a...
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...
01:20Mismatch Repair
Organisms are capable of detecting and fixing nucleotide mismatches that occur during DNA replication. This sophisticated process requires identifying the new strand and replacing the erroneous bases with correct nucleotides. Mismatch repair is coordinated by many proteins in both prokaryotes and eukaryotes.
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...
02:59Cancer Prevention
Several factors can increase the risk of cancer in an individual. About 50% of cancer cases can be prevented by adopting a healthy lifestyle, regular exercise, eating healthy, and following a modest cancer prevention diet. Epidemiological studies have consistently shown that populations with vegetable and fruit-rich diets have reduced the incidence of cancer. On the other hand, populations who have a diet rich in animal fat, red meat, junk food, or high calories are predisposed to cancer.
Some...
Some...
01:25Mutagenicity and Carcinogenicity
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
02:30Histone Variants at the Centromere
Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3 variants are also...