Association between TCF7L2 Gene Polymorphism and Cancer Risk: A Meta-Analysis

Chen, Jingxiang; Tao, Yuan; Liu, Menggang; Chen, Ping

doi:10.1371/journal.pone.0071730

Cited by 30 publications

(27 citation statements)

References 21 publications

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“…To our knowledge, this study is the largest and most comprehensive assessment of literatures on associations between genetic variants in the VTI1A‐TCF7L2 region and cancer risk done thus far. Several meta‐analyses have been conducted to evaluate candidate‐gene association studies of cancer risk for variants in the TCF7L2 gene . These preliminary analyses, however, were mostly limited to a single SNP in relation to one cancer, with 14,814 cases and 33,856 controls in the largest study .…”

Section: Discussionmentioning

confidence: 99%

Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence

Zhang

Tang

Fang

et al. 2017

Intl Journal of Cancer

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Genetic studies have linked the VTI1A-TCF7L2 region with risk of multiple cancers. However, findings from these studies were generally inconclusive. We aimed to provide a synopsis of current understanding of associations between variants in the VTI1A-TCF7L2 region and cancer susceptibility. We conducted a comprehensive research synopsis and meta-analysis to evaluate associations between 17 variants in this region and risk of seven cancers using data from 32 eligible articles totaling 224,656 cancer cases and 324,845 controls. We graded cumulative evidence of significant associations using Venice criteria and false-positive report probability tests. We also conducted analyses to evaluate potential function of these variants using data from the Encyclopedia of DNA Elements (ENCODE) Project. Eight variants showed a nominally significant association with risk of individual cancer (p < 0.05). Cumulative epidemiological evidence of an association was graded as strong for rs7903146 [odds ratio (OR) = 1.05, p = 4.13 × 10 ] and rs7904519 (OR = 1.07, p = 2.02 × 10 ) in breast cancer, rs11196172 (OR = 1.11, p = 2.22 × 10 ), rs12241008 (OR = 1.13, p = 1.36 × 10 ) and rs10506868 (OR = 1.10, p = 3.98 × 10 ) in colorectal cancer, rs7086803 in lung cancer (OR = 1.30, p = 3.54 × 10 ) and rs11196067 (OR = 1.18, p = 3.59 × 10 ) in glioma, moderate for rs12255372 (OR = 1.12, p = 2.52 × 10 ) in breast cancer and weak for rs7903146 (OR = 1.11, p = 0.007) in colorectal cancer. Data from ENCODE suggested that seven variants with strong evidence and other correlated variants might fall within putative functional regions. Collectively, our study provides summary evidence that common variants in the VTI1A and TCF7L2 genes are associated with risk of breast, colorectal, lung cancer and glioma and highlights the significant role of the VTI1A-TCF7L2 region in the pathogenesis of human cancers.

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Section: Discussionmentioning

confidence: 99%

Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence

Zhang

Tang

Fang

et al. 2017

Intl Journal of Cancer

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“…Such risk factors may include excess body weight, physical inactivity and smoking . Variants in gene transcription factor 7‐like 2 (TCF7 L2) were reported to be associated with the pathogenesis of T2DM, and both rs7903146 and rs12255372 in TCF7 L2 show associations with various cancer sites, including breast, colon and prostate, but the results were inconsistent . Medelian randomization analyses could be the ideally study design to explore the causality between T2DM and cancer, however, we have not blood samples in our database to explore this.…”

Section: Discussionmentioning

confidence: 99%

Cancer risk in patients with type 2 diabetes mellitus and their relatives

et al. 2015

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Epidemiological studies indicate that risks of certain cancers are increased in individuals hospitalized for type 2 diabetes mellitus (T2DM), which may not be representative of the entire population of T2DM patients as most of them are treated in primary health cares. To examine the subsequent cancer risk in individuals with T2DM from hospitals and primary health cares, and in their siblings and spouses, standardized incidence ratios (SIRs) were used to assess systematically risks of 35 cancer sites/types in individuals with T2DM using a nationwide Swedish database covering the period 1964 through 2010. Increased SIRs were recorded for 24 cancer sites/types in individuals with T2DM. The highest SIRs were for pancreatic cancer and liver cancer (2.98 and 2.43, respectively). A decreased SIR was noted for prostate cancer. Five cancers showed increased SIRs during the whole follow-up period: colon, liver, pancreatic, endometrial and kidney cancers. T2DM patients in inpatient, outpatient and primary health care showed similar risk patterns. The overall SIRs for cancer in the siblings and spouses of individuals with T2DM were 0.97 and 1.01, respectively. The insulin users showed an overall increased risk of cancer. This study showed increased risks of 24 cancers in individuals with T2DM, but not in their siblings or spouses, suggesting that the profound metabolic disturbances of the underlying disease may explain the observed increases. Further studies examining the endogenous and exogenous factors underlying these associations are needed.Type 2 diabetes mellitus (T2DM) is a common metabolic disorder, characterized by impaired pancreatic b-cell function and insulin action. The prevalence of T2DM varies between populations. It currently affects 9.3% of American population, while the rate in Sweden is 2 2 4%.1,2 The disease is likely to be caused by environmental and genetic factors with approximately similar contributions. 3A growing number of epidemiological studies have shown that T2DM is positively associated with risks of several common human malignancies, including cancers of the colon, [4][5][6][7] breast, 4,[6][7][8] endometrium, 4,6,7 lung, 4,6,7 pancreas 4-7 and liver. 4,6,7 T2DM shares risk factors with cancer, such as obesity and sedentary lifestyle. Cancer may be predisposed by the chronic metabolic and hormonal disturbances, which are the characteristics of T2DM, including aberrations in the insulin-like growth factor (IGF) pathway and steroid hormone metabolism. 5,6,8 However, it is less clear whether the increased risk of certain types of cancers is due to shared risk factors, shared genes or the metabolic disturbances of the underlying disease.The main aim of this study was to examine the impact of T2DM on risks of 35 cancer sites/types in individuals with T2DM from hospital (including inpatient and outpatient) and primary health care as most previous studies only examined inpatients T2DM and they were criticized for being not representative of the entire population of T2DM patients. In Sweden, >90% T2D...

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“…Furthermore, in a stratified analysis, rs7903146 (T) is positively correlated with BMI, which is one of the risk factors for breast cancer. rs7903146 (T) is also associated with LN status, which is reported by Naidu [20]. Patients with positive LN status had higher mortality.…”

Section: Discussionmentioning

confidence: 60%

Association of transcription factor 7-like 2 gene polymorphisms with breast cancer risk in northwest Chinese women

Wang

Liu

et al. 2016

Oncotarget

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Genetic variations in transcription factor 7-like 2 (TCF7L2) are associated with cancer risk. This study was conducted to establish the relationship between TCF7L2 polymorphisms (rs1225404, rs7003146, and rs7903146) and clinical features and risk of breast cancer in Northwest Chinese Han women. In this study, three polymorphisms of TCF7L2 (rs1225404, rs7003146, and rs7903146) were genotyped in 458 patients with breast cancer and 500 healthy controls using the Sequenom MassARRAY-iPLEX system. We evaluated the associations between the polymorphisms and breast cancer using odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs). The C allele of rs1225404 was associated with increased breast cancer risk (OR = 1.58, P = 0.0004, PC= 0.0012), whereas the G allele of rs7003146 was associated with decreased breast cancer risk (OR = 0.71, P = 0.01, PC= 0.03). Furthermore, the rs1225404 polymorphism positively correlated with negative progesterone receptor status. A positive correlation with positive estrogen receptor (ER) status was observed for the rs7003146 polymorphism. Our results suggest that TCF7L2 polymorphisms rs1225404 and rs7003146, but not rs7903146, may affect breast cancer risk in Northwest Chinese women. Additionally, the tag polymorphisms in TCF7L2 are associated with the clinical features of breast cancer, which may provide us novel insight into the pathogenesis of breast cancer.

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Association between TCF7L2 Gene Polymorphism and Cancer Risk: A Meta-Analysis

Cited by 30 publications

References 21 publications

Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence

Cumulative evidence for relationships between multiple variants in the VTI1A and TCF7L2 genes and cancer incidence

Cancer risk in patients with type 2 diabetes mellitus and their relatives

Association of transcription factor 7-like 2 gene polymorphisms with breast cancer risk in northwest Chinese women

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