Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

Gao, Chang–Ming; Ding, Jiannan; Li, Suping; Liu, Yanting; Cao, Hongyan; Wu, Jianzhong; Tajima, Kazuo

doi:10.7314/apjcp.2012.13.8.4087

Cited by 13 publications

(5 citation statements)

References 16 publications

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“…In addition, genetic association studies and their metaanalysis suggest a contribution of TYMS polymorphisms to CRC risk. 42,43 Data on folate, vitamin B12 and homocysteine, were available only for a small subgroup of the patients, however we observed a significant correlation between folate levels and hMLH1 promoter methylation in CRC tissues. Complex interactions among folate, hcy, vitamin B12, other B group vitamins and polymorphisms of one-carbon metabolic genes are known to affect DNA methylation in CRC, 5 that we could not evaluate due to the scarce availability of biochemical data.…”

Section: Discussionmentioning

confidence: 82%

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

et al. 2014

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Section: Discussionmentioning

confidence: 82%

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

et al. 2014

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“…Shen et al [40] found that the del6/del6 genotype of TS 3′-UTR was associated with significantly increased gastric cancer risk, Sumen et al [41] suggested that 3R allele, 2R/3R and 3R/3R genotypes were risk factors for gastric cancer, whereas Araújo et al [55] did not obtain a significant relationship between TS 5′-UTR 2R/3R and 3′-UTR del6/ins6 polymorphisms and gastric cancer susceptibility. Studies have also shown that TS polymorphisms might be associated with other cancers’ risks such as colon cancer [56], lung cancer [57] and oral squamous cell carcinoma [58]. In addition, genetic variation in TS gene may affect carcinogenesis through the regulation of gene expression, the status of the dNTP pool and drug sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Association between polymorphisms of thymidylate synthase gene 5′- and 3′-UTR and gastric cancer risk: meta-analysis

Zhao

Shi

et al. 2016

Bioscience Reports

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Gastric cancer is the most common cancer and the most frequent cause of cancer death worldwide. Several studies have identified the role of thymidylate synthase (TS) 5′- and 3′-UTR and gastric cancer susceptibility; however, the results still remain inconclusive. The purpose of this meta-analysis was to reinvestigate this correlation. In the present study, online databases were searched to retrieve relevant articles published between January 2000 and 2016. The odds ratio (OR) and 95% confidence interval (CI) were employed to calculate the strength of association. Overall, a total of 13 articles were screened out, including 2382 gastric cancer patients and 3171 healthy controls. We found that polymorphisms of TS 5′-UTR 2R (double repeats)/3R (triple repeats) of a 28-bp sequence (11 articles) and 3′-UTR del6/ins6 (seven articles) were not significantly associated with increased risk of gastric cancer. Subgroup analysis by ethnicity showed that 2R allele and 2R/2R genotype in TS 5′-UTR were associated with gastric cancer susceptibility in Caucasian and African populations; del6 allele, del6/del6 and del6/ins6 genotypes were correlated with gastric cancer in Caucasian population. In conclusion, our result suggested that TS polymorphisms might be the risk factors for gastric cancer risk in Caucasian population, although this association needs further study, and future large-scale researches are still required.

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“…Reduced DNA repair capacity for getting rid of tobacco-induced adducts provides some evidence of inter individuals variation in susceptibility to lung cancer, as less than 20% of lifetime smokers develop lung cancer (Shi et al, 2005;Wang et al, 2013a). Several studies were conducted to evaluate the effect of genetic polymorphisms involved in folate and one carbon unit metabolism pathway including; MTHFR, ts, and SLC19A1 and cancer incidence (Suzuki et al, 2007;Gao et al, 2012;Hu et al, 2012;Lu et al, 2012;Dajani et al, 2013;Galbiatti et al, 2013;Morita et al, 2013;Yousef et al, 2013;Rai, 2014;Al-Motassem et al, 2015;Awwad et al, 2015;Wang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

Qasem

Yousef²,

Yousef³

et al. 2016

Asian Pacific Journal of Cancer Prevention

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Background: Thymidylate synthase (TS) catalyzes the methylation of deoxyuridylate to deoxythymidylate and is involved in DNA methylation, synthesis and repair. Two common polymorphisms have been reported, tandem repeats in the promoter-enhancer region (TSER), and 6bp ins/del in the 5'UTR, that are implicated in a number of human diseases, including cancer. The association between the two polymorphisms in risk for lung cancer (LC) was here investigated in the Jordanian population. Materials and Methods: An age, gender, and smoking-matched case-control study involving 84 lung cancer cases and 71 controls was conducted. The polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) technique was used to detect the polymorphism of interest. Results: Individuals bearing the ins/ins genotype were 2.5 times more likely to have lung cancer [(95%CI: 0.98-6.37), p=0.051]. Individuals who were less than or equal to 57 years and carrying ins/ins genotype were 4.6 times more susceptible to lung cancer [OR<57 vs >57years: 4.6 (95%CI: 0.93-22.5), p=0.059)]. Genotypes and alleles of TSER were distributed similarly between cases and controls. Weak linkage disequilibrium existed between the two loci of interest (Lewontin's coefficient [D']) (LC: D' =0.03, r2: 0. 001, p= 0.8; Controls: D' =0.29, r2: 0.08, p=0.02). Carriers of the "3 tandem repeats_insertion" haplotype (3R_ins) were 2 times more likely to have lung cancer [2 (95%CI: 1.13-3.48), p=0.061]. Conclusions: Genetic polymorphism of TS at 3` UTR and its haplotype analysis may modulate the risk of lung cancer in Jordanians. The 6bp ins/del polymorphism of TS at 3 `UTR is more informative than TSER polymorphism in predicting increased risk.

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Polymorphisms in the Thymidylate Synthase Gene and Risk of Colorectal Cancer

Cited by 13 publications

References 16 publications

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

Gene promoter methylation in colorectal cancer and healthy adjacent mucosa specimens

Association between polymorphisms of thymidylate synthase gene 5′- and 3′-UTR and gastric cancer risk: meta-analysis

Thymidylate Synthase Polymorphisms and Risk of Lung Cancer among the Jordanian Population: a Case Control Study

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