Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis
<p>Abstract</p> <p>Background</p> <p>Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual s...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2006-05-01
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| Series: | BMC Cancer |
| Online Access: | http://www.biomedcentral.com/1471-2407/6/138 |
| _version_ | 1819203248278470656 |
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| author | Liu Jiyong Jin Guangfu Wang Xuechen Wang Shui Qin Jianwei Tang Jinhai Hu Zhibin Gao Jun Zhai Xiangjun Chen Wenshen Chen Feng Wang Xinru Wei Qingyi Shen Hongbing |
| author_facet | Liu Jiyong Jin Guangfu Wang Xuechen Wang Shui Qin Jianwei Tang Jinhai Hu Zhibin Gao Jun Zhai Xiangjun Chen Wenshen Chen Feng Wang Xinru Wei Qingyi Shen Hongbing |
| author_sort | Liu Jiyong |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the <it>TYMS </it>5'-untranslated enhanced region (<it>TSER</it>) and a 6-bp deletion/insertion in the <it>TYMS </it>3'-untranslated region (<it>TS 3'-UTR</it>)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk.</p> <p>Methods</p> <p>To test the hypothesis that polymorphisms of the <it>TYMS </it>gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population.</p> <p>Results</p> <p>We found that the distribution of <it>TS3'-UTR </it>(1494del6) genotype frequencies were significantly different between the cases and controls (<it>P </it>= 0.026). Compared with the <it>TS3'-UTR del6/del6 </it>wild-type genotype, a significantly reduced risk was associated with the <it>ins6/ins6 </it>homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35–0.97) but not the <it>del6/ins6 </it>genotype (OR = 1.09, 95% CI = 0.82–1.46). Furthermore, breast cancer risks associated with the <it>TS3'-UTR del6/del6 </it>genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the <it>TSER </it>polymorphism and breast cancer risks.</p> <p>Conclusion</p> <p>These findings suggest that the <it>TS3'-UTR del6 </it>polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings.</p> |
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| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
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| publishDate | 2006-05-01 |
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| spelling | doaj.art-6aeebfaab20b4c8da4f347b8cd4e87d82022-12-21T18:00:22ZengBMCBMC Cancer1471-24072006-05-016113810.1186/1471-2407-6-138Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysisLiu JiyongJin GuangfuWang XuechenWang ShuiQin JianweiTang JinhaiHu ZhibinGao JunZhai XiangjunChen WenshenChen FengWang XinruWei QingyiShen Hongbing<p>Abstract</p> <p>Background</p> <p>Accumulative evidence suggests that low folate intake is associated with increased risk of breast cancer. Polymorphisms in genes involved in folate metabolism may influence DNA methylation, nucleotide synthesis, and thus individual susceptibility to cancer. Thymidylate synthase (TYMS) is a key enzyme that participates in folate metabolism and catalyzes the conversion of dUMP to dTMP in the process of DNA synthesis. Two potentially functional polymorphisms [a 28-bp tandem repeat in the <it>TYMS </it>5'-untranslated enhanced region (<it>TSER</it>) and a 6-bp deletion/insertion in the <it>TYMS </it>3'-untranslated region (<it>TS 3'-UTR</it>)] were suggested to be correlated with alteration of thymidylate synthase expression and associated with cancer risk.</p> <p>Methods</p> <p>To test the hypothesis that polymorphisms of the <it>TYMS </it>gene are associated with risk of breast cancer, we genotyped these two polymorphisms in a case-control study of 432 incident cases with invasive breast cancer and 473 cancer-free controls in a Chinese population.</p> <p>Results</p> <p>We found that the distribution of <it>TS3'-UTR </it>(1494del6) genotype frequencies were significantly different between the cases and controls (<it>P </it>= 0.026). Compared with the <it>TS3'-UTR del6/del6 </it>wild-type genotype, a significantly reduced risk was associated with the <it>ins6/ins6 </it>homozygous variant genotype (adjusted OR = 0.58, 95% CI = 0.35–0.97) but not the <it>del6/ins6 </it>genotype (OR = 1.09, 95% CI = 0.82–1.46). Furthermore, breast cancer risks associated with the <it>TS3'-UTR del6/del6 </it>genotype were more evident in older women, postmenopausal subjects, individuals with a younger age at first-live birth and individuals with an older age at menarche. However, there was no evidence for an association between the <it>TSER </it>polymorphism and breast cancer risks.</p> <p>Conclusion</p> <p>These findings suggest that the <it>TS3'-UTR del6 </it>polymorphism may play a role in the etiology of breast cancer. Further larger population-based studies as well as functional evaluation of the variants are warranted to confirm our findings.</p>http://www.biomedcentral.com/1471-2407/6/138 |
| spellingShingle | Liu Jiyong Jin Guangfu Wang Xuechen Wang Shui Qin Jianwei Tang Jinhai Hu Zhibin Gao Jun Zhai Xiangjun Chen Wenshen Chen Feng Wang Xinru Wei Qingyi Shen Hongbing Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis BMC Cancer |
| title | Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis |
| title_full | Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis |
| title_fullStr | Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis |
| title_full_unstemmed | Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis |
| title_short | Polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a Chinese population: a case-control analysis |
| title_sort | polymorphisms in thymidylate synthase gene and susceptibility to breast cancer in a chinese population a case control analysis |
| url | http://www.biomedcentral.com/1471-2407/6/138 |
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