Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium
Genetic Variation in TYMS in the One-Carbon Transfer Pathway Is Associated with Ovarian Carcinoma Types in the Ovarian Cancer Association Consortium
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DOI：
10.1158/1055-9965.epi-09-1317
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发表时间：
2010-07-01
影响因子：
3.8
通讯作者：
Goode, Ellen L.
中科院分区：
文献类型：
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作者：
Kelemen, Linda E.;Goodman, Marc T.;Goode, Ellen L.
背景：我们先前报道了一碳转移基因中常见的多态与卵巢癌的风险。我们试图复制DPYD rs1801265、DNMT3A rs13420827、MTHFD1 rs1950902、MTHFS rs17284990和Tyms rs495139与总体卵巢癌风险的关联，并使用大样本集合病例来研究组织学类型的关联。方法：在卵巢癌协会联合会中对关联进行评估，包括对5,593例上皮性卵巢癌和9962例非西班牙裔白人对照的16项研究。结果：5个基因多态与卵巢癌总体上无关联(P-趋势和0.13)，但与粘液型(OR，1.19；95%CI，1.03-1.39；P=0.02)、透明细胞型(OR，0.86；95%CI，0.75-0.99；P=0.04)和子宫内膜样癌(OR，0.90；95%可信区间为0.81~0.99；P=0.04；P异质性=0.001)。对低度粘液性癌的限制进一步加强了粘液型的相关性(OR，1.32；95%CI，1.07-1.62；P=0.01)。Tyms rs495139与浆液性卵巢癌类型无关(OR，1.06；95%CI，1.00~1.13；P=0.05)。结论：Tyms rs495139可能与卵巢癌类型的不同风险相关，提示准确的组织病理学分类的重要性。癌症流行病学生物标记物；19(7)；1822-30。(C)2010年AACR。
Background: We previously reported the risks of ovarian carcinoma for common polymorphisms in one-carbon transfer genes. We sought to replicate associations for DPYD rs1801265, DNMT3A rs13420827, MTHFD1 rs1950902, MTHFS rs17284990, and TYMS rs495139 with risk of ovarian carcinoma overall and to use the large sample of assembled cases to investigate associations by histologic type.Methods: Associations were evaluated in the Ovarian Cancer Association Consortium, including 16 studies of 5,593 epithelial ovarian carcinoma cases and 9,962 controls of white non-Hispanic origin. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for age and study site.Results: The five polymorphisms were not associated with ovarian carcinoma overall (P-trend > 0.13); however, associations for the minor allele at TYMS rs495139 were observed for carcinomas of mucinous type (OR, 1.19; 95% CI, 1.03-1.39; P = 0.02), clear cell type (OR, 0.86; 95% CI, 0.75-0.99; P = 0.04), and endometrioid type (OR, 0.90; 95% CI, 0.81-0.99; P = 0.04; Pheterogeneity = 0.001). Restriction to low-grade mucinous carcinomas further strengthened the association for the mucinous type (OR, 1.32; 95% CI, 1.07-1.62; P = 0.01). TYMS rs495139 was not associated with serous type (OR, 1.06; 95% CI, 1.00-1.13; P = 0.05).Conclusions: TYMS rs495139 may be associated with a differential risk of ovarian carcinoma types, indicating the importance of accurate histopathologic classification.Impact: Biomarkers that distinguish ovarian carcinoma types are few, and TYMS rs495139 may provide a novel clue to type etiology. Cancer Epidemiol Biomarkers Prev; 19(7); 1822-30. (C) 2010 AACR.