Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.
Consortium analysis of gene and gene-folate interactions in purine and pyrimidine metabolism pathways with ovarian carcinoma risk.
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DOI：
10.1002/mnfr.201400068
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发表时间：
2014-10
影响因子：
5.2
通讯作者：
Le, Nhu D.
中科院分区：
文献类型：
--
作者：
Kelemen, Linda E.;Terry, Kathryn L.;Goodman, Marc T.;Webb, Penelope M.;Bandera, Elisa V.;McGuire, Valerie;Rossing, Mary Anne;Wang, Qinggang;Dicks, Ed;Tyrer, Jonathan P.;Song, Honglin;Kupryjanczyk, Jolanta;Dansonka-Mieszkowska, Agnieszka;Plisiecka-Halasa, Joanna;Timorek, Agnieszka;Menon, Usha;Gentry-Maharaj, Aleksandra;Gayther, Simon A.;Ramus, Susan J.;Narod, Steven A.;Risch, Harvey A.;McLaughlin, John R.;Siddiqui, Nadeem;Glasspool, Rosalind;Paul, James;Carty, Karen;Gronwald, Jacek;Lubinski, Jan;Jakubowska, Anna;Cybulski, Cezary;Kiemeney, Lambertus A.;Massuger, Leon F. A. G.;Van Altena, Anne M.;Aben, Katja K. H.;Olson, Sara H.;Orlow, Irene;Cramer, Daniel W.;Levine, Douglas A.;Bisogna, Maria;Giles, Graham G.;Southey, Melissa C.;Bruinsma, Fiona;Kjaer, Susanne K.;Hogdall, Estrid;Jensen, Allan;Hogdall, Claus K.;Lundvall, Lene;Engelholm, Svend-Aage;Heitz, Florian;Du Bois, Andreas;Harter, Philipp;Schwaab, Ira;Butzow, Ralf;Nevanlinna, Heli;Pelttari, Liisa M.;Leminen, Arto;Thompson, Pamela J.;Lurie, Galina;Wilkens, Lynne R.;Lambrechts, Diether;Van Nieuwenhuysen, Els;Lambrechts, Sandrina;Vergote, Ignace;Beesley, Jonathan;Investigators, Aocs Study Grp Acs;Fasching, Peter A.;Beckmann, Matthias W.;Hein, Alexander;Ekici, Arif B.;Doherty, Jennifer A.;Wu, Anna H.;Pearce, Celeste L.;Pike, Malcolm C.;Stram, Daniel;Chang-Claude, Jenny;Rudolph, Anja;Doerk, Thilo;Duerst, Matthias;Hillemanns, Peter;Runnebaum, Ingo B.;Bogdanova, Natalia;Antonenkova, Natalia;Odunsi, Kunle;Edwards, Robert P.;Kelley, Joseph L.;Modugno, Francesmary;Ness, Roberta B.;Karlan, Beth Y.;Walsh, Christine;Lester, Jenny;Orsulic, Sandra;Fridley, Brooke L.;Vierkant, Robert A.;Cunningham, Julie M.;Wu, Xifeng;Lu, Karen;Liang, Dong;Hildebrandt, Michelle A. T.;Weber, Rachel Palmieri;Iversen, Edwin S.;Tworoger, Shelley S.;Poole, Elizabeth M.;Salvesen, Helga B.;Krakstad, Camilla;Bjorge, Line;Tangen, Ingvild L.;Pejovic, Tanja;Bean, Yukie;Kellar, Melissa;Wentzensen, Nicolas;Brinton, Louise A.;Lissowska, Jolanta;Garcia-Closas, Montserrat;Campbell, Ian G.;Eccles, Diana;Whittemore, Alice S.;Sieh, Weiva;Rothstein, Joseph H.;Anton-Culver, Hoda;Ziogas, Argyrios;Phelan, Catherine M.;Moysich, Kirsten B.;Goode, Ellen L.;Schildkraut, Joellen M.;Berchuck, Andrew;Pharoah, Paul D. P.;Sellers, Thomas A.;Brooks-Wilson, Angela;Cook, Linda S.;Le, Nhu D.
关键词：
我们重新评估了先前报道的一碳（叶酸）转移基因途径变异与卵巢癌（OC）风险之间的相关性，以及嘌呤和嘧啶代谢的相关途径，并评估了与叶酸摄入的相互作用。在13，410例OC病例和22，635例对照以及2，281例病例和3，444例对照中估计了446种遗传变异的比值比（OR）。在多重检验校正后，最显著的主效应关联是DPYD变体rs 11587873（OR=0.92，P= 6x 10 −5）和rs 828054（OR=1.06，P= 1x 10 −4）。嘧啶代谢基因DPYD、DPYS、PPAT和TYMS中的13个变异体在多变异体分析中也与叶酸显著相互作用（校正P=9.9x10−6），但总共只能解释0.2%的OC风险。虽然在多重检验校正后没有其他相关性，但先前报道的OC中一碳转移中的SHMT 1变异表明叶酸水平较高时风险较低（P相互作用=0.03-0.006）。嘧啶代谢基因的变异，特别是DPYD，以前报道与OC相关，可能会影响风险;然而，叶酸摄入分层不太可能明显改变这些妇女的疾病风险。SHMT 1 SNP与叶酸的相互作用是合理的，但需要进一步验证。在选定的嘌呤代谢基因的多态性与OC无关。
We re-evaluated previously reported associations between variants in pathways of one-carbon (folate) transfer genes and ovarian carcinoma (OC) risk, and in related pathways of purine and pyrimidine metabolism, and assessed interactions with folate intake. Odds ratios (OR) for 446 genetic variants were estimated among 13,410 OC cases and 22,635 controls and among 2,281 cases and 3,444 controls with folate information. Following multiple testing correction, the most significant main effect associations were for DPYD variants rs11587873 (OR=0.92, P=6x10−5) and rs828054 (OR=1.06, P=1x10−4). Thirteen variants in the pyrimidine metabolism genes, DPYD, DPYS, PPAT and TYMS, also interacted significantly with folate in a multi-variant analysis (corrected P=9.9x10−6) but collectively explained only 0.2% of OC risk. Although no other associations were significant after multiple testing correction, variants in SHMT1 in one-carbon transfer, previously reported with OC, suggested lower risk at higher folate (Pinteraction=0.03-0.006). Variation in pyrimidine metabolism genes, particularly DPYD, which was previously reported to be associated with OC, may influence risk; however, stratification by folate intake is unlikely to modify disease risk appreciably in these women. SHMT1 SNP-byfolate interactions are plausible but require further validation. Polymorphisms in selected genes in purine metabolism were not associated with OC.
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影响因子：
3.7
作者：
Kelemen LE;Wang Q;Dinu I;Vierkant RA;Tsai YY;Cunningham JM;Phelan CM;Fridley BL;Amankwah EK;Iversen ES;Berchuck A;Schildkraut JM;Goode EL;Sellers TA
通讯作者：
Sellers TA
影响因子：
3.8
作者：
Kelemen, Linda E.;Goodman, Marc T.;Goode, Ellen L.
通讯作者：
Goode, Ellen L.
影响因子：
4.8
作者：
Khan, S;Abdelrahim, M;Safe, S
通讯作者：
Safe, S
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
168.9
作者：
Beral, V.;Doll, R.;Risch, H. A.
通讯作者：
Risch, H. A.