Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

作者：Ganna Chornokur, Hui‐Yi Lin, Jonathan P. Tyrer, Kate Lawrenson, Joe Dennis, Ernest K. Amankwah, Xiaotao Qu, Ya-Yu Tsai, Heather Jim, Zhihua Chen, Y. Ann Chen, Jennifer Permuth‐Wey, Katja K.H. Aben, Hoda Anton‐Culver, Natalia Antonenkova, Fiona Bruinsma, Elisa V. Bandera, Yukie T. Bean, Matthias W. Beckmann, Maria Bisogna, Line Bjørge, Natalia Bogdanova, Louise A. Brinton, Angela Brooks‐Wilson, Clareann H. Bunker, Ralf Bützow, Ian Campbell, Karen Carty, Jenny Chang‐Claude, Linda S. Cook, Daniel W. Cramer, Julie M. Cunningham, Cezary Cybulski, Agnieszka Dansonka‐Mieszkowska, Andreas du Bois, Evelyn Despierre, Ed Dicks, Jennifer A. Doherty, Thilo Dörk, Matthias Dürst, Douglas F. Easton, Diana M. Eccles, Robert P. Edwards, Arif B. Ekici, Peter A. Fasching, Brooke L. Fridley, Yu‐Tang Gao, Aleksandra Gentry‐Maharaj, Graham G. Giles, Rosalind Glasspool, Marc T. Goodman, Jacek Gronwald, Patricia Harrington, Philipp Harter, Alexander Hein, Florian Heitz, Michelle A.T. Hildebrandt, Peter Hillemanns, Claus Høgdall, Estrid Høgdall, Satoyo Hosono, Anna Jakubowska, Allan Jensen, Bu‐Tian Ji, Beth Y. Karlan, Linda E. Kelemen, Mellissa Kellar, Lambertus A. Kiemeney, Camilla Krakstad, Susanne K. Kjær, Jolanta Kupryjańczyk, Diether Lambrechts, Sandrina Lambrechts, Nhu D. Le, Alice W. Lee, Shashi Lele, Arto Leminen, Jenny Lester, Douglas A. Levine, Dong Liang, Boon Kiong Lim, Jolanta Lissowska, Karen H. Lu, Jan Lubiński, Lene Lundvall, Leon F.A.G. Massuger, Keitaro Matsuo, Valerie McGuire, John R. McLaughlin, Iain A. McNeish, Usha Menon, Roger L. Milne, Francesmary Modugno, Kirsten B. Moysich, Roberta B. Ness, Heli Nevanlinna, Ursula Eilber, Kunle Odunsi, Sara H. Olson, Irene Orlow, Sandra Oršulić, Rachel Palmieri Weber, James Paul, Celeste Leigh Pearce, Tanja Pejović, Liisa M. Pelttari, Malcolm C. Pike, Elizabeth M. Poole, Harvey A. Risch, Barry P. Rosen, Mary Anne Rossing, Joseph H. Rothstein, Anja Rudolph, Ingo B. Runnebaum, Iwona K. Rzepecka, Helga B. Salvesen, Eva Schernhammer, Ira Schwaab, Xiao‐Ou Shu, Yurii B. Shvetsov, Nadeem Siddiqui, Weiva Sieh, Honglin Song, Melissa C. Southey, Beata Śpiewankiewicz, Lara Sucheston, Soo‐Hwang Teo, Kathryn L. Terry, Pamela J. Thompson, Lotte Thomsen, Ingvild L. Tangen, Shelley S. Tworoger, Anne M. van Altena, Robert A. Vierkant, Ignace Vergote, Christine Walsh, Shan Wang‐Gohrke, Nicolas Wentzensen, Alice S. Whittemore, Kristine G. Wicklund, Lynne R. Wilkens, Anna H. Wu, Xifeng Wu, Yin Ling Woo, Hannah Yang, Wei Zheng, Argyrios Ziogas, Hanis Nazihah Hasmad, Andrew Berchuck, Georgia Chenevix-Trench on behalf of the AOCS management group, Edwin S. Iversen, Joellen M. Schildkraut, Susan J. Ramus, Ellen L. Goode, Álvaro N.A. Monteiro, Simon A. Gayther, Steven A. Narod, Paul D.P. Pharoah, Thomas A. Sellers, Catherine M. Phelan · 发表于：PLoS ONE · 年份：2015 · DOI：10.1371/journal.pone.0128106 · 被引用次数：906 · 研究领域：Ferroptosis and cancer prognosis、Trace Elements in Health、Glutathione Transferases and Polymorphisms

BACKGROUND: Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), ...