Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk
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Author
Chornokur, Ganna
Lin, Hui-Yi
Tyrer, Jonathan P.
Lawrenson, Kate
Dennis, Joe
Amankwah, Ernest K.
Qu, Xiaotao
Tsai, Ya-Yu
Jim, Heather S. L.
Chen, Zhihua
Chen, Ann Y.
Permuth-Wey, Jennifer
Aben, Katja KH.
Anton-Culver, Hoda
Antonenkova, Natalia
Bruinsma, Fiona
Bandera, Elisa V.
Bean, Yukie T.
Beckmann, Matthias W.
Bisogna, Maria
Bjorge, Line
Bogdanova, Natalia
Brinton, Louise A.
Brooks-Wilson, Angela
Bunker, Clareann H.
Butzow, Ralf
Campbell, Ian G.
Carty, Karen
Chang-Claude, Jenny
Cook, Linda S.
Cunningham, Julie M.
Cybulski, Cezary
Dansonka-Mieszkowska, Agnieszka
du Bois, Andreas
Despierre, Evelyn
Dicks, Ed
Doherty, Jennifer A.
Dörk, Thilo
Dürst, Matthias
Easton, Douglas F.
Eccles, Diana M.
Edwards, Robert P.
Ekici, Arif B.
Fasching, Peter A.
Fridley, Brooke L.
Gao, Yu-Tang
Gentry-Maharaj, Aleksandra
Giles, Graham G.
Glasspool, Rosalind
Goodman, Marc T.
Gronwald, Jacek
Harrington, Patricia
Harter, Philipp
Hein, Alexander
Heitz, Florian
Hildebrandt, Michelle A. T.
Hillemanns, Peter
Hogdall, Claus K.
Hogdall, Estrid
Hosono, Satoyo
Jakubowska, Anna
Jensen, Allan
Ji, Bu-Tian
Karlan, Beth Y.
Kelemen, Linda E.
Kellar, Mellissa
Kiemeney, Lambertus A.
Krakstad, Camilla
Kjaer, Susanne K.
Kupryjanczyk, Jolanta
Lambrechts, Diether
Lambrechts, Sandrina
Le, Nhu D.
Lee, Alice W.
Lele, Shashi
Leminen, Arto
Lester, Jenny
Levine, Douglas A.
Liang, Dong
Lim, Boon Kiong
Lissowska, Jolanta
Lu, Karen
Lubinski, Jan
Lundvall, Lene
Massuger, Leon F. A. G.
Matsuo, Keitaro
McGuire, Valerie
McLaughlin, John R.
McNeish, Iain
Menon, Usha
Milne, Roger L.
Modugno, Francesmary
Moysich, Kirsten B.
Ness, Roberta B.
Nevanlinna, Heli
Eilber, Ursula
Odunsi, Kunle
Olson, Sara H.
Orlow, Irene
Orsulic, Sandra
Weber, Rachel Palmieri
Paul, James
Pearce, Celeste L.
Pejovic, Tanja
Pelttari, Liisa M.
Pike, Malcolm C.
Risch, Harvey A.
Rosen, Barry
Rossing, Mary Anne
Rothstein, Joseph H.
Rudolph, Anja
Runnebaum, Ingo B.
Rzepecka, Iwona K.
Salvesen, Helga B.
Schwaab, Ira
Shu, Xiao-Ou
Shvetsov, Yurii B.
Siddiqui, Nadeem
Sieh, Weiva
Song, Honglin
Southey, Melissa C.
Spiewankiewicz, Beata
Sucheston, Lara
Teo, Soo-Hwang
Thompson, Pamela J.
Thomsen, Lotte
Tangen, Ingvild L.
van Altena, Anne M.
Vierkant, Robert A.
Vergote, Ignace
Walsh, Christine S.
Wang-Gohrke, Shan
Wentzensen, Nicolas
Whittemore, Alice S.
Wicklund, Kristine G.
Wilkens, Lynne R.
Wu, Anna H.
Wu, Xifeng
Woo, Yin-Ling
Yang, Hannah
Zheng, Wei
Ziogas, Argyrios
Hasmad, Hanis N.
Berchuck, Andrew
Iversen, Edwin S.
Schildkraut, Joellen M.
Ramus, Susan J.
Goode, Ellen L.
Monteiro, Alvaro N. A.
Gayther, Simon A.
Narod, Steven A.
Pharoah, Paul D. P.
Sellers, Thomas A.
Phelan, Catherine M.
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https://doi.org/10.1371/journal.pone.0128106Metadata
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Chornokur, G., H. Lin, J. P. Tyrer, K. Lawrenson, J. Dennis, E. K. Amankwah, X. Qu, et al. 2015. “Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk.” PLoS ONE 10 (6): e0128106. doi:10.1371/journal.pone.0128106. http://dx.doi.org/10.1371/journal.pone.0128106.Abstract
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), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). Conclusion: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474865/pdf/Terms of Use
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