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Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk
- Chornokur, Ganna;
- Lin, Hui-Yi;
- Tyrer, Jonathan P;
- Lawrenson, Kate;
- Dennis, Joe;
- Amankwah, Ernest K;
- Qu, Xiaotao;
- Tsai, Ya-Yu;
- Jim, Heather SL;
- 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;
- Cramer, Daniel W;
- 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 AT;
- 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 FAG;
- 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;
- Poole, Elizabeth M;
- Risch, Harvey A;
- Rosen, Barry;
- Rossing, Mary Anne;
- Rothstein, Joseph H;
- Rudolph, Anja;
- Runnebaum, Ingo B;
- Rzepecka, Iwona K;
- Salvesen, Helga B;
- Schernhammer, Eva;
- Schwaab, Ira;
- Shu, Xiao-Ou;
- Shvetsov, Yurii B;
- Siddiqui, Nadeem;
- Sieh, Weiva;
- Song, Honglin;
- Southey, Melissa C;
- Spiewankiewicz, Beata;
- Sucheston, Lara;
- Teo, Soo-Hwang;
- Terry, Kathryn L;
- Thompson, Pamela J;
- Thomsen, Lotte;
- Tangen, Ingvild L;
- Tworoger, Shelley S;
- 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 NA;
- Gayther, Simon A;
- Narod, Steven A;
- Pharoah, Paul DP;
- Sellers, Thomas A;
- Phelan, Catherine M
- Editor(s): Agoulnik, Irina U
- et al.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4474865No data is associated with this publication.
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.Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.