The University of Southampton
University of Southampton Institutional Repository

Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk

Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk
Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk
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.
1932-6203
e0128106-[17pp]
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Agoulnik, Irina U., Chornokur, Ganna and Lin, Hui-Yi et al. (2015) Common genetic variation in cellular transport genes and epithelial ovarian cancer (EOC) risk. PLoS ONE, 10 (6), e0128106-[17pp]. (doi:10.1371/journal.pone.0128106). (PMID:26091520)

Record type: Article

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.

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Accepted/In Press date: 22 April 2015
Published date: 19 June 2015
Organisations: Cancer Sciences

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Local EPrints ID: 382464
URI: https://eprints.soton.ac.uk/id/eprint/382464
ISSN: 1932-6203
PURE UUID: 78506a1a-bc0b-4a64-aab8-1685816584f4

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Date deposited: 05 Oct 2015 12:16
Last modified: 19 Jul 2019 20:31

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Contributors

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

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