title: Common variants in RB1 gene and risk of invasive ovarian cancer.
abstract: Somatic alteration of the RB1 gene is common in several types of cancer, and germ-line variants are implicated in others. We have used a single nucleotide polymorphism (SNP) tagging approach to evaluate the association between common variants (SNP) in RB1 and risks of invasive ovarian cancer. We genotyped 11 tagging SNPs in three ovarian case-control studies from the United Kingdom, United States, and Denmark, comprising >1500 cases and 4,800 controls. Two SNPs showed significant association with ovarian cancer risk: carriers of the minor allele of rs2854344 were at reduced risk compared with the common homozygotes [odds ratio (OR), 0.73; 95% confidence interval (95% CI), 0.61-0.89; P = 0.0009 dominant model]. Similarly, the minor allele of rs4151620 was found to be associated with reduced risk (rare versus common homozygote; OR, 0.19; 95% CI, 0.07-0.53; P = 0.00005 recessive model). After adjusting for multiple testing, the most significant association (rs4151620) was P = 0.001. A global test comparing common haplotype frequencies in cases and controls was of borderline significance (P(8df) = 0.04). There are no common coding SNPs in the RB1 gene. However, intron 17 of RB1 contains the open reading frame for the P2RY5 gene, and rs4151620 is perfectly correlated with rs2227311, which is located in the 5'-untranslated region of P2RY5 and is predicted to affect P2RY5 transcription. rs2854344 has been reported previously to be associated with breast cancer risk. The possible associations of rs2854344 and rs4151620 with ovarian cancer risk warrant confirmation in independent case-control studies before studies on their biological mode of action.
authors.affiliation: Cancer Research UK Department of Oncology, Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom. honglin@srl.cam.ac.uk
authors.forename: Honglin
authors.initials: H
authors.lastname: Song
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Ramus
authors.forename: Danielle
authors.initials: D
authors.lastname: Shadforth
authors.forename: Lydia
authors.initials: L
authors.lastname: Quaye
authors.forename: Susanne Kruger
authors.initials: SK
authors.lastname: Kjaer
authors.forename: Richard A
authors.initials: RA
authors.lastname: Dicioccio
authors.forename: Alison M
authors.initials: AM
authors.lastname: Dunning
authors.forename: Estrid
authors.initials: E
authors.lastname: Hogdall
authors.forename: Claus
authors.initials: C
authors.lastname: Hogdall
authors.forename: Alice S
authors.initials: AS
authors.lastname: Whittemore
authors.forename: Valerie
authors.initials: V
authors.lastname: McGuire
authors.forename: Fabienne
authors.initials: F
authors.lastname: Lesueur
authors.forename: Douglas F
authors.initials: DF
authors.lastname: Easton
authors.forename: Ian J
authors.initials: IJ
authors.lastname: Jacobs
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Paul D P
authors.initials: PD
authors.lastname: Pharoah
mesh_terms: D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016160:Retinoblastoma Protein / Q000235:genetics*
chemical_list: D016160:Retinoblastoma Protein