Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer.


Autoria(s): Schildkraut, JM; Iversen, ES; Wilson, MA; Clyde, MA; Moorman, PG; Palmieri, RT; Whitaker, R; Bentley, RC; Marks, JR; Berchuck, A
Data(s)

08/04/2010

Identificador

http://www.ncbi.nlm.nih.gov/pubmed/20386703

PLoS One, 2010, 5 (4), pp. e10061 - ?

http://hdl.handle.net/10161/8883

1932-6203

http://hdl.handle.net/10161/8883

Idioma(s)

ENG

en_US

Relação

PLoS One

10.1371/journal.pone.0010061

http://hdl.handle.net/10161/4535

10161/4535

Plos One

Tipo

Journal Article

Cobertura

United States

Resumo

BACKGROUND: We analyzed the association between 53 genes related to DNA repair and p53-mediated damage response and serous ovarian cancer risk using case-control data from the North Carolina Ovarian Cancer Study (NCOCS), a population-based, case-control study. METHODS/PRINCIPAL FINDINGS: The analysis was restricted to 364 invasive serous ovarian cancer cases and 761 controls of white, non-Hispanic race. Statistical analysis was two staged: a screen using marginal Bayes factors (BFs) for 484 SNPs and a modeling stage in which we calculated multivariate adjusted posterior probabilities of association for 77 SNPs that passed the screen. These probabilities were conditional on subject age at diagnosis/interview, batch, a DNA quality metric and genotypes of other SNPs and allowed for uncertainty in the genetic parameterizations of the SNPs and number of associated SNPs. Six SNPs had Bayes factors greater than 10 in favor of an association with invasive serous ovarian cancer. These included rs5762746 (median OR(odds ratio)(per allele) = 0.66; 95% credible interval (CI) = 0.44-1.00) and rs6005835 (median OR(per allele) = 0.69; 95% CI = 0.53-0.91) in CHEK2, rs2078486 (median OR(per allele) = 1.65; 95% CI = 1.21-2.25) and rs12951053 (median OR(per allele) = 1.65; 95% CI = 1.20-2.26) in TP53, rs411697 (median OR (rare homozygote) = 0.53; 95% CI = 0.35 - 0.79) in BACH1 and rs10131 (median OR( rare homozygote) = not estimable) in LIG4. The six most highly associated SNPs are either predicted to be functionally significant or are in LD with such a variant. The variants in TP53 were confirmed to be associated in a large follow-up study. CONCLUSIONS/SIGNIFICANCE: Based on our findings, further follow-up of the DNA repair and response pathways in a larger dataset is warranted to confirm these results.

Formato

e10061 - ?

Palavras-Chave #Bayes Theorem #Case-Control Studies #Cystadenocarcinoma, Serous #DNA Damage #DNA Repair #Data Collection #Female #Humans #Models, Statistical #Neoplasm Invasiveness #Ovarian Neoplasms #Polymorphism, Single Nucleotide #Probability #Risk #Tumor Suppressor Protein p53