title: Association between an interleukin 1 receptor, type I promoter polymorphism and self-reported attentional function in women with breast cancer.
abstract: Subgroups of patients with breast cancer may be at greater risk for cytokine-induced changes in cognitive function after diagnosis and during treatment. The purposes of this study were to identify subgroups of patients with distinct trajectories of attentional function and evaluate for phenotypic and genotypic (i.e., cytokine gene polymorphisms) predictors of subgroup membership. Self-reported attentional function was evaluated in 397 patients with breast cancer using the Attentional Function Index before surgery and for six months after surgery (i.e., seven time points). Using growth mixture modeling, three attentional function latent classes were identified: High (41.6%), Moderate (25.4%), and Low-moderate (33.0%). Patients in the Low-moderate class were significantly younger than those in the High class, with more comorbidities and lower functional status than the other two classes. No differences were found among the classes in years of education, race/ethnicity, or other clinical characteristics. DNA was recovered from 302 patients' samples. Eighty-two single nucleotide polymorphisms among 15 candidate genes were included in the genetic association analyses. After controlling for age, comorbidities, functional status, and population stratification due to race/ethnicity, IL1R1 rs949963 remained a significant genotypic predictor of class membership in the multivariable model. Carrying the rare "A" allele (i.e., GA+AA) was associated with a twofold increase in the odds of belonging to a lower attentional function class (OR: 1.98; 95% CI: 1.18, 3.30; p=.009). Findings provide evidence of subgroups of women with breast cancer who report distinct trajectories of attentional function and of a genetic association between subgroup membership and an IL1R1 promoter polymorphism.
authors: School of Nursing, University of Pittsburgh, 3500 Victoria Street, Pittsburgh, PA 15261, United States. Electronic address: jdm150@pitt.edu.
authors: John D
authors: JD
authors: Merriman
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States; Institute for Human Genetics, University of California, San Francisco, 513 Parnassus Avenue, Box 0794, San Francisco, CA 94143, United States. Electronic address: bradley.aouizerat@nursing.ucsf.edu.
authors: Bradley E
authors: BE
authors: Aouizerat
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: janine.cataldo@nursing.ucsf.edu.
authors: Janine K
authors: JK
authors: Cataldo
authors: School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0410, San Francisco, CA 94143, United States. Electronic address: laura.dunn@ucsf.edu.
authors: Laura
authors: L
authors: Dunn
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: bruce.cooper@nursing.ucsf.edu.
authors: Bruce A
authors: BA
authors: Cooper
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: claudia.west@nursing.ucsf.edu.
authors: Claudia
authors: C
authors: West
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: steven.paul@nursing.ucsf.edu.
authors: Steven M
authors: SM
authors: Paul
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: christina.baggott@ucsf.edu.
authors: Christina R
authors: CR
authors: Baggott
authors: School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0410, San Francisco, CA 94143, United States. Electronic address: adhruva@hemeonc.ucsf.edu.
authors: Anand
authors: A
authors: Dhruva
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: kord.kober@nursing.ucsf.edu.
authors: Kord
authors: K
authors: Kober
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: dale.langford@nursing.ucsf.edu.
authors: Dale J
authors: DJ
authors: Langford
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: heather.leutwyler@nursing.ucsf.edu.
authors: Heather
authors: H
authors: Leutwyler
authors: School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0410, San Francisco, CA 94143, United States. Electronic address: christine.ritchie@ucsf.edu.
authors: Christine S
authors: CS
authors: Ritchie
authors: School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0410, San Francisco, CA 94143, United States. Electronic address: gary.abrams@ucsf.edu.
authors: Gary
authors: G
authors: Abrams
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: marylin.dodd@nursing.ucsf.edu.
authors: Marylin
authors: M
authors: Dodd
authors: Redwood Regional Medical Group, 121 Sotoyome Street, Santa Rosa, CA 95405, United States. Electronic address: celboim@rrmg.com.
authors: Charles
authors: C
authors: Elboim
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: debby.hamolsky@ucsfmedctr.org.
authors: Deborah
authors: D
authors: Hamolsky
authors: School of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0410, San Francisco, CA 94143, United States. Electronic address: mmelisko@medicine.ucsf.edu.
authors: Michelle
authors: M
authors: Melisko
authors: School of Nursing, University of California, San Francisco, 2 Koret Way, Box 0610, San Francisco, CA 94143, United States. Electronic address: chris.miaskowski@nursing.ucsf.edu.
authors: Christine
authors: C
authors: Miaskowski
mesh_terms: D000483:Alleles; D001288:Attention; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D003710:Demography; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D016015:Logistic Models; D008875:Middle Aged; D008954:Models, Biological; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics*; D057566:Self Report
chemical_list: C508590:IL1R1 protein, human; D053573:Receptors, Interleukin-1 Type I
keywords: AFI; AIMs; Attention; Attentional Function Index; BIC; BLRT; BMI; Bayesian information criterion; Breast cancer; CI; CNS; Cytokine genes; DNA; GMM; Inflammation; Interleukin 1 receptor, type I; KPS; Karnofsky Performance Status; LD; MAF; OR; SCQ; SNP; Self-administered Comorbidity Questionnaire; VLMR; Vuong-Lo-Mendell-Rubin likelihood ratio test; ancestry informative markers; body mass index; bootstrapped likelihood ratio test; central nervous system; confidence interval; deoxyribonucleic acid; growth mixture modeling; linkage disequilibrium; minor allele frequency; odds ratio; single nucleotide polymorphism