title: Interaction between smoking history and gene expression levels impacts survival of breast cancer patients.
abstract: In contrast to studies focused on cigarette smoking and risk of breast cancer occurrence, this study explored the influence of smoking on breast cancer recurrence and progression. The goal was to evaluate the interaction between smoking history and gene expression levels on recurrence and overall survival of breast cancer patients. Multivariable Cox proportional hazards models were fitted for 48 cigarette smokers, 50 non-smokers, and the total population separately to determine which gene expressions and gene expression/cigarette usage interaction terms were significant in predicting overall and disease-free survival in breast cancer patients. Using methods similar to Andres et al. (BMC Cancer 13:326, 2013a; Horm Cancer 4:208-221, 2013b), multivariable analyses revealed CENPN, CETN1, CYP1A1, IRF2, LECT2, and NCOA1 to be important predictors for both breast carcinoma recurrence and mortality among smokers. Additionally, COMT was important for recurrence, and NAT1 and RIPK1 were important for mortality. In contrast, only IRF2, CETN1, and CYP1A1 were significant for disease recurrence and mortality among non-smokers, with NAT2 additionally significant for survival. Analysis of interaction between smoking status and gene expression values using the combined samples revealed significant interactions between smoking status and CYP1A1, LECT2, and CETN1. Signatures consisting of 7-8 genes were highly predictive for breast cancer recurrence and overall survival among smokers, with median C-index values of 0.8 and 0.73 for overall survival and recurrence, respectively. In contrast, median C-index values for non-smokers was only 0.59. Hence, significant interactions between gene expression and smoking status can play a key role in predicting breast cancer patient outcomes.
authors.affiliation: Department of Biochemistry & Molecular Biology, University of Louisville, Louisville, KY, 40202, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Andres
authors.forename: Katie E
authors.initials: KE
authors.lastname: Bickett
authors.forename: Mohammad A
authors.initials: MA
authors.lastname: Alatoum
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Kalbfleisch
authors.forename: Guy N
authors.initials: GN
authors.lastname: Brock
authors.forename: James L
authors.initials: JL
authors.lastname: Wittliff
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality*; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics; D016016:Proportional Hazards Models; D012907:Smoking / Q000009:adverse effects* / Q000235:genetics; D016019:Survival Analysis