Age at diagnosis, obesity, smoking, and molecular subtypes in muscle-invasive bladder cancer.
BACKGROUND
Heterogeneity of muscle-invasive bladder cancer (MIBC) has been characterized using whole-genome mRNA expression data, showing distinct molecular and clinicopathological characteristics by subtypes. However, associations between risk factors and molecular subtypes have not been reported.


METHODS
Four previously published schemes were used to categorize molecular subtypes in 372 MIBC patients from the Cancer Genome Atlas (TCGA). Data on gene expression (RNA-seq), demographic, and clinicopathological characteristics were retrieved through TCGA data portal. Polytomous logistic regression was used to estimate the associations of subtypes by different schemes with age at diagnosis, obesity, and smoking.


RESULTS
While some quantitative variation was evident, distinct molecular subtype schemes showed considerable consistency in the association with the risk factors. Generally, compared to patients with luminal-like tumors, patients with basal-like subtypes were more likely to be older (OR75 + yrs vs. <60 yearsrange = 1.32-2.89), obese (ORobese vs. normalrange = 1.30-3.05), and to start smoking at early age (OR<18 years vs. 25+ yearsrange = 1.11-4.57).


CONCLUSIONS
Different molecular subtypes of MIBC may have distinct risk profiles. Large population-based studies with detailed information on bladder cancer risk factors are needed to further define etiologic heterogeneity for bladder cancer.
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Suite 32, CVS Plaza, 137 East Franklin Street, CB#8050, Chapel Hill, NC, 27599, USA. amysun@email.unc.edu.
Xuezheng
X
Sun
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Katherine A
KA
Hoadley
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Medicine, Division of Hematology/Oncology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.|Department of Urology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
William Y
WY
Kim
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Helena
H
Furberg
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Suite 32, CVS Plaza, 137 East Franklin Street, CB#8050, Chapel Hill, NC, 27599, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Andrew F
AF
Olshan
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Suite 32, CVS Plaza, 137 East Franklin Street, CB#8050, Chapel Hill, NC, 27599, USA.|Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Melissa A
MA
Troester
D000328:Adult; D017668:Age of Onset; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009130:Muscle, Smooth / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology
Age; Molecular subtype; Muscle-invasive bladder cancer; Obesity; Smoking