Cancer
Association Between Pre-diagnostic Cigarette Smoking and Colorectal Cancer Survival by Molecular Subtypes and Age-onset Status. Herve* Herve Fossou Zacharie Eric Bakwa Lolema II Amanda I. Phipps
Background: Colorectal cancer (CRC) is the third most common malignancy in US adults, and approximately 36% of those diagnosed die within 5 years of diagnosis. Smoking, an established risk factor for CRC, is suggestively associated with poorer CRC survival. However, it is unclear if this association varies by molecular subtypes or age at diagnosis.
Methods: Using data from two complementary study populations: the Colon Cancer Family Registry and the Advanced Colorectal Cancer of Serrated Subtype, we assessed the association of smoking history with CRC survival, overall and across CRC case groups. Tumor markers were tested in centralized laboratories, including microsatellite instability status (MSI), BRAF and KRAS somatic mutation status, and CpG island methylator (CIMP) status. Combinations of these tumor markers were used to classify participants into several etiologically distinct subsets. Information on age at diagnosis was available from cancer registry records. We used Cox regression analyses to describe associations of smoking with CRC survival overall and within groups defined by age at diagnosis and molecular subtypes.
Results: Among 4,901 participants in this study, 1,378 died due to CRC during study follow-up (average follow-up period = 13.6 years). Those who reported having ever smoked were more likely to die from CRC than never-smokers (HR=1.27; 95% CI:1.13-1.42); this association persisted after multivariable adjustment (HR=1.21; 95% CI:1.06-1.38). In analyses stratified by age at diagnosis, the observed association with smoking was limited to individuals with later-onset CRC (HR= 1.26 1.06-1.50). In analyses stratified by tumor molecular subtypes, smoking was similarly associated with survival for most subtypes, although this association was only statistically significant among participants with tumors that were CIMP-low or negative, MSI-low or MSS, BRAF and KRAS wildtype (HR=1.23 1.03-1.47).
Conclusion: Cigarette smoking is associated with poorer survival after CRC diagnosis, particularly for individuals diagnosed with CRC at later ages.