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KRAS Sequence Variation as Prognostic Marker in Patients With Young- vs Late-Onset Colorectal Cancer
Mayada A Aljehani1, Jeffrey Bien2, Jerry S H Lee1,3,4,5
1Ellison Institute of Technology, Los Angeles, California.
JAMA Network Open
|November 30, 2023
Summary
KRAS sequence variation is linked to increased mortality in both young-onset and late-onset colorectal cancer (CRC). For young-onset CRC, variant KRAS is associated with higher mortality risk in distal tumors compared to proximal ones.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- The association between KRAS sequence variation and colorectal cancer (CRC) outcomes is crucial for personalized treatment strategies.
- Understanding how KRAS variants influence survival based on age at onset and tumor location is an evolving area in CRC research.
Purpose of the Study:
- To investigate the relationship between KRAS sequence variation, age at onset (young-onset vs. late-onset), and tumor sidedness with colorectal cancer-specific survival (CSS).
- To characterize the impact of KRAS variants on mortality risk across different patient demographics and tumor characteristics in CRC.
Main Methods:
- A cross-sectional study utilizing data from the Surveillance, Epidemiology, and End Results (SEER) database, including 21,661 patients diagnosed with CRC between 2010-2015.
- Survival analysis using Fine and Gray cumulative incidence, Kaplan-Meier curves, and competing risk models to estimate subdistribution hazard ratios (sHRs) for KRAS status, age at onset, and tumor location.
- Patients were categorized into young-onset (YO, 20-49 years) and late-onset (LO, ≥50 years) groups.
Main Results:
- KRAS sequence variation was significantly associated with reduced CSS in both YO (3.0 vs. 3.5 years, P=.02) and LO (2.5 vs. 3.4 years, P<.001) colorectal cancer patients.
- Variant KRAS tumors showed a higher risk of CRC-related death compared to wild-type KRAS tumors in both YO (sHR, 1.09) and LO (sHR, 1.06) groups.
- In YO CRC, mortality risk increased with distal tumor locations (left-sided and rectal) compared to right-sided tumors, a trend not observed in LO CRC.
Conclusions:
- KRAS sequence variation is an independent risk factor associated with increased mortality in both young-onset and late-onset colorectal cancer.
- For young-onset CRC, the mortality risk associated with variant KRAS is more pronounced in distal tumors, suggesting a role for tumor location in modulating outcomes.
- These findings underscore the importance of considering KRAS status, age at onset, and tumor location for prognostic assessments and therapeutic decisions in colorectal cancer management.
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