Association between lifetime smoking and cutaneous squamous cell carcinoma: A 2-sample Mendelian randomization study

Area of Science:

• Genetics and Epidemiology
• Cancer Research
• Public Health

Background:

• Cutaneous squamous cell carcinoma (cSCC) is a prevalent global malignancy.
• Existing evidence on the causal link between cigarette smoking and cSCC risk is conflicting.
• Identifying modifiable risk factors for cSCC is crucial for prevention.

Purpose of the Study:

• To evaluate the causal associations between cigarette smoking traits and cSCC risk.
• Investigated smoking initiation, amount smoked, and lifetime smoking exposure.

Main Methods:

• Employed two-sample Mendelian randomization analyses.
• Utilized genetic instruments from genome-wide association studies (GWASs) for smoking traits.
• Analyzed GWAS summary statistics for cSCC from the Kaiser Permanente GERA cohort.

Main Results:

• Found modest evidence that genetically determined lifetime smoking exposure is associated with increased cSCC risk (OR=1.47, P=0.012).
• This suggests lifetime smoking may be a causal risk factor for cSCC.
• No significant associations were detected for smoking initiation or amount smoked with cSCC risk.

Conclusions:

• Findings underscore the significance of smoking prevention strategies for reducing cSCC incidence.
• Results may inform risk-stratified screening for cSCC based on carcinogen exposure and other factors.