Risk of second primary cancer associated with pre-diagnostic smoking, alcohol, and obesity in women with keratinocyte carcinoma

- Keratinocyte carcinoma (KC) has been associated with an increased risk of second primary cancers (SPCs), though the reason for the increase is unknown.
- We found that pre-diagnostic smoking, alcohol and obesity prior to KC diagnosis were associated with overall higher risk of SPCs.
- When we compared these risk estimates for SPC to those estimated for first cancers, overall associations were similar.
- Only in the heavy smoking (≥25 cigarettes/day) category, the hazard ratio for SPC was slightly higher than that for first cancer.

Keratinocyte carcinoma (KC), which includes basal-cell carcinoma (BCC) and squamous-cell cancer (SCC), has been associated with an increased risk of second primary cancers (SPCs), although the reason for this increase is unknown. We assessed the effects of smoking, alcohol, and obesity prior to the diagnosis of KC on the development of SPCs, as these are well-established risk factors for multiple cancers and may also contribute to the increased risk of SPCs among those with KC. A total of 15,628 women with self-reported KC were identified in the Nurses' Health Study. Incident SPCs were assessed throughout the follow-up until June 2012. Cox proportional hazards models were used to calculate the hazard ratios (HRs) of SPC associated with pre-diagnostic smoking, alcohol and body mass index (BMI). We also compared these risk estimates to those for first cancers in all cohort participants. During 193,695 person-years of follow-up, we recorded 2839 SPC cases. Compared with never smokers, current smokers had a significantly elevated risk for SPC overall and specifically for lung, colorectal, and bladder cancers. We also found a positive association between higher BMI and risk for SPC overall as well as for endometrial and bladder SPCs. Women with KC who consumed alcohol ≥30 g/day had a marginally higher risk of SPC compared to non-drinkers. The associations between incident SPC risk among KC cases and smoking, alcohol, and obesity appeared similar to the associations between these risk factors and the incident first primary cancers in the whole cohort. Only in the heavy smoking (≥25 cigarettes/day) category was the HR for SPC after KC (2.34; 95% CI 1.98-2.76) slightly higher than that for the first cancer in the overall cohort (HR 1.86; 95% CI 1.75-1.98, Pheterogeneity = 0.01). In conclusion, pre-diagnostic smoking, alcohol and obesity prior to KC diagnosis were associated with risk of SPCs.