Dataset Information

Sunscreens With High Versus Low Sun Protection Factor and Cutaneous Squamous Cell Carcinoma Risk: A Population-Based Cohort Study.

ABSTRACT: Evidence on sunscreen use and cutaneous squamous cell carcinoma (cSCC) risk is limited. Most studies have not taken sun protection factor (SPF) into consideration and used nonusers of sunscreen as the reference group. Nonusers are likely a priori at lower cSCC risk than users. No study has investigated the effect of high- versus low-SPF sunscreens on cSCC, appropriately adjusting for time-varying confounding. Using data from the Norwegian Women and Cancer Study (1991-2016), we investigated whether use of SPF ≥15 versus SPF <15 sunscreens reduces cSCC risk. We used a marginal structural Cox proportional hazards model with inverse probability of treatment and censoring weights to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). During follow-up of 148,781 women (mean follow-up, 14.3 years), 653 women were diagnosed with cSCC. The effect on cSCC risk of sunscreens with SPF ≥15 versus SPF <15 was close to the null when used at any latitudes (HR = 1.02, 95% CI: 0.82, 1.27) and when used in lower-latitude settings (HR = 1.05, 95% CI: 0.84, 1.32). In conclusion, we found no indication that sunscreens with SPF ≥15 reduced Norwegian women's cSCC risk more than sunscreens with SPF <15, suggesting that either there is no difference in their effects long-term or the difference is diluted by incorrect application.

SUBMITTER: Lergenmuller S

PROVIDER: S-EPMC8751784 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Sunscreens With High Versus Low Sun Protection Factor and Cutaneous Squamous Cell Carcinoma Risk: A Population-Based Cohort Study.

Lergenmuller Simon S Ghiasvand Reza R Robsahm Trude E TE Green Adele C AC Lund Eiliv E Rueegg Corina S CS Veierød Marit B MB

American journal of epidemiology 20220101 1

Evidence on sunscreen use and cutaneous squamous cell carcinoma (cSCC) risk is limited. Most studies have not taken sun protection factor (SPF) into consideration and used nonusers of sunscreen as the reference group. Nonusers are likely a priori at lower cSCC risk than users. No study has investigated the effect of high- versus low-SPF sunscreens on cSCC, appropriately adjusting for time-varying confounding. Using data from the Norwegian Women and Cancer Study (1991-2016), we investigated wheth ...[more]

PMID: 34379745

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Project description:Cutaneous squamous cell carcinoma (cSCC) is a keratinocyte-derived invasive and metastatic tumor of the skin. It is the second-most commonly diagnosed form of skin cancer striking 200 000 Americans annually. Further, in organ transplant patients, there is a 65- to 100-fold increased incidence of cSCC compared to the general population. Excision of cSCC of the head and neck results in significant facial disfigurement. Therefore, increased understanding of the mechanisms involved in the pathogeneses of cSCC could identify means to prevent, inhibit, and reverse this process. In our previous studies, inhibition of fibroblast growth factor receptor (FGFR) significantly decreased ultraviolet B-induced epidermal hyperplasia and hyperproliferation in SKH-1 mice, suggesting an important role for FGFR signaling in skin cancer development. However, the role of FGFR signaling in the progression of cSCC is not yet elucidated. Analysis of the expression of FGFR in cSCC cells and normal epidermal keratinocytes revealed protein overexpression and increased FGFR2 activation in cSCC cells compared to normal keratinocytes. Further, tumor cell-specific overexpression of FGFR2 was detected in human cSCCs, whereas the expression of FGFR2 was low in premalignant lesions and normal skin. Pretreatment with the pan-FGFR inhibitor; AZD4547 significantly decreased cSCC cell-cycle traverse, proliferation, migration, and motility. Interestingly, AZD4547 also significantly downregulated mammalian target of rapamycin complex 1 and AKT activation in cSCC cells, suggesting an important role of these signaling pathways in FGFR-mediated effects. To further bolster the in vitro studies, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice with SCC12A tumor xenografts treated with AZD4547 (15 mg/kg/bw, twice weekly oral gavage) exhibited significantly decreased tumor volume compared to the vehicle-only treatment group. The current studies provide mechanistic evidence for the role of FGFR and selectively FGFR2 in the early progression of cSCC and identifies FGFR as a putative therapeutic target in the treatment of skin cancer.

Project description:ImportanceRisk of cutaneous squamous cell carcinoma (cSCC) after the diagnosis of actinic keratosis (AK) has not been studied during long follow-up periods.ObjectiveTo estimate the risk up to 10 years and identify risk factors for cSCC development.Design, setting, and participantsThis longitudinal cohort study, performed from January 1, 2009, to February 29, 2020, examined Kaiser Permanente Northern California patients with AK and control patients matched 1:1 on age, sex, race/ethnicity, medical center, and date of the initial diagnosis plus 30 days in the patients with AK.ExposuresPatients with AK and control participants were followed up for up to 10 years for incidence of cSCC.Main outcomes and measuresIncident cSCC was obtained from pathologic data, and subdistribution hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression analysis, accounting for competing risks, calendar year, demographic factors, and number of AKs.ResultsThe study included 220 236 patients with AK and 220 236 matched control patients (mean [SD] age, 64.1 [12.2] years; 231 248 [52.5%] female). After losses to follow-up were accounted for, risk of cSCC increased with each year of follow-up by 1.92% (95% CI, 1.89%-1.95%) in patients with AK and 0.83% (95% CI, 0.81%-0.85%) in matched control patients (subdistribution HR, 1.90; 95% CI, 1.85-1.95). However, among patients 49 years or younger, those diagnosed with AK were nearly 7 times more likely to be diagnosed with cSCC than those without AK (HR, 6.77; 95% CI, 5.50-8.32). At 10 years, the cumulative incidence of cSCC reached 17.1% (95% CI, 16.9%-17.4%) in patients with AK and 5.7% (95% CI, 5.5%-5.9%) in control patients. Increased numbers of AKs were modestly associated with increased cSCC risk (≥15 AKs vs 1 AK: subdistribution HR, 1.89; 95% CI, 1.75-2.04). Older patients had much higher risk of cSCC than younger patients (compared with those ≤49 years of age at AK diagnosis; ≥80 years of age: subdistribution HR, 8.18; 95% CI, 7.62-8.78). Other than AK, risk factors for cSCC included older age, White race (a proxy for skin type), history of basal cell carcinoma, and male sex. Risk decreased between 2009 and 2019 (2018-2019 vs 2009-2010: subdistribution HR, 0.67; 95% CI, 0.63-0.72).Conclusions and relevanceThe results of this longitudinal cohort study can be used to develop recommendations to increase early detection of cSCC. Additional research is needed to understand the effect of AK treatment on cSCC risk and outcomes of cSCC.

Dataset Information

Sunscreens With High Versus Low Sun Protection Factor and Cutaneous Squamous Cell Carcinoma Risk: A Population-Based Cohort Study.

Publications

Sunscreens With High Versus Low Sun Protection Factor and Cutaneous Squamous Cell Carcinoma Risk: A Population-Based Cohort Study.

Similar Datasets

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