Purpose: We sought to evaluate the risk effect of tanning bed use on skin cancers among teenage and young adults. We also expected to determine whether a dose-response relationship was evident.Patients and Methods: We observed 73,494 female nurses for 20 years (from 1989 to 2009) in a large and well-characterized cohort in the United States and investigated whether frequency of tanning bed use during high school/college and at ages 25 to 35 years were associated with a risk of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. We used Cox proportional hazards models and carefully adjusted for host risk factors, ultraviolet index of residence, and sun exposure behaviors at a young age.Results: During follow-up, 5,506 nurses were diagnosed with BCC, 403 with SCC, and 349 with melanoma. The multivariable-adjusted hazard ratio (HR) of skin cancer for an incremental increase in use of tanning beds of four times per year during both periods was 1.15 (95% CI, 1.11 to 1.19; P < .001) for BCC, 1.15 (95% CI, 1.01 to 1.31; P = .03) for SCC, and 1.11 (95% CI, 0.97 to 1.27; P = .13) for melanoma. Compared with tanning bed use at ages 25 to 35 years, we found a significantly higher risk of BCC for use during high school/college (multivariable-adjusted HR for use more than six times per year compared with no use was 1.73 during high school/college v 1.28 at ages 25 to 35 years; P for heterogeneity < .001).Conclusion: Our data provide evidence for a dose-response relationship between tanning bed use and the risk of skin cancers, especially BCC, and the association is stronger for patients with a younger age at exposure.

Background Constitutional factors and sun exposure are associated with skin cancer risk. However, these relations are complex and differ according to skin cancer type. Methods We examined the associations of constitutional risk factors and sun exposure with the risks of three types of skin cancer simultaneously and evaluated the interaction between constitutional susceptibility and sun exposure in a nested case–control study within the Nurses' Health Study [200 melanoma, 275 squamous cell carcinoma (SCC), and 283 basal cell carcinoma (BCC) cases, and 804 controls]. Information regarding skin cancer risk factors was obtained from the retrospective supplementary questionnaire. Results Constitutional susceptibility was an independent risk factor for all three types of skin cancer. Sunlamp usage or tanning salon attendance was a risk factor for melanoma after adjusting for potential confounding variables (OR for ever vs never usage, 2.06, 95% CI 1.30–3.26). Higher sun exposure while wearing a bathing suit was an independent risk factor for all three types of skin cancer. We observed a significant interaction between constitutional susceptibility and sun exposure while wearing a bathing suit on melanoma risk (P, interaction, 0.03); women with the highest susceptibility and highest exposure had an OR of 8.37 (95% CI 3.07–22.84). This interaction was weaker and non-significant for SCC and BCC. Conclusions These data largely confirm past studies on risk factors for skin cancer but provide evidence of difference on the strength of these risk factors for melanoma compared with SCC and BCC.

Current evidence about the association between pioglitazone and bladder cancer risk remains conflict. We aimed to assess the risk of bladder cancer associated with the use of pioglitazone and identify modifiers that affect the results. We systematically searched PubMed, Embase, and Cochrane Central Register of Controlled Trials from inception to 25 August 2016 for randomized controlled trials (RCTs) and observational studies that evaluated the association between pioglitazone and bladder cancer risk. Conventional and cumulative meta‐analyses were used to calculate the odds ratio (OR) with 95% confidence interval (CI). A restricted spline regression analysis was used to examine the dose–response relationship with a generalized least‐squares trend test. We included two RCTs involving 9114 patients and 20 observational studies (n = 4,846,088 individuals). An increased risk of bladder cancer in patients treated with pioglitazone versus placebo was noted from RCTs (OR, 1.84; 95%CI, 0.99 to 3.42). In observational studies, the increased risk of bladder cancer was slight but significant among ever‐users of pioglitazone versus never‐users (OR, 1.13; 95%CI, 1.03 to 1.25), which appeared to be both time‐ (P = 0.003) and dose‐dependent (P = 0.05). In addition, we observed the association differed by region of studies (Europe, United States, or Asia) or source of funding (sponsored by industry or not). Current evidence suggests that pioglitazone may increase the risk of bladder cancer, possibly in a dose‐ and time‐dependent manner. Patients with long‐term and high‐dose exposure to pioglitazone should be monitored regularly for signs of bladder cancer.

Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7–11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10⁻⁸) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. We identify an additional four susceptibility loci: 11q23.3 CADM1, a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR, the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A, a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma.