Potential Risk Factors for Cutaneous Squamous Cell Carcinoma include Oral Contraceptives: Results of a Nested Case-Control Study

Recently, a population-based case-control study observed a 60% increased odds ratio (OR) for cutaneous squamous cell carcinoma (SCC) among women who had ever used oral contraceptives (OCs) compared with non users (95% confidence interval (CI) = 1.0–2.5). To further characterize the putative association between OC use and SCC risk, we conducted a nested case-control study using a large retrospective cohort of 111,521 Kaiser Permanente Northern California members. Multivariable conditional logistic regression was used to estimate ORs and CIs adjusting for known and hypothesized SCC risk factors. Pre-diagnostic OC use was associated with a statistically significant increased OR for SCC in univariate analysis (OR = 2.4, CI = 1.2–4.8), with borderline statistical significance in multivariable analysis (CI = 2.0, CI = 0.91–4.5). Given the high incidence of SCC in the general population and the prevalent use of OCs among women in the United States, there is a need for more large, carefully designed epidemiologic studies to determine whether the observed association between OC use and SCC can be replicated and to better understand the etiologic basis of an association if one exists

PPARβ activation inhibits melanoma cell proliferation involving repression of the Wilms’ tumour suppressor WT1

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that strongly influence molecular signalling in normal and cancer cells. Although increasing evidence suggests a role of PPARs in skin carcinogenesis, only expression of PPARγ has been investigated in human melanoma tissues. Activation of PPARα has been shown to inhibit the metastatic potential, whereas stimulation of PPARγ decreased melanoma cell proliferation. We show here that the third member of the PPAR family, PPARβ/δ is expressed in human melanoma samples. Specific pharmacological activation of PPARβ using GW0742 or GW501516 in low concentrations inhibits proliferation of human and murine melanoma cells. Inhibition of proliferation is accompanied by decreased expression of the Wilms’ tumour suppressor 1 (WT1), which is implicated in melanoma proliferation. We demonstrate that PPARβ directly represses WT1 as (1) PPARβ activation represses WT1 promoter activity; (2) in chromatin immunoprecipitation and electrophoretic mobility shift assays, we identified a binding element for PPARβ in the WT1 promoter; (3) deletion of this binding element abolishes repression by PPARβ and (4) the WT1 downstream molecules nestin and zyxin are down-regulated upon PPARβ activation. Our findings elucidate a novel mechanism of signalling by ligands of PPARβ, which leads to suppression of melanoma cell growth through direct repression of WT1

State of the science 60th anniversary review

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/60971/1/23643_ftp.pd

Meta-analysis of the relation between European and American smokeless tobacco and oral cancer

<p>Abstract</p> <p>Background</p> <p>Smokeless tobacco is often referred to as a major contributor to oral cancer. In some regions, especially Southeast Asia, the risk is difficult to quantify due to the variety of products, compositions (including non-tobacco ingredients) and usage practices involved. In Western populations, the evidence of an increased risk in smokeless tobacco users seems unclear, previous reviews having reached somewhat differing conclusions. We report a detailed quantitative review of the evidence in American and European smokeless tobacco users, and compare our findings with previous reviews and meta-analyses.</p> <p>Methods</p> <p>Following literature review a meta-analysis was conducted of 32 epidemiological studies published between 1920 and 2005 including tests for homogeneity and publication bias.</p> <p>Results</p> <p>Based on 38 heterogeneous study-specific estimates of the odds ratio or relative risk for smokeless tobacco use, the random-effects estimate was 1.87 (95% confidence interval 1.40–2.48). The increase was mainly evident in studies conducted before 1980. No increase was seen in studies in Scandinavia. Restricting attention to the seven estimates adjusted for smoking and alcohol eliminated both heterogeneity and excess risk (1.02; 0.82–1.28). Estimates also varied by sex (higher in females) and by study design (higher in case-control studies with hospital controls) but more clearly in studies where estimates were unadjusted, even for age. The pattern of estimates suggests some publication bias. Based on limited data specific to never smokers, the random-effects estimate was 1.94 (0.88–4.28), the eight individual estimates being heterogeneous and based on few exposed cases.</p> <p>Conclusion</p> <p>Smokeless tobacco, as used in America or Europe, carries at most a minor increased risk of oral cancer. However, elevated risks in specific populations or from specific products cannot definitely be excluded.</p

Skin cancer in relation to tobacco use and organ transplantation

Background: Skin cancer incidence in fair-skinned populations has increased more rapidly than any other cancer form during the past several decades. The possible impact of common exposures in the population, such as tobacco use and overweight/obesity, is not established. The risk of cutaneous squamous cell carcinoma (CSCC) in organ transplant recipients (OTR) is substantially increased, although the underlying mechanism is not known. From previous studies of multi-drug regimens it has been suggested that risk of post-transplant CSCC is conferred by an overall immunosuppressive burden rather than by specific drugs. Aims and methods: The first aim of this thesis was to evaluate the impact of tobacco use and body mass index (BMI) on the risk of CSCC and cutaneous malignant melanoma (CMM), melanoma in situ (MIS), and intraocular malignant melanoma (IMM). To accomplish this aim we analyzed a large retrospective cohort of Swedish male construction workers (n≈340 000) with prospectively collected exposure information and virtually complete follow-up. The second aim was to separate the effects on post-transplant CSCC occurrence of immunosuppressive level, infections, immunosuppressive drug use, and other potential risk factors. For this purpose we designed a case-control study, nested in the population-based cohort of OTRs (n≈6 000), and collected detailed exposure information from patient medical records by use of a standardized questionnaire. Results: Current smokers were associated with a 30-50% risk reduction of CMM, MIS and IMM, compared to never tobacco users. Risk of CMM and MIS decreased with increasing smoking duration and quantity. Similarly, exclusive users of cigarettes, pipe and snuff were at reduced risks of CMM and MIS. Tobacco smoking was, however, unrelated to risk of CSCC. Snuff use was associated with a 40% decreased risk of CSCC, compared to non-tobacco users. A BMI ≥25 kg/m2 was associated with a 1.3-fold increased risk of CMM, compared to a BMI<25 kg/m2, but there was no effect on risk of MIS, IMM or CSCC. Azathioprine (Aza) treatment was found to considerably increase the risk of CSCC during all time periods analyzed post-transplantation. Additionally, a high accumulated dose of corticosteroids (Cs) after longer treatment durations conferred an increased risk of CSCC, compared to a very low accumulated dose of Cs. Cyclosporine treatment was unrelated to risk of CSCC. There were no significant associations between number or type of post-transplant infections and CSCC. HLA type and mismatch, number of transplantations and rejections, type of organ, as well as donor characteristics were not associated with risk of CSCC in OTRs. Conclusions: In our study, tobacco use was associated with a decreased risk of CMM and MIS, but unrelated to risk of CSCC. Likewise, we found a relation between overweight/obesity and an increased risk of CMM, but not of CSCC, MIS or IMM. These findings need further research in order to understand the underlying mechanisms. Post-transplant CSCC development seems not to be a result of immunosuppressive burden, instead we found important differences in risk conferred by specific immunosuppressive drugs. Other transplant-related factors were not associated with CSCC risk in our study. Future studies are required to further separate the direct carcinogenic, and the indirect immunosuppressive, effects of immunosuppressive drugs on risk of CSCC in OTRs and in other patient groups

Tobacco smoking, snuff dipping and the risk of cutaneous squamous cell carcinoma: A nationwide cohort study in Sweden

We investigated whether tobacco use causes cutaneous squamous cell carcinoma (CSCC) in a large cohort study with complete and long-term follow-up. A total of 756 incident cases occurred in a cohort of 337 311 men during a 30-year follow-up period, but no association was found between any kind of smoking tobacco use and CSCC risk, nor any risk change with increasing dose, duration or time since smoking cessation. Snuff use was associated with a decreased risk of CSCC. Overall, our study provides no evidence that tobacco use increases the risk of CSCC. \ua9 2005 Cancer Research UK

The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index

Background: The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown. Objectives: We designed a study to examine the effect of body mass index (BMI) and tobacco use on the risk for MM and MIS. Methods: Analyses were performed on a nationwide cohort of 339 802 Swedish construction workers. Exposure information was collected prospectively by questionnaires combined with personal interviews. Results: Follow up yielded a total of 7 663 400 person-years during which 1639 workers developed MM/MIS. The risk for MM/MIS was reduced in current or previous smokers compared with those who had never smoked, both when analysing all smoking tobacco products combined and when analysing cigarette and pipe smokers separately. The risk was further diminished with longer duration of smoking and greater quantity of tobacco smoked. The effect was more evident in CMM/MIS than in IMM. Snuff taking conferred a decreased risk for CMM/MIS, and a BMI over normal weight range conferred an increased risk for CMM. Conclusions: Tobacco smoking was found to be inversely associated with the risk for CMM and MIS. The mechanism of action is unknown but it has been suggested to be due to the immune suppressive effect that tobacco exerts which would be protective against deleterious immune reactions caused by, for example, the sun. Neither is the mechanism behind the higher risk for CMM due to being overweight known. One hypothesis is that it is an effect of a hormonal imbalance. Further studies are required to elucidate these mechanisms. \ua9 2007 British Association of Dermatologists

Tobacco use, body mass index, and the risk of leukemia and multiple myeloma: A nationwide cohort study in Sweden

In a prospective cohort study of more than 330,000 Swedish construction workers, we explored the effect of tobacco smoking, oral moist snuff use, and body mass index (BMI) on the risk of developing leukemia (excluding chronic lymphocytic leukemia) and multiple myeloma (MM). Study subjects were participants of a health surveillance system within the building industry. Record linkage to the nationwide Swedish cancer registry, migration registry, and cause of death registry made a comprehensive follow-up available. A total of 372 incident cases of leukemia and 520 subjects with MM was ascertained. An increase in risk of acute myelogenous leukemia (AML) was observed in current smokers (incidence rate ratio, 1.50; 95% confidence interval, 1.06-2.11). Furthermore, there was an indication of a possible association between smoking intensity and risk of acute lymphocytic leukemia. Results on snuff use as well as BMI showed no association. This study confirms the role of smoking as a risk factor for AML and gives no support to the hypothesis of a role of snuff use or BMI level on the risk of leukemia or MM. ©2007 American Association for Cancer Research