Search

This nationwide nested case–control study examined the association between statin use and risk of cutaneous melanoma. We included 12 048 adult patients with melanoma and 117 895 randomly selected cancer-free controls, matched on age and sex. Cancer data were obtained from the Cancer Registry of Norway and data on drug use was retrieved from the Norwegian Prescription Database. We estimated rate ratios with 95% confidence intervals and conducted sensitivity analyses. We observed an inverse dose–response association between statin use and melanoma risk, stronger in women. The highest statin intake was associated with a reduced risk of melanoma, particularly on the head/neck and lower limbs. Our finding may have implications for melanoma prevention in high-risk groups.

Organ transplant recipients (OTRs) are at greater risk of basal cell carcinomas (BCCs) than non-OTRs, but histopathologic differences between BCCs in OTRs and the general population are largely unknown. We compared clinicopathologic features of BCCs in OTRs vs the general population in Queensland, Australia. Details of BCC tumors (site, size, level of invasion, subtype, biopsy procedure) were collected from histopathology reports in two prospective skin cancer studies, one in OTRs and one general-population-based. We used log-binomial regression models to estimate age- and sex-adjusted prevalence ratios (PR) with 95% confidence intervals (CIs) for BCC features. Overall, there were 702 BCCs in 200 OTRs and 1725 BCCs in 804 population cases. Of these, 327 tumors in 128 OTRs were higher risk BCCs (any head and neck BCC; ≥ 2 cm on trunk/extremities), more per person than 703 higher risk BCCs in 457 cases in the general population (chi-square p = 0.008). Among head/neck BCCs, OTRs were more likely than general population cases to have BCCs on scalp/ear than on face/lip/neck (PR = 1.5, 95%CI 1.2–1.8). Although aggressive subtypes were less common among higher risk BCCs in OTRs, BCCs invading beyond the dermis were almost twice as prevalent in OTRs (PR = 1.8, 95% CI 1.3–2.6) than the general population.

Despite the established causal links to skin cancer, skin ageing and eye inflammation, people continue to use indoor tanning devices (hereafter 'sunbeds'). Understanding the reasons underlying the use of sunbeds is essential for developing effective interventions. The purpose of this study was to collate all existing evidence from qualitative papers published to date that had assessed motivations for using sunbeds.Six databases were searched from inception to February 2020 for qualitative studies that explored adults' experiences of using sunbeds. Sixteen studies met the inclusion criteria, and a narrative evidence synthesis was used to collate findings from each primary study.Users of sunbeds were motivated primarily by aesthetic concerns but also by perceived psychological benefits (well-being, confidence and 'fitting in') and physical benefits (improvement in skin conditions such as acne, acquiring vitamin D and preventing sunburn). People also chose indoor tanning over alternatives such as fake tans because they considered the alternatives unacceptable and did not consider indoor tanning a serious health risk. To date, no studies have explored alternatives to meeting non-aesthetic needs related to the use of sunbeds.This comprehensive explanation for the practice of indoor tanning provides the basis for development of complex interventions to reduce the harm caused by using sunbeds. Effective interventions should include promotion of alternatives, such as different methods of relaxing, to satisfy underlying motivations, changing social norms and correcting misperceptions about health benefits.

PDF file - 45K, Associations between cumulative HPV load and SCC, stratified by skin type and time since transplantation (for OTR). In each case the reference category is HPV negative combined with the lowest load tertile.

Background: Beta-human papillomavirus (betaPV) may play a role in the development of cutaneous squamous cell carcinoma (SCC). However betaPV is highly prevalent, and it may only be people with a higher viral load who have increased risk of SCCs. We therefore examined the association between betaPV load and SCCs.Methods: We recruited 448 immunocompetent cases with SCCs and 464 controls from Italy and Australia and 497 immunosuppressed organ transplant recipients (OTR; 179 cases and 318 controls) from Europe. We used reverse hybridization to genotype 25 betaPV types in eyebrow hair follicles and determined the viral load for eight selected types using quantitative PCR. We used logistic regression to assess associations between type-specific and cumulative viral load and SCCs.Results: Australian and OTR participants in the highest cumulative load tertile were at significantly higher risk of SCCs than those in the lowest tertile. Those with more than four betaPV types in the high load tertile were at approximately three-fold increased risk of SCCs. In Australia, HPV23 and 36 loads were significantly associated with SCCs, with borderline associations for HPV5 and 38. In OTR, HPV8 and 38 loads were significantly associated and HPV20 and 36 were borderline. We found little evidence for an association between load and SCCs in Italy.Conclusions: High viral load may be associated with risk of cutaneous SCCs, with total load seemingly more important than the load of any specific type.Impact: Our findings lend weight to the hypothesis that HPV plays a role in skin carcinogenesis. Cancer Epidemiol Biomarkers Prev; 22(4); 719–27. ©2013 AACR.

High-risk susceptibility genes explain CCND1, CCND2, CCND3, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, CDKN2A, CDKN2B, CDKN2C, and CDKN2D—and risk of invasive epithelial ovarian cancer. We used a two-stage, multicenter, case-control study. In stage 1, 88 SNPs that tag common variation in these genes were genotyped in three studies from the United Kingdom, United States, and Denmark (∼1,500 cases and 2,500 controls). Genotype frequencies in cases and controls were compared using logistic regression. In stage 2, eight other studies from Australia, Poland, and the United States (∼2,000 cases and ∼3,200 controls) were genotyped for the five most significant SNPs from stage 1. No SNP was significant in the stage 2 data alone. Using the combined stages 1 and 2 data set, CDKN2A rs3731257 and CDKN1B rs2066827 were associated with disease risk (unadjusted P trend = 0.008 and 0.036, respectively), but these were not significant after adjusting for multiple testing. Carrying the minor allele of these SNPs was found to be associated with reduced risk [OR, 0.91 (0.85–0.98) for rs3731257; and OR, 0.93 (0.87–0.995) for rs2066827]. In conclusion, we have found evidence that a single tagged SNP in both the CDKN2A and CDKN1B genes may be associated with reduced ovarian cancer risk. This study highlights the need for multicenter collaborations for genetic association studies. [Cancer Res 2007;67(7):3027–35]

Supplementary Figure 1 from Persistence of Betapapillomavirus Infections as a Risk Factor for Actinic Keratoses, Precursor to Cutaneous Squamous Cell Carcinoma

Human papillomaviruses from the β genus (βPV) are a possible cause of cutaneous squamous cell carcinoma (SCC). We assessed the extent to which βPV infections persisted long-term in a subtropical Australian community and whether βPV persistence is positively associated with actinic keratoses, precursor for SCC. Eyebrow hairs were collected from 171 participants of the community-based Nambour Skin Cancer Study in 1996 and 2003. Hair samples were tested for the presence of DNA from 25 different βPV types and assessed in relation to actinic keratosis presence in 2007. In 1996, a total of 413 βPV infections were found in 73% of participants, increasing to 490 infections among 85% in 2003. Of the total βPV infections detected, 211 (30%) were found to persist. Age was significantly associated with βPV persistence: those ages >60 years had 1.5-fold (95% confidence interval, 1.1-1.9) increased risk of type-specific viral persistence than those ages

Supplementary Tables 1-4 from Tagging Single Nucleotide Polymorphisms in Cell Cycle Control Genes and Susceptibility to Invasive Epithelial Ovarian Cancer

Supplementary Figure Legend from Persistence of Betapapillomavirus Infections as a Risk Factor for Actinic Keratoses, Precursor to Cutaneous Squamous Cell Carcinoma

Background: Evidence suggests that consumption of dark green leafy vegetables may influence the decrease in the risk of cutaneous squamous cell carcinoma (SCC). Dark green leafy vegetables contain folate as a main component among other nutrients; thus, we hypothesised that their possible observed protective effect on SCC, observed in previous studies, would be more evident in persons with specific genotypes related to folate metabolism. Methods: Genotyping of methylenetetrahydrofolate reductase (MTHFR) gene variants rs1801133 (C677T) and rs1801131 (A1298C) was carried out for 1,128 participants in an Australian community-based longitudinal study of skin cancer. Dietary intakes were assessed through repeated Food Frequency Questionnaires (1992–1996), and all incident skin cancers were recorded in 1992–2007 and histologically confirmed. We assessed associations between intake of dark green leafy vegetables and SCC development in strata defined by genotype, by calculating relative risks (RRs) with 95% confidence intervals (CIs) using generalised linear models with negative binomial distribution and person-years of follow-up as offset. Results: High versus low intake of dark green leafy vegetables was associated with a lower risk of SCC tumours in carriers of the C677T variant allele (RR = 0.42, 95% CI = 0.23–0.75), and within wild-type A1298C homozygotes (RR = 0.43, 95% CI = 0.22–0.85). Conclusion: The protective effect of dark green leafy vegetables on cutaneous SCC may be genotype-dependent. Folate metabolism-related gene polymorphisms should be considered when assessing the relation of green leafy vegetables to cancer risk.

Background The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients. Objectives To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. Methods OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. Results Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar. Conclusions Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials. What is already known about this topic? Cutaneous squamous cell carcinoma (cSCC) is significantly more common in immunocompromised individuals including organ transplant recipients (OTRs) compared with immunocompetent populations. cSCC chemoprevention activity of sunscreen and 5-fluorouracil-based (5-FU) actinic keratosis (AK) treatments has been demonstrated in randomized controlled trials (RCTs) in immunocompetent populations but not in OTRs. AKs are cSCC precursors and their clearance and prevention are generally regarded as surrogate endpoint biomarkers for potential cSCC chemoprevention activity. What does this study add? SPOT (SCC Prevention in OTRs using Topical treatments) has confirmed that RCTs of OTR-cSCC chemoprevention with topical AK treatments are feasible. It also suggests that topical 5-FU may be superior to 5% imiquimod and sunscreen in AK clearance and prevention. Together with recent evidence from several RCTs in the general population, these data provide a compelling rationale for further studies of intervention with 5-FU-based topical chemoprevention approaches in OTR-cSCC prevention.

Background Cutaneous melanomas are common cancers in white-skinned populations, and early detection is promoted as a means of reducing morbidity and mortality. There is concern that increased skin screening is leading to overdiagnosis of indolent melanomas with low risk of lethality. The extent of melanoma overdiagnosis associated with screening is unknown. Objectives To estimate possible overdiagnosis by comparing subsequent melanoma incidence and biopsy rates among people subjected to skin screening those who were not. Methods We recruited 43 762 residents of Queensland, Australia, aged 40–69 years, with no prior history of melanoma, selected at random from a population register in 2010. At baseline, participants completed a comprehensive melanoma risk factor survey and were asked if their skin had been examined by a doctor in the 3 years prior to baseline. We calculated incidence and relative risk of histologically confirmed melanoma (invasive and in situ) in years 2–7 of follow-up, obtained through linkage to the cancer registry. In secondary analyses, we measured biopsy rates in years 2–6 of follow-up. We used propensity score analysis to calculate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs). Results In total, 28 155 participants underwent skin screening prior to baseline. We observed 967 first-incident melanomas (381 invasive) during 197 191 person-years of follow-up. Those screened had higher rates of melanoma (aHR 1·29, 95% CI 1·02–1·63) and subsequent skin biopses (aHR 1·85, 95% CI 1·69–2·04) than unscreened participants. The higher risk associated with skin screening was evident for in situ melanoma (aHR 1·45, 95% CI 1·09–1·92) but not invasive melanoma (aHR 1·05, 95% CI 0·72–1·54). In secondary analyses, where screening was defined as having a skin biopsy in the first year after baseline, we observed significantly increased risks of melanoma (aHR 1·53, 95% CI 1·23–1·89) and subsequent biopsies (aHR 2·64, 95% CI 2·46–2·84) relative to those who did not have a biopsy. Conclusions People who undergo skin screening subsequently experience higher rates of biopsies and melanoma (especially in situ melanoma), even after adjusting for all known risk factors, consistent with overdiagnosis. What is already known about this topic? Cutaneous melanomas are common cancers in white-skinned populations for which early detection is promoted as a means of reducing morbidity and mortality.There is concern that increased surveillance is leading to the overdiagnosis of indolent melanomas that are not destined to be lethal.The extent of melanoma overdiagnosis associated with surveillance is not known. What does this study add? People subjected to skin examinations by a doctor or who undergo skin biopsies subsequently have higher numbers of biopsies and higher rates of melanoma than people not subjected to either, even after adjusting for all known risk factors.These findings suggest that heightened surveillance leads to a proportion of melanomas being diagnosed that otherwise may not have come to clinical attention.

Based on molecular evidence that melanomas with unknown primary (MUPs) arise from the skin, we hypothesised that sites of MUPs are disproportionately on trunk and lower limbs, sites that are not readily visible to patients and clinicians. We tested this hypothesis by inferring the anatomic site of origin of MUPs from the corresponding known cutaneous sites of melanoma patients with known primary tumours (MKPs). We analysed data from three separate cohorts of patients from Brisbane, Australia (n = 236); Manchester, UK (n = 51) and Padova, Italy (n = 33), respectively, who first presented with stage III melanoma with lymph node metastases. We matched two MKP patients to each MUP patient based on lymph node dissection (LND) site, age and sex, and imputed cutaneous sites of origin of MUPs from their two matched MKPs for study countries, giving two possible sites for each MUP per centre. Overall, results showed that MUP patients were predominantly male, and trunk was the most likely origin, comprising around a third to a half of MUPs across the three cohorts. The remaining MUP inferred sites varied by country. In the Australian cohort, the legs accounted for a third of imputed sites of MUPs, while in the UK and Italian cohorts, the most frequent site was the arms followed by the legs. Our findings suggest the need for regular and thorough skin examination on trunk and limbs, especially in males, to improve early detection of cutaneous melanoma and reduce the risk of metastatic disease at the time of presentation. © 2022 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.

BACKGROUND Digital 3D total-body photography of the skin surface is an emerging imaging modality that can facilitate the identification of new and changing nevi. OBJECTIVE We aimed to describe the experiences of study participants drawn from the general population who were provided 3D total-body photography and dermoscopy for the monitoring of nevi. METHODS A population-based prospective study of adults aged 20-70 years from South East Queensland, Australia was conducted. Participants underwent 3D total-body photography and dermoscopy every 6 months over a 3-year period. Participants were asked to provide closed and open-ended feedback on their 3D total-body photography and dermoscopy experience (eg, comfort, trust, intended future use, and willingness to pay) at the halfway study time point (18 months) and final study time point (36 months). We assessed changes in participants’ reported experience of 3D total-body photography, and patient characteristics associated with patient experience at the end of the study (36 months) were analyzed. RESULTS A total of 149 participants completed the surveys at both the 18- and 36-month time points (median age 55, range 23-70 years; n=94, 63.1% were male). At the 18-month time point, most participants (n=103, 69.1%) stated they completely trusted 3D total-body imaging for the diagnosis and monitoring of their nevi, and this did not change at the 36-month (n=104, 69.8%) time point. The majority of participants reported that they were very comfortable or comfortable with the technology at both the 18- (n=138, 92.6%) and 36-month (n=140, 94%) time points, respectively; albeit, the number of participants reporting that they were very comfortable reduced significantly between the 18- and 36-month time points, from 71.1% (n=106) to 61.1% (n=91; P=.01). Almost all participants (n=140, 94%) would consider using this technology if it were to become commercially available, and this did not change during the two study time points. Half of the participants (n=74) cited barriers to participating in 3D total-body photography, including trust in the ability of this technology to detect and monitor suspicious lesions, digital privacy, cost, and travel requirements. CONCLUSIONS The majority of participants expressed positive attitudes toward 3D total-body photography for the monitoring of their moles. Half of the participants identified potential barriers to uptake.

BACKGROUND: The use of indoor tanning devices causes melanoma and other skin cancers with resulting morbidity, mortality and increased healthcare costs. Policy-makers require robust economic evidence to inform decisions about a possible ban of such devices to mitigate these burdens.OBJECTIVES: To assess the health costs and consequences of introducing a policy-based intervention across England to ban commercial indoor tanning with an accompanying public information campaign.METHODS: A cost-effectiveness analysis, adopting a healthcare system perspective, was conducted using a decision-model to track a national cohort of 18-year-olds over a lifetime time horizon. A nationwide ban on commercial indoor tanning combined with a public information campaign (the policy-based intervention) was compared with the status quo of availability of commercial indoor tanning. The expected costs (currency: GBP, price year: 2019) and Quality Adjusted Life Years (QALYs) were calculated. Net Monetary Benefit (NMB; net benefit measured in cost compared to an accepted threshold) and Net Health Benefit (NHB; net gain in QALYs compared to an accepted threshold) of implementation were calculated. A probabilistic sensitivity analysis was used to calculate the probability the intervention was cost-effective.RESULTS: Compared to the current situation, a ban on commercial indoor tanning combined with a public information campaign would result in 1,206 avoided cases of melanoma, 207 fewer melanoma deaths, and 3,987 averted cases of keratinocyte cancers over the lifetime of all 18-year-olds (n=618,873) living in England in 2019. An additional 497 QALYs would be realised along with healthcare cost-savings of £697,858. This intervention would result in an NMB of £10.6m and a NHB of 530 QALYS. Multiple sensitivity analyses confirmed the robustness of findings. At a cost-effectiveness threshold of £20,000, there is a 99% likelihood of this policy-based intervention being cost-effective.CONCLUSIONS: The implementation of a ban on commercial indoor tanning across England with an accompanying public information campaign would be an effective use of healthcare resources.

Knowledge about factors associated with melanoma thickness, the most important prognostic factor for localized primary melanoma survival,1 may help reduce the risk of melanoma deaths. Previously reported associations of melanoma thickness with pigmentary characteristics, number of naevi, diet quality and body mass index (BMI)2–4 may be explained by behavioural and biological mechanisms. Physical activity (PA) has been associated with improved outcomes for several cancers,5 but its relation with melanoma thickness and prognosis is unknown.

Background Most antihypertensives can induce dermal photosensitivity, which may increase melanoma risk. However, corroborating evidence is limited. We examined the associations between use of antihypertensives and melanoma risk. Methods A nationwide nested case-control study was conducted using data from the Cancer Registry of Norway, the National Registry and the Norwegian Prescription Database in 2004–15. Ten controls were randomly selected for each melanoma case, matched on sex and birth year. The study included 12 048 cases and 117 895 controls. We estimated rate ratios (RRs) with 95% confidence intervals (CIs). All analyses were adjusted for ambient ultraviolet radiation (UVR). We additionally performed active comparator analyses, and sensitivity analyses by only including new users, distinguishing between exclusive and mixed users, allowing for different latency periods, and subgroup analyses by melanoma subtype and clinical stage. Results Compared with non-use, we observed a slightly increased melanoma risk in users of diuretics (RR 1.08, CI 1.01–1.15), calcium-channel blockers (RR 1.10, CI 1.04–1.18) and drugs affecting the renin-angiotensin system (RR 1.10, CI 1.04–1.16), but not for beta blockers (RR 0.97, CI 0.92–1.03). We found no heterogeneity of associations by melanoma subtype or clinical stage and no dose-response relationship between the cumulative defined daily doses (DDDs) and melanoma. No interaction was found between cumulative DDDs and ambient UVR. Conclusions Weak associations, with lack of a dose-response relationship and lack of interactions with ambient UVR, in the DDD analysis in this nationwide study do not support a causal relationship between antihypertensives and melanoma risk.

Background Sonic Hedgehog (SHH) pathway dysregulation is implicated in basal cell carcinoma (BCC) development. To evaluate the possible wider role of SHH gene variants in skin carcinogenesis, we assessed associations of genes in the SHH pathway with lifetime development of any keratinocyte cancer (KC), and with developing either BCCs or squamous cell carcinomas (SCCs) exclusively, in a 25-year prospective, population-based study of 1,621 Australians. Methods We genotyped 795 unrelated adults with available blood samples: 311 cases with any KC (186 developing BCCs-only, 55 SCCs-only, 70 BCCs and SCCs) and 484 controls. We compared allele frequencies of 158 independent SNPs across 43 SHH genes between cases and controls, and performed a gene-based analysis. Results We found associations between SNP rs4848627 (GLI2) (related to DNA synthesis in keratinocytes) and development of any KC (OR = 1.53; 95% CI = 1.06–2.13, P P CCND2 was associated with exclusive BCC development (OR = 1.43, CI = 1.12–1.82, P PRKACG (protein kinase cAMP-activated catalytic subunit gamma) with any KC (P = 0.013). Conclusion We conclude that variants located in genes in the SHH pathway may are involved in SCC as well as BCC development.

Human papillomaviruses (HPVs) cause superficial epidermal infections and are only cleared if they trigger an immunological response. We analysed SNPs that had previously been investigated for association with HPV infection to determine whether they play a role in the serological response to cutaneous beta-HPVs in an Australian population. Serum samples from 1,142 participants were analysed for seropositivity against the L1 protein of 21 beta-HPV types. Associations between seropositivity to beta-HPV types and the SNPs rs9264942 (HLA-C; HPV-9, p = 0.022, HPV-15, p = 0.043 and HPV-17, p = 0.004), rs12449858 (EVER1; HPV-23, p = 0.029), and rs2981451 (FGFR2; HPV-22, p = 0.049) were identified. We found that certain SNPs could be involved in the serological response to beta-HPVs.

Purpose Cutaneous melanoma is among the fastest growing malignancies in Norway and ultraviolet radiation (UVR) exposure is the primary environmental risk factor. Immunomodulating drugs can increase skin photosensitivity and suppress immune responses, and by such mechanisms influence melanoma risk. We, therefore, aimed to examine the associations between use of immunomodulating drugs and melanoma risk, at a nationwide population level. Patients and Methods In the Cancer Registry of Norway, we identified all cases aged 18–85 with a first primary cutaneous melanoma diagnosed in 2007–2015 (n=12,106). These were matched to population controls from the Norwegian National Registry 1:10 (n=118,564), on sex and year of birth using risk set sampling. Information on prescribed drugs (2004–2015) was obtained by linkage to the Norwegian Prescription Database (NorPD). Conditional logistic regression was used to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for associations between use of immunomodulating drugs (immunosuppressants and corticosteroids) and melanoma risk, adjusted for ambient UVR and other drug use. Results Compared with ≤1 prescription, use of ≥8 prescriptions of immunosuppressants was associated with increased risk of melanoma (RR 1.50, 95% CI 1.27, 1.77). Similar associations were found for subgroups of immunosuppressants: drugs typically prescribed to organ transplant recipients (OTRs) (RR 2.02, 95% CI 1.35, 3.03) and methotrexate (RR 1.27, 95% CI 1.04, 1.55). Similar results were found for high levels of cumulative doses and across all histological subtypes. Use of corticosteroids was not associated with melanoma risk. Conclusion We found a positive association between use of immunosuppressants and melanoma risk, with the highest risk seen for drugs prescribed to OTRs. Knowledge about this risk increase is important for physicians and users of these drugs, for intensified surveillance, awareness and cautious sun exposure.

Purpose Melanoma is the cancer with the most rapidly rising incidence rate in Norway. Although exposure to ultraviolet radiation (UVR) is the major environmental risk factor, other factors may also contribute. Antidepressants have cancer inhibiting and promoting side effects, and their prescription rates have increased in parallel with melanoma incidence. Thus, we aimed to prospectively examine the association between use of antidepressants and melanoma by using nation-wide data from the Cancer Registry of Norway, the National Registry, the Norwegian Prescription Database and the Medical Birth Registry of Norway. Patient and Methods All cases aged 18–85 with a primary cutaneous invasive melanoma diagnosed during 2007–2015 (n=12,099) were matched to population controls 1:10 (n=118,467) by sex and year of birth using risk-set sampling. We obtained information on prescribed antidepressants and other potentially confounding drug use (2004–2015). Conditional logistic regression was used to estimate adjusted rate ratios (RRs) and 95% confidence intervals (CIs) for the association between overall and class-specific use of antidepressants and incident melanoma. Results Compared with ≤1 prescription, ≥8 prescriptions of antidepressants overall were negatively associated with melanoma (RR 0.81 CI 0.75–0.87). Class-specific analyses showed decreased RRs for selective serotonin reuptake inhibitors (RR 0.82 CI 0.73–0.93) and mixed antidepressants (RR 0.77 CI 0.69–0.86). The negative association was found for both sexes, age ≥50 years, residential regions with medium and highest ambient UVR exposure, all histological subtypes, trunk, upper and lower limb sites and local disease. Conclusion Use of antidepressants was associated with decreased risk of melanoma. There are at least two possible explanations for our results; cancer-inhibiting actions induced by the drug and less UVR exposure among the most frequent users of antidepressants.

Basal cell and squamous cell carcinomas of the skin are the commonest cancers in humans, yet no validated tools exist to estimate future risks of developing keratinocyte carcinomas. To develop a prediction tool, we used baseline data from a prospective cohort study (n = 38,726) in Queensland, Australia, and used data linkage to capture all surgically excised keratinocyte carcinomas arising within the cohort. Predictive factors were identified through stepwise logistic regression models. In secondary analyses, we derived separate models within strata of prior skin cancer history, age, and sex. The primary model included terms for 10 items. Factors with the strongest effects were >20 prior skin cancers excised (odds ratio 8.57, 95% confidence interval [95% CI] 6.73–10.91), >50 skin lesions destroyed (odds ratio 3.37, 95% CI 2.85–3.99), age ≥ 70 years (odds ratio 3.47, 95% CI 2.53–4.77), and fair skin color (odds ratio 1.75, 95% CI 1.42–2.15). Discrimination in the validation dataset was high (area under the receiver operator characteristic curve 0.80, 95% CI 0.79–0.81) and the model appeared well calibrated. Among those reporting no prior history of skin cancer, a similar model with 10 factors predicted keratinocyte carcinoma events with reasonable discrimination (area under the receiver operator characteristic curve 0.72, 95% CI 0.70–0.75). Algorithms using self-reported patient data have high accuracy for predicting risks of keratinocyte carcinomas.

Globally, 39% of the world's adult population is overweight or obese and 23% is insufficiently active. These percentages are even larger in high-income countries with 58% overweight/obese and 33% insufficiently active. Fourteen cancer types have been declared by the World Cancer Research Fund to be causally associated with being overweight or obese: oesophageal adenocarcinoma, stomach cardia, colon, rectum, liver, gallbladder, pancreas, breast, endometrium, ovary, advanced/fatal prostate, kidney, thyroid and multiple myeloma. Colon, postmenopausal breast and endometrial cancers have also been judged causally associated with physical inactivity. We aimed to quantify the proportion of cancer cases that would be potentially avoidable in Australia if the prevalence of overweight/obesity and physical inactivity in the population could be reduced. We used the simulation modelling software PREVENT 3.01 to calculate the proportion of avoidable cancers over a 25-year period under different theoretical intervention scenarios that change the prevalence of overweight/obesity and physical inactivity in the population. Between 2013 and 2037, 10-13% of overweight/obesity-related cancers in men and 7-11% in women could be avoided if overweight and obesity were eliminated in the Australian population. If everyone in the population met the Australian physical activity guidelines for cancer prevention (i.e. engaged in at least 300 min of moderate-intensity physical activity per week), an estimated 2-3% of physical inactivity-related cancers could be prevented in men (colon cancer) and 1-2% in women (colon, breast and endometrial cancers). This would translate to the prevention of up to 190,500 overweight/obesity-related cancers and 19,200 inactivity-related cancers over 25 years.

Cancer is a leading cause of disease burden in Australia, particularly fatal burden, accounting for an estimated thirty percent of deaths. Many cancers develop because of exposure to lifestyle and environmental factors that are potentially modifiable. We aimed to quantify the proportions and numbers of cancer deaths and cases in Australia in 2013 attributable to 20 modifiable factors in eight broad groupings that are established causes of cancer, namely: tobacco smoke (smoking and second-hand), dietary factors (low intake of fruit, non-starchy vegetables and dietary fibre; and high intake of red and processed meat), overweight/obesity, alcohol, physical inactivity, solar ultraviolet radiation, infections (seven agents), and reproductive factors (lack of breastfeeding, menopausal hormone therapy use, combined oral contraceptive use). We estimated population attributable fractions (PAF) using standard formulae incorporating exposure prevalence and relative risk data. Of all cancer deaths in Australia in 2013, approximately 38% overall (males 41%, females 34%) could be attributed to the factors assessed; the corresponding PAF for cancer cases was 33% (males 34%, females 32%). Tobacco smoke was the leading cause of cancer deaths and cases, with PAFs of 23 and 13%, respectively, followed by dietary factors (5% deaths/5% cases), overweight/obesity (5%/4%) and infections (5%/3%). Cancer sites with the highest numbers of potentially preventable deaths/cases were lung (n = 6,776/9,272), colorectum (n = 1,974/7,380) and cutaneous melanoma (n = 1,390/7,918). We estimate that about 16,700 cancer deaths and 41,200 cancer cases could be prevented in Australia each year if people's exposures to 20 causal factors were aligned with levels recommended to minimise cancer risk.

Although most women diagnosed with ovarian cancer initially respond to first-line chemotherapy, the vast majority eventually relapses and requires retreatment with second-line chemotherapy. Patient response is classified as either platinum sensitive or platinum resistant on the basis of the time of relapse after first-line treatment. A cancer with a progression-free interval of more than 6 months after completion of first-line chemotherapy is classified as “platinum-sensitive disease” and responds well to retreatment. A cancer with a progression-free interval of less than 6 months after completion of first-line chemotherapy is classified as “platinum-resistant disease” and responds poorly to second-line retreatment. Cure is not possible in patients with platinum-resistant recurrent ovarian cancer, and long-term progression-free survival is rare. The goal of care in these patients should be to maximize their quality of life. The aim of this population-based longitudinal study was to determine whether quality of life improves after second-line chemotherapy among women with platinum-resistant recurrent ovarian cancer. A secondary aim was to evaluate treatment response. Data for 172 women from 2 studies were combined. All participants were treated with chemotherapy for recurrent ovarian cancer and completed a validated quality of life questionnaire every 3 months. Change in quality of life during the first 6 months after second-line chemotherapy was analyzed using mixed effect models. A comparison group was composed of women with platinum-sensitive disease. Among the 172 patients, 44 (25%) were classified as having platinum-resistant disease. After the start of second-line chemotherapy, there was no significant increase or decrease in quality of life of women with platinum-resistant disease (least square mean scores at chemotherapy start, 3 months later, and 6 months later: 107, 105, and 103, respectively), although 26% reported a meaningful increase and 31% reported a meaningful decline. One third of the women with platinum-resistant cancer responded (11% complete and 21% partial response) to second-line chemotherapy; the response rate increased to 54% among the subset retreated with platinum-based agents with or without other agents. Preliminary subgroup analysis suggested that quality of life in women whose disease responded may be higher at the start of chemotherapy (median score, 121 vs 110). These findings show that the overall quality of life is maintained among women with recurrent platinum-resistant disease after retreatment with chemotherapy; however, some patients showed a meaningful increase whereas some showed a decline.

The vitamin D endocrine system is implicated in skin carcinogenesis and polymorphisms in genes associated with the vitamin D receptor (VDR) gene may alter the risk of keratinocyte cancers (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)).In a nested case-control study of 1,124 adults, we investigated associations between polymorphisms in VDR-related pathways and incident keratinocyte cancers during 11 years of follow-up using adjusted multivariate regression analysis. We also performed a meta-analysis of rs2228570, rs7975232, rs1544410 and rs739837 polymorphisms.A total of 286 BCCs and 161 SCCs were newly-diagnosed during follow-up. Participants with rs2228570 and rs927650 recessive genotypes had a decreased risk of SCC (odds ratio (OR)=0.34, 95% confidence interval (CI)=0.17-0.68; OR=0.48, CI=0.27-0.84, respectively). Meta-analysis showed a lower SCC risk in rs1544410 recessive genotypes (summary OR (SOR)=0.74, CI=0.53-0.94), while rs7975232 and rs739837 recessive genotypes were associated with a decreased BCC risk (SOR=0.74, CI=0.56-0.98; SOR=0.65, CI=0.43-0.88).Our meta-analysis indicated that vitamin D receptor polymorphisms may be associated with the risk of keratinocyte cancers.