Publications by authors named "David C Whiteman"

343 Publications

Polygenic Risk Scores Stratify Keratinocyte Cancer Risk among Solid Organ Transplant Recipients with Chronic Immunosuppression in a High Ultraviolet Radiation Environment.

J Invest Dermatol 2021 Jun 2. Epub 2021 Jun 2.

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Biomedical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, Australia.

Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high UVR environments. We assessed whether polygenic risk scores can improve the prediction of BCC and SCC risks and multiplicity over and above the traditional risk factors in SOTRs in a high UV setting. We built polygenic risk scores for BCC (n = 594,881) and SCC (n = 581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Sun and Health Study cohort (n > 6,300), and applied them in SOTRs in the skin tumor in allograft recipients cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk = 45.45%, 95% confidence interval = 33.14-58.19%) and SCC (absolute risk = 44.12%, 95% confidence interval = 32.08-56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to those in the bottom quintile. The respective polygenic risk scores improved risk predictions by 2% for BCC (area under the curve = 0.77 vs. 0.75, P = 0.0691) and SCC (area under the curve = 0.84 vs. 0.82, P = 0.0260), over and above the established risk factors, and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The polygenic risk scores also added predictive accuracy for tumor multiplicity (BCC R = 0.21 vs. 0.19, P = 3.2 × 10; SCC R = 0.30 vs. 0.27, P = 4.6 × 10).
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http://dx.doi.org/10.1016/j.jid.2021.03.034DOI Listing
June 2021

Polyunsaturated Fatty Acid Levels and the Risk of Keratinocyte Cancer: A Mendelian Randomization Analysis.

Cancer Epidemiol Biomarkers Prev 2021 Jun 4. Epub 2021 Jun 4.

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Background: Keratinocyte cancer is the commonest cancer, imposing a high economic burden on the health care system. Observational studies have shown mixed associations between polyunsaturated fatty acids (PUFA) and keratinocyte cancer, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). We explored whether genetically predicted PUFA levels are associated with BCC and SCC risks.

Methods: We conducted a two-sample Mendelian randomization study using PUFA level genome-wide association studies (GWAS) from the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium ( > 8,000), and the meta-analysis GWASs from UKB, 23andMe, and Qskin for BCC ( = 651,138) and SCC ( = 635,331) risk.

Results: One SD increase in genetically predicted levels of linoleic acid [OR = 0.94, 95% confidence interval (CI) = 0.91-0.97, = 1.4 × 10] and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, = 5.1 × 10) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, = 3.2 × 10) and eicosapentaenoic acid (OR = 1.10, 95% CI = 1.04-1.16, = 1.5 × 10) were associated with an increased BCC risk.

Conclusions: Higher genetically predicted levels of linoleic acid and alpha-linolenic acid were associated with a reduced BCC risk, but arachidonic acid and eicosapentaenoic acid were associated with a higher BCC risk.

Impact: PUFA-related diet and supplementation could influence BCC etiology.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1765DOI Listing
June 2021

Patient and Tumour Characteristics of Keratoacanthoma in a Large, Community-based Cohort Study from Queensland, Australia.

Acta Derm Venereol 2021 Jun 2;101(6):adv00469. Epub 2021 Jun 2.

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.

Keratoacanthomas are common keratinocyte skin tumours. However, there is little community-based data published on the clinical features of keratoacanthoma. The aim of this study was to describe the patient and tumour characteristics of keratoacanthomas, as well as their treatment patterns. Data were obtained from the QSkin Sun and Health study, a prospective cohort of 40,438 randomly sampled and consented participants aged 40-69 years in Queensland, Australia. In 2010, a baseline survey collected data, including demography, phenotype, ultraviolet radiation exposure, medical history and lifestyle. Histopathological reports of keratoacanthomas arising until 30 June 2014 were reviewed. In total, 584 participants developed 738 keratoacanthomas; 18% of participants developed multiple tumours. Common patient characteristics were male sex (58%), age ≥60 years (76%), fair skin (80%), and previous history of actinic keratoses/keratinocyte cancers (89%). Keratoacanthomas were commonly located on the legs/feet (48%), and rarely on the the head/neck (7%). Excision was the most frequently used surgical method (71%) Evidence of histopathological regression was reported in 67% of keratoacanthomas, suggesting a potential for spontan-eous resolution in a significant proportion of keratoacanthomas.
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http://dx.doi.org/10.2340/00015555-3824DOI Listing
June 2021

International Increases in Merkel Cell Carcinoma Incidence Rates between 1997 and 2016.

J Invest Dermatol 2021 Apr 28. Epub 2021 Apr 28.

Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, Australia; Faculty of Medicine, The University of Queensland, Brisbane, Australia. Electronic address:

Relatively little is known about the epidemiology of Merkel cell carcinoma (MCC) with regard to international trends in incidence, specifically relating to differences by age, sex, and anatomic site. We examined the trends in sex-specific incidence of MCC in the United States, Australia, New Zealand, Scotland, and Norway over a 20-year period (1997-2016) as well as the site-specific incidence trends in the United States. We used Joinpoint regression models to estimate the average annual percentage change in the incidence. In the total United States population, we observed an average annual percentage change of 2.7% (95% confidence interval [CI] = 2.0-3.3) for MCC, with sex-specific incidence increasing from 0.55 to 1.03 per 100,000 in men and from 0.28 to 0.45 per 100,000 in women. MCC incidence also increased in Queensland, Australia (average annual percentage change 1.8%, 95% CI = 0.7-2.8), New Zealand (2.0%, 95% CI = 0.4-3.7), Scotland (3.7%, 95% CI = 2.0-5.5), and Norway (4.0%, 95% CI = 2.1-5.9). In all populations, MCC incidence was higher in men than in women. Between 1993 and 2016 in the United States, the incidence of MCC of the head and neck and upper and lower limbs increased in both sexes. Despite being an uncommon malignancy, our analyses show that MCC incidence is steadily increasing both in areas of low and those of high ambient UVR levels.
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http://dx.doi.org/10.1016/j.jid.2021.04.007DOI Listing
April 2021

International Trends in Esophageal Squamous Cell Carcinoma and Adenocarcinoma Incidence.

Am J Gastroenterol 2021 05;116(5):1072-1076

Section of Cancer Surveillance, International Agency for Research on Cancer, Lyon, France.

Introduction: We aimed to improve our understanding of the epidemiology of squamous cell carcinoma and adenocarcinoma of the esophagus.

Methods: We estimated average annual percent change and analyzed age-period-cohort trends on population-based cancer data.

Results: We found decreases in squamous cell carcinoma incidence in half of male populations (largest decrease in US black males [average annual percent change -7.6]) and increases in adenocarcinoma incidence in nearly a third of populations. Trends may be associated with a mix of birth cohort and period effects.

Discussion: More complete data and evidence are needed to conclude the reasons for the observed trends (see Visual Abstract, Supplementary Digital Content 4, http://links.lww.com/AJG/B823).
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http://dx.doi.org/10.14309/ajg.0000000000001121DOI Listing
May 2021

Predicting deseasonalised serum 25 hydroxy vitamin D concentrations in the D-Health Trial: An analysis using boosted regression trees.

Contemp Clin Trials 2021 May 6;104:106347. Epub 2021 Mar 6.

Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, Australia; School of Public Health, The University of Queensland, Brisbane, Australia. Electronic address:

Background: The D-Health Trial aims to determine whether monthly high-dose vitamin D supplementation can reduce the mortality rate and prevent cancer. We did not have adequate statistical power for subgroup analyses, so could not justify the high cost of collecting blood samples at baseline. To enable future exploratory analyses stratified by baseline vitamin D status, we developed models to predict baseline serum 25 hydroxy vitamin D [25(OH)D] concentration.

Methods: We used data and serum 25(OH)D concentrations from participants who gave a blood sample during the trial for compliance monitoring and were randomised to placebo. Data were partitioned into training (80%) and validation (20%) datasets. Deseasonalised serum 25(OH)D concentrations were dichotomised using cut-points of 50, 60 and 75 nmol/L. We fitted boosted regression tree models, based on 13 predictors, and evaluated model performance using the validation data.

Results: The training and validation datasets had 1788 (10.5% <50 nmol/L, 23.1% <60 nmol, 48.8 <75 nmol/L) and 447 (11.9% <50 nmol/L, 25.7% <60 nmol/L, and 49.2% <75 nmol/L) samples, respectively. Ambient UV radiation and total intake of vitamin D were the strongest predictors of 'low' serum 25(OH)D concentration. The area under the receiver operating characteristic curves were 0.71, 0.70, and 0.66 for cut-points of <50, <60 and <75 nmol/L respectively.

Conclusions: We exploited compliance monitoring data to develop models to predict serum 25(OH)D concentration for D-Health participants at baseline. This approach may prove useful in other trial settings where there is an obstacle to exhaustive data collection.
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http://dx.doi.org/10.1016/j.cct.2021.106347DOI Listing
May 2021

The effect of vitamin D supplementation on acute respiratory tract infection in older Australian adults: an analysis of data from the D-Health Trial.

Lancet Diabetes Endocrinol 2021 02 11;9(2):69-81. Epub 2021 Jan 11.

Population Health Department, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia; School of Public Health, the University of Queensland, Brisbane, QLD, Australia. Electronic address:

Background: Observational studies have linked vitamin D deficiency with acute respiratory tract infection, but results from randomised controlled trials are heterogeneous. We analysed data from the D-Health Trial to determine whether supplementing older Australian adults, recruited from the general population, with monthly doses of vitamin D reduced the risk, duration, and severity of acute respiratory tract infections.

Methods: We used data from the D-Health Trial, a randomised, double-blind, placebo-controlled trial of monthly vitamin D supplementation, for which acute respiratory infection was a pre-specified trial outcome. Participants were supplemented and followed for up to 5 years. The trial was set within the Australian general population, using the Commonwealth Electoral Roll as the sampling frame, but also allowing some volunteers to participate. Participants were men and women aged 60 to 79 years (with volunteers up to age 84 years). Participants were randomly assigned to receive either vitamin D or placebo (1:1) using computer-generated permuted block randomisation, which was stratified by age, sex, and state. This was an automated process and the assignment list was not visible to study staff or investigators. Active and placebo gel capsules, identical in appearance to ensure masking, were labelled A and B and the code was not available to study staff or investigators. Participants were asked to report occurrence of acute respiratory symptoms over the previous month via annual surveys, and a subset of participants completed 8-week respiratory symptom diaries in winter. As part of our process to maintain blinding, a random sample of participants was selected for analysis of survey data and a separate sample selected for analysis of diary data. Blood samples were obtained from a random sample of participants (about 450 per group per year) and serum 25-hydroxy vitamin D (25[OH]D) concentrations were measured to monitor adherence. We used regression models to estimate odds ratios (OR), rate ratios, and rate differences. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12613000743763.

Findings: Between Jan 13, 2014, and May 26, 2015, 421 207 invitations were sent, 40 824 people were interested in participating, and 21 315 participants were recruited and randomised. Of the 16 000 participants selected for potential analysis of survey data, 15 373 were included in the analysis; 295 in the vitamin D group and 332 in the placebo group who were missing data for all five annual surveys were excluded from the analysis. Of the 3800 selected for potential analysis of diary data, 3070 were invited to complete the diaries because 730 had already withdrawn. 2598 people were included in the analysis; 218 people in the vitamin D group and 254 in the placebo group were missing data and were therefore excluded from the analysis. In blood samples collected from randomly sampled participants throughout the trial, the mean serum 25(OH)D concentration was 114·8 (SD 30·3) nmol/L in the vitamin D group and 77·5 (25·2) nmol/L in the placebo group. Vitamin D supplementation did not reduce the risk of acute respiratory tract infection (survey OR 0·98, 95% CI 0·93 to 1·02; diary OR 0·98, 0·83 to 1·15). Analyses of diary data showed reductions in the overall duration of symptoms and of severe symptoms, but these were small and unlikely to be clinically significant.

Interpretation: Monthly bolus doses of 60 000 IU of vitamin D did not reduce the overall risk of acute respiratory tract infection, but could slightly reduce the duration of symptoms in the general population. These findings suggest that routine vitamin D supplementation of a population that is largely vitamin D replete is unlikely to have a clinically relevant effect on acute respiratory tract infection.

Funding: National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S2213-8587(20)30380-6DOI Listing
February 2021

Germline variants are associated with increased primary melanoma tumor thickness at diagnosis.

Hum Mol Genet 2021 01;29(21):3578-3587

Statistical Genetics, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, 4006, Australia.

Germline genetic variants have been identified, which predispose individuals and families to develop melanoma. Tumor thickness is the strongest predictor of outcome for clinically localized primary melanoma patients. We sought to determine whether there is a heritable genetic contribution to variation in tumor thickness. If confirmed, this will justify the search for specific genetic variants influencing tumor thickness. To address this, we estimated the proportion of variation in tumor thickness attributable to genome-wide genetic variation (variant-based heritability) using unrelated patients with measured primary cutaneous melanoma thickness. As a secondary analysis, we conducted a genome-wide association study (GWAS) of tumor thickness. The analyses utilized 10 604 individuals with primary cutaneous melanoma drawn from nine GWAS datasets from eight cohorts recruited from the general population, primary care and melanoma treatment centers. Following quality control and filtering to unrelated individuals with study phenotypes, 8125 patients were used in the primary analysis to test whether tumor thickness is heritable. An expanded set of 8505 individuals (47.6% female) were analyzed for the secondary GWAS meta-analysis. Analyses were adjusted for participant age, sex, cohort and ancestry. We found that 26.6% (SE 11.9%, P = 0.0128) of variation in tumor thickness is attributable to genome-wide genetic variation. While requiring replication, a chromosome 11 locus was associated (P < 5 × 10-8) with tumor thickness. Our work indicates that sufficiently large datasets will enable the discovery of genetic variants associated with greater tumor thickness, and this will lead to the identification of host biological processes influencing melanoma growth and invasion.
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http://dx.doi.org/10.1093/hmg/ddaa222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7788289PMC
January 2021

Genetically determined risk of keratinocyte carcinoma and risk of other cancers.

Int J Epidemiol 2020 Dec 28. Epub 2020 Dec 28.

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Australia.

Background: Epidemiological studies have consistently documented an increased risk of developing primary non-cutaneous malignancies among people with a history of keratinocyte carcinoma (KC). However, the mechanisms underlying this association remain unclear. We conducted two separate analyses to test whether genetically predicted KC is related to the risk of developing cancers at other sites.

Methods: In the first approach (one-sample), we calculated the polygenic risk scores (PRS) for KC using individual-level data in the UK Biobank (n = 394 306) and QSkin cohort (n = 16 896). The association between the KC PRS and each cancer site was assessed using logistic regression. In the secondary (two-sample) approach, we used genome-wide association study (GWAS) summary statistics identified from the most recent GWAS meta-analysis of KC and obtained GWAS data for each cancer site from the UK-Biobank participants only. We used inverse-variance-weighted methods to estimate risks across all genetic variants.

Results: Using the one-sample approach, we found that the risks of cancer at other sites increased monotonically with KC PRS quartiles, with an odds ratio (OR) of 1.16, 95% confidence interval (CI): 1.13-1.19 for those in KC PRS quartile 4 compared with those in quartile 1. In the two-sample approach, the pooled risk of developing other cancers was statistically significantly elevated, with an OR of 1.05, 95% CI: 1.03-1.07 per doubling in the odds of KC. We observed similar trends of increasing cancer risk with increasing KC PRS in the QSkin cohort.

Conclusion: Two different genetic approaches provide compelling evidence that an instrumental variable for KC constructed from genetic variants predicts the risk of cancers at other sites.
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http://dx.doi.org/10.1093/ije/dyaa265DOI Listing
December 2020

Early detection of melanoma in specialised primary care practice in Australia.

Cancer Epidemiol 2021 02 24;70:101872. Epub 2020 Dec 24.

Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006, Australia. Electronic address:

Background: Primary care skin cancer clinics facilitate early treatment of melanoma in Australia. We investigated the clinical and histopathological features of melanomas diagnosed and treated in an established clinic in Brisbane.

Methods: Retrospective audit of medical records of patients diagnosed with in situ or invasive primary cutaneous melanoma in a primary care clinic specializing in skin cancer, 2000-2017. Demographic and clinical data were standardly extracted by a medically-trained investigator. We used descriptive analyses to assess characteristics of patients and melanomas, and examine surgical management according to tumour thickness.

Results: Of 380 patients (median age 57 years; 57 % male) newly diagnosed with 497 histologically-confirmed primary cutaneous melanomas, 369 were in situ and 128 invasive. Of the 369 in situ melanomas, 143 (39 %) were on the trunk and 87 (24 %) on the head and neck; 247 (67 %) were diagnosed by shave biopsy; and 141 (38 %) referred for wide local excision (WLE). Of the 128 invasive melanomas, only 21 (16 %) had thickness ≥ 0.8 mm and these occurred more often on head and neck than thin invasive melanomas (p = 0.02). The majority of invasive melanomas were diagnosed by excision biopsy, and WLE was carried out in a median of 3 days (melanomas ≥ 0.8 mm) and 2 days (<0.8 mm). The doctor detected the majority of in situ (83 %) and thin invasive (73 %) melanomas during surveillance, compared with 48 % of thicker invasive melanomas ≥ 0.8 mm (p < 0.001).

Conclusion: In Australia, specialised primary care practice plays a major role in detection and treatment of early primary melanoma.
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http://dx.doi.org/10.1016/j.canep.2020.101872DOI Listing
February 2021

Accuracy of mobile digital teledermoscopy for skin self-examinations in adults at high risk of skin cancer: an open-label, randomised controlled trial.

Lancet Digit Health 2020 03 20;2(3):e129-e137. Epub 2020 Feb 20.

The Diamantina Institute, The University of Queensland, Brisbane, QLD, Australia; Dermatology Department, Princess Alexandra Hospital, Brisbane, QLD, Australia.

Background: Skin self-examinations supplemented with mobile teledermoscopy might improve early detection of skin cancers compared with naked-eye skin self-examinations. We aimed to assess whether mobile teledermoscopy-enhanced skin self-examination can improve sensitivity and specificity of self-detection of skin cancers when compared with naked-eye skin self-examination.

Methods: This randomised, controlled trial was done in Brisbane (QLD, Australia). Eligible participants (aged ≥18 years) had at least two skin cancer risk factors as self-reported in the eligibility survey and had to own or have access to an iPhone compatible with a dermatoscope attachment (iPhone versions 5-8). Participants were randomly assigned (1:1), via a computer-generated randomisation procedure, to the intervention group (mobile dermoscopy-enhanced self-skin examination) or the control group (naked-eye skin self-examination). Control group and intervention group participants received web-based instructions on how to complete a whole body skin self-examination. All participants completed skin examinations at baseline, 1 month, and 2 months; intervention group participants submitted photographs of suspicious lesions to a dermatologist for telediagnosis after each skin examination and control group participants noted lesions on a body chart that was sent to the research team after each skin examination. All participants had an in-person whole-body clinical skin examination within 3 months of their last skin self-examination. Primary outcomes were sensitivity and specificity of skin self-examination, patient selection of clinically atypical lesions suspicious for melanoma or keratinocyte skin cancers (body sites examined, number of lesions photographed, types of lesions, and lesions missed), and diagnostic concordance of telediagnosis versus in-person whole-body clinical skin examination diagnosis. All primary outcomes were analysed in the modified intention-to-treat population, which included all patients who had a clinical skin examination within 3 months of their last skin self-examination. This trial was registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12616000989448.

Findings: Between March 6, 2017, and June 7, 2018, 234 participants consented to enrol in the study, of whom 116 (50%) were assigned to the intervention group and 118 (50%) were assigned to the control group. 199 participants (98 participants in the intervention group and 101 participants in the control group) attended the clinical skin examination and thus were eligible for analyses. Participants in the intervention group submitted 615 lesions (median 6·0 per person; range 1-24) for telediagnosis and participants in the control group identified and recorded 673 lesions (median 6·0 per person; range 1-16). At the lesion level, sensitivity for lesions clinically suspicious for skin cancer was 75% (95% CI 63-84) in the intervention group and 88% (95% CI 80-91) in the control group (p=0·04). Specificity was 87% (95% CI 85-90) in the intervention group and 89% (95% CI 87-91) in the control group (p=0·42). At the individual level, the intervention group had a sensitivity of 87% (95% CI 76-99) compared with 97% (95% CI 91-100) in the control group (p=0·26), and a specificity of 95% (95% CI 90-100) compared with 96% (95% CI 91-100) in the control group. The overall diagnostic concordance between the telediagnosis and in-person clinical skin examination was 88%.

Interpretation: The use of mobile teledermoscopy did not increase sensitivity for the detection of skin cancers compared with naked-eye skin self-examination; thus, further evidence is necessary for inclusion of skin self-examination technology for public health benefit.

Funding: National Health and Medical Research Council (Australia).
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http://dx.doi.org/10.1016/S2589-7500(20)30001-7DOI Listing
March 2020

Natural history of oral HPV infection: Longitudinal analyses in prospective cohorts from Australia.

Int J Cancer 2021 04 27;148(8):1964-1972. Epub 2020 Dec 27.

Department of Population Health, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Herston, Queensland, Australia.

Oral infection with human papillomavirus (HPV) is likely to underpin the rapidly rising incidence of oropharyngeal squamous cell carcinoma; however, there are few data describing the natural history of oral HPV infection. We recruited 704 participants aged 20 to 70 years from worksites, universities and primary care practices in Brisbane, Australia. Participants completed questionnaires at baseline, 12 and 24 months and donate four saliva samples at baseline, 6, 12 and 24 months for HPV polymerase chain reaction testing and typing. We estimated the prevalence of oral HPV infection at baseline, incidence of new infections among those HPV-negative at baseline, clearance rate and persistent infections. At baseline, 10.7% of participants had oral HPV infections from 26 different HPV types. Sexual behaviours were associated with oral HPV infection, including more partners for passionate kissing (29 or more; odds ratio [OR] 3.4, 95% confidence interval [CI] 1.5-8.0), and giving and receiving oral sex (16 or more; OR 5.4, 95% CI 1.6-17.7 and OR 5.6, 95% CI 1.6-18.7, respectively). Of 343 participants, HPV-free at baseline and with subsequent saliva samples, 87 (25%) acquired new infections over the 24 months. Sixty-eight of 87 people included in the clearance analysis (78%) cleared their oral HPV infections. Clearance was associated with being a nonsmoker (OR 12.7, 95% CI 1.3-122.8), and no previous diagnosis of a sexually transmitted infection (OR 6.2, 95% CI 2.0-19.9). New oral infections with HPV in this sample were not rare. Although most infections were cleared, clearance was not universal suggesting a reservoir of infection exists that might predispose to oropharyngeal carcinogenesis.
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http://dx.doi.org/10.1002/ijc.33442DOI Listing
April 2021

Clinical pathways and outcomes of patients with Barrett's esophagus in tertiary care settings: a prospective longitudinal cohort study in Australia, 2008-2016.

Dis Esophagus 2020 Dec 12. Epub 2020 Dec 12.

Population Health Department, QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.

Background: Clinical services for Barrett's esophagus have been rising worldwide including Australia, but little is known of the long-term outcomes of such patients. Retrospective studies using data at baseline are prone to both selection and misclassification bias. We investigated the clinical characteristics and outcomes of Barrett's esophagus patients in a prospective cohort.

Methods: We recruited patients diagnosed with Barrett's esophagus in tertiary settings across Australia between 2008 and 2016. We compared baseline and follow-up epidemiological and clinical data between Barrett's patients with and without dysplasia. We calculated age-adjusted incidence rates and estimated minimally and fully adjusted hazard ratios (HR) to identify those clinical factors related to disease progression.

Results: The cohort comprised 268 patients with Barrett's esophagus (median follow-up 5 years). At recruitment, 224 (84%) had no dysplasia, 44 (16%) had low-grade or indefinite dysplasia (LGD/IND). The age-adjusted incidence of esophageal adenocarcinoma (EAC) was 0.5% per year in LGD/IND compared with 0.1% per year in those with no dysplasia. Risk of progression to high-grade dysplasia/EAC was associated with prior LGD/IND (fully adjusted HR 6.55, 95% confidence interval [CI] 1.96-21.8) but not long-segment disease (HR 1.03, 95%CI 0.29-3.58).

Conclusions: These prospective data suggest presence of dysplasia is a stronger predictor of progression to cancer than segment length in patients with Barrett's esophagus.
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http://dx.doi.org/10.1093/dote/doaa119DOI Listing
December 2020

Germline variation in the insulin-like growth factor pathway and risk of Barrett's esophagus and esophageal adenocarcinoma.

Carcinogenesis 2021 04;42(3):369-377

Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK.

Genome-wide association studies (GWAS) of esophageal adenocarcinoma (EAC) and its precursor, Barrett's esophagus (BE), have uncovered significant genetic components of risk, but most heritability remains unexplained. Targeted assessment of genetic variation in biologically relevant pathways using novel analytical approaches may identify missed susceptibility signals. Central obesity, a key BE/EAC risk factor, is linked to systemic inflammation, altered hormonal signaling and insulin-like growth factor (IGF) axis dysfunction. Here, we assessed IGF-related genetic variation and risk of BE and EAC. Principal component analysis was employed to evaluate pathway-level and gene-level associations with BE/EAC, using genotypes for 270 single-nucleotide polymorphisms (SNPs) in or near 12 IGF-related genes, ascertained from 3295 BE cases, 2515 EAC cases and 3207 controls in the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) GWAS. Gene-level signals were assessed using Multi-marker Analysis of GenoMic Annotation (MAGMA) and SNP summary statistics from BEACON and an expanded GWAS meta-analysis (6167 BE cases, 4112 EAC cases, 17 159 controls). Global variation in the IGF pathway was associated with risk of BE (P = 0.0015). Gene-level associations with BE were observed for GHR (growth hormone receptor; P = 0.00046, false discovery rate q = 0.0056) and IGF1R (IGF1 receptor; P = 0.0090, q = 0.0542). These gene-level signals remained significant at q < 0.1 when assessed using data from the largest available BE/EAC GWAS meta-analysis. No significant associations were observed for EAC. This study represents the most comprehensive evaluation to date of inherited genetic variation in the IGF pathway and BE/EAC risk, providing novel evidence that variation in two genes encoding cell-surface receptors, GHR and IGF1R, may influence risk of BE.
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http://dx.doi.org/10.1093/carcin/bgaa132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8052954PMC
April 2021

Prospective validation of a risk stratification tool for keratinocyte cancer.

Australas J Dermatol 2021 May 18;62(2):223-225. Epub 2020 Oct 18.

Department of Population Health, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

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http://dx.doi.org/10.1111/ajd.13485DOI Listing
May 2021

Assessment of Incidence Rate and Risk Factors for Keratoacanthoma Among Residents of Queensland, Australia.

JAMA Dermatol 2020 12;156(12):1324-1332

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Importance: Keratoacanthoma (KA) is a common and generally benign keratinocyte skin tumor. Reports of the incidence rates of KA are scant. In addition, the risk factors for KA are not well understood, although associations with UV radiation exposure and older age have been described.

Objective: To investigate the incidence rate of KA and the risk factors for developing KA.

Design, Setting, And Participants: The study included data from 40 438 of 193 344 randomly selected residents of Queensland, Australia, who participated in the QSkin Sun and Health (QSkin) prospective population-based cohort study. All participants completed a baseline survey between 2010 and 2011 and were ages 40 to 69 years at baseline. Histopathologic reports of KA were prospectively collected until June 30, 2014, through data linkage with pathologic records. Cox proportional hazards models were used to identify risk factors associated with KA while controlling for potential confounding variables. Data were analyzed from January 2 to April 8, 2020.

Exposures: Demographic characteristics, phenotypes, UV radiation exposure, medical history, and lifestyle.

Results: Among 40 438 participants (mean [SD] age, 56 [8] years; 18 240 men [45.1%]), 596 individuals (mean [SD] age, 62 [6] years; 349 men [58.6%]) developed 776 KA tumors during a median follow-up period of 3.0 years (interquartile range, 2.8-3.3 years). The person-based age-standardized incidence rate for KA in the age-restricted cohort was 409 individuals per 100 000 person-years (based on the 2001 Australian population). Risk factors after adjustment for potential confounders were older age (age ≥60 years vs age <50 years; hazard ratio [HR], 6.38; 95% CI, 4.65-8.75), male sex (HR, 1.56; 95% CI, 1.33-1.84), fair skin (vs olive, dark, or black skin; HR, 3.42; 95% CI, 1.66-7.04), inability to tan (vs ability to tan deeply; HR, 1.69; 95% CI, 1.19-2.40), previous excisions of keratinocyte cancers (ever had an excision vs never had an excision; HR, 6.28; 95% CI, 5.03-7.83), current smoking (vs never smoking, HR, 2.02; 95% CI, 1.59-2.57), and high alcohol use (≥14 alcoholic drinks per week vs no alcoholic drinks per week; HR, 1.42; 95% CI, 1.09-1.86).

Conclusions And Relevance: This is, to date, the first large prospective population-based study to report the incidence rate and risk factors for KA. The high person-based incidence rate (409 individuals per 100 000 person-years) highlights the substantial burden of KA in Queensland, Australia. Furthermore, the study's findings suggest that older age (≥60 years), male sex, UV radiation-sensitive phenotypes, indications of high sun exposure (eg, previous keratinocyte cancer excisions), smoking, and high alcohol use are independent risk factors for the development of KA.
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http://dx.doi.org/10.1001/jamadermatol.2020.4097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542522PMC
December 2020

Can People Correctly Assess their Future Risk of Melanoma?

J Invest Dermatol 2021 Mar 12;141(3):695-698. Epub 2020 Sep 12.

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia; Faculty of Medicine, The University of Queensland, Herston, Queensland, Australia. Electronic address:

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http://dx.doi.org/10.1016/j.jid.2020.07.018DOI Listing
March 2021

Sex-Specific Genetic Associations for Barrett's Esophagus and Esophageal Adenocarcinoma.

Gastroenterology 2020 12 9;159(6):2065-2076.e1. Epub 2020 Sep 9.

Institute for Genomic Statistics and Bioinformatics, Medical Faculty, University of Bonn, Germany.

Background & Aims: Esophageal adenocarcinoma (EA) and its premalignant lesion, Barrett's esophagus (BE), are characterized by a strong and yet unexplained male predominance (with a male-to-female ratio in EA incidence of up to 6:1). Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for these conditions. However, potential sex differences in genetic associations with BE/EA remain largely unexplored.

Methods: Given strong genetic overlap, BE and EA cases were combined into a single case group for analysis. These were compared with population-based controls. We performed sex-specific GWAS of BE/EA in 3 separate studies and then used fixed-effects meta-analysis to provide summary estimates for >9 million variants for male and female individuals. A series of downstream analyses were conducted separately in male and female individuals to identify genes associated with BE/EA and the genetic correlations between BE/EA and other traits.

Results: We included 6758 male BE/EA cases, 7489 male controls, 1670 female BE/EA cases, and 6174 female controls. After Bonferroni correction, our meta-analysis of sex-specific GWAS identified 1 variant at chromosome 6q11.1 (rs112894788, KHDRBS2-MTRNR2L9, P = .039) that was statistically significantly associated with BE/EA risk in male individuals only, and 1 variant at chromosome 8p23.1 (rs13259457, PRSS55-RP1L1, P = 0.057) associated, at borderline significance, with BE/EA risk in female individuals only. We also observed strong genetic correlations of BE/EA with gastroesophageal reflux disease in male individuals and obesity in female individuals.

Conclusions: The identified novel sex-specific variants associated with BE/EA could improve the understanding of the genetic architecture of the disease and the reasons for the male predominance.
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http://dx.doi.org/10.1053/j.gastro.2020.08.052DOI Listing
December 2020

Omega-3 fatty acid intake and decreased risk of skin cancer in organ transplant recipients.

Eur J Nutr 2021 Jun 9;60(4):1897-1905. Epub 2020 Sep 9.

Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, QLD, Australia.

Purpose: Organ transplant recipients have over 100-fold higher risk of developing skin cancer than the general population and are in need of further preventive strategies. We assessed the possible preventive effects of omega-3 polyunsaturated fatty acid (PUFA) intake from food on the two main skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in kidney and liver transplant recipients.

Methods: Adult kidney or liver transplant recipients transplanted for at least 1 year and at high risk of skin cancer were recruited from the main transplant hospital in Queensland, 2012-2014 and followed until mid-2016. We estimated their dietary total long-chain omega-3 PUFAs and α-linolenic acid intakes at baseline using a food frequency questionnaire and ranked PUFA intakes as low, medium, or high. Relative risks (RRs) of skin cancer adjusted for confounding factors with 95% confidence intervals (CIs) were calculated.

Results: There were 449 transplant recipients (mean age, 55 years; 286 (64%) male). During follow-up, 149 (33%) patients developed SCC (median 2/person; range 1-40) and 134 (30%), BCC. Transplant recipients with high total long-chain omega-3 PUFA compared with low intakes showed substantially reduced SCC tumour risk (RR 0.33, 95% CI 0.18-0.60), and those with high α-linolenic acid intakes experienced significantly fewer BCCs (RR 0.40, 95% CI 0.22-0.74). No other significant associations were seen.

Conclusion: Among organ transplant recipients, relatively high intakes of long-chain omega-3 PUFAs and of α-linolenic acid may reduce risks of SCC and BCC, respectively.
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http://dx.doi.org/10.1007/s00394-020-02378-yDOI Listing
June 2021

Destructive and topical treatments of skin lesions in organ transplant recipients and relation to skin cancer.

Arch Dermatol Res 2020 Sep 5. Epub 2020 Sep 5.

Statistics Unit, QIMR Berghofer Medical Research Institute, Brisbane, Australia.

Various treatments of keratotic skin lesions and early skin cancers are performed in organ transplant recipients (OTRs) at high risk of skin malignancies but the frequency of their use is unknown. We prospectively assessed the frequency of use of cryotherapy, diathermy, and topical therapies and also investigated their associations with background incidence of histologically-confirmed squamous-cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of OTRs in Queensland, Australia. Median follow-up ranged from 1.7 to 3.2 years across organ transplant groups. Among 285 kidney, 125 lung and 203 liver transplant recipients [382 (62%) male, 380 (62%) immunosuppressed > 5 years, 394 (64%) previously diagnosed with skin cancer], 306 (50%) reported treatment of skin lesions with major types of non-excision therapies during follow-up: 278 (45%) cryotherapy or diathermy; 121 (20%) topical treatments. Of these 306, 150 (49%) developed SCC at double the incidence of those who did not receive these treatments, as assessed by incidence rate ratio (IRR) adjusted for age, sex, type of organ transplant, skin color and history of skin cancer at baseline, calculated by multivariable Poisson regression (IRR = 2.1, 95% confidence interval (CI) 1.4-3.1). BCC incidence was not associated with these therapies. Skin lesions in OTRs that are treated with cryotherapy, diathermy, or topical treatment warrant judicious selection and careful follow-up.
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http://dx.doi.org/10.1007/s00403-020-02136-4DOI Listing
September 2020

Web Application for the Automated Extraction of Diagnosis and Site From Pathology Reports for Keratinocyte Cancers.

JCO Clin Cancer Inform 2020 08;4:711-723

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane Queensland, Australia.

Purpose: Keratinocyte cancers are exceedingly common in high-risk populations, but accurate measures of incidence are seldom derived because the burden of manually reviewing pathology reports to extract relevant diagnostic information is excessive. Thus, we sought to develop supervised learning algorithms for classifying basal and squamous cell carcinomas and other diagnoses, as well as disease site, and incorporate these into a Web application capable of processing large numbers of pathology reports.

Methods: Participants in the QSkin study were recruited in 2011 and comprised men and women age 40-69 years at baseline (N = 43,794) who were randomly selected from a population register in Queensland, Australia. Histologic data were manually extracted from free-text pathology reports for participants with histologically confirmed keratinocyte cancers for whom a pathology report was available (n = 25,786 reports). This provided a training data set for the development of algorithms capable of deriving diagnosis and site from free-text pathology reports. We calculated agreement statistics between algorithm-derived classifications and 3 independent validation data sets of manually abstracted pathology reports.

Results: The agreement for classifications of basal cell carcinoma (κ = 0.97 and κ = 0.96) and squamous cell carcinoma (κ = 0.93 for both) was almost perfect in 2 validation data sets but was slightly lower for a third (κ = 0.82 and κ = 0.90, respectively). Agreement for total counts of specific diagnoses was also high (κ > 0.8). Similar levels of agreement between algorithm-derived and manually extracted data were observed for classifications of keratoacanthoma and intraepidermal carcinoma.

Conclusion: Supervised learning methods were used to develop a Web application capable of accurately and rapidly classifying large numbers of pathology reports for keratinocyte cancers and related diagnoses. Such tools may provide the means to accurately measure subtype-specific skin cancer incidence.
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http://dx.doi.org/10.1200/CCI.19.00152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469600PMC
August 2020

Polygenic Risk Scores Allow Risk Stratification for Keratinocyte Cancer in Organ-Transplant Recipients.

J Invest Dermatol 2021 Feb 29;141(2):325-333.e6. Epub 2020 Jun 29.

Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia; School of Biomedical Sciences, Faculty of Health, and Institute of Health and Biomedical Innovation, Queensland University of Technology, Kelvin Grove, Queensland, Australia.

Organ-transplant recipients have an elevated risk of keratinocyte cancers: basal cell carcinoma (BCC) and squamous cell carcinoma. We assessed whether polygenic risk scores (PRSs) generated in nontransplantees from the UK Biobank and 23andMe (13,981 squamous cell carcinoma, 33,736 BCC, and >560,000 controls) can predict keratinocyte cancer risk in an independent organ-transplant recipient cohort. After adjusting for traditional risk factors, compared with the bottom 20%, organ-transplant recipients in the top 20% PRS had an increased risk of BCC (OR = 3.25, 95% confidence interval = 1.44-7.31, P = 4.4 × 10) and squamous cell carcinoma (OR = 2.11, 95% confidence interval = 0.98-4.53, P = 0.055). For BCC, the top 20% PRS individuals had an absolute risk of 23%, whereas the risk in the bottom 20% was similar to that in the general nontransplantee population. Adding PRS to a model containing traditional skin cancer risk factors yielded a 3% increase in the area under the curve for receiver operating characteristic curve for BCC (0.73 vs. 0.70); adding the PRS did not significantly increase the area under the curve for receiver operating characteristic curve for squamous cell carcinoma. Organ-transplant recipients in the highest genetic risk quintile could benefit from more intense keratinocyte cancer screening and preventive strategies compared with their counterparts. The BCC PRS improves prediction over and above the traditional skin cancer risk factors by 3%.
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http://dx.doi.org/10.1016/j.jid.2020.06.017DOI Listing
February 2021

The proportion of cancers attributable to social deprivation: A population-based analysis of Australian health data.

Cancer Epidemiol 2020 08 5;67:101742. Epub 2020 Jun 5.

Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland, 4006, Australia; The University of Queensland, Faculty of Medicine, Herston Road, Herston, Queensland, 4006, Australia.

Background: Cancer is a major disease burden globally and people who are socioeconomically disadvantaged have a higher incidence of many types of cancer. We investigated the potential to reduce socioeconomic disparities in cancer incidence in Australia by lowering the prevalence of exposure to four modifiable causes: smoking, alcohol, overweight/obesity and physical inactivity.

Methods: We used cancer incidence data from the Australian Cancer Database and risk factor prevalence data from the Australian National Health Survey to estimate the proportions of cancers attributable to the four factors, by area-level socioeconomic disadvantage. For the three risk factors where prevalence was lowest among the least disadvantaged (smoking, overweight/obesity, physical inactivity), we also estimated the potential impact of reducing prevalence in the most disadvantaged areas to that in the least disadvantaged areas.

Results: The proportion of cancer attributable to the four factors in combination ranged from 22 % in the most disadvantaged areas to 14 % in the least disadvantaged areas. If the prevalence of tobacco smoking, overweight/obesity and physical inactivity in the more disadvantaged areas were the same as that in the least disadvantaged, an estimated 19,500 cancers (4 % of all cancers diagnosed) could have been prevented in Australia between 2009 and 2013.

Conclusions: Reducing the prevalence of key causal factors in areas of greater social disadvantage would prevent many cases of cancer. Strategies to achieve this in highly disadvantaged areas are needed.
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http://dx.doi.org/10.1016/j.canep.2020.101742DOI Listing
August 2020

Regular opium use and subsequent incidence of cancer.

Authors:
David C Whiteman

Lancet Glob Health 2020 05;8(5):e613-e614

QIMR Berghofer Medical Research Institute, Brisbane, QLD 4006, Australia. Electronic address:

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http://dx.doi.org/10.1016/S2214-109X(20)30089-9DOI Listing
May 2020

Genome-wide association meta-analyses combining multiple risk phenotypes provide insights into the genetic architecture of cutaneous melanoma susceptibility.

Nat Genet 2020 05 27;52(5):494-504. Epub 2020 Apr 27.

Department of Dermatology, Instituto Valenciano de Oncología, Valencia, Spain.

Most genetic susceptibility to cutaneous melanoma remains to be discovered. Meta-analysis genome-wide association study (GWAS) of 36,760 cases of melanoma (67% newly genotyped) and 375,188 controls identified 54 significant (P < 5 × 10) loci with 68 independent single nucleotide polymorphisms. Analysis of risk estimates across geographical regions and host factors suggests the acral melanoma subtype is uniquely unrelated to pigmentation. Combining this meta-analysis with GWAS of nevus count and hair color, and transcriptome association approaches, uncovered 31 potential secondary loci for a total of 85 cutaneous melanoma susceptibility loci. These findings provide insights into cutaneous melanoma genetic architecture, reinforcing the importance of nevogenesis, pigmentation and telomere maintenance, together with identifying potential new pathways for cutaneous melanoma pathogenesis.
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http://dx.doi.org/10.1038/s41588-020-0611-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7255059PMC
May 2020

Keratinocyte cancer with incidental perineural invasion: A registry analysis of management and 5-year outcomes.

Australas J Dermatol 2020 Aug 13;61(3):226-230. Epub 2020 Apr 13.

QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.

Background/objectives: Perineural invasion within keratinocyte cancer is a hallmark of tumour aggression, and a definitive treatment paradigm for this condition remains undetermined. Our aim was to investigate the treatment and outcomes of keratinocyte cancer with incidental perineural invasion within two skin cancer databases to refine treatment protocols.

Methods: We retrospectively assessed the Queensland Perineural Invasion Registry for surgery, histopathology, adjuvant radiotherapy and recurrence of keratinocyte cancer five years post-definitive treatment. We also reviewed the Princess Alexandra Hospital Head and Neck clinical perineural invasion database, specifically looking at surgical margins and adjuvant radiotherapy of cutaneous squamous cell carcinoma (cSCC) with incidental perineural invasion in the primary lesion.

Results: There was no recurrence at 5 years in the Perineural Invasion Registry. Basal cell carcinoma (BCC) lesions with nerves <0.1 mm were more commonly treated with surgery alone, compared to lesions with nerves ≥0.1 mm which were offered adjuvant radiotherapy. Of the total BCC lesions with incidental perineural invasion, those with perineural margins ≥5 mm and peripheral tumour margins ≥3 mm were predominantly treated with surgery alone. Eighty-nine per cent of cSCC lesions with incidental perineural invasion were treated with surgery and adjuvant radiotherapy.

Conclusion: Surgery alone is suitable for BCC lesions with incidental perineural invasion. The majority of BCC lesions achieved ≥5 mm perineural and ≥3 mm peripheral tumour margins. Future research can guide if adjuvant radiation is required for BCC with perineural invasion. The treatment of cSCC with incidental perineural invasion with surgery alone remains undetermined.
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http://dx.doi.org/10.1111/ajd.13290DOI Listing
August 2020

Evaluation of Sex-Specific Incidence of Melanoma.

JAMA Dermatol 2020 05;156(5):553-560

Cancer Control Group, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Importance: Men and women develop melanoma at different rates on different body sites, with variation across countries, but explanations for these disparities remain elusive.

Objective: To test whether observed differences in melanoma incidence between men and women vary by population, age, or anatomic site.

Design: Cross-sectional analysis of sex- and site-specific temporal trends in melanoma incidence over 3 decades was conducted for men and women diagnosed with invasive melanoma in the US (limited to white race), Canada, Australia, New Zealand, the UK, Sweden, Norway, and Denmark. Using cancer registry data, male to female incidence rate ratios (IRRs) were calculated overall and by anatomic site, and Joinpoint regression models were used to estimate the annual percentage rate changes in sex- and site-specific incidence in each population. Incidence rates were standardized to the US 2000 population. Data on the incidence between January 1, 1982, and December 31, 2015, were obtained; analysis was conducted from March 1 to October 15, 2019.

Main Outcomes And Measures: Male to female IRRs and annual percentage change in rates.

Results: Total melanoma incidence was higher in men than women in US individuals (limited to white race), Canada, Australia, and New Zealand, but not in Denmark, the UK, Norway, and Sweden. In all populations, men had higher rates of melanoma of the head and neck and trunk than women (male to female IRR >1), but lower melanoma rates on the lower limbs (ie, male to female IRR approximately 0.5). The male to female IRR increased log linearly with age, with excess melanomas in women younger than 45 years in all populations (eg, IRR for 20-24 y age group, 0.3 in Denmark and 0.7 in Australia), and excess melanomas in men older than 69 years (eg, IRR for 70-74 y age group, 1.1 in Denmark and 2.1 in the US white population). The age at which the melanoma incidence in men exceeded the melanoma incidence in women differed by population, being achieved the earliest in Australia (45-49 years) and latest in Denmark (65-69 years).

Conclusions And Relevance: In predominantly fair-skinned populations, melanoma incidence appears to differ systematically and consistently between men and women by age and anatomic site.
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http://dx.doi.org/10.1001/jamadermatol.2020.0470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097866PMC
May 2020

Early detection of melanoma: a consensus report from the Australian Skin and Skin Cancer Research Centre Melanoma Screening Summit.

Aust N Z J Public Health 2020 Apr 19;44(2):111-115. Epub 2020 Mar 19.

QIMR Berghofer Medical Research Institute, Queensland.

Introduction: A Melanoma Screening Summit was held in Brisbane, Australia, to review evidence regarding current approaches for early detection of melanomas and explore new opportunities.

Results: Formal population-based melanoma screening is not carried out in Australia, but there is evidence of considerable opportunistic screening as well as early detection. Biopsy rates are rising and most melanomas are now diagnosed when in situ. Based on evidence review and expert opinion, the Summit attendees concluded that there is currently insufficient information in terms of comparative benefits, harms and costs to support change from opportunistic to systematic screening. Assessment of gains in precision and cost-effectiveness of integrating total body imaging, artificial intelligence algorithms and genetic risk information is required, as well as better understanding of clinical and molecular features of thin fatal melanomas.

Conclusions: Research is needed to understand how to further optimise early detection of melanoma in Australia. Integrating risk-based population stratification and more precise diagnostic tests is likely to improve the balance of benefits and harms of opportunistic screening, pending assessment of cost-effectiveness. Implications for public health: The Summit Group identified that the personal and financial costs to the community of detecting and treating melanoma are rising, and this may be mitigated by developing and implementing a more systematic process for diagnosing melanoma.
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http://dx.doi.org/10.1111/1753-6405.12972DOI Listing
April 2020

Prevention versus early detection for long-term control of melanoma and keratinocyte carcinomas: a cost-effectiveness modelling study.

BMJ Open 2020 02 26;10(2):e034388. Epub 2020 Feb 26.

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

Objective: To compare the long-term economic impact of melanoma prevention by sun protection, with the corresponding impact of early detection of melanoma to decrease melanoma deaths.

Design: Cost-effectiveness analysis using Markov cohort model. Data were primarily from two population-based randomised controlled trials, epidemiological and costing reports, and included flow-on effects for keratinocyte cancers (previously non-melanoma skin cancers) and actinic keratoses.

Setting: Queensland, Australia.

Participants: Men and women with a mean age 50 years modelled for 30 years.

Interventions: Daily sunscreen use (prevention) compared with annual clinical skin examinations (early detection) and comparing these in turn with the status quo.

Primary And Secondary Outcomes: Costs, counts of melanoma, melanoma deaths, keratinocyte cancers, life years and quality-adjusted life years.

Results: Per 100 000 individuals, for early detection, primary prevention and without intervention, there were 2446, 1364 and 2419 new melanomas, 556, 341 and 567 melanoma deaths, 64 452, 47 682 and 64 659 keratinocyte cancers and £493.5, £386.4 and £406.1 million in economic costs, respectively. There were small differences between prevention and early detection in life years saved (0.09%) and quality-adjusted life years gained (0.10%).

Conclusions: Compared with early detection of melanoma, systematic sunscreen use at a population level will prevent substantial numbers of new skin tumours, melanoma deaths and save healthcare costs. Primary prevention through daily use of sunscreen is a priority for investment in the control of melanoma.
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http://dx.doi.org/10.1136/bmjopen-2019-034388DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7202703PMC
February 2020

Body mass index and height and risk of cutaneous melanoma: Mendelian randomization analyses.

Int J Epidemiol 2020 08;49(4):1236-1245

Department of Population Health, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.

Background: Height and body mass index (BMI) have both been positively associated with melanoma risk, although findings for BMI have been less consistent than height. It remains unclear, however, whether these associations reflect causality or are due to residual confounding by environmental and lifestyle risk factors. We re-evaluated these associations using a two-sample Mendelian randomization (MR) approach.

Methods: We identified single nucleotide polymorphisms (SNPs) for BMI and height from separate genome-wide association study (GWAS) meta-analyses. We obtained melanoma SNPs from the most recent melanoma GWAS meta-analysis comprising 12 874 cases and 23 203 controls. We used the inverse variance-weighted estimator to derive separate causal risk estimates across all SNP instruments for BMI and height.

Results: Based on the combined estimate derived from 730 SNPs for BMI, we found no evidence of an association between genetically predicted BMI and melanoma [odds ratio (OR) per one standard deviation (1 SD) (4.6 kg/m2) increase in BMI 1.00, 95% confidence interval (CI): 0.91-1.11]. In contrast, we observed a positive association between genetically-predicted height (derived from a pooled estimate of 3290 SNPs) and melanoma risk [OR 1.08, 95% CI: 1.02-1.13, per 1 SD (9.27 cm) increase in height]. Sensitivity analyses using two alternative MR methods yielded similar results.

Conclusions: These findings provide no evidence for a causal association between higher BMI and melanoma, but support the notion that height is causally associated with melanoma risk. Mechanisms through which height influences melanoma risk remain unclear, and it remains possible that the effect could be mediated through diverse pathways including growth factors and even socioeconomic status.
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http://dx.doi.org/10.1093/ije/dyaa009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778056PMC
August 2020
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