High-risk Prognostic Tumor Features of Squamous Cell Carcinomas in Organ Transplant Recipients Compared With the General Population.

Importance: The extent to which major high-risk features of squamous cell carcinomas (SCCs) in organ transplant recipients (OTRs) differ from SCCs in the general population is not known. Objective: To quantify the relative frequency of perineural invasion, invasion below the dermis, lack of cellular differentiation, and tumor diameter greater than 20 mm in SCCs in OTRs and the general population, by anatomic site. Design, Setting, and Participants: This dual-cohort study in Queensland, Australia, included a cohort of OTRs at high risk of skin cancer ascertained from 2012 to 2015 (Skin Tumours in Allograft Recipients [STAR] study) and a population-based cohort ascertained from 2011 (QSkin Sun and Health Study). The STAR study comprised population-based lung transplant recipients and kidney and liver transplant recipients at high risk of skin cancer recruited from tertiary centers and diagnosed with histopathologically confirmed SCC from 2012 to 2015. The QSkin participants were recruited from Queensland's general adult population, and primary SCCs diagnosed from 2012 to 2015 were ascertained through Medicare (national health insurance scheme) and linked with histopathology records. Data analysis was performed from July 2022 to April 2023. Main Outcomes and Measures: Prevalence ratio (PR) of head/neck location, perineural invasion, tumor invasion to/beyond subcutaneous fat, poor cellular differentiation, and tumor diameter greater than 20 mm among SCCs in OTRs vs the general population. Results: There were 741 SCCs excised from 191 OTRs (median [IQR] age, 62.7 [56.7-67.1] years; 149 [78.0%] male) and 2558 SCCs from 1507 persons in the general population (median [IQR] age, 63.7 [58.0-68.8] years; 955 [63.4%] male). The SCCs developed most frequently on the head/neck in OTRs (285, 38.6%), but on arms/hands in the general population (896, 35.2%) (P < .001). After adjusting for age and sex, perineural invasion was more than twice as common in OTRs as in population cases (PR, 2.37; 95% CI, 1.70-3.30), as was invasion to/beyond subcutaneous fat (PR, 2.37; 95% CI, 1.78-3.14). Poorly vs well-differentiated SCCs were more than 3-fold more common in OTRs (PR, 3.45; 95% CI, 2.53-4.71), and prevalence of tumors greater than 20 mm vs 20 mm or smaller was moderately higher in OTRs (PR, 1.52; 95% CI, 1.08-2.12). Conclusions and Relevance: In this dual-cohort study, SCCs in OTRs had significantly worse prognostic features than SCCs in the general population, reinforcing the necessity of early diagnosis and definitive management of SCCs in OTRs.

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

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 (n > 8,000), and the meta-analysis GWASs from UKB, 23andMe, and Qskin for BCC (n = 651,138) and SCC (n = 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, P = 1.4 × 10-4] and alpha-linolenic acid (OR = 0.91, 95% CI = 0.86-0.96, P = 5.1 × 10-4) was associated with a reduced BCC risk, while arachidonic acid (OR = 1.04, 95% CI = 1.02-1.06, P = 3.2 × 10-4) and eicosapentaenoic acid (OR = 1.10, 95% CI = 1.04-1.16, P = 1.5 × 10-3) 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.

Keratinocyte cancer excisions in Australia: Who performs them and associated costs.

BACKGROUND/OBJECTIVE: To describe the clinical settings in which keratinocyte cancers are excised in Queensland and describe the types of practitioners who excise them; to examine costs; and to identify predictors of hospital admission. METHODS: We used linked data for participants from the QSkin study (n = 43 794), including Medicare claims and Queensland hospital admissions relating to treatment episodes for incident keratinocyte cancers from July 2011 to June 2015. We used multinomial logistic regression to measure associations between demographic and clinical characteristics and treatment setting. The median costs of Medicare claims (AU$) were calculated. RESULTS: During 4 years of follow-up, there were 18 479 skin cancer excision episodes among 8613 people. Most excisions took place in private clinical rooms (89.7%), the remainder in hospitals (7.9% private; 2.4% public). Compared with other anatomical sites, skin cancers on the nose, eyelid, ear, lip, finger or genitalia were more likely to be treated in hospitals than in private clinical rooms (public hospital OR 5.7; 95%CI 4.5-7.2; private hospital OR 8.3; 95%CI 7.3-9.4). Primary care practitioners excised 83% of keratinocyte cancers, followed by plastic surgeons (9%) and dermatologists (6%). The median Medicare benefit paid was $253 in private clinical rooms and $334 in private hospitals. Out-of-pocket payments by patients treated in private hospitals were fourfold higher than those in private clinical rooms ($351 vs $80). CONCLUSIONS: Most keratinocyte cancers are excised in primary care, although more than 10% of excisions occur in hospital settings.

The incidence and multiplicity rates of keratinocyte cancers in Australia.

OBJECTIVES: To assess the incidence and multiplicity of keratinocyte cancers (basal cell carcinoma [BCC] and squamous cell carcinoma [SCC]) excised in Australia, and to examine variations by age, sex, state, and prior skin cancer history. DESIGN: Analysis of individual-level Medicare data for keratinocyte cancer treatments (identified by eight specific MBS item codes) during 2011-2014. Histological data from the QSkin prospective cohort study were analysed to estimate BCC and SCC incidence. SETTING: A 10% systematic random sample of all people registered with Medicare during 1997-2014. PARTICIPANTS: People aged at least 20 years in 2011 who made at least one claim for any MBS medical service during 2011-2014 (1 704 193 individuals). MAIN OUTCOME MEASURES: Age-standardised incidence rates (ASRs) and standardised incidence ratios (SIRs). RESULTS: The person-based incidence of keratinocyte cancer excisions in Australia was 1531 per 100 000 person-years; incidence increased with age, and was higher for men than women (SIR, 1.43; 95% CI, 1.42-1.45). Lesion-based incidence was 3154 per 100 000 person-years. The estimated ASRs for BCC and SCC were 770 per 100 000 and 270 per 100 000 person-years respectively. During 2011-2014, 3.9% of Australians had one keratinocyte cancer excised, 2.7% had more than one excised; 74% of skin cancers were excised from patients who had two or more lesions removed. Multiplicity was strongly correlated with age; most male patients over 70 were treated for multiple lesions. Keratinocyte cancer incidence was eight times as high among people with a prior history of excisions as among those without. CONCLUSIONS: The incidence and multiplicity of keratinocyte cancer in Australia are very high, causing a large disease burden that has not previously been quantified.

Consumption of omega-3 fatty acids and the risk of skin cancers: a systematic review and meta-analysis.

Skin cancers have a higher incidence than all other cancers combined and are a major cause of morbidity worldwide. Laboratory data suggest certain dietary constituents, notably omega-3 polyunsaturated fatty acids (n-3 PUFAs), could potentially protect against skin malignancy, although no large-scale review has been conducted in humans. The objective of this review and meta-analysis was to determine the relationship between dietary n-3 PUFAs and skin cancer incidence. It considered all published randomized controlled trials and observational studies up to March 2013. Five studies (two case-control and three cohort) were identified pertaining to oral n-3 PUFA consumption and incidence of basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma (or a combination) and were included in a random-effects meta-analysis. A further six studies considering nondietary n-3 PUFA exposure (e.g., by tissue analysis) and/or recognized biological markers of skin cancer risk (e.g., p53 expression) were analyzed qualitatively. Dietary n-3 PUFAs were not associated with BCC (pooled OR 1.05, 95% CIs 0.86-1.28). Consumption of high levels of n-3 PUFAs were inversely associated with melanoma, although with only one estimate available (OR 0.52, 95% CI 0.34-0.78), and SCC, although nonsignificantly (pooled OR 0.86, 95% CIs 0.59-1.23). Available evidence is suggestive, but currently inadequate, to support the hypothesis that n-3 PUFAs protect against skin malignancy.

Tea consumption and risk of ovarian cancer.

OBJECTIVE: Although the growth inhibitory effects of tea, particularly green tea, and tea polyphenols have been demonstrated in animal models of ovarian cancer, the results of epidemiological studies have been inconclusive. METHODS: We investigated this issue using data from an Australian population-based, case-control study (1,368 cases; 1,416 controls). We also systemically reviewed all the available evidence regarding the potential association between green tea and risk of ovarian cancer, given the abundance of bioavailable polyphenols and higher antioxidant capacity of green tea than black tea, to provide the best summary estimate of the association. RESULTS: In our case-control study, while we found uniformly inverse odds ratios (OR) for tea drinkers compared to non-tea drinkers [4 + cups/day any tea OR 0.71 (95% CI 0.52-0.97); green tea OR 0.82 (95% CI 0.38-1.79); herbal tea OR 0.77 (95% CI 0.28-2.14): black tea OR 0.88 (95% CI 0.66-1.18)], we saw no dose-response trends. Our meta-analysis provided some evidence that women who drink green tea have a lower risk of ovarian cancer, although the summary estimate did not reach statistical significance (0.58, 95% CI 0.33-1.01 for >or=1 cup/green tea day). This result is consistent with two recent meta-analyses that evaluated the association of tea (all types combined) and ovarian cancer risk. CONCLUSION: Overall, our findings provide some support for the hypothesis that tea consumption reduces the risk of ovarian cancer.