Polygenic risk score as a determinant of risk of keratinocyte cancer in an Australian population-based cohort.

BACKGROUND: Keratinocyte cancer (KC) risk is determined by genetic and environmental factors. Genetic risk can be quantified by polygenic risk scores (PRS), which sum the combined effects of single nucleotide polymorphisms (SNPs). OBJECTIVES: Our objective here was to evaluate the contribution of the summed genetic score to predict the KC risk in the phenotypically well-characterized Nambour population. METHODS: We used PLINK v1.90 to calculate PRS for 432 cases, 566 controls, using 78 genome-wide independent SNPs that are associated with KC risk. We assessed the association between PRS and KC using logistic regression, stratifying the cohort into three risk groups (high 20%, intermediate 60%, low 20%). RESULTS: The fully adjusted model including traditional risk factors (phenotypic and sun exposure-related), showed a significant 50% increase in odds of KC per standard deviation of PRS (odds ratio (OR) = 1.51; 95% confidence interval (CI) = 1.30-1.76, P = 5.75 × 10-8 ). Those in the top 20% PRS had over three times the risk of KC of those in the lowest 20% (OR = 3.45; 95% CI = 2.18-5.50, P = 1.5 × 10-7 ) and higher absolute risk of KC per 100 person-years of 2.96 compared with 1.34. Area under the ROC curve increased from 0.72 to 0.74 on adding PRS to the fully adjusted model. CONCLUSIONS: These results show that PRS can enhance the prediction of KC above traditional risk factors.

Diet quality is associated with primary melanoma thickness.

BACKGROUND: Patients' diets can influence the outcome of several common cancers, but the effect on melanoma prognosis is unknown. OBJECTIVE: To assess the association between quality of melanoma patients' prediagnosis diets and primary tumour thickness, the main prognostic indicator for melanoma. METHODS: We used baseline data from patients newly diagnosed with tumour stage Ib to IV cutaneous melanoma, with completed questionnaires about food intake in the past year and other factors. Diet quality was measured by the Healthy Eating Index (HEI) and melanoma thickness was extracted from histopathology reports. We estimated prevalence ratios (PRadj ) and 95% confidence intervals (CIs) adjusted for confounding factors using Poisson regression models to assess associations between HEI scores and melanoma thickness. RESULTS: Of 634 study patients, 238 (38%) had melanomas >2 mm thick at diagnosis. Patients with the highest HEI scores were significantly less likely to be diagnosed with thick melanoma than patients with lowest HEI scores (PRadj 0.93, 95% CI 0.86-0.99) (Ptrend = 0.03). There was no evidence of effect modification by age, sex, previous melanoma or comorbidities. CONCLUSIONS: Melanoma thickness at diagnosis is significantly associated with quality of patients' diets before diagnosis.

Statins may reduce disease recurrence in patients with ulcerated primary melanoma.

BACKGROUND: Statins may restrict the cellular functions required for melanoma growth and metastasis. OBJECTIVES: To determine whether long-term statin use commenced before diagnosis of a primary melanoma is associated with reduced risk of melanoma recurrence. METHODS: We prospectively followed a cohort of patients newly diagnosed between 2010 and 2014 with localized tumour-stage T1b to T4b melanoma in Queensland, Australia. We used Cox regression analyses to examine associations between long-term statin use and melanoma recurrence for the entire cohort, and then separately by sex and by presence of ulceration, due to evidence of effect modification. RESULTS: Among 700 patients diagnosed with stage T1b to T4b primary melanoma (mean age 62 years, 59% male, 28% with ulcerated tumours), 94 patients (13%) developed melanoma recurrence within 2 years. Long-term statin users (n = 204, 29%) had a significantly lower risk of disease recurrence than nonusers [adjusted hazard ratio (HRadj ) 0·55, 95% confidence Interval (CI) 0·32-0·97] regardless of statin subtype or potency. Compared with nonusers of statins, risk of recurrence was significantly decreased in male statin users (HRadj 0·39, 95% CI 0·19-0·79) but not in female statin users (HRadj 0·82, 95% CI 0·29-2·27) and in statin users with ulcerated (HRadj 0·17, 95% CI 0·05-0·52) but not nonulcerated (HRadj 0·91, 95% CI 0·46-1·81) primary melanoma. CONCLUSIONS: Statins commenced before melanoma diagnosis may reduce the risk of melanoma recurrence, especially in men and in those with ulcerated tumours. Clinical trial evaluation of the potential role of statins in improving the prognosis of high-risk melanoma is warranted.

A prospective study of cigarette smoking and basal cell carcinoma.

To investigate the relationship between smoking and primary basal cell carcinoma (BCC), we analyzed data from a 16 year prospective study among randomly selected adults in Nambour, Queensland, Australia. Participants underwent a skin examination in 1992 and took part in an intervention study and follow-up. Information about complexion type and smoking habits including duration and number of cigarettes smoked per day and sun exposure behavior were collected at baseline in 1992, with updates to end of follow-up in 2007. Newly-diagnosed BCCs were ascertained from regional pathology laboratories. Relative risks (RR) of BCC among former and current smokers were estimated using generalized linear models specifying a Poisson distribution with robust error variance and (log) person-years at-risk as offset, adjusting for BCC risk factors. From 1992 to 2007, 281 BCCs were diagnosed in 1,277 participants with available smoking history and no past BCC. Relative to non-smokers, a non-significant inverse association between current smoking and BCC was seen (RR 0.69; 95 % CI 0.45-1.05) but not for former smokers (RR 1.05; 95 % CI 0.84-1.31). Amongst current smokers, inverse associations with BCC were found in those who smoked for up to 18 years (RR 0.44) but not more and those who smoked up to 15 cigarettes per day but not more. The associations with both current and former smoking varied by degree of sunburn propensity. The modest inverse association between current smoking and BCC is considered unlikely to be causal given lack of clear relation with duration or intensity of smoking.

Factors associated with premature skin aging (photoaging) before the age of 55: a population-based study.

BACKGROUND: Precise factors associated with premature skin aging, or photoaging, in the general population are unknown. OBJECTIVE: To examine the risk factors for photoaging in a Queensland community. METHODS: A cross-sectional study of 1,400 randomly selected residents aged 20-54 years, using casts of the back of the hand (surface microtopography) and dermatological assessment of photoaging. RESULTS: 83% of the participants had premature skin aging, worsening after the age of 30. Severe neck wrinkling was 3 times more likely in men and some 4 times more likely in fair-skinned people (odds ratio, OR=3.86, 95% confidence interval, CI=2.40-6.23). Red hair and mainly outdoor work or leisure raised the odds of microtopographic photoaging. Current smoking was strongly associated with facial comedones and telangiectasia, and among current smokers, the microtopography grade was significantly associated with moderate and heavy smoking measured by pack-years of exposure, with OR=3.18 (95% CI=1.38-7.35) in the heaviest (>20 pack-years) smoking category compared with 1-7 pack-years. CONCLUSIONS: Premature skin aging is common in the subtropics, more severe in men and the fair-skinned. It is associated with high sun exposure during leisure or work, and moderate to heavy smoking, and therefore is preventable.

Food intake and risk of basal cell carcinoma in an 11-year prospective study of Australian adults.

BACKGROUND/OBJECTIVE: Experimental studies suggest that dietary factors may influence skin cancer risk, but there have been few human studies of diet and basal cell carcinoma (BCC), the most common type of skin cancer. The objective was to prospectively investigate the association between food intake and incidence of BCC skin cancers. SUBJECTS/METHODS: At baseline in 1992, 1056 adults in a subtropical Australian community completed a validated food-frequency questionnaire from which we estimated the intake of 15 food groups, selected based on hypothesized associations in the literature. Between 1992 and 2002, incident, histologically confirmed BCCs were recorded in terms of number of persons newly affected by BCC, as well as BCC tumor counts. RESULTS: Intakes of the food groups were not associated with the incidence of persons affected by BCC. However, there was a borderline positive association between intake of eggs and incidence of BCC tumors (highest vs lowest tertile adjusted relative risk (RR) 1.5; 95% confidence interval (CI): 1.0-2.2; P for trend = 0.06). A borderline inverse association with potato intake (highest vs lowest tertile RR 0.7; 95% CI: 0.4-1.0, P for trend = 0.06) disappeared after exclusion of three subjects with more than 10 BCCs. CONCLUSION: Despite some suggestive evidence that egg and potato consumption may be associated with BCC tumor incidence, there are no plausible grounds for considering these as truly causal rather than chance associations. This study provides little evidence for a role of food intake in BCC prevention.

Dairy consumption and patterns of mortality of Australian adults.

BACKGROUND/OBJECTIVES: Dairy foods contain various nutrients that may affect health. We investigated whether intake of dairy products or related nutrients is associated with mortality due to cardiovascular disease (CVD), cancer and all causes. SUBJECTS/METHODS: We carried out a 16-year prospective study among a community-based sample of 1529 adult Australians aged 25-78 years at baseline. Habitual intakes of dairy products (total, high/low-fat dairy, milk, yoghurt and full-fat cheese), calcium and vitamin D were estimated as mean reported intake using validated food frequency questionnaires (FFQs) self-administered in 1992, 1994 and 1996. National Death Index data were used to ascertain mortality and cause of death between 1992 and 2007. Hazard ratios (HRs) were calculated using Cox regression analysis. RESULTS: During an average follow-up time of 14.4 years, 177 participants died, including 61 deaths due to CVD and 58 deaths due to cancer. There was no consistent and significant association between total dairy intake and total or cause-specific mortality. However, compared with those with the lowest intake of full-fat dairy, participants with the highest intake (median intake 339 g/day) had reduced death due to CVD (HR: 0.31; 95% confidence interval (CI): 0.12-0.79; P for trend=0.04) after adjustment for calcium intake and other confounders. Intakes of low-fat dairy, specific dairy foods, calcium and vitamin D showed no consistent associations. CONCLUSIONS: Overall intake of dairy products was not associated with mortality. A possible beneficial association between intake of full-fat dairy and cardiovascular mortality needs further assessment and confirmation.