Inflammatory potential of diet and mortality in Australian adults.

OBJECTIVE: Inflammation is implicated in chronic diseases including cancer and CVD, which are major causes of mortality. Diet can influence inflammation status. We therefore examined whether the inflammatory potential of a person's diet is associated with mortality. DESIGN: The inflammatory potential of the usual diet was assessed by calculating Dietary Inflammatory Index (DII) scores from repeated FFQ data (collected in 1992, 1994 and 1996), placing each participant's diet on a continuum from anti- to pro-inflammatory. DII scores were analysed as a continuous variable and as categories by creating quartile groups. Death registry data were used to ascertain all-cause mortality and separately mortality from CVD, cancers and other causes between 1992 and 2022. Cox proportional hazard regression analysis was used to calculate adjusted hazard ratios (HR) with 95 % CI, comparing higher and lowest quartile groups, or HR change per one DII unit increase. SETTING: Nambour, Australia. PARTICIPANTS: A community-based sample of 1440 adults aged 25-75 years. RESULTS: During follow-up, 488 participants died, including 188 from CVD, 151 from cancer and 170 from other causes. Participants in the most pro-inflammatory diet group were at increased risk of all-cause mortality (HRQ4 v. Q1 = 1·55; 95 % CI 1·19, 2·03; P < 0·001) and other-cause mortality (HRQ4 v. Q1 = 1·69; 95 % CI 1·12, 2·54; P 0·01). A one-unit increase in DII score was associated with a 36 % increased risk of CVD among those younger than 55 years of age (HR for a one-unit increase in DII score 1·36, 95 % CI 1·04, 1·78). The risk of cancer mortality was also increased for those with a more pro-inflammatory diet in age ≤ 55 years (HR for a one-unit increase in DII score 1·20, 95 % CI 1·02, 1·40) and age 56-65 years (HR for a one-unit increase in DII score 1·11, 95 % CI 1·00, 1·23). CONCLUSIONS: A pro-inflammatory diet increases the risk of all-cause mortality. Our results support the promotion of anti-inflammatory diets to help promote longevity.

Hypothesised cutaneous sites of origin of stage III melanomas with unknown primary: A multicentre study.

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.

Associations of keratinocyte cancers with snp variants in the sonic hedgehog pathway.

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 < 0.01) and SCCs exclusively (OR = 2.12; 95%CI = 1.39-3.23, P < 0.01). SNP rs3217882 located in CCND2 was associated with exclusive BCC development (OR = 1.43, CI = 1.12-1.82, P < 0.01). The gene-based analysis suggested an association of 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.

Dark Green Leafy Vegetable Intake, MTHFR Genotype, and Risk of 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.

Host genetic polymorphisms associated with beta human papillomavirus seropositivity.

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.

Sun protection behavior after diagnosis of high-risk primary melanoma and risk of a subsequent primary.

BACKGROUND: Melanoma survivors are at high risk of further primary melanomas. OBJECTIVE: To assess sun behavior after melanoma diagnosis and in relation to further primary melanomas. METHODS: We applied repeated measures latent class analysis to reported primary prevention behavior at time of diagnosis and every 6 months for 2 years after diagnosis in patients with clinical stage IB or II melanoma. Correlates of behavior trajectories and risk of subsequent primaries were determined by using multivariable logistic and Cox regression analyses, respectively. RESULTS: Among the 448 male and 341 female patients, sunscreen use fell into 3 trajectories: stable never-use (26% of males and 12% of females), stable sometimes-use (35% of males and 29% of females), and increased to often-use (39% of males and 59% of females). Most reduced their weekend sun exposure, but in 82% of males and 69% of females it remained increased. Males, smokers, the less educated, those who tanned, and those not self-checking their skin were more likely to have trajectories of inadequate protection. Patients with a history of melanoma before the study doubled their risk of another primary melanoma in the next 2 years if sunscreen use in that time was inadequate (hazard ratio, 2.45; 95% confidence interval, 1.00-6.06). LIMITATIONS: Patient-reported data are susceptible to recall bias. CONCLUSION: Our results may assist clinicians in identifying patients not using adequate sun protection and providing information for patient counseling.

Clustering of prevention behaviours in patients with high-risk primary melanoma.

OBJECTIVE: Because melanoma patients are at high risk of further disease, we aimed to study their melanoma prevention behaviours. METHODS: In a large cohort of patients newly diagnosed with high-risk melanoma in Queensland, Australia, we assessed clustering of preventive behaviours using latent class analysis. We assessed associated factors with prevalence proportion ratios (PPRs) and 95% confidence intervals (CIs) estimated by Poisson regression and also if preventive behaviour was associated with better tumour prognosis at diagnosis. RESULTS: Among 789 primary melanoma patients (57% male; 21% with previous melanoma), we identified 4 different behaviour clusters: "no/ low prevention" (34% of cohort), "sun protection only" (25%), "skin checks only" (25%), and "sun protection and skin checks" (17%). Prevalence of clusters differed between males and females and also the component behaviours. Preventive behaviours were associated with having skin that burned and past cutaneous cancer, and for males, combined sun protective and skin checking behaviour was associated with higher education and non-smoking. In patients with no past history of cutaneous cancer, males in the "skin checks only" cluster had significantly reduced chances of a thick (poor prognosis) melanoma (PPR = 0.79, 95% CI 0.68, 0.91) and females in the "sun protection and skin checks" cluster were significantly less likely to have an ulcerated melanoma (PPR = 0.85, 95% CI 0.74, 0.98) compared with the "no/ low prevention" cluster. CONCLUSION: These findings allow tailoring of preventive advice to melanoma patients to reduce their risk of future primary and recurrent disease.

Absolute versus relative measures of plasma fatty acids and health outcomes: example of phospholipid omega-3 and omega-6 fatty acids and all-cause mortality in women.

PURPOSE: In a well-characterised community-based prospective study, we aimed to systematically assess the differences in associations of plasma omega-3 and omega-6 fatty acid (FA) status with all-cause mortality when plasma FA status is expressed in absolute concentrations versus relative levels. METHODS: In a community sample of 564 women aged 25-75 years in Queensland, Australia, baseline plasma phospholipid FA levels were measured using gas chromatography. Specific FAs analysed were eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, total long-chain omega-3 FAs, linoleic acid, arachidonic acid, and total omega-6 FAs. Levels of each FA were expressed in absolute amounts (µg/mL) and relative levels (% of total FAs) and divided into thirds. Deaths were monitored for 17 years and hazard ratios and 95% confidence intervals calculated to assess risk of death according to absolute versus relative plasma FA levels. RESULT: In total 81 (14%) women died during follow-up. Agreement between absolute and relative measures of plasma FAs was higher in omega-3 than omega-6 FAs. The results of multivariate analyses for risk of all-cause mortality were generally similar with risk tending to inverse associations with plasma phospholipid omega-3 FAs and no association with omega-6 FAs. Sensitivity analyses examining effects of age and presence of serious medical conditions on risk of mortality did not alter findings. CONCLUSIONS: The directions and magnitude of associations with mortality of absolute versus relative FA levels were comparable. However, plasma FA expressed as absolute concentrations may be preferred for ease of comparison and since relative units can be deduced from absolute units.

Dietary patterns and weight change: 15-year longitudinal study in Australian adults.

BACKGROUND: Dietary intake is one of the most modifiable risk factors associated with obesity. However, data on the relationship between dietary patterns and long-term weight change are limited. PURPOSE: We therefore investigated the association between dietary patterns and 15-year weight change in a sample of 1186 Australian adults (1992-2007). METHODS: We measured body weight and collected data on socio-demographic and lifestyle characteristics in 1992 and 2007. Applying principal component analysis to 38 food groups from a food frequency questionnaire collected at baseline, we identified two dietary patterns: 'meat-and-fat' and 'fruit-and-vegetable.' Using generalized estimating equations, multivariable regression models, stratified by sex, were adjusted for concurrent changes in socio-demographic and lifestyle variables. RESULTS: The average increase in body weight of men in the highest tertile of the meat-and-fat pattern was more than twice that of men in the lowest tertile; mean weight change (95 % CI): 4.8 (-0.1, 9.7) kg versus 2.3 (-2.6, 7.1) kg, P-for-trend = 0.02. In contrast, average weight gain of men in the highest tertile of the fruit-and-vegetable pattern was only about half that of men in the lowest tertile; mean weight change (95 % CI): 2.9 (-2.0, 7.8) kg versus 5.4 (-1.5, 10.4) kg, P-for-trend = 0.02. Among women, dietary patterns were not related to weight change. CONCLUSIONS: These dietary patterns predict change in body weight in men, but not in women. In this cohort, a dietary pattern high in fruit and vegetables was related to less weight gain in men than a dietary pattern high in meat and fat.

Molecular markers to complement sentinel node status in predicting survival in patients with high-risk locally invasive melanoma.

Sentinel lymph node status is a major prognostic marker in locally invasive cutaneous melanoma. However, this procedure is not always feasible, requires advanced logistics and carries rare but significant morbidity. Previous studies have linked markers of tumour biology to patient survival. In this study, we aimed to combine the predictive value of established biomarkers in addition to clinical parameters as indicators of survival in addition to or instead of sentinel node biopsy in a cohort of high-risk melanoma patients. Patients with locally invasive melanomas undergoing sentinel lymph node biopsy were ascertained and prospectively followed. Information on mortality was validated through the National Death Index. Immunohistochemistry was used to analyse proteins previously reported to be associated with melanoma survival, namely Ki67, p16 and CD163. Evaluation and multivariate analyses according to REMARK criteria were used to generate models to predict disease-free and melanoma-specific survival. A total of 189 patients with available archival material of their primary tumour were analysed. Our study sample was representative of the entire cohort (N = 559). Average Breslow thickness was 2.5 mm. Thirty-two (17%) patients in the study sample died from melanoma during the follow-up period. A prognostic score was developed and was strongly predictive of survival, independent of sentinel node status. The score allowed classification of risk of melanoma death in sentinel node-negative patients. Combining clinicopathological factors and established biomarkers allows prediction of outcome in locally invasive melanoma and might be implemented in addition to or in cases when sentinel node biopsy cannot be performed.

Black Tea Consumption and Risk of Skin Cancer: An 11-Year Prospective Study.

Tea consumption has been shown to protect against skin carcinogenesis in laboratory-based studies; however, epidemiological evidence is limited and inconsistent. This prospective study examined the association between black tea consumption and the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Usual black tea consumption was estimated from food frequency questionnaires completed in 1992, 1994, and 1996 by 1,325 Australian adults. All histologically confirmed skin cancers diagnosed in participants from 1997 to 2007 were recorded. Relative risks (RRs) and 95% confidence intervals (CIs) were assessed using generalized linear models with Poisson and negative binomial distributions and adjusted for confounding factors including skin phenotype and sun exposure. Compared with never drinking black tea, drinking ≥4 cups/day was not associated with BCC (RR = 1.03, 95% CI: 0.70-1.53; P-trend = 0.74) or SCC (RR = 1.25, 95% CI: 0.71-2.19; P-trend = 0.29) in person-based analyses. Stratification by previous history of skin cancer as well as tumor-based analyses also showed no significant associations between black tea intake and incidence of BCC or SCC tumors. Our results do not support the hypothesis that high black tea consumption reduces risk of skin cancer, including in people with a previous history of skin cancer.

Supportive care needs, anxiety, depression and quality of life amongst newly diagnosed patients with localised invasive cutaneous melanoma in Queensland, Australia.

OBJECTIVE: The aim of this paper is to determine levels of supportive care needs, anxiety, depression and symptoms amongst patients newly diagnosed with localised invasive primary melanoma and if these varied amongst patients who had a sentinel lymph node biopsy (SLNB). We also considered quality of life compared with general population norms. METHODS: Patients newly diagnosed with clinical stage IB-II invasive melanoma were ascertained through Queensland hospitals, specialist clinics and pathology laboratories. Validated surveys measured 46 need items (Supportive Care Needs Survey-Short Form + melanoma subscale), anxiety and depression (Hospital Anxiety and Depression Scale) and quality of life and symptoms (Functional Assessment of Cancer Therapy-Melanoma). Regression models compared outcomes according to whether or not participants had a SLNB. RESULTS: We surveyed 386 patients, 155 before and 231 after wide local excision, of whom 46% reported ≥1 moderate-level or high-level unmet need. The three highest needs were for help with fears about cancer spreading (17%), information about risk of recurrence (17%) and outcomes when spread occurred (16%). Those who had a SLNB were more likely to report a moderate or high unmet need for help with uncertainty about the future or with lymphoedema (p < 0.05). Overall, 32% of participants had anxiety and 15% had depression regardless of performance of SLNB. Melanoma-specific symptoms were worse in SLNB patients (p = 0.03). Compared with the general population, emotional well-being was lower amongst melanoma patients. CONCLUSIONS: A substantial proportion of newly diagnosed patients with localised invasive melanoma need further melanoma-specific information and support with psychological concerns. Patients who have a SLNB clear of disease may need help with symptoms after surgery.

Prospective study of patterns of surgical management in adults with primary cutaneous melanoma at high risk of spread, in Queensland, Australia.

BACKGROUND: Knowledge of variation in diagnosis and surgery in high-risk primary melanoma patients is limited. We assessed frequency and determinants of diagnostic procedures, wide local excision (WLE) and sentinel lymph node biopsy (SLNB). METHODS: People in Queensland newly diagnosed with melanoma, clinical stage 1b or 2, were recruited prospectively. Patient information was collected from questionnaires and pathology records. Differences in surgical procedures in relation to host and tumor characteristics were assessed. RESULTS: In 787 participants, primary melanoma was diagnosed by surgical excision (74%), shave (14%), punch (12%) or incisional (1%) biopsy. General practitioners (GPs) diagnosed 80%. Diagnostic procedure differed by remoteness of residence, health sector, treating doctor's specialty and melanoma site and thickness. 766 patients had WLE, 86% by surgeons. Of 134 residual melanomas, 13 (10%) were ≤ 1 mm at diagnosis but > 1 mm at WLE, mostly after shave biopsy. SLNB was performed in 261 (33%) patients. SLNB was more common in those under 50, in remoter locations or treated by GP initially, and less common with head and neck melanoma. CONCLUSION: Diagnostic and surgical procedures for primary melanoma vary substantially and partial biopsy can influence initial tumor microstaging. Patient, tumor and doctor characteristics influence SLNB practice.

Dietary phyto-oestrogens and the risk of ovarian and endometrial cancers: findings from two Australian case-control studies.

Phyto-oestrogens have been suggested to have a protective effect on hormone-sensitive cancers. However, few studies have investigated the association between dietary phyto-oestrogens and gynaecological cancers. In the present study, we analysed data from two population-based case-control studies of ovarian (1366 cases and 1414 controls) and endometrial (1288 cases and 1435 controls) cancers. Dietary intake information was obtained using a 135-item FFQ, and phyto-oestrogen intake was estimated using published food composition databases. Unconditional logistic regression was used to estimate adjusted OR and 95% CI. In multivariable analyses, there was a suggestive pattern of inverse associations between increasing intakes of total phyto-oestrogens, isoflavones and enterolignans and the risk of ovarian cancer. However, the results only reached statistical significance for the lignan compounds matairesinol and lariciresinol, where the OR for the highest v. the lowest intake category was 0.72 (95% CI 0.54, 0.96; P for trend = 0.02) for matairesinol and 0.72 (95% CI 0.55, 0.96; P for trend = 0.03) for lariciresinol. When the risk of ovarian cancer was assessed by subtype, there was an indication that increasing intakes of phyto-oestrogens may be associated with a decreased risk of mucinous (cases n 158) ovarian tumours (OR for the highest v. the lowest intake category: 0.47 (95% CI 0.24, 0.93); P for trend = 0.04). However, there were no significant associations with other histological subtypes. In contrast, dietary phyto-oestrogens (total or any subclass) were unrelated to the risk of endometrial cancer cases overall or by subtype.

Caffeine intake and risk of basal cell and squamous cell carcinomas of the skin in an 11-year prospective study.

PURPOSE: Caffeine may repair skin damage induced by excessive exposure to ultraviolet light. The purpose of this study was to investigate the association between caffeine intake and incidence of basal cell (BCC) and squamous cell carcinoma (SCC). We also assessed the associations between coffee consumption and incidence of these skin cancers. METHODS: Caffeine intake and consumption of coffee were estimated from food frequency questionnaires assessed in 1992, 1994, and 1996 among 1,325 randomly selected adult residents of a subtropical Australian community. All histologically confirmed tumours of BCC and SCC occurring between 1997 and 2007 were recorded. Associations with BCC and SCC were assessed using Poisson and negative binomial regression models and were adjusted for confounders including skin type and indicators of past sun exposure. RESULTS: There was no association between total caffeine intake and incidence of BCC or SCC. Participants with prior skin cancers, however, had a 25% lower risk of BCC if they were in the highest tertile of total caffeine intake (equivalent to daily consumption of four cups of regular coffee) compared with the lowest tertile (multivariable RR 0.75; 95% CI 0.57-0.97, P trend = 0.025). There was no dose-response relationship with SCC. Consumption of neither caffeinated nor decaffeinated coffee was associated with BCC or SCC. CONCLUSIONS: Among people with prior skin cancers, a relatively high caffeine intake may help prevent subsequent BCC development. However, caffeine intake appears not to influence the risk of SCC.

Effects of sunscreen on skin cancer and photoaging.

Application of sunscreen to the skin is widely used as an adjunct strategy, along with wearing protective clothing and seeking shade, to protect against skin cancer and photoaging that result from excessive sun exposure. Many epidemiological studies of case-control and cohort study design have studied the effects of sunscreen use on skin cancer, and more recently photoaging, but their findings have been mostly uninformative. This review of results of randomized controlled trials shows that the evidence, though limited, supports beneficial effects of sunscreen application on the occurrence of skin cancers and skin photoaging.

Sunscreen and prevention of skin aging: a randomized trial.

BACKGROUND: Sunscreen use and dietary antioxidants are advocated as preventives of skin aging, but supporting evidence is lacking. OBJECTIVE: To determine whether regular use of sunscreen compared with discretionary use or ß-carotene supplements compared with placebo retard skin aging, measured by degree of photoaging. DESIGN: Randomized, controlled, community-based intervention. (Australian New Zealand Clinical Trials Registry: ACTRN12610000086066). SETTING: Nambour, Australia (latitude 26° S). PATIENTS: 903 adults younger than 55 years out of 1621 adults randomly selected from a community register. INTERVENTION: Random assignment into 4 groups: daily use of broad-spectrum sunscreen and 30 mg of ß-carotene, daily use of sunscreen and placebo, discretionary use of sunscreen and 30 mg of ß-carotene, and discretionary use of sunscreen and placebo. MEASUREMENTS: Change in microtopography between 1992 and 1996 in the sunscreen and ß-carotene groups compared with controls, graded by assessors blinded to treatment allocation. RESULTS: The daily sunscreen group showed no detectable increase in skin aging after 4.5 years. Skin aging from baseline to the end of the trial was 24% less in the daily sunscreen group than in the discretionary sunscreen group (relative odds, 0.76 [95% CI, 0.59 to 0.98]). ß-Carotene supplementation had no overall effect on skin aging, although contrasting associations were seen in subgroups with different severity of aging at baseline. LIMITATION: Some outcome data were missing, and power to detect moderate treatment effects was modest. CONCLUSION: Regular sunscreen use retards skin aging in healthy, middle-aged men and women. No overall effect of ß-carotene on skin aging was identified, and further study is required to definitively exclude potential benefit or potential harm. PRIMARY FUNDING SOURCE: National Health and Medical Research Council of Australia.