Maria Celia Hughes

Anatomic Site, Sun Exposure, and Risk of Cutaneous Melanoma

PURPOSE Sunlight is the principal environmental risk factor for cutaneous melanoma. A current hypothesis postulates that the role of sunlight in causing melanoma differs according to anatomic site. We tested this hypothesis in a population-based case-case comparative study of melanoma patients. METHODS Patients were sampled from the Queensland cancer registry in three groups: superficial spreading or nodular melanomas of the trunk (n = 154), of the head and neck (HN; n = 76), and lentigo maligna (LM) and lentigo maligna melanoma (LMM; for both LM and LMM, n = 76). Data were collected on school-age sun exposure and occupational and recreational sun exposure in adulthood. Odds ratios (OR) and 95% CIs were calculated using polytomous logistic regression. RESULTS HN melanoma patients were substantially more likely than trunk patients to have higher levels of sun exposure in adulthood (OR, 2.43; 95% CI, 0.98 to 5.99) and specifically, higher levels of occupational exposure (OR, 3.25; 95% CI, 1.32 to 8.00), but lower levels of recreational sun exposure (OR, 0.50; 95% CI, 0.21 to 1.19). LM and LMM patients reported higher occupational exposure and lower recreational sun exposure than trunk melanoma patients, although this was not significant. We found no significant differences between the groups for school-age sun exposures. CONCLUSION Melanomas developing at different body sites are associated with distinct patterns of sun exposure. Melanomas of the head and neck are associated with chronic patterns of sun exposure whereas trunk melanomas are associated with intermittent patterns of sun exposure, supporting the hypothesis that melanomas may arise through divergent causal pathways.

Validation of a FFQ to estimate the intake of PUFA using plasma phospholipid fatty acids and weighed foods records

Due to the growing knowledge about the role of specific fatty acids in health and disease, dietary intake measurements of individual fatty acids or classes of fatty acids are becoming increasingly important. The objective of this study was to evaluate the ability of the Nambour FFQ to estimate intakes of specific fatty acids, particularly PUFA. The study population was a sub-sample of adult participants in a randomised controlled trial of beta-carotene and sunscreen in the prevention of skin cancer (n 43). Dietary intake was assessed by a self-administered FFQ and a weighed food record (WFR). Non-fasting blood samples were collected and analysed for plasma phospholipid fatty acids. Median intakes on the FFQ were generally higher than the WFR except for the n-3 PUFA groups, where the FFQ estimated higher intakes. Correlations between the FFQ and WFR were moderate (r 0 x 32-0 x 59) except for trans fatty acids (r 0 x 03). Correlations between each of the dietary assessment methods and the plasma phospholipids were poor for all fatty acids other than the PUFA. Using the methods of triads approach, the FFQ validity coefficients for total n-3 fatty acids, total long chain n-3 fatty acids, EPA, arachidonic acid, docosapentaenoic acid and DHA were 0 x 50, 0 x 63, 0 x 45 and 0 x 62 and 0 x 62, respectively. For most fatty acids, the FFQ adequately estimates group mean fatty acid intakes and can adequately rank individuals; however, the ability of this FFQ to estimate trans fatty acids was poor.

The effect of personal characteristics on the validity of nutrient intake estimates using a food-frequency questionnaire.

OBJECTIVE To assess validity of the Nambour food-frequency questionnaire (FFQ) relative to weighed food records (WFRs), and the extent to which selected demographic, anthropometric and social characteristics explain differences between the two dietary methods. DESIGN Inter-method validity study; 129-item FFQ vs. 12 days of WFR over 12 months. SETTING Community-based Nambour Skin Cancer Prevention Trial. SUBJECTS One hundred and fifteen of 168 randomly selected participants in the trial (68% acceptance rate) aged 25-75 years. RESULTS Spearman correlations between intakes from the two methods ranged from 0.18 to 0.71 for energy-adjusted values. Differences between FFQ and WFR regressed on personal characteristics were significantly associated with at least one characteristic for 16 of the 21 nutrients. Sex was significantly associated with differences for nine nutrients; body mass index (BMI), presence of any medical condition and age were each significantly associated with differences for three to six nutrients; use of dietary supplements and occupation were associated with differences for one nutrient each. There was no consistency in the direction of the significant associations. Regression models explained from 7% (riboflavin) to 27% (saturated fat) of variation in differences in intakes. CONCLUSIONS The relative validity of FFQ estimates for many nutrients is quite different for males than for females. Age, BMI, medical condition and level of intake were also associated with relative validity for some nutrients, resulting in the need to adjust intakes estimates for these in modelling diet-disease relationships. Estimates for cholesterol, beta-carotene equivalents, retinol equivalents, thiamine, riboflavin and calcium would not benefit from this.

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 β-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 β-carotene, daily use of sunscreen and placebo, discretionary use of sunscreen and 30 mg of β-carotene, and discretionary use of sunscreen and placebo. MEASUREMENTS Change in microtopography between 1992 and 1996 in the sunscreen and β-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]). β-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 β-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.

High Intake of Folate from Food Sources Is Associated with Reduced Risk of Esophageal Cancer in an Australian Population

Folate plays a key role in DNA synthesis and methylation. Limited evidence suggests high intake may reduce risks of esophageal cancer overall; however, associations with esophageal cancer subtypes and Barretts esophagus (BE), a precancerous lesion, remain unexplored. We evaluated the relation between intake of folate, B vitamins, and methyl-group donors (methionine, choline, betaine) from foods and supplements, polymorphisms in key folate-metabolizing genes, and risk of BE, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC) in 2 population-based case-control studies in Australia. BE patients without (n = 266) or with (n = 101) dysplasia were compared with population controls (n = 577); similarly, EAC (n = 636) or ESCC (n = 245) patients were compared with population controls (n = 1507) using multivariable adjusted logistic regression. Increasing intake of folate from foods was associated with reduced EAC risk (P-trend = 0.01) and mitigated the increased risks of ESCC associated with smoking and alcohol consumption. In contrast, high intake of folic acid from supplements was associated with a significantly elevated risk of BE with dysplasia. High intakes of riboflavin and methionine from food were associated with increased EAC risk, whereas increasing betaine intake was associated with reduced risks of BE without (P-trend = 0.004) or with dysplasia (P-trend = 0.02). Supplemental thiamin, riboflavin, niacin, and vitamin B-12 were associated with increased EAC risk. There were no consistent associations between genetic polymorphisms studied and BE or EAC risk. High intake of folate-containing foods may reduce risk of EAC, but our data raise the possibility that folic acid supplementation may increase risks of BE with dysplasia and EAC.

Reproducibility of food and nutrient intake estimates using a semi-quantitative FFQ in Australian adults

OBJECTIVE To assess the reproducibility of a 135-item self-administered semi-quantitative FFQ. DESIGN Control subjects who had previously completed an FFQ relating to usual dietary intake in a nationwide case-control study of cancer between November 2003 and April 2004 were randomly selected, re-contacted, and invited to complete the same FFQ a second time approximately one year later (between January and April 2005). Agreement between the two FFQ was compared using weighted kappa statistics and intraclass correlation coefficients (ICC) for food groups and nutrients. Summary questions, included in the FFQ, were used to assess overall intakes of vegetables, fruits and meat. SETTING General community in Australia. SUBJECTS One hundred men and women aged 22-79 years, randomly selected from the previous control population. RESULTS The weighted kappa and ICC measures of agreement for food groups were moderate to substantial for seventeen of the eighteen food groups. For nutrients, weighted kappa ranged from 0.44 for starch to 0.83 for alcohol while ICC ranged from 0.51 to 0.91 for the same nutrients. Estimates of meat, fruit and vegetable intake using summary questions were similar for both survey periods, but were significantly lower than estimates from summed individual food items. CONCLUSIONS The FFQ produced reproducible results and is reasonable in assessing the usual intake of various foods and nutrients among an Australian adult population.

Meat, fish, and ovarian cancer risk: results from 2 Australian case-control studies, a systematic review, and meta-analysis

BACKGROUND Variation in meat and fish intakes has been associated with a risk of some cancers, but evidence for ovarian cancer is limited and inconsistent. OBJECTIVE We examined the association between intakes of total meat, red meat, processed meat, poultry, and fish and ovarian cancer risk. DESIGN Data came from 2 Australian population-based case-control studies conducted 10 y apart. Analyses included a total of 2049 cases and 2191 control subjects. We obtained dietary information via a food-frequency questionnaire. We estimated multivariable-adjusted odds ratios (ORs) for each study by using logistic regression and combined results of the 2 studies by using random-effects models. We also assembled the published evidence in a systematic review and meta-analysis. RESULTS Although there was no association between total or red meat intake and ovarian cancer risk, women with the highest intake of processed meat had a significantly increased risk of ovarian cancer in the 2 case-control studies (combined OR: 1.18; 95% CI: 1.15, 1.21) and the meta-analysis [7 studies; pooled relative risk (RR): 1.20; 95% CI: 1.07, 1.34]. In contrast, a frequent intake of poultry was associated with borderline significant reductions in risk in the 2 case-control studies (combined OR: 0.83; 95% CI: 0.67, 1.03) and the meta-analysis including 7 additional studies (pooled RR: 0.90; 95% CI: 0.79, 1.01). High fish intake was associated with a significantly reduced risk in the 2 case-control studies (combined OR: 0.76; 95% CI: 0.62, 0.94) and a smaller borderline significant reduction in the meta-analysis (6 additional studies; pooled RR: 0.84; 95% CI: 0.68, 1.03). CONCLUSION Our results suggest that low consumption of processed meat and higher consumption of poultry and fish may reduce the risk of ovarian cancer.

Food intake and risk of squamous cell carcinoma of the skin in a community: the Nambour skin cancer cohort study.

There is some evidence that dietary factors may modify the risk of squamous cell carcinoma (SCC) of the skin, but the association between food intake and SCC has not been evaluated prospectively. We examined the association between food intake and SCC incidence among 1,056 randomly selected adults living in an Australian sub‐tropical community. Measurement‐error corrected estimates of intake in 15 food groups were defined from a validated food frequency questionnaire in 1992. Associations with SCC risk were assessed using Poisson and negative binomial regression to the persons affected and tumour counts, respectively, based on incident, histologically confirmed tumours occurring between 1992 and 2002. After multivariable adjustment, none of the food groups was significantly associated with SCC risk. Stratified analysis in participants with a past history of skin cancer showed a decreased risk of SCC tumours for high intakes of green leafy vegetables (RR = 0.45, 95% CI = 0.22–0.91; p for trend = 0.02) and an increased risk for high intake of unmodified dairy products (RR = 2.53, 95% CI: 1.15–5.54; p for trend = 0.03). Food intake was not associated with SCC risk in persons who had no past history of skin cancer. These findings suggest that consumption of green leafy vegetables may help prevent development of subsequent SCCs of the skin among people with previous skin cancer and that consumption of unmodified dairy products, such as whole milk, cheese and yoghurt, may increase SCC risk in susceptible persons.

The Queensland Study of Melanoma: Environmental and Genetic Associations (Q-MEGA); Study Design, Baseline Characteristics, and Repeatability of Phenotype and Sun Exposure Measures

Cutaneous malignant melanoma (CMM) is a major health issue in Queensland, Australia, which has the worlds highest incidence. Recent molecular and epidemiologic studies suggest that CMM arises through multiple etiological pathways involving gene-environment interactions. Understanding the potential mechanisms leading to CMM requires larger studies than those previously conducted. This article describes the design and baseline characteristics of Q-MEGA, the Queensland Study of Melanoma: Environmental and Genetic Associations, which followed up 4 population-based samples of CMM patients in Queensland, including children, adolescents, men aged over 50, and a large sample of adult cases and their families, including twins. Q-MEGA aims to investigate the roles of genetic and environmental factors, and their interaction, in the etiology of melanoma. Three thousand, four hundred and seventy-one participants took part in the follow-up study and were administered a computer-assisted telephone interview in 2002-2005. Updated data on environmental and phenotypic risk factors, and 2777 blood samples were collected from interviewed participants as well as a subset of relatives. This study provides a large and well-described population-based sample of CMM cases with follow-up data. Characteristics of the cases and repeatability of sun exposure and phenotype measures between the baseline and the follow-up surveys, from 6 to 17 years later, are also described.

Dietary antioxidants and risk of Barrett's esophagus and adenocarcinoma of the esophagus in an Australian population.

While dietary antioxidants are emerging as potentially modifiable risk factors for esophageal adenocarcinoma (EAC), studies on dietary antioxidants and its precursor Barretts esophagus (BE) are limited. The present study extends previous work on BE by investigating risks of nondysplastic BE, dysplastic BE and EAC associated with intake of antioxidants such as vitamin C, vitamin E, β‐carotene, and selenium. Age and sex matched control subjects (n=577 for BE; n=1,507 for EAC) were sampled from an Australian population register. Information on demography, and well established EAC risk factors were obtained using self‐administered questionnaires. Intake of antioxidants for patients newly diagnosed with nondysplastic BE (n=266), dysplastic BE (n=101), or EAC (n=299), aged 18–79 years, were obtained using a food frequency questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariable adjusted logistic regression models. High intake of β‐carotene from food and supplement sources combined was inversely associated with risk of dysplastic BE (OR Q4 vs. Q1=0.45; 95%CI: 0.20–1.00). High intake of vitamin E from food sources (OR Q4 vs. Q1=0.43; 95%CI: 0.28–0.67), from food and supplements combined (OR Q4 vs. Q1=0.64; 95%CI: 0.43–0.96), and a high antioxidant index score were inversely associated with risk of EAC. We found no significant trends between intake of β–carotene, vitamin C, vitamin E, and selenium and risk of nondysplastic or dysplastic BE. However, our data suggest that a high intake of β‐carotene may be associated with decreased risk of dysplastic BE.