Patterns of Omega-3 and Omega-6 Fatty Acid Dietary Intake and Melanoma Thickness at Diagnosis.

BACKGROUND: Experimental evidence suggests that dietary intakes of omega-3 and omega-6 polyunsaturated fatty acids have divergent effects on melanoma growth, but epidemiologic evidence on their combined effect is lacking. METHODS: In 634 Australian patients with primary melanoma, we assessed prediagnosis consumption of 39 food groups by food frequency questionnaires completed within 2 months of diagnosis. We derived, by reduced rank regression, dietary patterns that explained variability in selected omega-3 and omega-6 fatty acid intakes. Prevalence ratios (PR) and 95% confidence intervals (CI) for the association between tertiles of dietary patterns and melanoma thickness >2 mm versus ≤2 mm were estimated using Poisson regression. RESULTS: Overall omega-3 fatty acid intakes were low. Two major fatty acid dietary patterns were identified: "meat, fish, and fat," positively correlated with intakes of all fatty acids; and "fish, low-meat, and low-fat," positively correlated with long-chain omega-3 fatty acid intake, and inversely with medium-chain omega-3 and omega-6 fatty acid intakes. Prevalence of thick melanomas was significantly higher in those in the highest compared with lowest tertile of the "meat, fish, and fat" pattern (PR, 1.40; 95% CI, 1.01-1.94), especially those with serious comorbidity (PR, 1.83; 95% CI, 1.15-2.92) or a family history (PR, 2.32; 95% CI, 1.00-5.35). The "fish, low-meat, and low-fat" pattern was not associated with melanoma thickness. CONCLUSIONS: People with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas. IMPACT: High omega-3 and omega-6 fatty acid intakes may contribute to patients' presentation with thick melanomas.

Could worry and rumination mediate relationships between self-compassion and psychological distress in breast cancer survivors?

Many breast cancer (BCa) patients experience clinically significant anxiety and depression in survivorship. Self-compassion offers a bulwark to anxiety and depression in nonclinical, mental health, and some chronic physical health populations. We examined whether self-compassion predicted lower anxiety and depression symptoms in survivors and whether this might be mediated by lower worry and rumination. The design was a cross-sectional survey using self-report measures. Female adult BCa survivors of mixed stages who had finished primary surgical, radiotherapy, or chemotherapy treatments completed self-compassion subscales and worry, rumination, and anxiety and depression scales. Higher self-compassion subscale scores were negatively associated with anxiety and depression. Depressive brooding and worry mediated any effects of self-kindness and mindfulness on depression and anxiety, whereas common humanity directly predicted lower depression scores. Findings are consistent with the view that self-compassion reduces threat-related rumination and worry in BCa survivors, consequently reducing anxiety and depression. This may form a basis for prevention and treatment.

A Review of Nonantibiotic Agents to Prevent Urinary Tract Infections in Older Women.

OBJECTIVE: This article provides a comprehensive literature review on nonantibiotic agents used for the prevention of urinary tract infections (UTIs) in women ≥45 years of age. DESIGN: A structured review was performed by conducting a literature search to identify relevant studies pertaining to the use of nonantibiotic agents to prevent UTIs in women who were perimenopausal through postmenopausal. Recommendations were made for or against the use of each nonantibiotic agent, unless data were unavailable. Levels of evidence were assigned to each recommendation made. SETTING AND PARTICIPANTS: Studies on the prevention of UTIs with women subjects ≥45 years of age in the community, inpatient, and long-term care settings were considered for inclusion. MEASURE: The efficacy and safety of using ascorbic acid, cranberry products, d-mannose, estrogens, lactobacilli, and methenamine hippurate for prevention of UTIs was assessed. RESULTS: There is evidence to support use of estrogens (A-I) in postmenopausal women, and cranberry capsules (C-I) in women ≥45 years of age for the prevention of UTIs. There was a lack of evidence to make recommendations for or against the use of ascorbic acid, cranberry juice, cranberry capsules with high proanthocyanidin (PAC) content, d-mannose, lactobacillus, and methenamine hippurate in this population. CONCLUSIONS/IMPLICATIONS: Current studies support that estrogens and cranberry capsules may have a role in preventing UTIs in women ≥45 years of age. Further research is needed to elucidate the role of these nonantibiotic agents and how they may be used to decrease antibiotic use.

Personalized Cardio-Metabolic Responses to an Anti-Inflammatory Nutrition Intervention in Obese Adolescents: A Randomized Controlled Crossover Trial.

SCOPE: Chronic inflammation and hypoadiponectinemia are characteristics of obesity-induced insulin resistance (IR). The effect of an anti-inflammatory nutrition supplement (AINS) on IR and adiponectin biology in overweight adolescents was investigated. The secondary objective was to examine the extent to which individuals' biomarker profiles, derived from baseline phenotypes, predicted response or not to the AINS. Additionally, the impact of DNA methylation on intervention efficacy was assessed. METHODS AND RESULTS: Seventy overweight adolescents (13-18 years) were recruited to this randomized controlled crossover trial. Participants received an AINS (long chain n-3 PUFA, vitamin C, α-tocopherol, green tea extract, and lycopene) and placebo for 8 weeks each. Homeostatic model assessment (HOMA)-IR, adiponectin, inflammatory profiles, and DNA methylation were assessed. HOMA-IR was unchanged in the total cohort. High-molecular-weight (HMW) adiponectin was maintained following the AINS while it decreased over time following the placebo intervention. HOMA-IR decreased in 40% of subjects (responders) following the AINS. Responders' pretreatment phenotype was characterized by higher HOMA-IR, total and LDL cholesterol, but similar BMI in comparison to nonresponders. HMW adiponectin response to the AINS was associated with bidirectional modulation of adipogenic gene methylation. CONCLUSION: The AINS modulated adiponectin biology, an early predictor of type 2 diabetes risk, was associated with bidirectional modulation of adipogenic gene methylation in weight-stable overweight adolescents. HOMA-IR decreased in a sub-cohort of adolescents with an adverse metabolic phenotype. Thus, suggesting that more stratified or personalized nutrition approaches may enhance efficacy of dietary interventions.

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.

Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States.

OBJECTIVE: To investigate the association between serum 25-hydroxyvitamin D concentrations (25(OH)D) and mortality in a large consortium of cohort studies paying particular attention to potential age, sex, season, and country differences. DESIGN: Meta-analysis of individual participant data of eight prospective cohort studies from Europe and the US. SETTING: General population. PARTICIPANTS: 26,018 men and women aged 50-79 years. MAIN OUTCOME MEASURES: All-cause, cardiovascular, and cancer mortality. RESULTS: 25(OH)D concentrations varied strongly by season (higher in summer), country (higher in US and northern Europe) and sex (higher in men), but no consistent trend with age was observed. During follow-up, 6695 study participants died, among whom 2624 died of cardiovascular diseases and 2227 died of cancer. For each cohort and analysis, 25(OH)D quintiles were defined with cohort and subgroup specific cut-off values. Comparing bottom versus top quintiles resulted in a pooled risk ratio of 1.57 (95% CI 1.36 to 1.81) for all-cause mortality. Risk ratios for cardiovascular mortality were similar in magnitude to that for all-cause mortality in subjects both with and without a history of cardiovascular disease at baseline. With respect to cancer mortality, an association was only observed among subjects with a history of cancer (risk ratio, 1.70 (1.00 to 2.88)). Analyses using all quintiles suggest curvilinear, inverse, dose-response curves for the aforementioned relationships. No strong age, sex, season, or country specific differences were detected. Heterogeneity was low in most meta-analyses. CONCLUSIONS: Despite levels of 25(OH)D strongly varying with country, sex, and season, the association between 25(OH)D level and all-cause and cause-specific mortality was remarkably consistent. Results from a long term randomised controlled trial addressing longevity are being awaited before vitamin D supplementation can be recommended in most individuals with low 25(OH)D levels.

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.

RNA sequencing of the human milk fat layer transcriptome reveals distinct gene expression profiles at three stages of lactation.

Aware of the important benefits of human milk, most U.S. women initiate breastfeeding but difficulties with milk supply lead some to quit earlier than intended. Yet, the contribution of maternal physiology to lactation difficulties remains poorly understood. Human milk fat globules, by enveloping cell contents during their secretion into milk, are a rich source of mammary cell RNA. Here, we pair this non-invasive mRNA source with RNA-sequencing to probe the milk fat layer transcriptome during three stages of lactation: colostral, transitional, and mature milk production. The resulting transcriptomes paint an exquisite portrait of human lactation. The resulting transcriptional profiles cluster not by postpartum day, but by milk Na:K ratio, indicating that women sampled during similar postpartum time frames could be at markedly different stages of gene expression. Each stage of lactation is characterized by a dynamic range (10(5)-fold) in transcript abundances not previously observed with microarray technology. We discovered that transcripts for isoferritins and cathepsins are strikingly abundant during colostrum production, highlighting the potential importance of these proteins for neonatal health. Two transcripts, encoding ß-casein (CSN2) and α-lactalbumin (LALBA), make up 45% of the total pool of mRNA in mature lactation. Genes significantly expressed across all stages of lactation are associated with making, modifying, transporting, and packaging milk proteins. Stage-specific transcripts are associated with immune defense during the colostral stage, up-regulation of the machinery needed for milk protein synthesis during the transitional stage, and the production of lipids during mature lactation. We observed strong modulation of key genes involved in lactose synthesis and insulin signaling. In particular, protein tyrosine phosphatase, receptor type, F (PTPRF) may serve as a biomarker linking insulin resistance with insufficient milk supply. This study provides the methodology and reference data set to enable future targeted research on the physiological contributors of sub-optimal lactation in humans.

Plasma omega-3 and omega-6 concentrations and risk of cutaneous basal and squamous cell carcinomas in Australian adults.

Laboratory-based evidence suggests that omega-3 and omega-6 polyunsaturated fatty acids may affect skin photocarcinogenesis, but epidemiologic evidence is inconsistent. In 1,191 White Australian adults, we prospectively investigated associations between baseline plasma concentrations of omega-3 and omega-6 fatty acids and cutaneous basal cell carcinomas (BCC) and squamous cell carcinomas (SCC). Relative risks (RR) and 95% confidence intervals (CI) were estimated on the basis of number of histologically confirmed tumors diagnosed during follow-up (1997-2007). Plasma eicosapentaenoic acid (EPA) concentrations and omega-3/-6 ratio showed significant inverse associations with SCC tumors, comparing higher tertiles with the lowest, in age- and sex-adjusted models (Ptrend = 0.02 and 0.03, respectively) which weakened after adjustment for past sun exposure. Associations between EPA and SCC were stronger among participants with a history of skin cancer at baseline (n = 378; highest vs. lowest tertile: RR = 0.50; 95% CI, 0.28-0.92; Ptrend = 0.01). Total omega-6 was inversely associated with BCC tumors in multivariate models (P = 0.04; highest vs. lowest tertile: RR = 0.71; 95% CI, 0.51-0.99), and more strongly in the subgroup with past skin cancer. Linoleic and linolenic acids were also inversely associated with BCC occurrence in this subgroup. When fatty acids were analyzed as continuous variables, however, there was no evidence of any linear or nonlinear associations. This study provides some support for reduced skin cancer risk with high plasma concentrations of omega-3 and omega-6 fatty acids, but results depended on how fatty acid data were modeled. Further investigation of these associations in larger datasets is needed.

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.

Vitamin D intake in Australian adults and the modeled effects of milk and breakfast cereal fortification.

OBJECTIVE: Vitamin D intake from foods or supplements is a safe and attractive means to improve vitamin D status of populations. The aim of this study was to help identify population subgroups that would benefit most from efforts to increase intake. To do so, we investigated which personal characteristics are associated with vitamin D intake in an Australian population and modeled possible effects of expanded food fortification practices. METHODS: We investigated vitamin D intake in a population-based random sample of 785 adults, using a validated food frequency questionnaire, and assessed associations with personal and behavioral characteristics. We identified vitamin D food sources and modeled the hypothetical effects of blanket fortification of milk and breakfast cereals. RESULTS: Average total vitamin D intake was 4.4 (±4.0) µg/g and below adequate intake for most participants in all age and sex subgroups. Higher intake was associated with being female, having a serious medical condition, energy intake below the median, and vitamin D supplement use (all P < 0.05). The "meat, fish, and eggs" food group contributed most to total vitamin D intake (51%), followed by dairy products and related foods (43%). If all milk and breakfast cereals were to be fortified with vitamin D, the average intake of vitamin D from foods would increase from 3.6 (±2.4) µg/d to 6.3 (±3.2) µg/d, with similar increases in all age and sex subgroups. CONCLUSIONS: Vitamin D intake in Australia is generally below recommended levels, and few personal characteristics help to identify subgroups with low intake. Blanket vitamin D fortification of milk and breakfast cereals would substantially increase average vitamin D intake in Australian adults of all ages.

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 Barrett's 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, ß-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 ß-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 ß-carotene, vitamin C, vitamin E, and selenium and risk of nondysplastic or dysplastic BE. However, our data suggest that a high intake of ß-carotene may be associated with decreased risk of dysplastic BE.

Three-way assessment of long-chain n-3 PUFA nutrition: by questionnaire and matched blood and skin samples.

The long-chain n-3 PUFA, EPA, is believed to be important for skin health, including roles in the modulation of inflammation and protection from photodamage. FFQ and blood levels are used as non-invasive proxies for assessing skin PUFA levels, but studies examining how well these proxies reflect target organ content are lacking. In seventy-eight healthy women (mean age 42·8, range 21-60 years) residing in Greater Manchester, we performed a quantitative analysis of long-chain n-3 PUFA nutrition estimated from a self-reported FFQ (n 75) and correlated this with n-3 PUFA concentrations in erythrocytes (n 72) and dermis (n 39). Linear associations between the three n-3 PUFA measurements were assessed by Spearman correlation coefficients and agreement between these measurements was estimated. Average total dietary content of the principal long-chain n-3 PUFA EPA and DHA was 171 (SD 168) and 236 (SD 248) mg/d, respectively. EPA showed significant correlations between FFQ assessments and both erythrocyte (r 0·57, P< 0·0001) and dermal (r 0·33, P= 0·05) levels, as well as between erythrocytes and dermis (r 0·45, P= 0·008). FFQ intake of DHA and the sum of n-3 PUFA also correlated well with erythrocyte concentrations (r 0·50, P< 0·0001; r 0·27, P= 0·03). Agreement between ranked thirds of dietary intake, blood and dermis approached 50% for EPA and DHA, though gross misclassification was lower for EPA. Thus, FFQ estimates and circulating levels of the dietary long-chain n-3 PUFA, EPA, may be utilised as well-correlated measures of its dermal bioavailability.

Intake of omega-3 and omega-6 fatty acids and risk of basal and squamous cell carcinomas of the skin: a longitudinal community-based study in Australian adults.

Intake of omega-3 and omega-6 fatty acids may modify the risk of basal and squamous cell carcinoma of the skin (BCC and SCC), but population-based evidence is limited and inconsistent. We examined prospectively associations between intake of omega-3 and omega-6 fatty acids estimated from food frequency questionnaires and BCC and SCC incidence among 1322 randomly selected adults in Nambour, Australia. Relative risks (RR) and 95% confidence intervals (CI) were estimated based on histologically confirmed tumors diagnosed between 1997 and 2007. Incidence of BCC was lowest in the middle third of both total omega-6 intake (RR(mv.adj) = 0.74, 95% CI = 0.56-0.97) and linoleic acid intake (RR(mv.adj) = 0.75, 95% CI = 0.57-0.99) compared with the lowest third of intake. Evidence for associations with SCC was weak, though persons with arachidonic acid intake in the middle third had a marginally increased risk of SCC (RR(mv.adj) = 1.42, 95% CI = 1.00-2.02). Consumption of omega-3 fatty acids was not associated with subsequent skin cancer risk. Suggestion that intake of arachidonic acid may be associated with increased SCC incidence and total omega-6 with reduced BCC from our study is still highly uncertain and may be due to chance. These data do not support an association between these fatty acids and risk of BCC or SCC.

Serum omega-3 and omega-6 fatty acids and cutaneous p53 expression in an Australian population.

BACKGROUND: There is some evidence from experimental studies that long-chain n-3 and n-6 fatty acids may be able to modify early skin carcinogenesis, but whether this applies in the general population is not known. METHODS: We investigated associations between serum polyunsaturated fatty acid concentrations and p53 expression in normal skin, as a biomarker of early UV-induced carcinogenesis, in an unselected sample of Australian adults. Participants in the Nambour Skin Cancer Prevention Trial provided a dorsal hand punch biopsy which was used for immunohistochemical assessment of p53 immunoreactivity. Cross-sectional associations with serum fatty acid concentrations were analyzed in 139 participants, adjusting for confounding variables including skin phenotype, past sun exposure, and smoking status. RESULTS: There was an inverse association, showing a dose-response relationship, between total n-3 fatty acid serum concentrations and p53 immunoreactivity in the whole epidermis and the basal layer. This was particularly due to eicosapentanoic acid and docosahexanoic acid concentrations. There was no evidence for increased p53 immunoreactivity in participants with relatively high serum n-6 fatty acid concentrations. The ratio of n-3 to n-6 fatty acid concentrations was not associated with p53 immunoreactivity. CONCLUSION: These results add to growing evidence that long-chain fatty acids may be able to modify early skin carcinogenesis. IMPACT: The prospect that increased intake of n-3 fatty acids could help prevent skin cancer is attractive.

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 Barrett's 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.

Intake of antioxidant nutrients and the risk of skin cancer.

To investigate the associations between intake of antioxidant nutrients and risk of basal cell (BCC) and squamous cell carcinomas (SCC) of the skin, we carried out a prospective study among 1001 randomly selected adults living in an Australian community. Intake of antioxidants was estimated in 1996. Incident, histologically-confirmed BCC and SCC were recorded between 1996 and 2004. High dietary intake of lutein and zeaxanthin was associated with a reduced incidence of SCC in persons who had a history of skin cancer at baseline (highest versus lowest tertile, multivariable adjusted relative risk (RR)=0.47, 95% confidence interval (CI): 0.25-0.89; P for trend=0.02). In persons without a history of skin cancer at baseline, development of BCC was positively associated with intake of vitamins C and E from foods plus supplements (RR=3.1, 95% CI: 1.1-8.6; P for trend=0.03 and RR=2.6, 95% CI: 1.1-6.3; P for trend=0.02, respectively). In those with a skin cancer history at baseline, dietary intake in the second tertile for beta-carotene (multivariable adjusted RR=2.2, 95% CI: 1.2-4.1) and for vitamin E (multivariable adjusted RR=2.1, 95% CI: 1.1-3.9) was associated with increased BCC risk, with no trend, and similar results were seen in those with a specific history of BCC. These data suggest quite different associations between antioxidant intake and SCC compared with BCC, consistent with other evidence of their different causal pathways.

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.