Toenail zinc as a biomarker: Relationship with sources of environmental exposure and with genetic variability in MCC-Spain study.

BACKGROUND: Toenails are commonly used as biomarkers of exposure to zinc (Zn), but there is scarce information about their relationship with sources of exposure to Zn. OBJECTIVES: To investigate the main determinants of toenail Zn, including selected sources of environmental exposure to Zn and individual genetic variability in Zn metabolism. METHODS: We determined toenail Zn by inductively coupled plasma mass spectrometry in 3,448 general population controls from the MultiCase-Control study MCC-Spain. We assessed dietary and supplement Zn intake using food frequency questionnaires, residential proximity to Zn-emitting industries and residential topsoil Zn levels through interpolation methods. We constructed a polygenic score of genetic variability based on 81 single nucleotide polymorphisms in genes involved in Zn metabolism. Geometric mean ratios of toenail Zn across categories of each determinant were estimated from multivariate linear regression models on log-transformed toenail Zn. RESULTS: Geometric mean toenail Zn was 104.1 µg/g in men and 100.3 µg/g in women. Geometric mean toenail Zn levels were 7 % lower (95 % confidence interval 1-13 %) in men older than 69 years and those in the upper tertile of fibre intake, and 9 % higher (3-16 %) in smoking men. Women residing within 3 km from Zn-emitting industries had 4 % higher geometric mean toenail Zn levels (0-9 %). Dietary Zn intake and polygenic score were unrelated to toenail Zn. Overall, the available determinants only explained 9.3 % of toenail Zn variability in men and 4.8 % in women. DISCUSSION: Sociodemographic factors, lifestyle, diet, and environmental exposure explained little of the individual variability of toenail Zn in the study population. The available genetic variants related to Zn metabolism were not associated with toenail Zn.

Type does matter. Use VIRGIN olive oil as your preferred fat to reduce your risk of breast cancer: case-control EpiGEICAM study.

The Epi-GEICAM study comprises 1017 invasive BC cases matched with controls of similar age (49 ± 9 years) and residence. Diet and OO consumption were collected through a validated food frequency questionnaire. 75% of women referred OO, common (refined) or virgin, as the main fat source. Using conditional logistic regression models, we compared different scenarios of type and frequency of OO consumption, using as reference those women not always using OO for the three culinary practices (seasoning, cooking, and frying) and adding <2 tablespoons (tbsps.) per day during the meal to bread, salad, or dishes. A substantial inverse association was observed in those women always using VOO for the three culinary practices and consuming ≥2 tbsps. of OO per day during meals (adjusted OR, 0.72; 95% CI: 0.51, 1.03; P = 0.07). Potential benefits from OO consumption, at least as regards the protection provided for BC, could be mostly conferred with VOO, and when its consumption is high.

Factors Associated with Serum Vitamin D Metabolites and Vitamin D Metabolite Ratios in Premenopausal Women.

The most representative indicator of vitamin D status in clinical practice is 25(OH)D3, but new biomarkers could improve the assessment of vitamin D status and metabolism. The objective of this study is to investigate the association of serum vitamin D metabolites and vitamin D metabolite ratios (VMRs) with potentially influential factors in premenopausal women. This is a cross-sectional study based on 1422 women, aged 39-50, recruited from a Madrid Medical Diagnostic Center. Participants answered an epidemiological and a food frequency questionnaire. Serum vitamin D metabolites were determined using an SPE-LC-MS/MS platform. The association between participant's characteristics, vitamin D metabolites, and VMRs was quantified by multiple linear regression models. Mean 25(OH)D3 concentration was 49.2 + 18.9 nmol/L, with greater deficits among obese, nulliparous, dark-skinned women, and with less sun exposure. A lower R2 ratio (1,25(OH)2D3/25(OH)D3) and a higher R4 (24,25(OH)2D3/1,25(OH)2D3) were observed in nulliparous women, with high sun exposure, and those with low caloric intake or high consumption of calcium, vitamin D supplements, or alcohol. Nulliparous women had lower R1 (25(OH)D3/Vit D3) and R3 (24,25(OH)2D3/25(OH)D3), and older women showed lower R3 and R4. Vitamin D status modified the association of the VMRs with seasons. VMRs can be complementary indicators of vitamin D status and its endogenous metabolism, and reveal the influence of certain individual characteristics on the expression of hydroxylase enzymes.

Coffee consumption and colorectal cancer risk: a multicentre case-control study from Italy and Spain.

BACKGROUND: Coffee contains many bioactive substances that can play a role on colorectal cancer. Epidemiological evidence of coffee intake and colorectal cancer is, however, inconsistent. AIM: To provide further information on the risk of colorectal cancer in relation to coffee consumption. METHODS: Data derive from two companion case-control studies conducted in Italy and Spain within the European Union Project on Health Impacts of long-term exposure to disinfection by-products in Drinking Water and the Spanish Multi-Case Control study on Cancer. These included a total of 2289 incident cases with colorectal cancer and 3995 controls with information on coffee intake. Odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were derived from unconditional logistic regression models, adjusted for study centre, sex, age, education, smoking, and other covariates. RESULTS: Compared with never coffee drinkers, the OR was 0.99 (95% CI 0.95-1.02) for total coffee consumption. There was no significant trend in risk with dose or duration, the ORs being 0.95 (95% CI 0.72-1.25) for an amount of five or more cups per day of coffee and 0.95 (95% CI 0.75-1.19) for a duration of consumption of 50 years or longer. The OR was 1.04 (95% CI 0.87-1.25) for two or more cups per day of decaffeinated coffee. There were no heterogeneity across strata of various covariates, as well as no apparent differences between various anatomical subsites. CONCLUSION: This large pooled analysis of two studies shows no association of coffee and decaffeinated coffee with colorectal cancer risk.

Arsenic, cadmium, and selenium exposures and bone mineral density-related endpoints: The HORTEGA study.

BACKGROUND AND OBJECTIVES: Experimental data suggest that trace elements, such as arsenic (As), cadmium (Cd), and selenium (Se) can influence the bone remodeling process. We evaluated the cross-sectional association between As, Cd, and Se biomarkers with bone mineral density (BMD) measured at the calcaneus, in a representative sample of a general population from Spain. As secondary analyses we evaluated the associations of interest in subgroups defined by well-established BMD determinants, and also conducted prospective analysis of osteoporosis-related incident bone fractures restricted to participants older than 50 years-old. METHODS: In N = 1365 Hortega Study participants >20 years-old, urine As and Cd were measured by inductively coupled-plasma mass spectrometry (ICPMS); plasma Se was measured by atomic absorption spectrometry (AAS) with graphite furnace; and BMD at the calcaneus was measured using the Peripheral Instaneuous X-ray Imaging system (PIXI). As levels were corrected for arsenobetaine (Asb) to account for inorganic As exposure. RESULTS: The median of total urine As, Asb-corrected urine As, urine Cd, and plasma Se was 61.3, 6.53 and 0.39 µg/g creatinine, and 84.9 µg/L, respectively. In cross-sectional analysis, urine As and Cd were not associated with reduced BMD (T-score < -1 SD). We observed a non-linear dose-response of Se and reduced BMD, showing an inverse association below ~105 µg/L, which became increasingly positive above ~105 µg/L. The evaluated subgroups did not show differential associations. In prospective analysis, while we also observed a U-shape dose-response of Se with the incidence of osteoporosis-related bone fractures, the positive association above ~105 µg/L was markedly stronger, compared to the cross-sectional analysis. CONCLUSIONS: Our results support that Se, but not As and Cd, was associated to BMD-related disease. The association of Se and BMD-related disease was non-linear, including a strong positive association with osteoporosis-related bone fractures risk at the higher Se exposure range. Considering the substantial burden of bone loss in elderly populations, additional large prospective studies are needed to confirm the relevance of our findings to bone loss prevention in the population depending on Se exposure levels.

Quality of Life in a Cohort of 1078 Women Diagnosed with Breast Cancer in Spain: 7-Year Follow-Up Results in the MCC-Spain Study.

Breast cancer is the most frequent cause of tumors and net survival is increasing. Achieving a higher survival probability reinforces the importance of studying health-related quality of life (HR-QoL). The main aim of this work is to test the relationship between different sociodemographic, clinical and tumor-intrinsic characteristics, and treatment received with HR-QoL measured using SF-12 and the FACT/NCCN (National Comprehensive Cancer Network/Functional Assessment of Cancer Therapy) Breast Symptom Index (FBSI). Women with breast cancer recruited between 2008 and 2013 and followed-up until 2017-2018 in a prospective cohort answered two HR-QoL surveys: the SF-12 and FBSI. The scores obtained were related to woman and tumor characteristics using linear regression models. The telephone survey was answered by 1078 women out of 1685 with medical record follow-up (64%). Increases in all three HR-QoL scores were associated with higher educational level. The score differences between women with university qualifications and women with no schooling were 5.43 for PCS-12, 6.13 for MCS-12 and 4.29 for FBSI. Histological grade at diagnosis and recurrence in the follow-up displayed a significant association with mental and physical HR-QoL, respectively. First-line treatment received was not associated with HR-QoL scores. On the other hand, most tumor characteristics were not associated with HR-QoL. As breast cancer survival is improving, further studies are needed to ascertain if these differences still hold in the long run.

Toenails as biomarker of exposure to essential trace metals: A review.

Health problems associated with essential trace metals can result from both inadequate (i.e., low intake) and excessive exposures (i.e., from environmental and/or occupational source). Thus, measuring the exposure level is a real challenge for epidemiologists. Among non-invasive biomarkers that intend to measure long-term exposure to essential trace metals, the toenail is probably the biological matrix with the greatest potential. This systematic review collects the current evidence regarding the validity of toenail clippings as exposure biomarker for trace metals such as boron, cobalt, copper, iron, manganese, molybdenum, selenium, silicon, vanadium and zinc. Special attention was paid to the time-window of exposure reflected by the toenail, the intraindividual variability in exposure levels over time in this matrix, and the relationship of toenail with other biomarkers, personal characteristics and environmental sources. Our search identified 139 papers, with selenium and zinc being the most studied elements. The variability among studies suggests that toenail levels may reflect different degrees of exposure and probably correspond to exposures occurred 3-12 months before sampling (i.e., for manganese/selenium). Few studies assessed the reproducibility of results over time and, for samples obtained 1-6 years apart, the correlation coefficient were between 0.26 and 0.66. Trace metal levels in toenails did not correlate well with those in the blood and urine and showed low-moderate correlation with those in the hair and fingernails. Available data suggests that for some elements (Se, Mn, Zn) toenail concentrations reflect long-term external exposures in fairly reproducible levels, while for other metals, this association has not yet been assessed. Among dietary factors, only toenail selenium showed clear associations with the intake of supplements or specific foods. The toenail levels could also represent occupational exposure, for instance, Mn exposure in welders. The scarcity of information on other essential trace elements, together with the great heterogeneity among studies makes the validation of the usage of toenails as biomarkers of exposure to these elements difficult. Standardization of sample collection, quality control, analytical techniques and reporting procedures might facilitate further research focused on the clear understanding of the significance of essential levels in this promising matrix and would enhance its utility in epidemiological research.

Possible role of chondroitin sulphate and glucosamine for primary prevention of colorectal cancer. Results from the MCC-Spain study.

A safe and effective colorectal cancer (CRC) chemoprevention agent remains to be discovered. We aim to evaluate the association between the use of glucosamine and/or chondroitin sulphate and risk of colorectal cancer (CRC) in the MCC-Spain study, a case-control study performed in Spain that included 2140 cases of CRC and 3950 population controls. Subjects were interviewed on sociodemographic factors, lifestyle, family and medical history and regular drug use. Adjusted odds ratios and their 95% confidence intervals were estimated. The reported frequency of chondroitin and/or glucosamine use was 2.03% in controls and 0.89% in cases. Users had a reduced risk of CRC (OR: 0.47; 95% CI: 0.28-0.79), but it was no longer significant when adjusted for NSAID (nonsteroidal anti-inflammatory drugs) use (OR: 0.82; 95% CI: 0.47-1.40). A meta-analysis with previous studies suggested a protective effect, overall and stratified by NSAID use (OR: 0.77; 95% CI: 0.62-0.97). We have not found strong evidence of an independent preventive effect of CG on CRC in our population because the observed effects of our study could be attributed to NSAIDs concurrent use. These results merit further research due to the safety profile of these drugs.

Adherence to nutrition-based cancer prevention guidelines and breast, prostate and colorectal cancer risk in the MCC-Spain case-control study.

Prostate, breast and colorectal cancer are the most common tumours in Spain. The aim of the present study was to evaluate the association between adherence to nutrition-based guidelines for cancer prevention and prostate, breast and colorectal cancer, in the MCC-Spain case-control study. A total of 1,718 colorectal, 1,343 breast and 864 prostate cancer cases and 3,431 population-based controls recruited between 2007 and 2012, were included in the present study. The World Cancer Research Fund/American Institute for Cancer Research (WCRC/AICR) score based on six recommendations for cancer prevention (on body fatness, physical activity, foods and drinks that promote weight gain, plant foods, animal foods and alcoholic drinks; score range 0-6) was constructed. We used unconditional logistic regression analysis adjusting for potential confounders. One-point increment in the WCRF/AICR score was associated with 25% (95% CI 19-30%) lower risk of colorectal, and 15% (95% CI 7-22%) lower risk of breast cancer; no association with prostate cancer was detected, except for cases with a Gleason score ≥7 (poorly differentiated/undifferentiated tumours) (OR 0.87, 95% CI 0.76-0.99). These results add to the wealth of evidence indicating that a great proportion of common cancer cases could be avoided by adopting healthy lifestyle habits.

Calorie intake, olive oil consumption and mammographic density among Spanish women.

High mammographic density (MD) is one of the main risk factors for development of breast cancer. To date, however, relatively few studies have evaluated the association between MD and diet. In this cross-sectional study, we assessed the association between MD (measured using Boyd's semiquantitative scale with five categories: <10%, 10-25%, 25-50%, 50-75% and >75%) and diet (measured using a food frequency questionnaire validated in a Spanish population) among 3,548 peri- and postmenopausal women drawn from seven breast cancer screening programs in Spain. Multivariate ordinal logistic regression models, adjusted for age, body mass index (BMI), energy intake and protein consumption as well as other confounders, showed an association between greater calorie intake and greater MD [odds ratio (OR) = 1.23; 95% confidence interval (CI) = 1.10-1.38, for every increase of 500 cal/day], yet high consumption of olive oil was nevertheless found to reduce the prevalence of high MD (OR = 0.86;95% CI = 0.76-0.96, for every increase of 22 g/day in olive oil consumption); and, while greater intake of whole milk was likewise associated with higher MD (OR = 1.10; 95%CI 1.00-1.20, for every increase of 200 g/day), higher consumption of protein (OR = 0.89; 95% CI 0.80-1.00, for every increase of 30 g/day) and white meat (p for trend 0.041) was found to be inversely associated with MD. Our study, the largest to date to assess the association between diet and MD, suggests that MD is associated with modifiable dietary factors, such as calorie intake and olive oil consumption. These foods could thus modulate the prevalence of high MD, and important risk marker for breast cancer.

Mortality due to lung, laryngeal and bladder cancer in towns lying in the vicinity of combustion installations.

BACKGROUND: Installations that burn fossil fuels to generate power may represent a health problem due to the toxic substances which they release into the environment. OBJECTIVES: To investigate whether there might be excess mortality due to tumors of lung, larynx and bladder in the population residing near Spanish combustion installations included in the European Pollutant Emission Register. METHODS: Ecologic study designed to model sex-specific standardized mortality ratios for the above three tumors in Spanish towns, over the period 1994-2003. Population exposure to pollution was estimated on the basis of distance from town of residence to pollution source. Using mixed Poisson regression models, we analyzed: risk of dying from cancer in a 5-kilometer zone around installations that commenced operations before 1990; effect of type of fuel used; and risk gradient within a 50-kilometer radius of such installations. RESULTS: Excess mortality (relative risk, 95% confidence interval) was detected in the vicinity of pre-1990 installations for lung cancer (1.066, 1.041-1.091 in the overall population; 1.084, 1.057-1.111 in men), and laryngeal cancer among men (1.067, 0.992-1.148). Lung cancer displayed excess mortality for all types of fuel used, whereas in laryngeal and bladder cancer, the excess was associated with coal-fired industries. There was a risk gradient effect in the proximity of a number of installations. CONCLUSIONS: Our results could support the hypothesis of an association between risk of lung, laryngeal and bladder cancer mortality and proximity to Spanish combustion installations.

Health-related quality of life and mental health in the medium-term aftermath of the Prestige oil spill in Galiza (Spain): a cross-sectional study.

BACKGROUND: In 2002 the oil-tanker Prestige sank off the Galician coast. This study analyzes the effect of this accident on health-related quality of life (HRQoL) and mental health in the affected population. METHODS: Using random sampling stratified by age and sex, 2700 residents were selected from 7 coastal and 7 inland Galician towns. Two exposure criteria were considered: a) residential exposure, i.e., coast versus interior; and b) individual exposure-unaffected, slightly affected, or seriously affected-according to degree of personal affectation. SF-36, GHQ-28, HADS and GADS questionnaires were used to assess HRQoL and mental health. Association of exposure with suboptimal scores was summarized using adjusted odds ratios (OR) obtained from logistic regression. RESULTS: For residential exposure, the SF-36 showed coastal residents as having a lower likelihood of registering suboptimal HRQoL values in physical functioning (OR:0.69; 95%CI:0.54-0.89) and bodily pain (OR:0.74; 95%CI:0.62-0.91), and a higher frequency of suboptimal scores in mental health (OR:1.28; 95%CI:1.02-1.58). None of the dimensions of the other questionnaires displayed statistically significant differences. For individual exposure, no substantial differences were observed, though the SF-36 physical functioning dimension rose (showed better scores) with level of exposure (91.51 unaffected, 93.86 slightly affected, 95.28 seriously affected, p < 0.001). CONCLUSION: Almost one and a half years after the accident, worse HRQoL and mental health levels were not in evidence among subjects exposed to the oil-spill. Nevertheless, some of the scales suggest the possibility of slight impact on the mental health of residents in the affected areas.