Ingested nitrate leads to the endogenous synthesis of N‐nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated ...with nitrate exposure in drinking water and diet. A case‐control study in Spain and Italy during 2008‐2013 was conducted. Hospital‐based incident cases and population‐based (Spain) or hospital‐based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long‐term waterborne ingested nitrate was derived from routine monitoring records, linked to subjects’ residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors and other covariables. Generalized additive models (GAMs) were used to analyze exposure‐response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. In total 1,869 cases and 3,530 controls were analyzed. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 versus ≤5 mg/day, overall. Associations were larger among men versus women, and among subjects with high red meat intake. GAMs showed increasing exposure‐response relationship among men. Animal‐derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.
What's new?
Nitrate ingested in food and water can react with amines and amides in the gastrointestinal tract, leading to the formation of N‐nitroso compounds (NOCs), which are carcinogenic in animals. In humans, nitrate and several NOCs are probable carcinogens. The aim of the present investigation, a case–control study in Europe, was to examine links between nitrate intake and colorectal cancer (CRC). The findings indicate that CRC risk is increased for waterborne nitrate intake at levels below current international guidelines, particularly in subgroups with other risk factors. Nitrate intake from animal sources was further associated with increased rectal cancer risk.
Modern life involves mistimed sleeping and eating patterns that in experimental studies are associated with adverse health effects. We assessed whether timing of meals is associated with breast and ...prostate cancer risk taking into account lifestyle and chronotype, a characteristic correlating with preference for morning or evening activity. We conducted a population‐based case‐control study in Spain, 2008–2013. In this analysis we included 621 cases of prostate and 1,205 of breast cancer and 872 male and 1,321 female population controls who had never worked night shift. Subjects were interviewed on timing of meals, sleep and chronotype and completed a Food Frequency Questionaire. Adherence to the World Cancer Research Fund/American Institute of Cancer Research recommendations for cancer prevention was examined. Compared with subjects sleeping immediately after supper, those sleeping two or more hours after supper had a 20% reduction in cancer risk for breast and prostate cancer combined (adjusted Odds Ratio OR = 0.80, 95%CI 0.67–0.96) and in each cancer individually (prostate cancer OR = 0.74, 0.55–0.99; breast cancer OR = 0.84, 0.67–1.06). A similar protection was observed in subjects having supper before 9 pm compared with supper after 10 pm. The effect of longer supper‐sleep interval was more pronounced among subjects adhering to cancer prevention recommendations (OR both cancers= 0.65, 0.44–0.97) and in morning types (OR both cancers = 0.66, 0.49–0.90). Adherence to diurnal eating patterns and specifically a long interval between last meal and sleep are associated with a lower cancer risk, stressing the importance of evaluating timing in studies on diet and cancer.
What's new?
Evidence shows that long‐term disruption of endogenous circadian rhythms may be associated with cancer. The effects of mistimed sleeping and eating patterns that come with modern life are however less clear. This large Spanish population‐based study examined whether meal timing and sleep patterns are associated with the two most common nightshift‐related cancers. Adherence to a more diurnal eating pattern, and specifically an early supper and a long interval between last meal and sleep were associated with a lower breast and prostate cancer risk, stressing the importance of evaluating circadian rhythms in diet and cancer studies and revisiting recommendations for prevention.
Background: Bladder cancer has been linked with long-term exposure to disinfection by-products (DBPs) in drinking water. Objectives: In this study we investigated the combined influence of DBP ...exposure and polymorphisms in glutathione S-transferase (GSTT1, GSTZ1) and cytochrome P450 (CYP2E1) genes in the metabolic pathways of selected by-products on bladder cancer in a hospital-based casecontrol study in Spain. Methods: Average exposures to trihalomethanes (THMs; a surrogate for DBPs) from 15 years of age were estimated for each subject based on residential history and information on municipal water sources among 680 cases and 714 controls. We estimated effects of THMs and GSTT1, GSTZ1, and CYP2E1 polymorphisms on bladder cancer using adjusted logistic regression models with and without interaction terms. Results: THM exposure was positively associated with bladder cancer: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were 1.2 (0.8-1.8), 1.8 (1.1-2.9), and 1.8 (0.9-3.5) for THM quartiles 2, 3, and 4, respectively, relative to quartile 1. Associations between THMs and bladder cancer were stronger among subjects who were GSTT1 +/+ or +/— versus GSTT1 null (Pinteraction = 0.021), GSTZ1 rs1046428 CT/TT versus CC (Pinteraction = 0.018), or CYP2E1 rs2031920 CC versus CT/TT (Pinteraction = 0.035). Among the 195 cases and 192 controls with high-risk forms of GSTT1 and GSTZ1, the ORs for quartiles 2, 3, and 4 of THMs were 1.5 (0.7-3.5), 3.4 (1.4-8.2), and 5.9 (1.8-19.0), respectively. Conclusions: Polymorphisms in key metabolizing enzymes modified DBP-associated bladder cancer risk. The consistency of these findings with experimental observations of GSTT1, GSTZ1, and CYP2E1 activity strengthens the hypothesis that DBPs cause bladder cancer and suggests possible mechanisms as well as the classes of compounds likely to be implicated.
Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 ...colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (<third quartile) and high consumers (≥ third quartile) vs non consumers (reference category), distinguishing aspartame-containing products and other AS. Unconditional logistic regression models were used to estimate adjusted OR and 95%CI, and results were stratified by diabetes status. Overall, we found no associations between the consumption of aspartame or other AS and cancer. Among participants with diabetes, high consumption of other AS was associated with colorectal cancer (OR = 1.58, 95% CI 1.05-2.41, P trend = .03) and stomach cancer (OR = 2.27 0.99-5.44, P trend = .06). High consumption of aspartame, was associated with stomach cancer (OR = 2.04 0.7-5.4, P trend = .05), while a lower risk was observed for breast cancer (OR = 0.28 0.08-0.83, P trend = .03). In some cancers, the number of cases in participants with diabetes were small and results should be interpreted cautiously. We did not find associations between use of AS and cancer, but found associations between high consumption of aspartame and other AS and different cancer types among participants with diabetes.
We explored the association of the previously described Western, prudent and Mediterranean dietary patterns with prostate cancer risk by tumor aggressiveness and extension.
MCC-Spain ...(Multicase-Control Study on Common Tumors in Spain) is a population based, multicase-control study that was done in 7 Spanish provinces between September 2008 and December 2013. It collected anthropometric, epidemiological and dietary information on 754 histologically confirmed incident cases of prostate cancer and 1,277 controls 38 to 85 years old. Three previously identified dietary patterns, including Western, prudent and Mediterranean, were reconstructed using MCC-Spain data. The association of each pattern with prostate cancer risk was assessed by logistic regression models with random, province specific intercepts. Risk according to tumor aggressiveness (Gleason score 6 vs greater than 6) and extension (cT1-cT2a vs cT2b-cT4) was evaluated by multinomial regression models.
High adherence to a Mediterranean dietary pattern rich not only in fruits and vegetables but also in fish, legumes and olive oil was specifically associated with a lower risk of Gleason score greater than 6 prostate cancer (quartile 3 vs 1 relative RR 0.66, 95% CI 0.46–0.96 and quartile 4 vs 1 relative RR 0.68, 95% CI 0.46–1.01, p-trend = 0.023) or with higher clinical stage (cT2b-T4 quartile 4 vs 1 relative RR 0.49, 95% CI 0.25–0.96, p-trend = 0.024). This association was not observed with the prudent pattern, which combines vegetables and fruits with low fat dairy products, whole grains and juices. The Western pattern did not show any association with prostate cancer risk.
Nutritional recommendations for prostate cancer prevention should consider whole dietary patterns instead of individual foods. We found important differences between the Mediterranean dietary pattern, which was associated with a lower risk of aggressive prostate cancer, and Western and prudent dietary patterns, which had no relationship with prostate cancer risk.
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.
What's new?
Prostate, breast and colon cancer share common environmental risk factors, but preventable causes remain largely unknown. Here the authors evaluated adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) guidelines on diet, physical activity and body fat for cancer prevention and risk of these cancers in Spain. They found an inverse association between adherence to the recommendations and colon cancer, postmenopausal breast cancer and poorly differentiated prostate cancer, underscoring the important role of preventable causes in the development of these cancers.
Most studies on endocrine-disrupting chemicals and breast cancer have focused on single compounds and have produced inconclusive findings.
We assessed the combined estrogenic effects of mixtures of ...xenoestrogens in serum and their relationship to breast cancer risk.
A total of 186 incident pretreatment breast cancer cases and 196 frequency-matched controls were randomly sampled from a large population-based multicase-control study in Spain. The total effective xenoestrogen burden attributable to organohalogenated xenoestrogens (TEXB-α) and endogenous hormones and more polar xenoestrogens (TEXB-β) was determined in serum samples using high-performance liquid chromatography and E-Screen bioassay. Odds ratios for breast cancer comparing tertiles of serum TEXB-α and TEXB-β were estimated using logistic models, and smooth risk trends were obtained using spline models.
Cases had higher geometric mean TEXB-α and TEXB-β levels (8.32 and 9.94 Eeq pM/mL, respectively) than controls (2.99 and 5.96 Eeq pM/mL, respectively). The fully adjusted odds ratios for breast cancer (95% confidence intervals) comparing the second and third tertiles of TEXB-α with the first tertile were 1.77 (0.76, 4.10) and 3.45 (1.50, 7.97), respectively, and those for TEXB-β were 2.35 (1.10, 5.03) and 4.01 (1.88, 8.56), respectively. A steady increase in risk was evident across all detected TEXB-α levels and a sigmoidal trend was observed for TEXB-β. Individual xenoestrogens showed weak and opposing associations with breast cancer risk.
This is the first study to show a strong positive association between serum total xenoestrogen burden and breast cancer risk, highlighting the importance of evaluating xenoestrogen mixtures, rather than single compounds, when studying hormone-related cancers.
Pastor-Barriuso R, Fernández MF, Castaño-Vinyals G, Whelan D, Pérez-Gómez B, Llorca J, Villanueva CM, Guevara M, Molina-Molina JM, Artacho-Cordón F, Barriuso-Lapresa L, Tusquets I, Dierssen-Sotos T, Aragonés N, Olea N, Kogevinas M, Pollán M. 2016. Total effective xenoestrogen burden in serum samples and risk for breast cancer in a population-based multicase-control study in Spain. Environ Health Perspect 124:1575-1582; http://dx.doi.org/10.1289/EHP157.
Purpose
The variation in breast cancer (BC)-risk factor associations between screen-detected (SD) and non-screen-detected (NSD) tumors has been poorly studied, despite the interest of this aspect in ...risk assessment and prevention. This study analyzes the differences in breast cancer-risk factor associations according to detection method and tumor phenotype in Spanish women aged between 50 and 69.
Methods
We examined 900 BC cases and 896 controls aged between 50 and 69, recruited in the multicase–control MCC-Spain study. With regard to the cases, 460 were detected by screening mammography, whereas 144 were diagnosed by other means. By tumor phenotype, 591 were HR+, 153 were HER2+, and 58 were TN. Lifestyle, reproductive factors, family history of BC, and tumor characteristics were analyzed. Logistic regression models were used to compare cases vs. controls and SD vs. NSD cases. Multinomial regression models (controls used as a reference) were adjusted for case analysis according to phenotype and detection method.
Results
TN was associated with a lower risk of SD BC (OR 0.30 IC 0.10–0.89), as were intermediate (OR 0.18 IC 0.07–0.44) and advanced stages at diagnosis (OR 0.11 IC 0.03–0.34). Nulliparity in postmenopausal women and age at menopause were related to an increased risk of SD BC (OR 1.60 IC 1.08–2.36; OR 1.48 IC 1.09–2.00, respectively). Nulliparity in postmenopausal women was associated with a higher risk of HR+ (OR 1.66 IC 1.15–2.40). Age at menopause was related to a greater risk of HR+ (OR 1.60 IC 1.22–2.11) and HER2+ (OR 1.59 IC 1.03–2.45) tumors.
Conclusion
Reproductive risk factors are associated with SD BC, as are HR+ tumors. Differences in BC-risk factor associations according to detection method may be related to prevailing phenotypes among categories.
Breast cancer is the main cause of cancer mortality among women. Green spaces have been recently associated with reduced cancer mortality among women. Mechanisms explaining the beneficial effect of ...green spaces include increased levels of physical activity and reduced exposure to air pollution, which have been both associated with cancer development.
To investigate the associations between presence of urban green areas, presence of agricultural areas and surrounding greenness and risk of breast cancer, and to assess whether these associations are mediated by physical activity and/or air pollution levels.
We geocoded the current residence of 1129 breast cancer cases and 1619 controls recruited between 2008 and 2013 in ten provinces of Spain, as part of the MCC-Spain study. We assigned different indicators of exposure to green spaces in a buffer of 300 m, and in nested buffers of 100 m and 500 m around the residence: presence of urban green areas according to Urban Atlas, presence of agricultural areas according to CORINE Land Cover 2006, and surrounding greenness according to the average of the Normalized Difference Vegetation Index. We used logistic mixed-effects regression models with a random effect for hospital adjusting for potential confounders. We explored the effect of several potential effect modifiers. We assessed mediation effect by physical activity and levels of air pollution.
Presence of urban green areas was associated with reduced risk of breast cancer after adjusting for age, socio-economic status at individual and at area level, education, and number of children OR (95%CI) = 0.65 (0.49–0.86). There was evidence of a linear trend between distance to urban green areas and risk of breast cancer. On the contrary, presence of agricultural areas and surrounding greenness were associated with increased risk of breast cancer adjusted OR (95%CI) = 1.33 (1.07–1.65) and adjusted OR (95%CI) = 1.27 (0.92–1.77), respectively. None of the associations observed were mediated by levels of physical activity or levels or air pollution.
The association between green spaces and risk of breast cancer is dependent on land-use. The confirmation of these results in other settings and the study of potential mechanisms for the associations observed are needed to advance the understanding on the potential effects of green spaces on health.
•High levels of serum Vitamin D seems to protect against breast cancer risk.•The protective effect seems to be stronger for triple negative tumors.•No differences were observed by menopausal status, ...TNM staging or main risk factors.•Similar results were observed using cases sampled in the 1st month after diagnosis.
Epidemiologic evidence on the association between vitamin D and breast cancer is still inconclusive. This study analyzes the association between serum 25-hydroxyvitamin D (25(OH)D) and breast cancer risk by pathologic subtype, stage at diagnosis and specific breast cancer risk factors. We conducted a population-based multicase-control study where 546 histologically-confirmed breast cancer cases and 558 population controls, frequently matched by geographic area, age and body mass index, were recruited in 12 Spanish provinces (MCC-Spain). Information was collected by a questionnaire and plasma 25(OH)D was measured by solid-phase extraction on-line coupled to liquid chromatography–tandem mass spectrometry (SPE–LC–MS/MS). Odds ratios and 95% confidence intervals were calculated using logistic and multinomial mixed regression models. We found a clear protective effect between 25(OH)D levels and breast cancer risk, with a significant dose-response trend (OR per 10 nmol/L = 0.88; 95%CI = 0.82–0.94). While no differences were observed between pre and postmenopausal women, stage at diagnosis, or across strata of the main breast cancer risk factors, the protection was more pronounced for triple negative tumors (OR per 10 nmol/L = 0.64; p-heterogeneity = 0.038). Similar results were observed when only cases sampled in the first month after diagnosis were considered. The protective effect of vitamin D on breast cancer risk may be subtype specific, being stronger for more aggressive tumors, which provides a new approach to prevent this disease.
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