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2.
Nutrients ; 14(13)2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35807763

RESUMO

Zinc has been suggested to play a role in breast cancer progression; however, no previous study on zinc levels and the potential effect on breast cancer survival has been conducted. This study investigates recurrence-free survival (RFS), breast cancer-specific survival (BCSS) and overall survival (OS) in relation to zinc levels, in serum and diet, overall and stratified for phosphorus and selenium levels. The Malmö Diet and Cancer Study, a prospective population-based cohort in Sweden including 17,035 women, was used to identify breast cancer patients diagnosed in the period 1991-2013. Diet was assessed by a validated modified diet history method. A Cox regression analysis yielded hazard ratios (HRs) with 95% confidence intervals adjusted for potential confounders. Out of 1062 patients with invasive breast cancer, 268 recurrences, 205 breast cancer deaths and 228 deaths from other causes were recorded. No overall associations were seen between zinc and RFS, BCSS or OS. However, in women with a high phosphorus intake, a higher BCSS and OS were seen in zinc intake Q2 to Q4 versus Q1; the adjusted HR was 0.41 (0.23-0.73) and 0.64 (0.41-1.00), respectively. The results indicate that the combination of intermediate/high zinc intake and high phosphorus intake may lead to a better breast cancer survival.


Assuntos
Neoplasias da Mama , Fósforo na Dieta , Estudos de Coortes , Dieta , Ingestão de Alimentos , Feminino , Humanos , Estudos Prospectivos , Zinco
3.
Redox Biol ; 53: 102346, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35636018

RESUMO

BACKGROUND: Low concentrations of serum selenium (Se) and its main transporter selenoprotein P (SELENOP) are associated with a poor prognosis following breast cancer diagnosis. Recently, natural autoantibodies (aAb) with antagonistic properties to SELENOP uptake have been identified in healthy subjects, and in patients with thyroid disease. Given the potential transport disrupting properties, we hypothesized that breast cancer patients with SELENOP-aAb may have a poor prognosis. METHODS: SELENOP-aAb along with serum Se, SELENOP and GPX3 activity were determined in serum samples of 1988 patients with a new diagnosis of breast cancer enrolled in the multicentre SCAN-B study. Patients were followed for ∼9 years and multivariate Cox regression models were applied to assess hazard ratios. RESULTS: Applying a cut-off based on outlier detection, we identified 7.65% of patients with SELENOP-aAb. Autoantibody titres correlated positively to total Se and SELENOP concentrations, but not to GPX3 activity, supporting a negative role of SELENOP-aAb on Se transport. SELENOP-aAb were associated with age, but independent of tumor characteristics. After fully adjusting for potential confounders, SELENOP-aAb were associated with higher recurrence, HR(95%CI) = 1.87(1.17-2.99), particularly in patients with low Se concentrations, HR(95%CI) = 2.16(1.20-3.88). Associations of SELENOP-aAb with recurrence and mortality were linear and dose-dependent, with fully adjusted HR(95%CI) per log increase of 1.25(1.01-1.55) and 1.31(1.13-1.51), respectively. CONCLUSION: Our results indicate a prognostic and pathophysiological relevance of SELENOP-aAb in breast cancer, with potential relevance for other malignancies. Assessment of SELENOP-aAb at time of diagnosis identifies patients with a distinctly elevated risk for a poor prognosis, independent of established prognostic factors, who may respond favourably to Se supplementation.


Assuntos
Neoplasias da Mama , Selênio , Selenoproteína P/imunologia , Autoanticorpos , Autoimunidade , Feminino , Humanos
4.
Environ Int ; 163: 107213, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35364416

RESUMO

BACKGROUND: Dioxins and polychlorobiphenyls (PCBs) are persistent organic pollutants that have demonstrated endocrine disrupting properties. Several of these chemicals are carcinogenic and positive associations have been suggested with breast cancer risk. In general population, diet represents the main source of exposure. METHODS: Associations between dietary intake of 17 dioxins and 35 PCBs and breast cancer were evaluated in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort from nine European countries using multivariable Cox regressions. The present study included 318,607 women (mean ± SD age: 50.7 ± 9.7) with 13,241 incident invasive breast cancers and a median follow-up of 14.9 years (IQR = 13.5-16.4). Dietary intake of dioxins and PCBs was assessed combining EPIC food consumption data with food contamination data provided by the European Food Safety Authority. RESULTS: Exposure to dioxins, dioxins + Dioxin-Like-PCBs, Dioxin-Like-PCBs (DL-PCBs), and Non-Dioxin-Like-PCBs (NDL-PCBs) estimated from reported dietary intakes were not associated with breast cancer incidence, with the following hazard ratios (HRs) and 95% confidence intervals for an increment of 1 SD: HRdioxins = 1.00 (0.98 to 1.02), HRdioxins+DL-PCB = 1.01 (0.98 to 1.03), HRDL-PCB = 1.01 (0.98 to 1.03), and HRNDL-PCB = 1.01 (0.99 to 1.03). Results remained unchanged when analyzing intakes as quintile groups, as well as when analyses were run separately per country, or separating breast cancer cases based on estrogen receptor status or after further adjustments on main contributing food groups to PCBs and dioxins intake and nutritional factors. CONCLUSIONS: This large European prospective study does not support the hypothesis of an association between dietary intake of dioxins and PCBs and breast cancer risk.


Assuntos
Neoplasias da Mama , Dioxinas , Bifenilos Policlorados , Adulto , Neoplasias da Mama/epidemiologia , Dioxinas/efeitos adversos , Dioxinas/análise , Ingestão de Alimentos , Feminino , Contaminação de Alimentos/análise , Humanos , Masculino , Pessoa de Meia-Idade , Bifenilos Policlorados/efeitos adversos , Bifenilos Policlorados/análise , Estudos Prospectivos
5.
Nutrients ; 14(4)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35215475

RESUMO

Selenium has been suggested to be protective regarding breast cancer risk but no overall effect has been established. Genetics may modify the effect. This study compares the effect of selenium exposure on breast cancer risk between women with different alleles in single-nucleotide polymorphisms (SNPs). The Malmö Cancer and Diet Study, a cohort including 17,035 women and >25 years of follow-up on breast cancer diagnosis, was used. Five promising SNPs regarding interaction with selenium exposure were selected from the literature: rs1050450, rs4880, rs3877899, rs7579, and rs71304. Selenium exposure was assessed in three ways: genetically elevated (n = 16,429), dietary intake (n = 15,891) and serum levels (n = 2037) at baseline. Cox regression and logistic regression analyses evaluated breast cancer risk from selenium exposure, stratified for the SNPs and adjusted for risk factors. A total of 1946 women were diagnosed with breast cancer. Women with T/T alleles in rs1050450 had lower breast cancer risk compared with C/C, HR 0.81 (0.68-0.96). Interaction by rs1050450 limited a protective effect of higher selenium intake to T/T carriers, HR 0.68 (0.43-1.08) for intermediate intake and HR 0.63 (0.40-1.00) for high intake. No interactions or risk differences were seen for other SNPs or for serum selenium or genetically elevated selenium. The results indicate that genetic variation in rs1050450 might affect breast cancer risk and that selenium exposure could be a possible modifiable risk factor for breast cancer among women with that variation.


Assuntos
Neoplasias da Mama , Selênio , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Ingestão de Alimentos , Feminino , Humanos , Polimorfismo de Nucleotídeo Único , Fatores de Risco
6.
Nutrients ; 13(12)2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34959986

RESUMO

Advanced glycation end-products (AGEs) may promote oxidative stress and inflammation and have been linked to multiple chronic diseases, including cancer. However, the association of AGEs with mortality after colorectal cancer (CRC) diagnosis has not been previously investigated. Multivariable Cox proportional hazards models were used to calculate hazard ratios and corresponding 95% confidence intervals for associations between dietary intake of AGEs with CRC-specific and all-cause mortality among 5801 participant cases diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition study between 1993 and 2013. Dietary intakes of AGEs were estimated using country-specific dietary questionnaires, linked to an AGE database, that accounted for food preparation and processing. During a median of 58 months of follow-up, 2421 cases died (1841 from CRC). Individually or combined, dietary intakes of AGEs were not associated with all-cause and CRC-specific mortality among cases. However, there was a suggestion for a positive association between AGEs and all-cause or CRC-specific mortality among CRC cases without type II diabetes (all-cause, Pinteraction = 0.05) and CRC cases with the longest follow-up between recruitment and cancer diagnosis (CRC-specific, Pinteraction = 0.003; all-cause, Pinteraction = 0.01). Our study suggests that pre-diagnostic dietary intakes of AGEs were not associated with CRC-specific or all-cause mortality among CRC patients. Further investigations using biomarkers of AGEs and stratifying by sex, diabetes status, and timing of exposure to AGEs are warranted.


Assuntos
Neoplasias Colorretais/mortalidade , Dieta/mortalidade , Ingestão de Alimentos , Produtos Finais de Glicação Avançada/análise , Idoso , Causas de Morte , Inquéritos sobre Dietas , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos
7.
Breast Cancer Res ; 23(1): 117, 2021 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930399

RESUMO

BACKGROUND: The active thyroid hormone triiodothyronine (T3) has been found to have an estrogen-like effect on breast cancer cells. Thyroid hormone receptor alpha-2 (THRα-2) acts as an antagonist for triiodothyronine (T3) signaling, and a low expression has been associated with unfavorable tumor characteristics and a higher mortality in breast cancer. However, the evidence are not conclusive. The present study evaluates tumor-specific THRα-2 expression in invasive breast cancers and its association with tumor characteristics and long-term mortality in a large population. METHOD: The Malmö Diet and Cancer Study (MDCS), a population-based cohort in Sweden that included 17,035 women from 1991 to 1996, was used. Women diagnosed with breast cancer during 1991-2010 were eligible for inclusion. A tissue micro array was constructed from stored tumor material and stained for THRα-2 using immunohistochemistry. Tumors from 654 patients were scored regarding the intensity and the fraction of cells stained, then dichotomized into low or high expression. Date and cause of death were collected up until 2018-12-31. Tumor- and patient characteristics were available from the MDCS. Missing data was imputed using chained equations. Logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) for low vs high expression of THRα-2 related to specific tumor factors. Mortality was evaluated with Kaplan-Meier curves and Cox regression, rendering hazard ratios (HRs). Analyses were also stratified for estrogen receptor (ER) status. RESULTS: We found strong evidence of an association between low THRα-2 and unfavorable tumor characteristics, including estrogen receptor negativity: OR 4.04 (95% CI 2.28-7.15) and tumor size > 20-50 mm: OR 2.20 (95% CI 1.39-3.49). We found evidence of increased breast cancer-specific mortality for women with low THRα-2, HR 1.38 (95% CI 0.96-1.99), which remained after adjusting for age at diagnosis, HR 1.48 (95% CI 1.03-2.14), but not after adjusting for relevant prognostic factors, HR 0.98 (95% CI 0.66-1.45). THRα-2 expression in ER-negative tumors had an inverse correlation with overall mortality, HR 0.27 (95% CI 0.11-0.65). CONCLUSION: Low tumor-specific THRα-2 expression was in this study associated with prognostically unfavorable tumor characteristics and a higher mortality in breast cancer, but not independent from other prognostic factors.


Assuntos
Neoplasias da Mama , Receptores alfa dos Hormônios Tireóideos , Mama/patologia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Prognóstico , Modelos de Riscos Proporcionais , Receptores alfa dos Hormônios Tireóideos/genética , Receptores alfa dos Hormônios Tireóideos/metabolismo , Tri-Iodotironina
8.
Redox Biol ; 47: 102145, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34563873

RESUMO

The trace element selenium is of essential importance for the synthesis of a set of redox active proteins. We investigated three complementary serum selenium status biomarkers in relation to overall survival and recurrence following diagnosis of primary invasive breast cancer in a large prospective cohort study. The Sweden Cancerome Analysis Network - Breast Initiative (SCAN-B) is a prospective population-based study including multiple participating hospitals. Main analyses included 1996 patients with a new diagnosis of primary invasive breast cancer, with blood sampling at the time of diagnosis. In sera of the patients, total serum selenium, selenoprotein P (SELENOP), and glutathione peroxidase 3 (GPx3) activity was analysed. All three biomarkers showed a positive correlation (p < 0.001), supporting the high quality of samples and analytical techniques. During a total of 13,306 person years of follow-up, 310 deaths and 167 recurrent breast cancer events occurred. In fully adjusted Cox models, all three biomarkers correlated inversely with mortality (p trend <0.001) and compared with the lowest quintile, hazard ratios (95% confidence interval) for overall survival in the highest quintile of selenium, SELENOP and GPx3 were 0.42 (0.28-0.63), 0.51 (0.36-0.73) and 0.52 (0.36-0.75), respectively. Low GPx3 activity was associated with more recurrences (Q5 vs Q1: fully adjusted HR (95%CI); 0.57 (0.35-0.92), (p trend = 0.005). Patients with low selenium status according to all three biomarkers (triple deficient) had the highest mortality risk with an overall survival probability of ∼50% after 8 years, in particular as compared to those having at least one marker in the highest quintile; fully adjusted HR (95%CI); 0.30 (0.21-0.43). Prediction of mortality based on all three biomarkers outperformed established tumour characteristics like histologic grade, number of involved lymph nodes or tumour size. An assessment of Se status at breast cancer diagnosis identifies patients at exceptionally high risk for a poor prognosis.


Assuntos
Neoplasias da Mama , Glutationa Peroxidase , Selênio , Selenoproteína P , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Estudos de Coortes , Feminino , Humanos , Estudos Prospectivos
9.
Nutrients ; 13(9)2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34579010

RESUMO

Dietary advanced glycation end-products (dAGEs) have been hypothesized to be associated with a higher risk of colorectal cancer (CRC) by promoting inflammation, metabolic dysfunction, and oxidative stress in the colonic epithelium. However, evidence from prospective cohort studies is scarce and inconclusive. We evaluated CRC risk associated with the intake of dAGEs in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Dietary intakes of three major dAGEs: Nε-carboxy-methyllysine (CML), Nε-carboxyethyllysine (CEL), and Nδ-(5-hydro-5-methyl-4-imidazolon-2-yl)-ornithine (MG-H1) were estimated in 450,111 participants (median follow-up = 13 years, with 6162 CRC cases) by matching to a detailed published European food composition database. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of dAGEs with CRC were computed using multivariable-adjusted Cox regression models. Inverse CRC risk associations were observed for CML (HR comparing extreme quintiles: HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00) and MG-H1 (HRQ5vs.Q1 = 0.92, 95% CI = 0.85-1.00), but not for CEL (HRQ5vs.Q1 = 0.97, 95% CI = 0.89-1.05). The associations did not differ by sex or anatomical location of the tumor. Contrary to the initial hypothesis, our findings suggest an inverse association between dAGEs and CRC risk. More research is required to verify these findings and better differentiate the role of dAGEs from that of endogenously produced AGEs and their precursor compounds in CRC development.


Assuntos
Neoplasias Colorretais/etiologia , Dieta/efeitos adversos , Produtos Finais de Glicação Avançada/efeitos adversos , Adulto , Idoso , Neoplasias Colorretais/epidemiologia , Dieta/estatística & dados numéricos , Inquéritos sobre Dietas , Ingestão de Alimentos , Europa (Continente)/epidemiologia , Feminino , Produtos Finais de Glicação Avançada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Prospectivos , Medição de Risco
10.
Breast Cancer Res Treat ; 189(2): 571-583, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34224055

RESUMO

PURPOSE: Zinc has been suggested to be protective against breast cancer, but the evidence remains inconclusive. One reason for inconsistent findings in previous studies may be that zinc only influences the risk of developing certain subtypes of breast cancer. Our study is the first study assessing zinc levels in relation to the risk of different breast cancer subgroups, defined by their tumor characteristics. In addition, we analyze serum zinc as a marker of dietary intake. METHODS: The Malmö Diet and Cancer Study is a population-based cohort study that took place 1991-1996 in Malmö, Sweden. Until end of follow-up, 31 December 2013, 1186 incident cases were identified and matched to an equal number of controls. Odds ratios (ORs) for breast cancer, and having a certain tumor characteristic, were estimated in quartiles of baseline serum zinc and zinc intake and adjusted for potential confounders. RESULTS: No associations were found between zinc, measured in serum or diet pre-diagnostically, and breast cancer risk. The adjusted OR for breast cancer in serum zinc Q4 compared to Q1 was 1.09 (0.85-1.41) and in zinc intake Q4 versus Q1 was 0.97 (0.77-1.23). Moreover, there were no clear associations between zinc and any breast cancer characteristics. The kappa value, 0.025 (P = 0.022), showed poor agreement between serum zinc and zinc intake. CONCLUSION: Our findings indicate that there is no clear association between zinc and overall breast cancer risk or risk of different breast cancer subgroups. Finally, our results suggest that serum zinc is a poor marker of zinc intake.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Estudos de Coortes , Dieta , Ingestão de Alimentos , Feminino , Humanos , Estudos Prospectivos , Fatores de Risco , Zinco
11.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1744-1752, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244159

RESUMO

BACKGROUND: Some studies have shown that cadmium (Cd) is associated with breast cancer risk. One hypothesis is that Cd has estrogen-like properties. This case-control study investigated the association between breast cancer risk and blood Cd (BCd) levels. METHODS: All breast cancers in the Malmö Diet and Cancer cohort were identified through linkage to the Swedish Cancer Registry, baseline (1991-1996) through 2014. Two controls per case were selected from the same cohort. BCd was analyzed at baseline. Associations were analyzed using logistic regression. RESULTS: Mean BCd was 0.51 µg/L among 1,274 cases and 0.46 among 2,572 controls. There was an overall increased risk of breast cancer [OR, 1.18; 95% confidence interval (CI), 1.05-1.36] per µg/L of BCd. An increased risk was, however, only found at high BCd [OR, 1.34 (95% CI, 1.05-1.73)] for BCd more than 1.20 µg/L. The group with the highest BCd was mainly smokers. A spline indicated that at BCd less than 1.0 µg/L, the OR was not increased. The association with BCd was stronger in current smokers and at body mass index (BMI) above 25, while no modification due to receptor status was found. CONCLUSIONS: The results indicated increased risk of breast cancer only for high Cd exposure, which occurred mainly among smokers. This made it difficult to disentangle the effects of smoking and Cd, despite inclusion of smoking habits in the models. IMPACT: This study provides support for reducing Cd exposure through smoking cessation and dietary choice. On the population level, preventive measures against Cd pollution are warranted.


Assuntos
Neoplasias da Mama/sangue , Cádmio/sangue , Adulto , Idoso , Neoplasias da Mama/induzido quimicamente , Neoplasias da Mama/epidemiologia , Cádmio/efeitos adversos , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Medição de Risco , Fumantes/estatística & dados numéricos , Suécia/epidemiologia
12.
Sci Rep ; 11(1): 13805, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226613

RESUMO

Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.


Assuntos
Biomarcadores/sangue , Carbono/metabolismo , Inflamação/genética , Rim/metabolismo , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Proteína C-Reativa/genética , Feminino , Humanos , Inflamação/sangue , Inflamação/metabolismo , Inflamação/patologia , Cinurenina/sangue , Masculino , Pessoa de Meia-Idade , Fumar/genética , Abandono do Hábito de Fumar , Vitaminas/sangue
13.
Cancer Epidemiol Biomarkers Prev ; 30(8): 1489-1497, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34162656

RESUMO

BACKGROUND: The inverse observational association between body mass index (BMI) and lung cancer risk remains unclear. We assessed whether the association is explained by metabolic aberrations, residual confounding, and within-person variability in smoking, and compared against other smoking-related cancers. METHODS: We investigated the association between BMI, and its combination with a metabolic score (MS) of mid-blood pressure, glucose, and triglycerides, with lung cancer and other smoking-related cancers in 778,828 individuals. We used Cox regression, adjusted and corrected for within-person variability in smoking (status/pack-years), calculated from 600,201 measurements in 221,958 participants. RESULTS: Over a median follow-up of 20 years, 20,242 smoking-related cancers (6,735 lung cancers) were recorded. Despite adjustment and correction for substantial within-person variability in smoking, BMI remained inversely associated with lung cancer [HR per standard deviation increase, 0.87 (95% confidence interval 0.85-0.89)]. Individuals with BMI less than 25 kg/m2 and high MS had the highest risk [HR 1.52 (1.44-1.60) vs. BMI ≥25 with low MS]. These associations were weaker and nonsignificant among nonsmokers. Similar associations were observed for head and neck cancers and esophageal squamous cell carcinoma, whereas for other smoking-related cancers, we generally observed positive associations with BMI. CONCLUSIONS: The increased lung cancer risk with low BMI and high MS is unlikely due to residual confounding and within-person variability in smoking. However, similar results for other cancers strongly related to smoking suggest a remaining, unknown, effect of smoking. IMPACT: Extensive smoking-adjustments may not capture all the effects of smoking on the relationship between obesity-related factors and risk of smoking-related cancers.


Assuntos
Índice de Massa Corporal , Neoplasias Pulmonares/epidemiologia , Fumar/efeitos adversos , Adulto , Áustria/epidemiologia , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Fatores de Risco , Suécia/epidemiologia
14.
Nutrients ; 13(6)2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34071317

RESUMO

(1) Background: Methyl-group donors (MGDs), including folate, choline, betaine, and methionine, may influence breast cancer (BC) risk through their role in one-carbon metabolism; (2) Methods: We studied the relationship between dietary intakes of MGDs and BC risk, adopting data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort; (3) Results: 318,686 pre- and postmenopausal women were followed between enrolment in 1992-2000 and December 2013-December 2015. Dietary MGD intakes were estimated at baseline through food-frequency questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary intake of MGDs, measured both as a calculated score based on their sum and individually, and BC risk. Subgroup analyses were performed by hormone receptor status, menopausal status, and level of alcohol intake. During a mean follow-up time of 14.1 years, 13,320 women with malignant BC were identified. No associations were found between dietary intakes of the MGD score or individual MGDs and BC risk. However, a potential U-shaped relationship was observed between dietary folate intake and overall BC risk, suggesting an inverse association for intakes up to 350 µg/day compared to a reference intake of 205 µg/day. No statistically significant differences in the associations were observed by hormone receptor status, menopausal status, or level of alcohol intake; (4) Conclusions: There was no strong evidence for an association between MGDs involved in one-carbon metabolism and BC risk. However, a potential U-shaped trend was suggested for dietary folate intake and BC risk. Further research is needed to clarify this association.


Assuntos
Neoplasias da Mama/epidemiologia , Dieta/estatística & dados numéricos , Adulto , Idoso , Betaína/análise , Colina/análise , Europa (Continente) , Feminino , Ácido Fólico/análise , Humanos , Metionina/análise , Metilação , Pessoa de Meia-Idade , Avaliação Nutricional , Estudos Prospectivos , Fatores de Risco
15.
Am J Clin Nutr ; 114(1): 338-347, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33829249

RESUMO

BACKGROUND: Vitamin B6 insufficiency has been linked to increased risk of cancer and other chronic diseases. The circulating concentration of pyridoxal 5'-phosphate (PLP) is a commonly used measure of vitamin B6 status. Ratios of substrates indicating PLP coenzymatic function and metabolism may be useful complementary measures to further explore the role of vitamin B6 in health. OBJECTIVES: We explored the sensitivity of 5 outcomes, namely PLP concentration, homocysteine:cysteine (Hcy:Cys), cystathionine:cysteine (Cysta:Cys), the 3´-hydroxykynurenine ratio (HKr), and the 4-pyridoxic acid ratio (PAr) to vitamin B6 intake as well as personal and lifestyle characteristics. MEDTHODS: Dietary intake and biomarker data were collected from participants from 3 nested case-control studies within the European Prospective Investigation into Cancer and Nutrition (EPIC). Bayesian regression models assessed the associations of the 5 biomarker outcomes with vitamin B6 intake and personal and lifestyle covariates. Analogous models examined the relations of Hcy:Cys, Cysta:Cys, and HKr with PLP. RESULTS: In total, 4608 participants were included in the analyses. Vitamin B6 intake was most strongly associated with PLP, moderately associated with Hcy:Cys, Cysta:Cys, and HKr, and not associated with PAr (fold change in marker given a doubling of vitamin B6 intake: PLP 1.60 [95% credible interval (CrI): 1.50, 1.71]; Hcy:Cys 0.87 [95% CrI: 0.84, 0.90]; Cysta:Cys 0.89 [95% CrI: 0.84, 0.94]; HKr 0.88 [95% CrI: 0.85, 0.91]; PAr 1.00 [95% CrI: 0.95, 1.05]). PAr was most sensitive to age, and HKr was least sensitive to BMI and alcohol intake. Sex and menopause status were strongly associated with all 5 markers. CONCLUSIONS: We found that 5 different markers, capturing different aspects of vitamin B6-related biological processes, varied in their associations with vitamin B6 intake and personal and lifestyle predictors.


Assuntos
Neoplasias/epidemiologia , Neoplasias/etiologia , Vitamina B 6/sangue , Idoso , Estudos de Casos e Controles , Europa (Continente) , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Deficiência de Vitamina B 6
16.
Cancer Causes Control ; 32(8): 815-826, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33914217

RESUMO

PURPOSE: Selenium has been suggested to be protective against breast cancer, but the evidence remains inconclusive. Hence, it is important to further examine the potential protective effect. This prospective cohort study investigates pre-diagnostic selenium intake in relation to breast cancer risk. In addition, we analyze serum selenium as a marker of dietary intake. METHODS: This study includes 17,035 women in the Malmö Diet and Cancer cohort. Dietary assessment and serum samples were collected at baseline (1991-1996). During 344,584 person-years of follow-up, 1,427 incident cases were retrieved. Cox regression analysis examined breast cancer risks adjusted for potential confounding factors. In addition, odds ratios (ORs) were estimated for 1186 cases and an equal number of controls in relation to quartiles (Q) of selenium intake and groups consisting of a combination of intake and serum selenium levels. RESULTS: No overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk was found. The adjusted relative risk for breast cancer in selenium intake Q4 versus Q1 was 0.96 (0.83-1.12) (Ptrend = 0.65). Similarly, adjusted the OR for breast cancer in selenium intake for Q4 versus Q1 was 0.97 (0.76-1.23). The kappa value, 0.096 (p = 0.001), showed poor agreement between serum selenium and selenium intake. CONCLUSION: Our findings suggest that there is no overall association between selenium intake, or a combination of intake and serum levels, and breast cancer risk. Finally, our results showed a poor correlation between estimated selenium intake and serum selenium.


Assuntos
Neoplasias da Mama/epidemiologia , Dieta , Estado Nutricional , Selênio/sangue , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Risco
17.
NPJ Breast Cancer ; 6: 28, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32656317

RESUMO

The extent and composition of the immune response in a breast cancer is one important prognostic factor for the disease. The aim of the current work was to refine the analysis of the humoral component of an immune response in breast tumors by quantifying mRNA expression of different immunoglobulin classes and study their association with prognosis. We used RNA-Seq data from two local population-based breast cancer cohorts to determine the expression of IGJ and immunoglobulin heavy (IGH) chain-encoding RNAs. The association with prognosis was investigated and public data sets were used to corroborate the findings. Except for IGHE and IGHD, mRNAs encoding heavy chains were generally detected at substantial levels and correlated with other immune-related genes. High IGHG1 mRNA was associated with factors related to poor prognosis such as estrogen receptor negativity, HER2 amplification, and high grade, whereas high IGHA2 mRNA levels were primarily associated with lower age at diagnosis. High IGHA2 and IGJ mRNA levels were associated with a more favorable prognosis both in univariable and multivariable Cox models. When adjusting for other prognostic factors, high IGHG1 mRNA levels were positively associated with improved prognosis. To our knowledge, these results are the first to demonstrate that expression of individual Ig class types has prognostic implications in breast cancer.

18.
Cancer Epidemiol Biomarkers Prev ; 29(7): 1335-1340, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32457181

RESUMO

BACKGROUND: Iodine has been suggested to protect against breast cancer, but there are no epidemiologic studies on individual risk. An interesting finding is that in areas where the exposure to both selenium and iodine are high (e.g., Japan), the risk of breast cancer is lower than in areas where selenium is high and iodine low (e.g., United States), or in areas where both are low (e.g., Northern Europe). The aim of this study was to investigate the association between prediagnostic serum iodine levels and subsequent breast cancer risk, and to investigate if this potential association was modified by selenium levels. METHODS: The Malmö Diet and Cancer Study provided prediagnostic serum samples and the current analysis included 1,159 breast cancer cases and 1,136 controls. Levels of baseline serum iodine and selenium were analyzed. A logistic regression analysis yielded ORs with 95% confidence intervals adjusted for potential confounders. RESULTS: There was no evidence of an overall association between iodine levels and risk of breast cancer. Among women with high selenium levels (above the median), high iodine levels were associated with a lower risk of breast cancer; the OR for above versus below the median was 0.75 (0.57-0.99). The corresponding OR for women with low selenium was 1.15 (0.87-1.50), and the P interaction was 0.06. CONCLUSIONS: The combination of high serum iodine levels and high selenium levels was associated with a lower risk of breast cancer. IMPACT: A high iodine and selenium exposure may decrease the risk of breast cancer.


Assuntos
Neoplasias da Mama/etiologia , Iodo/sangue , Selênio/sangue , Neoplasias da Mama/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Fatores de Risco
19.
Int J Cancer ; 147(9): 2424-2436, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32378183

RESUMO

Women with lower levels of serum selenium (Se) may have a worse survival in breast cancer than women with higher levels, despite no difference in incidence of the disease. Our study was conducted to test whether Se is associated with the aggressiveness of breast tumors. Both the risk of having a tumor characteristic associated with worse prognosis, as well as the overall and breast cancer-specific mortality, were studied. We identified breast cancer cases and controls within the Malmö Diet and Cancer Study, a population-based cohort with 17 035 women recruited between 1991 and 1996. Inclusion criteria were incident breast cancer. Exclusion criteria were carcinoma in situ and bilateral breast cancer. Controls were selected among breast cancer-free women both from matching (n = 694) as well as randomization (n = 492). After exclusion, 1066 cases remained and were compared to controls regarding their prediagnostic serum Se levels and subsequent risk of having a certain tumor characteristic or intrinsic subtype. We also followed breast cancer patients regarding overall and breast cancer-specific mortality, comparing different Se quartiles. No association between serum Se quartile and any tumor characteristic or intrinsic subtype was found. Lower overall mortality was found among women in the highest Se quartile compared to the lowest using an adjusted Cox proportional hazards model, hazard ratio 0.63 (95% confidence interval: 0.44-0.89). Similar results were seen for breast cancer-specific mortality, 0.60 (0.37-0.98). The results of our study support that Se is associated with a lower mortality in breast cancer, not related to established prognostic factors.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/mortalidade , Selênio/sangue , Idoso , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Causas de Morte , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sistema de Registros/estatística & dados numéricos , Suécia/epidemiologia , Análise Serial de Tecidos
20.
Nat Commun ; 11(1): 27, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31911640

RESUMO

Impaired lung function is often caused by cigarette smoking, making it challenging to disentangle its role in lung cancer susceptibility. Investigation of the shared genetic basis of these phenotypes in the UK Biobank and International Lung Cancer Consortium (29,266 cases, 56,450 controls) shows that lung cancer is genetically correlated with reduced forced expiratory volume in one second (FEV1: rg = 0.098, p = 2.3 × 10-8) and the ratio of FEV1 to forced vital capacity (FEV1/FVC: rg = 0.137, p = 2.0 × 10-12). Mendelian randomization analyses demonstrate that reduced FEV1 increases squamous cell carcinoma risk (odds ratio (OR) = 1.51, 95% confidence intervals: 1.21-1.88), while reduced FEV1/FVC increases the risk of adenocarcinoma (OR = 1.17, 1.01-1.35) and lung cancer in never smokers (OR = 1.56, 1.05-2.30). These findings support a causal role of pulmonary impairment in lung cancer etiology. Integrative analyses reveal that pulmonary function instruments, including 73 novel variants, influence lung tissue gene expression and implicate immune-related pathways in mediating the observed effects on lung carcinogenesis.


Assuntos
Neoplasias Pulmonares/genética , Pulmão/fisiopatologia , Adulto , Idoso , Feminino , Volume Expiratório Forçado , Predisposição Genética para Doença , Humanos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/fisiopatologia , Masculino , Análise da Randomização Mendeliana , Pessoa de Meia-Idade , Fenótipo , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Testes de Função Respiratória , Capacidade Vital
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