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1.
Cancer Res ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31932455

RESUMO

Repeated exposure to the acute pro-inflammatory environment that follows ovulation at the ovarian surface and distal fallopian tube over a woman's reproductive years may increase ovarian cancer risk. To address this, analyses included individual-level data from 558,709 naturally menopausal women across 20 prospective cohorts, among whom 3,246 developed invasive epithelial ovarian cancer (2045 serous, 319 endometrioid, 184 mucinous, 121 clear cell, 577 other/unknown). Cox models were used to estimate multivariable-adjusted hazard ratios (HR) between lifetime ovulatory cycles (LOC) and its components and ovarian cancer risk overall and by histotype. Women in the 90th percentile of LOC (>514 cycles) were almost twice as likely to be diagnosed with ovarian cancer than women in the 10th percentile (<294) [HR (95% confidence interval): 1.92 (1.60-2.30)]. Risk increased 14% per five-year increase in LOC (60 cycles) [(1.10-1.17)]; this association remained after adjustment for LOC components: number of pregnancies and oral contraceptive use [1.08 (1.04-1.12)]. The association varied by histotype, with increased risk of serous [1.13 (1.09-1.17)], endometrioid [1.20 (1.10-1.32)], and clear cell [1.37 (1.18-1.58)], but not mucinous [0.99 (0.88-1.10), P-heterogeneity=0.01] tumors. Heterogeneity across histotypes was reduced [P-heterogeneity=0.15] with adjustment for LOC components [1.08 serous, 1.11 endometrioid, 1.26 clear cell, 0.94 mucinous]. Although the 10-year absolute risk of ovarian cancer is small, it roughly doubles as the number of LOC rises from ~300 to 500. The consistency and linearity of effects strongly support the hypothesis that each ovulation leads to small increases in the risk of most ovarian cancers, a risk which cumulates through life, suggesting this as an important area for identifying intervention strategies.

2.
Int J Cancer ; 146(3): 759-768, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30968961

RESUMO

Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.

3.
BMC Med ; 17(1): 221, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31787099

RESUMO

BACKGROUND: Even though in situ breast cancer (BCIS) accounts for a large proportion of the breast cancers diagnosed, few studies have investigated potential risk factors for BCIS. Their results suggest that some established risk factors for invasive breast cancer have a similar impact on BCIS risk, but large population-based studies on lifestyle factors and BCIS risk are lacking. Thus, we investigated the association between lifestyle and BCIS risk within the European Prospective Investigation into Cancer and Nutrition cohort. METHODS: Lifestyle was operationalized by a score reflecting the adherence to the World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) cancer prevention recommendations. The recommendations utilized in these analyses were the ones pertinent to healthy body weight, physical activity, consumption of plant-based foods, energy-dense foods, red and processed meat, and sugary drinks and alcohol, as well as the recommendation on breastfeeding. Cox proportional hazards regression was used to assess the association between lifestyle score and BCIS risk. The results were presented as hazard ratios (HR) and corresponding 95% confidence intervals (CI). RESULTS: After an overall median follow-up time of 14.9 years, 1277 BCIS cases were diagnosed. Greater adherence to the WCRF/AICR cancer prevention recommendations was not associated with BCIS risk (HR = 0.98, 95% CI 0.93-1.03; per one unit of increase; multivariable model). An inverse association between the lifestyle score and BCIS risk was observed in study centers, where participants were recruited mainly via mammographic screening and attended additional screening throughout follow-up (HR = 0.85, 95% CI 0.73-0.99), but not in the remaining ones (HR = 0.99, 95% CI 0.94-1.05). CONCLUSIONS: While we did not observe an overall association between lifestyle and BCIS risk, our results indicate that lifestyle is associated with BCIS risk among women recruited via screening programs and with regular screening participation. This suggests that a true inverse association between lifestyle habits and BCIS risk in the overall cohort may have been masked by a lack of information on screening attendance. The potential inverse association between lifestyle and BCIS risk in our analyses is consistent with the inverse associations between lifestyle scores and breast cancer risk reported from previous studies.

4.
J Ovarian Res ; 12(1): 116, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771659

RESUMO

BACKGROUND: Cancer Antigen 125 (CA125) is currently the best available ovarian cancer screening biomarker. However, CA125 has been limited by low sensitivity and specificity in part due to normal variation between individuals. Personal characteristics that influence CA125 could be used to improve its performance as screening biomarker. METHODS: We developed and validated linear and dichotomous (≥35 U/mL) circulating CA125 prediction models in postmenopausal women without ovarian cancer who participated in one of five large population-based studies: Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO, n = 26,981), European Prospective Investigation into Cancer and Nutrition (EPIC, n = 861), the Nurses' Health Studies (NHS/NHSII, n = 81), and the New England Case Control Study (NEC, n = 923). The prediction models were developed using stepwise regression in PLCO and validated in EPIC, NHS/NHSII and NEC. RESULT: The linear CA125 prediction model, which included age, race, body mass index (BMI), smoking status and duration, parity, hysterectomy, age at menopause, and duration of hormone therapy (HT), explained 5% of the total variance of CA125. The correlation between measured and predicted CA125 was comparable in PLCO testing dataset (r = 0.18) and external validation datasets (r = 0.14). The dichotomous CA125 prediction model included age, race, BMI, smoking status and duration, hysterectomy, time since menopause, and duration of HT with AUC of 0.64 in PLCO and 0.80 in validation dataset. CONCLUSIONS: The linear prediction model explained a small portion of the total variability of CA125, suggesting the need to identify novel predictors of CA125. The dichotomous prediction model showed moderate discriminatory performance which validated well in independent dataset. Our dichotomous model could be valuable in identifying healthy women who may have elevated CA125 levels, which may contribute to reducing false positive tests using CA125 as screening biomarker.

5.
Int J Cancer ; 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31506954

RESUMO

Evidence suggests an influence of sex hormones on cutaneous melanoma risk, but epidemiologic findings are conflicting. We examined the associations between use of oral contraceptives (OCs) and menopausal hormone therapy (MHT) and melanoma risk in women participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). EPIC is a prospective cohort study initiated in 1992 in 10 European countries. Information on exogenous hormone use at baseline was derived from country-specific self-administered questionnaires. We used Cox proportional hazards regression models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Over 1992-2015, 1,696 melanoma cases were identified among 334,483 women, whereof 770 cases among 134,758 postmenopausal women. There was a positive, borderline-significant association between OC use and melanoma risk (HR = 1.12, 95% CI = 1.00-1.26), with no detected heterogeneity across countries (phomogeneity = 0.42). This risk increased linearly with duration of use (ptrend = 0.01). Among postmenopausal women, ever use of MHT was associated with a nonsignificant increase in melanoma risk overall (HR = 1.14, 95% CI = 0.97-1.43), which was heterogeneous across countries (phomogeneity = 0.05). Our findings do not support a strong and direct association between exogenous hormone use and melanoma risk. In order to better understand these relations, further research should be performed using prospectively collected data including detailed information on types of hormone, and on sun exposure, which may act as an important confounder or effect modifier on these relations.

6.
BMC Med ; 17(1): 178, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31547832

RESUMO

BACKGROUND: Metabolomics is a promising molecular tool to identify novel etiologic pathways leading to cancer. Using a targeted approach, we prospectively investigated the associations between metabolite concentrations in plasma and breast cancer risk. METHODS: A nested case-control study was established within the European Prospective Investigation into Cancer cohort, which included 1624 first primary incident invasive breast cancer cases (with known estrogen and progesterone receptor and HER2 status) and 1624 matched controls. Metabolites (n = 127, acylcarnitines, amino acids, biogenic amines, glycerophospholipids, hexose, sphingolipids) were measured by mass spectrometry in pre-diagnostic plasma samples and tested for associations with breast cancer incidence using multivariable conditional logistic regression. RESULTS: Among women not using hormones at baseline (n = 2248), and after control for multiple tests, concentrations of arginine (odds ratio [OR] per SD = 0.79, 95% confidence interval [CI] = 0.70-0.90), asparagine (OR = 0.83 (0.74-0.92)), and phosphatidylcholines (PCs) ae C36:3 (OR = 0.83 (0.76-0.90)), aa C36:3 (OR = 0.84 (0.77-0.93)), ae C34:2 (OR = 0.85 (0.78-0.94)), ae C36:2 (OR = 0.85 (0.78-0.88)), and ae C38:2 (OR = 0.84 (0.76-0.93)) were inversely associated with breast cancer risk, while the acylcarnitine C2 (OR = 1.23 (1.11-1.35)) was positively associated with disease risk. In the overall population, C2 (OR = 1.15 (1.06-1.24)) and PC ae C36:3 (OR = 0.88 (0.82-0.95)) were associated with risk of breast cancer, and these relationships did not differ by breast cancer subtype, age at diagnosis, fasting status, menopausal status, or adiposity. CONCLUSIONS: These findings point to potentially novel pathways and biomarkers of breast cancer development. Results warrant replication in other epidemiological studies.


Assuntos
Biomarcadores/sangue , Neoplasias da Mama/sangue , Metabolômica/métodos , Adulto , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/epidemiologia , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Incidência , Espectrometria de Massas , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco
7.
Cancer Res ; 79(20): 5442-5451, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31462430

RESUMO

Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57; P heterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (P interaction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. SIGNIFICANCE: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.

8.
Cancer Epidemiol Biomarkers Prev ; 28(10): 1746-1754, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31292137

RESUMO

BACKGROUND: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women. METHODS: This study includes 2,016 controls [n = 1,552 (76%) postmenopausal, n = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. RESULTS: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women (P trend ≤ 0.03) and higher OPG concentrations in all women (P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking (P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI (P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. CONCLUSIONS: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women. IMPACT: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

9.
Bull Cancer ; 106(7-8): 635-646, 2019.
Artigo em Francês | MEDLINE | ID: mdl-31227175

RESUMO

In the past decades, obesity and overweight prevalence has been rising worldwide, in both men and women. In France, the prevalence of overweight in adults was 49% in 2015 (54% among men and 44% among women), including 17% of obese adults. According to the last evaluation performed by IARC in 2017, overweight and obesity are established risk factors for 13 cancer sites with risk estimates per 5kg/m2 varying largely depending on the cancer site. In 2015 in France, 5.4% of cancer cases could be attributed to excess weight, corresponding to 18,600 cases, including 3400 colon cancers, 2600 kidney cancers, 4500 breast cancers and 2500 endometrial cancers. Obesity is also related to worse prognosis for some cancers, in particular breast and colon cancers. Obesity in children and adolescents, also rising in many countries, has also been associated to an increase in adult cancer risk. A major cause of obesity is a disequilibrium in energy balance favoured by a diet rich in processed food, red meat, trans and saturated fatty acids, sweetened foods and beverages and poor in fruits and vegetables, legumes and whole grains. Main national and international recommendations to reduce the prevalence of obesity are to have a balanced diet and regular physical activity.


Assuntos
Neoplasias/epidemiologia , Sobrepeso/epidemiologia , Adulto , Criança , Cocarcinogênese , Comorbidade , Dieta/efeitos adversos , Metabolismo Energético , Exercício , Feminino , Saúde Global , Hormônios Esteroides Gonadais/fisiologia , Guias como Assunto , Humanos , Inflamação , Insulina/fisiologia , Fator de Crescimento Insulin-Like I/fisiologia , Masculino , Neoplasias/etiologia , Neoplasias/prevenção & controle , Especificidade de Órgãos , Sobrepeso/complicações , Sobrepeso/fisiopatologia , Prevalência , Fatores de Risco , Organização Mundial da Saúde
10.
Cancer Epidemiol ; 60: 216-220, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31054835

RESUMO

INTRODUCTION: Insufficient physical activity is a known risk factor for various co-morbidities, including cancer. Globally, its prevalence has increased markedly over the past decades. The aim of this study was to estimate the proportion and number of cancers that were attributable to insufficient physical activity in France in 2015. METHODS: Population attributable fractions (PAFs) and numbers of cancer cases attributable to insufficient physical activity (<30 min daily of moderate-to-vigorous physical activity) were estimated by age, sex and cancer site. Assuming a 10-year lag-period, PAFs were calculated using physical activity prevalence from a cross-sectional French population survey and cancer-specific relative risks. RESULTS: About half of all French adults were found to be insufficiently physically active, with great variation by age and sex. In 2015, an estimated 2973 cancer cases diagnosed in French adults aged 30y+ were attributable to insufficient physical activity, corresponding to 0.8% of all cancer cases (0.2% in men and 1.6% in women). This comprised 3.8% of all postmenopausal breast cancers (1620 cases), 3.6% of all colon cancers (902 cases) and 6.0% of all cancers of the corpus uteri (450 cases). If at least half of the recommended physical activity level was achieved, 1095 cancer cases could have been avoided. CONCLUSION: Insufficient physical activity is associated to about 3000 cancer cases in France, a country with comparatively low but increasing prevalence of this risk factor. This result is important for setting priorities in cancer prevention programmes aiming to increase physical activity in France and Europe in general.

11.
Cancer Epidemiol Biomarkers Prev ; 28(6): 1076-1085, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30948451

RESUMO

BACKGROUND: Cancer antigen 125 (CA125) is the most promising ovarian cancer screening biomarker to date. Multiple studies reported CA125 levels vary by personal characteristics, which could inform personalized CA125 thresholds. However, this has not been well described in premenopausal women. METHODS: We evaluated predictors of CA125 levels among 815 premenopausal women from the New England Case Control Study (NEC). We developed linear and dichotomous (≥35 U/mL) CA125 prediction models and externally validated an abridged model restricting to available predictors among 473 premenopausal women in the European Prospective Investigation into Cancer and Nutrition Study (EPIC). RESULTS: The final linear CA125 prediction model included age, race, tubal ligation, endometriosis, menstrual phase at blood draw, and fibroids, which explained 7% of the total variance of CA125. The correlation between observed and predicted CA125 levels based on the abridged model (including age, race, and menstrual phase at blood draw) had similar correlation coefficients in NEC (r = 0.22) and in EPIC (r = 0.22). The dichotomous CA125 prediction model included age, tubal ligation, endometriosis, prior personal cancer diagnosis, family history of ovarian cancer, number of miscarriages, menstrual phase at blood draw, and smoking status with AUC of 0.83. The abridged dichotomous model (including age, number of miscarriages, menstrual phase at blood draw, and smoking status) showed similar AUCs in NEC (0.73) and in EPIC (0.78). CONCLUSIONS: We identified a combination of factors associated with CA125 levels in premenopausal women. IMPACT: Our model could be valuable in identifying healthy women likely to have elevated CA125 and consequently improve its specificity for ovarian cancer screening.

12.
Nutrients ; 11(3)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871053

RESUMO

This cross-sectional study aimed to evaluate associations between a priori defined dietary patterns and anthropometric measures in Mexican women. A total of 1062 women aged 35 to 69 years old from the control participants of the CAMA (Cancer de Mama) study, a multi-center population-based case-control study on breast cancer conducted in Mexico, were interviewed and dietary intakes were assessed using questionnaires. The following indices were derived from these data: Dietary Approaches to Stop Hypertension (DASH) score, the Healthy Eating Index (HEI), the Mediterranean Diet Score (aMED), the Diet Quality Index (DQI), glycemic index (GI) and glycemic load (GL). Adjusting for age, center, educational level, physical activity and energy intake, a high GI was positively associated with a higher body mass index (BMI) and waist circumference (WC). Higher adherence to aMED was associated with lower WC and waist-to-hip ratio (WHR) but no significant association was observed with other a priori dietary patterns. In this population of Mexican women, higher adherence to Mediterranean diet was associated with lower WC but other a priori dietary scores appeared to be of limited value in exploring the association between diet and anthropometric measures.


Assuntos
Antropometria , Dieta , Comportamento Alimentar , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , México , Pessoa de Meia-Idade
13.
Environ Int ; 124: 236-248, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30658268

RESUMO

BACKGROUND: Dioxins, Group 1 carcinogens, are emitted by industrial chlorinated combustion processes and suspected to increase breast cancer risk through receptor-mediated pathways. OBJECTIVES: We estimated breast cancer risk associated with airborne dioxin exposure, using geographic information system (GIS) methods and historical exposure data. METHODS: We designed a case-control study (429 breast cancer cases diagnosed between 1990 and 2008, matched to 716 controls) nested within the E3N (Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale) cohort. Airborne dioxin exposure was assessed using a GIS-based metric including participants' residential history, technical characteristics of 222 dioxin sources, residential proximity to dioxin sources, exposure duration and wind direction. Odds ratios (OR) and 95% confidence intervals (CI) associated with quintiles of cumulative exposure were estimated using multivariate logistic regression models. RESULTS: We observed no increased risk of breast cancer for higher dioxin exposure levels overall and according to hormone-receptor status. We however observed a statistically significant OR for Q2 versus Q1 overall (1.612, 95% CI: 1.042-2.493) and for estrogen-receptor (ER) positive breast cancer (1.843, 95% CI: 1.033-3.292). CONCLUSIONS: Overall, as well as according to hormone-receptor status, no increased risk was observed for higher airborne dioxin exposure. The increased risk for low exposure levels might be compatible with non-monotonic dose-response relationship. Confirmation of our findings is required. Our GIS-based metric may provide an alternative in absence of ambient dioxin monitoring and may allow assessing exposure to other pollutants.


Assuntos
Poluentes Atmosféricos/toxicidade , Neoplasias da Mama/etiologia , Carcinógenos/toxicidade , Dioxinas/toxicidade , Exposição Ambiental , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Receptor alfa de Estrogênio/metabolismo , Feminino , França , Sistemas de Informação Geográfica , Humanos , Pessoa de Meia-Idade , Razão de Chances , Estudos Prospectivos , Medição de Risco
14.
Cancer Epidemiol ; 58: 160-166, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30597481

RESUMO

BACKGROUND: Some modifiable risk factors have been independently associated with breast cancer (BC) risk in Moroccan women, but no studies have investigated their joint association. This study aimed to investigate the association between a Healthy Lifestyle Index (HLI) score and BC risk among Moroccan women. METHODS: In this case-control study, 300 incident BC cases and 300 controls, matched by age and area of residence were recruited. Cases were women newly-diagnosed with histopathologically-confirmed BC at the University Hospital in Fez, Morocco. Controls were randomly selected healthy women recruited from 6 primary health centers in Fez. HLI scores developed within this study were assigned to participants based on 11 factors (red and processed meat, white meat, cream, cheese, fish, fruit and vegetables, physical activity, BMI, smoking, alcohol consumption, and breastfeeding), where 0 was given to unhealthy and 0.5 or 1 to healthy levels of each factor. Conditional and unconditional logistic regression models were used to assess the association between HLI scores and BC risk. RESULTS: Mean of HLI scores were 8.1 (±1.1) and 9.0 (±0.9) in cases and controls, respectively, p < 0.01. After adjusting for potential confounders, one-point increment in the HLI score was associated with 56% (95% CI, CI: 39-68%), 49% (95% CI: 30-63%), and 59% (95% CI: 40-72%) lower risks of BC in all, premenopausal, and postmenopausal women, respectively. CONCLUSION: High HLI scores were associated with decreased risk of BC in Moroccan women. These findings suggest that BC prevention policies should include strategies for engaging Moroccan women in healthy lifestyles.


Assuntos
Neoplasias da Mama/prevenção & controle , Exercício , Estilo de Vida Saudável , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Marrocos/epidemiologia , Prognóstico , Fatores de Risco , Comportamento de Redução do Risco , Saúde da Mulher , Adulto Jovem
15.
Br J Nutr ; 121(2): 130-136, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30477593

RESUMO

Non-communicable diseases are projected to become the most common causes of death in Africa by 2030. The impact on health of epidemiological and nutritional transitions in sub-Saharan Africa remains unclear. To assess the trends of dietary fatty acids over time in Uganda, we examined fatty acids in serum collected from individuals in rural south-west Uganda, at three time points over two decades. Independent cross-sectional samples of 915 adults and children were selected from the general population cohort in 1990 (n 281), 2000 (n 283) and 2008 (n 351). Serum phospholipid fatty acids were measured by GC. Multivariate regression analyses were performed to compare the geometric means of fatty acids by time period. Serum fatty acid profiling showed high proportions of SFA, cis-MUFA and industrial trans-fatty acids (iTFA), likely to be biomarkers of high consumption of palm oil and hydrogenated fats. In contrast, proportions of n-6 and n-3 PUFA from vegetable oils and fish were low. From 1990 to 2008, serum phospholipids showed increases in absolute amounts of SFA (17·3 % increase in adults and 26·4 % in children), MUFA (16·7 % increase in adults and 16·8 % in children) and n-6:n-3 PUFA (40·1 % increase in adults and 39·8 % in children). The amount of elaidic acid, iTFA from hydrogenated fats, increased in children (60·1 % increase). In this rural Ugandan population, we show evidence of unfavourable trends over time of dietary fatty acids.


Assuntos
Dieta/tendências , Gorduras na Dieta/administração & dosagem , Ácidos Graxos/sangue , População Rural , Adolescente , Adulto , Biomarcadores/sangue , Criança , Estudos Transversais , Ácidos Graxos/administração & dosagem , Ácidos Graxos Monoinsaturados/sangue , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-6/administração & dosagem , Feminino , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição , Ácidos Oleicos/sangue , Óleo de Palmeira/administração & dosagem , Fosfolipídeos/sangue , Uganda
16.
Ann Intern Med ; 170(1): 22-30, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30534999

RESUMO

Background: Parity is widely recognized as protective for breast cancer, but breast cancer risk may be increased shortly after childbirth. Whether this risk varies with breastfeeding, family history of breast cancer, or specific tumor subtype has rarely been evaluated. Objective: To characterize breast cancer risk in relation to recent childbirth. Design: Pooled analysis of individual-level data from 15 prospective cohort studies. Setting: The international Premenopausal Breast Cancer Collaborative Group. Participants: Women younger than 55 years. Measurements: During 9.6 million person-years of follow-up, 18 826 incident cases of breast cancer were diagnosed. Hazard ratios (HRs) and 95% CIs for breast cancer were calculated using Cox proportional hazards regression. Results: Compared with nulliparous women, parous women had an HR for breast cancer that peaked about 5 years after birth (HR, 1.80 [95% CI, 1.63 to 1.99]) before decreasing to 0.77 (CI, 0.67 to 0.88) after 34 years. The association crossed over from positive to negative about 24 years after birth. The overall pattern was driven by estrogen receptor (ER)-positive breast cancer; no crossover was seen for ER-negative cancer. Increases in breast cancer risk after childbirth were pronounced when combined with a family history of breast cancer and were greater for women who were older at first birth or who had more births. Breastfeeding did not modify overall risk patterns. Limitations: Breast cancer diagnoses during pregnancy were not uniformly distinguishable from early postpartum diagnoses. Data on human epidermal growth factor receptor 2 (HER2) oncogene overexpression were limited. Conclusion: Compared with nulliparous women, parous women have an increased risk for breast cancer for more than 20 years after childbirth. Health care providers should consider recent childbirth a risk factor for breast cancer in young women. Primary Funding Source: The Avon Foundation, the National Institute of Environmental Health Sciences, Breast Cancer Now and the UK National Health Service, and the Institute of Cancer Research.


Assuntos
Neoplasias da Mama/epidemiologia , Parto , Adolescente , Adulto , Aleitamento Materno , Neoplasias da Mama/diagnóstico , Feminino , Predisposição Genética para Doença , Humanos , Idade Materna , Pessoa de Meia-Idade , Paridade , Gravidez , Pré-Menopausa , Modelos de Riscos Proporcionais , Estudos Prospectivos , Receptores Estrogênicos/análise , Fatores de Risco , Adulto Jovem
17.
Breast Cancer Res ; 20(1): 147, 2018 12 03.
Artigo em Inglês | MEDLINE | ID: mdl-30509329

RESUMO

BACKGROUND: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction. METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention. RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+ and 3.0 × 10- 6 for ModelGail. CONCLUSIONS: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/diagnóstico , Modelos Biológicos , Receptores Estrogênicos/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Feminino , Seguimentos , Humanos , Incidência , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco
18.
Eur J Cancer ; 105: 103-113, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30445359

RESUMO

BACKGROUND: Cancer is a major cause of premature illness and death in France. To quantify how cancer prevention could reduce the burden, we present estimates of the contribution of lifestyle and environmental risk factors to cancer incidence in France in 2015, comparing these with other high-income countries. METHOD: Prevalences of, and relative risks for tobacco smoking, alcohol consumption, inadequate diet, overweight and obesity, physical inactivity, exogenous hormones, suboptimal breastfeeding, infectious agents, ionising radiation, air pollution, ultraviolet exposure, occupational exposures, arsenic in drinking water and indoor benzene were obtained to estimate the population attributable fraction (PAF) and the number of attributable cancers by the cancer site and sex. RESULTS: In 2015, 41% (or 142,000 of 346,000) of all new cancers diagnosed in France could be attributed to the aforementioned risk factors. The numbers and PAF were slightly higher in men than in women (84,000 versus 58,000 cases and 44% versus 37%, respectively). Smoking (PAF: 20%), alcohol consumption (PAF: 8%), dietary factors (PAF: 5%) and excess weight (PAF: 5%) were the most important factors. Infections and occupational exposures each contributed to an additional 4% of the cancer cases in 2015. CONCLUSION: Today, two-fifths of cancers in France are attributable to preventable risk factors. The variations in the key amenable factors responsible in France relative to other economically similar countries highlight the need for tailored approaches to cancer education and prevention. Reducing smoking and alcohol consumption and the adoption of healthier diet and body weight remain important targets to reduce the increasing number of new cancer patients in France in the decades to follow.


Assuntos
Exposição Ambiental , Estilo de Vida , Neoplasias/epidemiologia , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Cocarcinogênese , Países Desenvolvidos , Dieta/efeitos adversos , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/etiologia , Neoplasias/prevenção & controle , Neoplasias Induzidas por Radiação/epidemiologia , Obesidade/epidemiologia , Exposição Ocupacional , Fatores de Risco , Comportamento Sedentário , Fumar/efeitos adversos
19.
BMC Cancer ; 18(1): 1010, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30348163

RESUMO

BACKGROUND: Receptor activator of nuclear factor kappa-B (RANK)-signaling is involved in tumor growth and spread in experimental models. Binding of RANK ligand (RANKL) to RANK activates signaling, which is inhibited by osteoprotegerin (OPG). We have previously shown that circulating soluble RANKL (sRANKL) and OPG are associated with breast cancer risk. Here we extend these findings to provide the first data on pre-diagnosis concentrations of sRANKL and OPG and risk of breast cancer-specific and overall mortality after a breast cancer diagnosis. METHODS: Two thousand six pre- and postmenopausal women with incident invasive breast cancer (1620 (81%) with ER+ disease) participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were followed-up for mortality. Pre-diagnosis concentrations of sRANKL and OPG were quantified in baseline serum samples using an enzyme-linked immunosorbent assay and electrochemiluminescent assay, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) for breast cancer-specific and overall mortality were calculated using Cox proportional hazards regression models. RESULTS: Especially in women with ER+ disease, higher circulating OPG concentrations were associated with higher risk of breast cancer-specific (quintile 5 vs 1 HR 1.77 [CI 1.03, 3.04]; ptrend 0.10) and overall mortality (q5 vs 1 HR 1.39 [CI 0.94, 2.05]; ptrend 0.02). sRANKL and the sRANKL/OPG ratio were not associated with mortality following a breast cancer diagnosis. CONCLUSIONS: High pre-diagnosis endogenous concentrations of OPG, the decoy receptor for RANKL, were associated with increased risk of death after a breast cancer diagnosis, especially in those with ER+ disease. These results need to be confirmed in well-characterized patient cohorts.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Osteoprotegerina/metabolismo , Ligante RANK/metabolismo , Adulto , Idoso , Neoplasias da Mama/diagnóstico , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Limite de Detecção , Pessoa de Meia-Idade , Osteoprotegerina/sangue , Prognóstico , Risco
20.
JAMA Oncol ; 4(11): e181771, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-29931120

RESUMO

Importance: The association between increasing body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) and risk of breast cancer is unique in cancer epidemiology in that a crossover effect exists, with risk reduction before and risk increase after menopause. The inverse association with premenopausal breast cancer risk is poorly characterized but might be important in the understanding of breast cancer causation. Objective: To investigate the association of BMI with premenopausal breast cancer risk, in particular by age at BMI, attained age, risk factors for breast cancer, and tumor characteristics. Design, Setting, and Participants: This multicenter analysis used pooled individual-level data from 758 592 premenopausal women from 19 prospective cohorts to estimate hazard ratios (HRs) of premenopausal breast cancer in association with BMI from ages 18 through 54 years using Cox proportional hazards regression analysis. Median follow-up was 9.3 years (interquartile range, 4.9-13.5 years) per participant, with 13 082 incident cases of breast cancer. Participants were recruited from January 1, 1963, through December 31, 2013, and data were analyzed from September 1, 2013, through December 31, 2017. Exposures: Body mass index at ages 18 to 24, 25 to 34, 35 to 44, and 45 to 54 years. Main Outcomes and Measures: Invasive or in situ premenopausal breast cancer. Results: Among the 758 592 premenopausal women (median age, 40.6 years; interquartile range, 35.2-45.5 years) included in the analysis, inverse linear associations of BMI with breast cancer risk were found that were stronger for BMI at ages 18 to 24 years (HR per 5 kg/m2 [5.0-U] difference, 0.77; 95% CI, 0.73-0.80) than for BMI at ages 45 to 54 years (HR per 5.0-U difference, 0.88; 95% CI, 0.86-0.91). The inverse associations were observed even among nonoverweight women. There was a 4.2-fold risk gradient between the highest and lowest BMI categories (BMI≥35.0 vs <17.0) at ages 18 to 24 years (HR, 0.24; 95% CI, 0.14-0.40). Hazard ratios did not appreciably vary by attained age or between strata of other breast cancer risk factors. Associations were stronger for estrogen receptor-positive and/or progesterone receptor-positive than for hormone receptor-negative breast cancer for BMI at every age group (eg, for BMI at age 18 to 24 years: HR per 5.0-U difference for estrogen receptor-positive and progesterone receptor-positive tumors, 0.76 [95% CI, 0.70-0.81] vs hormone receptor-negative tumors, 0.85 [95% CI: 0.76-0.95]); BMI at ages 25 to 54 years was not consistently associated with triple-negative or hormone receptor-negative breast cancer overall. Conclusions and Relevance: The results of this study suggest that increased adiposity is associated with a reduced risk of premenopausal breast cancer at a greater magnitude than previously shown and across the entire distribution of BMI. The strongest associations of risk were observed for BMI in early adulthood. Understanding the biological mechanisms underlying these associations could have important preventive potential.


Assuntos
Fatores Etários , Índice de Massa Corporal , Neoplasias da Mama/etiologia , Adolescente , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade , Pré-Menopausa , Fatores de Risco , Adulto Jovem
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