Abstract
STUDY QUESTION
Are body size across the life course and adult height associated with endometriosis?
SUMMARY ANSWER
Endometriosis is associated with lean body size during childhood, ...adolescence and adulthood; tall total adult height; and tall sitting height.
WHAT IS KNOWN ALREADY
The literature suggests that both adult body size and height are associated with endometriosis risk, but few studies have investigated the role of body size across the life course. Additionally, no study has investigated the relationships between components of height and endometriosis.
STUDY DESIGN, SIZE, DURATION
We used a nested case-control design within E3N (Etude Epidémiologique auprès de femmes de l'Education Nationale), a prospective cohort of French women. Data were updated every 2–3 years through self-administered questionnaires. Odds ratios (ORs) and 95% CIs were computed using logistic regression models adjusted for a priori confounding factors.
PARTICIPANTS/MATERIALS, SETTING, METHODS
A total of 2416 endometriosis cases were reported as surgically ascertained among the 61 208 included women.
MAIN RESULTS AND THE ROLE OF CHANCE
The odds of endometriosis were lower among women who reported having a large versus lean body size at 8 years (P for trend = 0.003), at menarche (P for trend < 0.0001) and at ages 20–25 years (P for trend < 0.0001). Women in the highest quartiles of height had statistically significantly increased odds of endometriosis compared to those in the lowest (<158 cm) (162–164 cm: OR = 1.28, 95% CI = 1.12–1.46; ≥165 cm: OR = 1.33, 95% CI = 1.18–1.49, P for trend < 0.0001). Statistically significantly increased odds were also observed among women with a taller sitting height (OR = 1.24, 95% CI = 1.05–1.47, P for trend = 0.01). Leg length was not statistically significantly associated with endometriosis.
LIMITATIONS REASONS FOR CAUTION
Endometriosis cases may be prone to misclassification; however, we restricted our case definition to surgically-confirmed cases, which showed a high validation rate. Body size is based on retrospective self-report, which may be subject to recall bias.
WIDER IMPLICATIONS OF THE FINDINGS
The results of this study suggest that endometriosis is positively associated with lean body size across the life course and total adult height. They also suggest that components of height are associated with endometriosis, which should be investigated further.
STUDY FUNDING/COMPETING INTEREST(S)
The Mutuelle Générale de l'Education Nationale (MGEN); the European Community; the French League against Cancer (LNCC); Gustave Roussy; the French Institute of Health and Medical Research (Inserm). L.V.F. was supported by a T32 grant (#HD060454) in reproductive, perinatal and pediatric epidemiology from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Cancer Institute (3R25CA057711) National Institutes of Health. M.K. was supported by a Marie Curie Fellowship within the seventh European Community Framework Programme (#PIOF-GA-2011–302078). The authors have no conflicts of interest to declare.
The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at ...diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45-0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12-2.38) and 1.35 (95% CI 1.02-1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60-1.04), 0.69 (95% CI 0.54-0.88), 0.66 (95% CI 0.51-0.85) and 0.64 (95% CI 0.48-0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer.
Since evidence relating diet to breast cancer risk is not sufficiently consistent to elaborate preventive proposals, the authors examined the association between dietary patterns and breast cancer ...risk in a large French cohort study. The analyses included 2,381 postmenopausal invasive breast cancer cases diagnosed during a median 9.7-year follow-up period (1993–2005) among 65,374 women from the E3N-EPIC cohort. Scores for dietary patterns were obtained by factor analysis, and breast cancer hazard ratios were estimated by Cox proportional hazards regression for the highest quartile of dietary pattern score versus the lowest. Two dietary patterns were identified: “alcohol/Western” (essentially meat products, French fries, appetizers, rice/pasta, potatoes, pulses, pizza/pies, canned fish, eggs, alcoholic beverages, cakes, mayonnaise, and butter/cream) and “healthy/Mediterranean” (essentially vegetables, fruits, seafood, olive oil, and sunflower oil). The first pattern was positively associated with breast cancer risk (hazard ratio = 1.20, 95% confidence interval (CI): 1.03, 1.38; P = 0.007 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-positive. The “healthy/Mediterranean” pattern was negatively associated with breast cancer risk (hazard ratio = 0.85, 95% CI: 0.75, 0.95; P = 0.003 for linear trend), especially when tumors were estrogen receptor-positive/progesterone receptor-negative. Adherence to a diet comprising mostly fruits, vegetables, fish, and olive/sunflower oil, along with avoidance of Western-type foods, may contribute to a substantial reduction in postmenopausal breast cancer risk.
Epidemiological evidence suggests that the Mediterranean diet (MD) could reduce the risk of breast cancer (BC). As evidence from the prospective studies remains scarce and conflicting, we ...investigated the association between adherence to the MD and risk of BC among 335,062 women recruited from 1992 to 2000, in ten European countries, and followed for 11 years on average. Adherence to the MD was estimated through an adapted relative Mediterranean diet (arMED) score excluding alcohol. Cox proportional hazards regression models were used while adjusting for BC risk factors. A total of 9,009 postmenopausal and 1,216 premenopausal first primary incident invasive BC were identified (5,862 estrogen or progesterone receptor positive ER+/PR+ and 1,018 estrogen and progesterone receptor negative ER−/PR−). The arMED was inversely associated with the risk of BC overall and in postmenopausal women (high vs. low arMED score; hazard ratio HR = 0.94 95% confidence interval CI: 0.88, 1.00 ptrend = 0.048, and HR = 0.93 95% CI: 0.87, 0.99 ptrend = 0.037, respectively). The association was more pronounced in ER−/PR− tumors (HR = 0.80 95% CI: 0.65, 0.99 ptrend = 0.043). The arMED score was not associated with BC in premenopausal women. Our findings show that adherence to a MD excluding alcohol was related to a modest reduced risk of BC in postmenopausal women, and this association was stronger in receptor‐negative tumors. The results support the potential scope for BC prevention through dietary modification.
What's new?
Many factors can affect susceptibility to breast cancer, including menopausal status and diet. This study investigated the association between breast cancer and an adapted version of the “Mediterranean diet,” excluding alcohol. They found that the diet reduced the risk of breast cancer by 6% overall, and by 7% in postmenopausal women. For tumors lacking the estrogen or progesterone receptors, however, the diet reduced risk by 20% in postmenopausal women. This study also confirmed a previously observed lack of association between Mediterranean diet and breast cancer in premenopausal women.
MicroRNAs (miRNAs) are post‐transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer ...but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single‐nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log‐additive model. Furthermore, several of these miRNAs passed the gene‐based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR‐29a/miR‐29b‐1 cluster were associated with diffuse subtype (minimum p‐value = 1.7 × 10−4; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30–2.28), two tagSNPs of the miR‐25/miR‐93/miR‐106b cluster were associated with cardia GC (minimum p‐value = 5.38 × 10−3; OR = 0.56, 95% CI = 0.37–0.86) and one tagSNP of the miR‐363/miR‐92a‐2/miR‐19b‐2/miR‐20b/miR‐18b/miR‐106a cluster was associated with noncardia GC (minimum p‐value = 5.40 × 10−3; OR = 1.41, 95% CI = 1.12–1.78). Some functionally validated target genes of these miRNAs are implicated in cancer‐related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.
What's New?
Even though deregulation of miRNA expression has been associated with human cancers, the contribution of miRNAs to cancer genetic susceptibility is unclear. Here the authors designed a panel of 133 SNPs tagging 104 candidate miRNA genes and analysed their association with gastric cancer (GC). They describe an unreported significant genetic association of GC with miRNA clusters in chromosomes 7 and X including miR‐29, miR‐25, miR‐93, and miR‐106. These miRNAs have been previously involved in the pathophysiology of GC and have functionally validated target genes implicated in cancer‐related processes. The data suggest these miRNAs as novel genetic susceptibility factors for GC.
To investigate the association between various anthropometric characteristics and breast cancer.
Longitudinal prospective cohort study. Follow-up between 1995 and 2000.
In total, 69 116 women (age: ...45-70 years; mean follow-up: 3.6 years), 275 premenopausal and 860 postmenopausal incident invasive breast cancers.
Self-reported height, weight, breast, thorax, waist and hip circumferences and calculated body mass index (BMI) and waist-to-hip ratio (WHR) at baseline.
A slight increase in risk with increasing height was found. Weight, BMI, thorax and waist circumferences and WHR were negatively related to breast cancer risk among premenopausal women. The relationships became non significant after additional adjustment for BMI. An increased risk of premenopausal breast cancer with an android body shape (WHR>0.87) might possibly be confined to obese women. Among postmenopausal women, all anthropometric measurements of corpulence were positively associated with breast cancer risk but became non significant after additional adjustment for BMI. No difference in risk of postmenopausal breast cancer according to HRT use was observed.
The study confirmed that adiposity was negatively associated to premenopausal breast cancer risk and positively associated to postmenopausal breast cancer risk. Further studies will be needed to specify clearly the association between WHR and breast cancer risk, particularly before menopause.
Epidemiological studies have suggested that female hormones might play a role in asthma and that menopausal hormone therapy (MHT or hormone replacement therapy (HRT)) might increase the risk of ...asthma in postmenopausal women. The only prospective study addressing this issue reports an increase in the risk of developing asthma which was similar for oestrogen alone and oestrogen/progestagen treatment.
The association between the use of different types of MHT and the risk of asthma onset in postmenopausal women was investigated prospectively from 1990 to 2002 by biennial questionnaires as part of the French E3N cohort study. Asthma onset was considered to be the time of medical diagnosis of asthma cases occurring during the follow-up of women who were asthma free at baseline. Cox proportional hazards models were used, adjusting for potential confounding factors.
Among 57 664 women free of asthma at menopause, 569 incident cases of asthma were identified during 495 448 years of follow-up. MHT was related to an increased risk of asthma onset (HR=1.20, 95% CI 0.98 to 1.46) among recent users. The increase in risk of asthma onset was only significant among women reporting the use of oestrogen alone (HR=1.54, 95% CI 1.13 to 2.09) particularly in never smokers (HR=1.80, 95% CI 1.15 to 2.80) and women reporting allergic disease prior to asthma onset (HR=1.86, 95% CI 1.18 to 2.93). A small increase in the risk of asthma onset associated with the use of oestrogen/progestagen was also observed in these subgroups.
Postmenopausal use of oestrogen alone was associated with an increased rate of newly diagnosed asthma in menopausal women.
. Beulens JWJ, van der Schouw YT, Bergmann MM, Rohrmann S, B Schulze M, Buijsse B, Grobbee DE, Arriola L, Cauchi S, Tormo M‐J, Allen NE, van der A DL, Balkau B, Boeing H, Clavel‐Chapelon F, de ...Lauzon‐Guillan B, Franks P, Froguel P, Gonzales C, Halkjær J, Huerta JM, Kaaks R, Key TJ, Khaw KT, Krogh V, Molina‐Montes E, Nilsson P, Overvad K, Palli D, Panico S, Ramón Quirós J, Ronaldsson O, Romieu I, Romaguera D, Sacerdote C, Sánchez M‐J, Spijkerman AMW, Teucher B, Tjonneland A, Tumino R, Sharp S, Forouhi NG, Langenberg C, Feskens EJM, Riboli E, Wareham NJ (University Medical Center Utrecht, The Netherlands; German Institute of Human Nutrition, Potsdam‐Rehbrücke, Germany; German Cancer Research Centre, Heidelberg, Germany; Basque Government, San Sebastian, CIBERESP, Spain; Institut de Biologie de Lille, Lille, France; Murcia Regional Health Council, Murcia, Spain; CIBER Epidemiologia y Salud Publica (CIBERESP), Spain; University of Oxford, Oxford, UK; National Institute of Public Health and the Environment, Bilthoven, The Netherlands; Inserm, CESP Centre for Research in Epidemiology and Population Health, Villejuif Cedex, France; Lund University, Malmö, Sweden; Imperial College, London, UK; Department of Epidemiology, Barcelona, Spain; Danish Cancer Society, Copenhagen, Denmark; University of Cambridge, Cambridge, UK; Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy; Andalusian School of Public Health, Granada, Spain; School of Public Health, Aarhus, Denmark; Cancer Research and Prevention Institute (ISPO), Florence, Italy; Università Federico II, Napoli, Italy; Consejeria de Salud y Servicios Sanitarios, Oviedo‐Asturias, Spain; Umea University, Umea, Sweden; International Agency for Research of Cancer, Lyon, France; Center for Cancer Prevention (CPO‐Piemonte), Torino, Italy; “Civile ‐ M.P. Arezzo” Hospital, Ragusa, Italy; Addenbrooke’s Hospital, Cambridge, UK; and Wageningen University, Wageningen, The Netherlands). Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size. The EPIC–InterAct study. J Intern Med 2012; 272: 358–370.
Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type.
Design: Multicentre prospective case–cohort study.
Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort.
Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes.
Interventions: Alcohol consumption assessed using validated dietary questionnaires.
Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self‐reports), verified against medical information.
Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78–1.05) for 6.1–12.0 versus 0.1–6.0 g day−1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1–96.0 g day−1 with an HR of 0.86 (95% CI: 0.75–0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72–0.92) for 6.1–12.0 g day−1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI ≥ 25 kg m−2) than normal‐weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.79–1.03 for 6.1–12.0 g day−1). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes.
Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal‐weight women and men.
Diets high in vegetables and fruits have been suggested to be inversely associated with risk of gastric cancer. However, the evidence of the effect of variety of consumption is limited. We therefore ...investigated whether consumption of a variety of vegetables and fruit is associated with gastric and esophageal cancer in the European Prospective Investigation into Cancer and Nutrition study. Data on food consumption and follow‐up on cancer incidence were available for 452,269 participants from 10 European countries. After a mean follow‐up of 8.4 years, 475 cases of gastric and esophageal adenocarcinomas (180 noncardia, 185 cardia, gastric esophageal junction and esophagus, 110 not specified) and 98 esophageal squamous cell carcinomas were observed. Diet Diversity Scores were used to quantify the variety in vegetable and fruit consumption. We used multivariable Cox proportional hazard models to calculate risk ratios. Independent from quantity of consumption, variety in the consumption of vegetables and fruit combined and of fruit consumption alone were statistically significantly inversely associated with the risk of esophageal squamous cell carcinoma (continuous hazard ratio per 2 products increment 0.88; 95% CI 0.79–0.97 and 0.76; 95% CI 0.62–0.94, respectively) with the latter particularly seen in ever smokers. Variety in vegetable and/or fruit consumption was not associated with risk of gastric and esophageal adenocarcinomas. Independent from quantity of consumption, more variety in vegetable and fruit consumption combined and in fruit consumption alone may decrease the risk of esophageal squamous cell carcinoma. However, residual confounding by lifestyle factors cannot be excluded.
The aim of the present study was to determine dietary patterns and investigate their association with asthma incidence, current asthma and frequent asthma exacerbations. Dietary habits and asthma ...data were collected from the large E3N study (of French females, mostly teachers). Of the 54,672 females followed-up in 2003, 2,634 reported ever-adulthood asthma, 1,063 reported current asthma, 206 reported frequent asthma attacks (one or more a week), and 628 reported asthma onset between 1993 and 2003. Using principal component analysis, three dietary patterns were identified: the "prudent" pattern (fruits and vegetables); the "Western" pattern (pizza/salty pies, dessert and cured meats); and the "nuts and wine" pattern. Pattern scores were categorised into tertiles, and the incidence and prevalence of asthma was compared between tertiles. After adjustment for confounders, no association of dietary patterns was observed with asthma incidence, ever-asthma or current asthma. The Western pattern was associated with an increased risk of reporting frequent asthma attacks (highest versus lowest tertile odds ratio (OR) 1.79, 95% confidence interval (CI) 1.11-3.73). Increasing scores of the nuts and wine pattern were associated with a decreased risk of reporting frequent asthma attacks (highest versus lowest tertile OR 0.65, 95% CI 0.31-0.96). The results of the present study suggest that overall diet could be involved in frequent asthma exacerbations, one aspect of asthma severity.
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