Metabolic syndrome and risk of endometrial cancer in postmenopausal women: a prospective study.
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ABSTRACT:
SUBMITTER: Arthur RS
PROVIDER: S-EPMC6886235 | biostudies-literature | 2019 Apr
REPOSITORIES: biostudies-literature
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Project description:Greater adiposity in early life has been linked to increased endometrial cancer risk in later life, but the extent to which this association is mediated through adiposity in later life is unclear.Among postmenopausal women who had never used menopausal hormone therapies and reported not having had a hysterectomy, adjusted relative risks (RRs) of endometrial cancer were estimated using Cox regression.Among 249 791 postmenopausal women with 7.3 years of follow-up on average (1.8 million person-years), endometrial cancer risk (n=1410 cases) was strongly associated with current body mass index (BMI) at baseline (RR=1.87 per 5 kg m(-2) increase in BMI, 95% confidence interval (CI): 1.77-1.96). Compared with women thinner than average at age 10, the increased risk among women plumper at age 10 (RR=1.27, 95% CI: 1.09-1.49) disappeared after adjustment for current BMI (RR=0.90, 95% CI: 0.77-1.06). Similarly, compared with women with clothes size 12 or less at age 20, the increased risk among women with clothes size 16 or larger (RR=1.87, 95% CI: 1.61-2.18) was not significant after adjustment for current BMI (RR=1.03, 95% CI: 0.88-1.22).Among women who have never used hormone therapy for menopause, the association between body size in early life and endometrial cancer risk in postmenopausal women can be largely explained by women's current BMI.
| S-EPMC3389421 | biostudies-other
Project description:ObjectiveThis study investigated the associations between obesity, metabolic syndrome (MetS), the combination of these two components as a metabolic obesity phenotype, and endometrial cancer risk in East Asian women.MethodsA total of 6,097,686 cancer-free women aged 40-74 years who underwent the National Health Insurance Service health examination between 2009 and 2010 were included. Cancer incidence was identified using the healthcare utilization database. Associations between baseline obesity (body mass index <23 kg/m², 23-24.9 kg/m², ≥25 kg/m²), MetS, each component of MetS, MetS stratified by obesity status, combination of obesity and MetS, and endometrial cancer risk were investigated using hazard ratios (HRs).ResultsObesity, each component of MetS, and MetS increased the endometrial cancer risk. After these factors were mutually adjusted for, the association did not change. When stratified by obesity, MetS and MetS components were not associated with endometrial cancer in normal-weight or overweight women. However, in obese women, MetS and MetS components increased the risk of endometrial cancer (HR=1.29; 95% confidence interval [CI]=1.20-1.39). Compared with normal-weight women without MetS, endometrial cancer risk was not increased in normal-weight women with MetS. Overweight women showed an increased risk of endometrial cancer irrespective of the presence of MetS (HR=1.37 and 1.38, respectively). The HR of obese women with MetS was higher than that of obese women without MetS (HR=2.18 and 1.75).ConclusionThe association between MetS and endometrial cancer was most prominent in obese women, suggesting that obese women with MetS would be more vulnerable to endometrial cancer.
| S-EPMC9250850 | biostudies-literature
Project description:BACKGROUND:Although endometrial cancer is clearly influenced by hormonal factors, few epidemiologic studies have investigated the role of endogenous estrogens or especially estrogen metabolites. METHODS:We conducted a nested case-control study within the Women's Health Initiative Observational Study (WHI-OS), a cohort of 93,676 postmenopausal women recruited between 1993 and 1998. Using baseline serum samples from women who were non-current hormone users with intact uteri, we measured 15 estrogens/estrogen metabolites via HPLC/MS-MS among 313 incident endometrial cancer cases (271 type I, 42 type II) and 354 matched controls, deriving adjusted ORs and 95% confidence intervals (CI) for overall and subtype-specific endometrial cancer risk. RESULTS:Parent estrogens (estrone and estradiol) were positively related to endometrial cancer risk, with the highest risk observed for unconjugated estradiol (OR 5th vs. 1st quintile = 6.19; 95% CI, 2.95-13.03, Ptrend = 0.0001). Nearly all metabolites were significantly associated with elevated risks, with some attenuation after adjustment for unconjugated estradiol (residual risks of 2- to 3-fold). Body mass index (kg/m(2), BMI) relations were somewhat reduced after adjustment for estrogen levels. The association with unconjugated estradiol was stronger for type I than type II tumors (Phet = 0.01). CONCLUSIONS:Parent estrogens as well as individual metabolites appeared to exert generalized uterotropic activity, particularly for type I tumors. The effects of obesity on risk were only partially explained by estrogens. IMPACT:These findings enhance our understanding of estrogen mechanisms involved in endometrial carcinogenesis but also highlight the need for studying additional markers that may underlie the effects on risk of certain risk factors, for example, obesity. Cancer Epidemiol Biomarkers Prev; 25(7); 1081-9. ©2016 AACR.
| S-EPMC4930692 | biostudies-literature
Project description:BackgroundCoffee and its compounds have been proposed to inhibit endometrial carcinogenesis. Studies in the Norwegian population can be especially interesting due to the high coffee consumption and increasing incidence of endometrial cancer in the country.MethodsA total of 97 926 postmenopausal Norwegian women from the population-based prospective Norwegian Women and Cancer (NOWAC) Study, were included in the present analysis. We evaluated the general association between total coffee consumption and endometrial cancer risk as well as the possible impact of brewing method. Multivariate Cox regression analysis was used to estimate risks, and heterogeneity tests were performed to compare brewing methods.ResultsDuring an average of 10.9 years of follow-up, 462 incident endometrial cancer cases were identified. After multivariate adjustment, significant risk reduction was found among participants who drank ≥8 cups/day of coffee with a hazard ratio of 0.52 (95% confidence interval, CI 0.34-0.79). However, we did not observe a significant dose-response relationship. No significant heterogeneity in risk was found when comparing filtered and boiled coffee brewing methods. A reduction in endometrial cancer risk was observed in subgroup analyses among participants who drank ≥8 cups/day and had a body mass index ≥25 kg/m2, and in current smokers.ConclusionsThese data suggest that in this population with high coffee consumption, endometrial cancer risk decreases in women consuming ≥8 cups/day, independent of brewing method.
| S-EPMC3986939 | biostudies-literature
Project description:The aim of the study was to determine an association of TP53 codon 72 (Arg72Pro, G>C transversion, rs1042522) and MDM2 SNP309 (T>G change, rs2279744) polymorphisms in endometrial cancer (EC) of postmenopausal women, regarding grading and staging of EC. In the study, endometrial samples from 202 postmenopausal female patients (the study group, n = 152, was women with EC; the control group, n = 50, cancer-free patients) were taken for the evaluation of two gene polymorphisms: TP53 codon 72 and MDM2 SNP309, respectively. Genotypic analyses were performed using the PCR-RFLP technique. There were significant differences in the frequency of TP53 and MDM2 genotypes in EC patients-increased EC occurrence was observed with the presence of MDM2 G/G and TP53 Arg/Arg genotypes, while allele Pro of TP53 decreased cancer risk. Analysis of combined MDM2/TP53 polymorphisms revealed that T/T-Pro/Arg genotype decreased EC risk, whereas G/G-Arg/Arg genotype increased it. Association of these genetic polymorphisms with histological grading showed increased MDM2 G/G homozygote and TP53 Arg/Arg homozygote frequencies in grading 2 as well as allele G overrepresentation in G1 and G3 EC patients. Finally, with clinical FIGO staging under evaluation, an increase in MDM2 G/G and TP53 Arg/Arg homozygote frequencies in staging I and TP53 Arg/Arg homozygote frequencies in staging II were observed. Co-occurrence of some MDM2 SNP309 and TP53 codon 72 polymorphisms seems to influence EC risk, involving grading and staging of this neoplasm at the same time.
| S-EPMC4197345 | biostudies-literature
Project description:Obesity has been postulated to increase the risk of colorectal cancer by mechanisms involving insulin resistance and the metabolic syndrome. We examined the associations of body mass index (BMI), waist circumference, the metabolic syndrome, metabolic obesity phenotypes and homeostasis model-insulin resistance (HOMA-IR-a marker of insulin resistance) with risk of colorectal cancer in over 21,000 women in the Women's Health Initiative CVD Biomarkers subcohort. Women were cross-classified by BMI (18.5-<25.0, 25.0-<30.0 and ?30.0 kg/m2 ) and presence of the metabolic syndrome into 6 phenotypes: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight (MHOW), metabolically unhealthy overweight (MUOW), metabolically healthy obese (MHO) and metabolically unhealthy obese (MUO). Neither BMI nor presence of the metabolic syndrome was associated with risk of colorectal cancer, whereas waist circumference showed a robust positive association. Relative to the MHNW phenotype, the MUNW phenotype was associated with increased risk, whereas no other phenotype showed an association. Furthermore, HOMA-IR was not associated with increased risk. Overall, our results do not support a direct role of metabolic dysregulation in the development of colorectal cancer; however, they do suggest that higher waist circumference is a risk factor, possibly reflecting the effects of increased levels of cytokines and hormones in visceral abdominal fat on colorectal carcinogenesis.
| S-EPMC6876750 | biostudies-literature
Project description:BackgroundDisinfection byproducts (DBPs) and N-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.ObjectivesWe investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.MethodsAmong postmenopausal women in the Iowa Women's Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (NO3-N) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986-2014). For women using their PWS >10y at enrollment (n=10,501; cases=261), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible ≥95th percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (>½ MCL; 40μg/L TTHM; 30μg/L HAA5; 5mg/L NO3-N). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for DBPs or NO3-N. We evaluated associations for low-grade (cases=99) vs. high-grade (cases=114) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation.ResultsHigher average concentrations of DBPs (95th percentile: TTHM ≥93μg/L, HAA5 ≥49μg/L) were associated with endometrial cancer risk (TTHM: HR95vsQ1=2.19, 95% CI: 1.41, 3.40; HAA5: HR95vsQ1=1.84, 95% CI: 1.19, 2.83; ptrend<0.01). Associations were similarly observed for women greater than median years of PWS use with levels >½ MCL, in comparison with zero years (TTHM: HR36+vs0y=1.61, 95% CI: 1.18, 2.21; HAA5: HR38+vs0y=1.85, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM: HRQ4vsQ1=2.12, 95% CI: 1.17, 3.83; p-trend=0.008) than for high-grade tumors (TTHM: HRQ4vsQ1=1.40, 95% CI: 0.80, 2.44; p-trend=0.339), but differences were not statistically significant (p-heterogeneity=0.43). Associations with TTHM were stronger among ever HRT users than non-HRT users (p-interaction<0.01). We observed no associations with NO3-N in drinking water or diet.DiscussionWe report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation. https://doi.org/10.1289/EHP10207.
| S-EPMC9138501 | biostudies-literature
Project description:Although adult obesity is known to increase endometrial cancer risk, evidence for childhood obesity is limited. We prospectively examined the association between body fatness throughout life and endometrial cancer risk. 47,289 participants in the Nurses' Health Study (NHS) and 105,386 of the Nurses' Health Study II (NHS II) recalled their body fatness at ages 5, 10 and 20 using a pictogram. Childhood and adolescent body fatness were derived as the average at ages 5 and 10 and ages 10 and 20, respectively. We obtained adult weight from concurrent questionnaires. We calculated hazard ratios (HR) of endometrial cancer using Cox proportional hazards models. During follow-up, 757 incident cases of endometrial cancer were diagnosed. Body fatness in childhood, at age 10, in adolescence and at age 20 were positively associated with endometrial cancer risk (HR for ≥ Level 5 versus ≤ Level 2 in adolescence: 1.83 (95% CI 1.41-2.37). After adjusting for most recent BMI, none of the associations persisted. Weight change since age 18 was positively associated with endometrial cancer risk [HR for ≥ 25 kg gain versus stable: 2.54 (95% CI 1.80-3.59). Adult BMI was strongly associated with endometrial cancer risk [HR BMI ≥ 35 kg/m(2) versus BMI ≤ 25 kg/m(2) : 4.13 (95% CI 3.29-5.16)]. In postmenopausal women, the association with BMI was significantly stronger among non-users of hormone therapy. In conclusion, obesity throughout life is positively associated with endometrial cancer risk, with adult obesity one of the strongest risk factors. Maintaining a healthy weight throughout life remains important.
| S-EPMC5241095 | biostudies-literature
Project description:Background: Depression and antidepressant use is highly prevalent among U.S. women and may be related to increased breast cancer risk. However, prior studies are not in agreement regarding an increase in risk.Methods: We conducted a prospective cohort study within the Nurses' Health Study (NHS) and NHSII among females age 25 and older. Over more than 10 years of follow-up in each cohort, 4,014 incident invasive breast cancers were diagnosed. We used Cox proportional hazards regressions with updating of exposures and covariates throughout follow-up to estimate HRs and 95% confidence intervals (CIs) for associations between clinical depression and antidepressant use with invasive breast cancer risk. Analyses were repeated separately for in situ disease, as well as stratified by estrogen receptor (ER) subtype and menopausal status at diagnosis.Results: No statistically significant associations were observed between clinical depression (HR for reporting ?3 times vs. 0, 1.13; 95% CI, 0.85-1.49) or antidepressant use (HR for reporting ?3 times vs. 0, 0.92; 95% CI, 0.80-1.05) and invasive breast cancer risk in multivariable analyses. Likewise, we observed no significant associations between clinical depression or antidepressant use and risk of in situ, ER+, ER-, premenopausal, or postmenopausal breast cancer.Conclusions: In the largest prospective study to date, we find no evidence that either depression or antidepressant use increase risk of breast cancer.Impact: The results of this study are reassuring in that neither depression nor antidepressant use appear to be related to subsequent breast cancer risk. Cancer Epidemiol Biomarkers Prev; 27(3); 306-14. ©2017 AACR.
| S-EPMC5835185 | biostudies-literature
Project description:The prevalence of metabolically unhealthy phenotype in normal-weight adults is 30%, and few studies have explored the association between metabolic phenotype and colorectal cancer incidence in normal-weight individuals. Our aim was to compare the risk of colorectal cancer in normal-weight postmenopausal women who were characterized by either the metabolically healthy phenotype or the metabolically unhealthy phenotype.A large prospective cohort, the Women's Health Initiative, was used. The analytic sample included 5,068 postmenopausal women with BMI 18.5 to <25 kg/m2 Metabolic phenotype was defined using the Adult Treatment Panel-III definition, excluding waist circumference; therefore, women with one or none of the four components (elevated triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure, and elevated fasting glucose) were classified as metabolically healthy. Multivariable Cox proportional hazards regression was used to estimate adjusted HRs for the association between metabolic phenotype and risk of colorectal cancer.Among normal-weight women, those who were metabolically unhealthy had higher risks of colorectal cancer (HR, 1.49; 95% CI, 1.02-2.18) compared with those who were metabolically healthy.A metabolically unhealthy phenotype was associated with higher risk of colorectal cancer among normal-weight women.Normal-weight women should still be evaluated for metabolic health and appropriate steps taken to reduce their risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 155-61. ©2017 AACR.
| S-EPMC5301805 | biostudies-literature