Plasma sex hormones and risk of conventional and serrated precursors of colorectal cancer in postmenopausal women.
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ABSTRACT: Background
Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown.Methods
We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P?ResultsDuring 20?years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend ConclusionsThe findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.
SUBMITTER: Hang D
PROVIDER: S-EPMC7841996 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Plasma sex hormones and risk of conventional and serrated precursors of colorectal cancer in postmenopausal women.
Hang Dong D He Xiaosheng X Kværner Ane Sørlie AS Chan Andrew T AT Wu Kana K Ogino Shuji S Hu Zhibin Z Shen Hongbing H Giovannucci Edward L EL Song Mingyang M
BMC medicine 20210128 1
<h4>Background</h4>Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown.<h4>Methods</h4>We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from th ...[more]
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Project description:BackgroundPhosphodiesterase 5 (PDE5) inhibitors have been hypothesized to have chemoprotective effects in colorectal cancer. Current population-based epidemiologic evidence is, however, limited and inconsistent.MethodsAmong 18,123 men in the Health Professionals Follow-up Study who had at least one lower gastrointestinal endoscopy, we evaluated the association between PDE5 inhibitor use and risk of conventional adenoma and serrated lesion between 2000 and 2010, adjusted for repeated observations and multiple risk factors. We stratified by erectile dysfunction to account for potential "confounding by indication."ResultsWe documented 2,595 conventional adenomas and 1,395 serrated lesion polyps during the follow-up period. Using people without erectile dysfunction as reference group, recent PDE5 inhibitor use at baseline was not associated with lower risk of conventional adenoma [erectile dysfunction with PDE5 inhibitors: OR = 1.08; 95% confidence interval (CI) = 0.92-1.26; erectile dysfunction without PDE5 inhibitors: OR = 0.95; 95% CI, 0.85-1.06], serrated lesions (erectile dysfunction with PDE5 inhibitors: OR = 1.19; 95% CI = 0.97-1.45; erectile dysfunction without PDE5 inhibitors: OR = 1.03; 95% CI = 0.89-1.19), or advanced conventional adenomas (erectile dysfunction with PDE5 inhibitors: OR = 1.20; 95% CI = 0.94-1.53; erectile dysfunction without PDE5 inhibitors: OR = 0.95; 95% CI = 0.79-1.14). No association was found for PDE5 inhibitor use ever before as well.ConclusionsWe found no evidence of an association between PDE5 inhibitor use and risk of conventional and serrated precursors of colorectal cancer.ImpactWe show that PDE5 inhibitor use is not associated with precursors of colorectal cancer adjusted for medical and lifestyle risk factors among a large population of men with 10 years of follow-up.
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Project description:ObjectiveThe consumption of dairy is associated with decreased risk of colorectal cancer (CRC), but few studies have assessed the relationship between dairy consumption and precursors of CRC. Therefore, we performed the first meta-analysis to further evaluate this association.MethodsPubMed, Embase, Scopus, and Web of Science databases were searched through July 2020 for observational studies. Study-specific risk estimates for the highest versus lowest category were pooled using the random-effects and fixed-effects model. The methodological quality of included studies was assessed using the ROBINS-I Scale.ResultsA total of 12 studies were included (3 cohort studies and 9 case-control studies). Compared with the lowest level consumption, fermented dairy products had a decreased risk of precursors of CRC in both cohort (RR = 0.92 95% CI: 0.87-0.97) and case-control studies (RR = 0.98 95% CI: 0.96-0.99). Total dairy (RR = 0.80 95% CI: 0.68-0.96) and cheese (RR = 0.96 95% CI: 0.93-0.99) consumption was inversely associated with the risk in case-control studies whereas yogurt consumption was inversely associated with the risk in cohort studies (RR = 0.91 95%CI: 0.86-0.96). No significant associations were found for consumption of total milk and non/low-fat milk. For dose-response analyses, evidence of linear association was found in total dairy and yogurt consumption. The risk decreased by 12% for an increment of 200 g/d total dairy consumption (RR = 0.88 95% CI: 0.81-0.95) and decreased by 8% for an increment of 50 g/d yogurt consumption (RR = 0.92 95% CI: 0.85-0.99).ConclusionsFermented dairy products, specifically yogurt and cheese, were significantly associated with decreased risk of conventional and serrated precursors of colorectal cancer.
| S-EPMC8172303 | biostudies-literature
Project description:Sex hormones, adipokines, and ghrelin have been implicated in central control of appetite, energy homeostasis, maintenance of fat mass, and inflammation. Women tend to gain weight after menopause and adipose tissue is a major source of sex steroid postmenopause. Understanding the dynamics of these analytes are of particular importance in postmenopausal women, who are at greater risk for cardiometabolic diseases.This study sought to evaluate the associations of adipokines and ghrelin with sex hormone concentrations in postmenopausal women.We conducted a cross-sectional analysis of baseline clinical trial data.The parent trial was conducted at a university clinical research facility.Baseline data from 634 postmenopausal women participating in the Early vs Late Intervention Trial with Estradiol (ELITE). PARTICIPANTS had no history of chronic illness in the past 5 years and were not taking exogenous hormone therapy.Serum levels of estrone (E1), total estradiol (E2), free estradiol (FE2), free testosterone (FT), total testosterone (T), and sex hormone-binding globulin (SHBG).Adjusted for age, race, time since menopause, and body mass index (BMI), leptin concentrations were significantly positively associated with E1, E2, FE2, and FT and inversely associated with SHBG levels. Only the associations of adiponectin with FE2 (inverse) and SHBG (positive) remained significant after controlling for BMI. The inverse associations of adiponectin with E1, E2, and FT were substantially mediated by BMI. Associations of ghrelin with E1, E2, FE2, and SHBG were not independent of BMI. Waist-to-hip circumference ratio was not a mediator in any of the associations.In postmenopausal women, leptin and adiponectin concentrations are substantially correlated with sex hormone and SHBG concentrations regardless of obesity status.
| S-EPMC4318897 | biostudies-literature
Project description:ContextSex differences exist in heart failure (HF) phenotypes, but there is limited research on the role of sex hormones in HF and its subtypes.ObjectiveTo examine the associations of total testosterone, dehydroepiandrosterone sulfate (DHEA-S), and sex hormone-binding globulin (SHBG) with incident HF, HF with preserved ejection fraction (HFpEF), and HF with reduced ejection fraction (HFrEF).DesignAtherosclerosis Risk in Communities (ARIC) study (prospective cohort study). Median follow-up is 19.2 years.SettingGeneral community.Participants4107 men and 4839 postmenopausal women, with mean age of 63.2 (standard deviation [SD] 5.7) and 62.8 (5.5) years, respectively.ExposurePlasma sex hormone levels were measured at visit 4 (1996-1998).Main outcome measuresIncident HF events were identified through hospital discharge codes and death certificates.ResultsThe Hazard Ratios for HF associated with 1 SD decrease in log-transformed total testosterone, DHEA-S, and SHBG were 1.10 (95% confidence interval 1.03, 1.17), 1.07 (1.00, 1.15), and 1.04 (0.96, 1.11) in men, and 1.05 (0.99, 1.13), 1.17 (1.09, 1.24), and 0.93 (0.85, 1.01) in women, respectively. The associations between sex hormones with subtypes of HF had similar patterns but were attenuated and became statistically insignificant.ConclusionIn this prospective cohort, lower levels of endogenous testosterone and DHEA-S in men and DHEA-S in postmenopausal women were associated with the development of HF. Similar directions of association in both sexes and both HF subtypes suggest that sex hormones play a role in the development of HF through common pathways regardless of sex.
| S-EPMC7455306 | biostudies-literature
Project description:How metabolome changes influence the early process of colorectal cancer (CRC) development remains unknown. We conducted a 1:2 matched nested case-control study to examine the associations of pre-diagnostic plasma metabolome (profiled using LC-MS) with risk of CRC precursors, including conventional adenomas (n = 586 vs. 1141) and serrated polyps (n = 509 vs. 993), in the Nurses' Health Study (NHS) and NHSII. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). We used the permutation-based Westfall and Young approach to account for multiple testing. Subgroup analyses were performed for advanced conventional adenomas (defined as at least one adenoma of ≥ 10 mm or with high-grade dysplasia, or tubulovillous or villous histology) and high-risk serrated polyps that were located in the proximal colon or with size of ≥ 10 mm. After multiple testing correction, among 207 metabolites, higher levels of C36:3 phosphatidylcholine (PC) plasmalogen were associated with lower risk of conventional adenomas, with the OR (95% CI) comparing the 90th to the 10th percentile of 0.62 (0.48-0.81); C54:8 triglyceride (TAG) was associated with higher risk of serrated polyps (OR = 1.79, 95% CI: 1.31-2.43), and phenylacetylglutamine (PAG) was associated with lower risk (OR = 0.57, 95% CI:0.43-0.77). PAG was also inversely associated with advanced adenomas (OR = 0.57, 95% CI: 0.36-0.89) and high-risk serrated polyps (OR = 0.54, 95% CI: 0.32-0.89), although the multiple testing-corrected p value was > 0.05. Our findings suggest potential roles of lipid metabolism and phenylacetylglutamine, a microbial metabolite, in the early stage of colorectal carcinogenesis, particularly for the serrated pathway.
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Project description:BACKGROUND & AIMS:Serrated polyps (SPs) and conventional adenomas are precursor lesions for colorectal cancer (CRC), but they are believed to arise via distinct pathways. We characterized risk factor profiles for SPs and conventional adenomas in a post hoc analysis of data from 3 large prospective studies. METHODS:We collected data from the Nurses' Health Study, the Nurses' Health Study 2, and the Health Professionals Follow-up Study on subjects who developed SPs or conventional adenomas. Our analysis comprised 141,143 participants who had undergone lower gastrointestinal endoscopy, provided updated diet and lifestyle data every 2-4 years, and were followed until diagnosis of a first polyp. We assessed 13 risk factors for CRC in patients with SPs or conventional adenomas and examined the associations according to histopathology features. RESULTS:We documented 7945 SPs, 9212 conventional adenomas, and 2382 synchronous SPs and conventional adenomas during 18-20 years of follow-up. Smoking, body mass index, alcohol intake, family history of CRC, and height were associated with higher risk of SPs and conventional adenomas, whereas higher intake of vitamin D and marine omega-3 fatty acid were associated with lower risk. The associations tended to be stronger for synchronous SPs and conventional adenomas. Smoking, body mass index, and alcohol intake were more strongly associated with SPs than conventional adenomas (P for heterogeneity <.05), whereas physical activity and intake of total folate and calcium were inversely associated with conventional adenomas but not SPs. For SPs and conventional adenomas, the associations tended to be stronger for polyps in the distal colon and rectum, of 10 mm or larger or with advanced histology. CONCLUSIONS:In an analysis of data from 3 large prospective studies, we found that although SPs and conventional adenomas share many risk factors, some factors are more strongly associated with one type of lesion than the other. These findings provide support for the etiologic heterogeneity of colorectal neoplasia.
| S-EPMC6067965 | biostudies-literature
Project description:BackgroundPostmenopausal hormone therapy use has been associated with lower colorectal cancer risk in observational studies. However, the role of endogenous sex hormones in colorectal cancer development in postmenopausal women is uncertain.MethodsThe relation of colorectal cancer risk with circulating levels of estradiol, estrone, free (bioactive) estradiol, progesterone and sex hormone-binding globulin (SHBG) was determined in a nested case-control study of 1203 postmenopausal women (401 case patients and 802 age and race/ethnicity-matched control patients) enrolled in the Women's Health Initiative Clinical Trial (WHI-CT) who were not assigned to the estrogen-alone or combined estrogen plus progestin intervention groups. We used multivariable-adjusted conditional logistic regression models that included established colorectal cancer risk factors. All statistical tests were two-sided.ResultsComparing extreme quartiles, estrone (odds ratio [OR]q4-q1 = 0.44, 95% confidence interval [CI] = 0.28 to 0.68, P trend = .001), free estradiol (ORq4-q1 = 0.43, 95% CI = 0.27 to 0.69, P trend ? .0001), and total estradiol (ORq4-q1 = 0.58, 95% CI = 0.38 to 0.90, P trend = .08) were inversely associated with colorectal cancer risk. SHBG levels were positively associated with colorectal cancer development (OR[q4-q1] = 2.30, 95% CI = 1.51 to 3.51, P trend ? .0001); this association strengthened after further adjustment for estradiol and estrone (ORq4-q1 = 2.50, 95% CI = 1.59 to 3.92, P trend < .0001). Progesterone was not associated with colorectal cancer risk.ConclusionEndogenous estrogen levels were inversely, and SHBG levels positively, associated with colorectal cancer risk, even after control for several colorectal cancer risk factors. These results suggest that endogenous estrogens may confer protection against colorectal tumorigenesis among postmenopausal women.
| S-EPMC5964717 | biostudies-literature
Project description:Sex steroid hormones have been postulated to involve in blood pressure (BP) regulation. We examine the association of endogenous sex hormone levels with longitudinal change of BP and risk of developing hypertension in initially normotensive postmenopausal women.We conducted prospective analysis among 619 postmenopausal women free of hypertension at baseline in the Multi-Ethnic Study of Atherosclerosis (MESA). Change of BP and development of incident hypertension were assessed during a mean of 4.8 years follow-up.After adjusting for age, race/ethnicity, and lifestyle factors, baseline serum estradiol (E(2)), total and bioavailable testosterone (T), dehydroepiandrosterone (DHEA) were each positively associated and sex-hormone binding globulin (SHBG) was inversely associated with risk of hypertension. Additional adjustment for body mass index eliminated the associations for E(2) and T but only attenuated the associations for DHEA and SHBG. The corresponding multivariable hazard ratios (95% CIs) in the highest quartile were 1.28 (0.83-1.97) for E(2), 1.38 (0.89-2.14) for total T, 1.42 (0.90-2.23) for bioavailable T, 1.54 (1.02-2.31) for DHEA, and 0.48 (0.30-0.76) for SHBG. Adjustment for fasting glucose, insulin, and C-reactive protein further attenuated the association for DHEA but not for SHBG. Associations of sex hormones with longitudinal BP change were similar.In postmenopausal women, higher endogenous E(2), T, and DHEA and lower SHBG were associated with higher incidence of hypertension and greater longitudinal rise in BP. The associations for E(2), T, and DHEA were mostly explained by adiposity, while the association for SHBG was independent of measures of adiposity, insulin resistance, and systemic inflammation.
| S-EPMC3428144 | biostudies-literature
Project description:Background & aimsEndoscopic screening reduces incidence and mortality of colorectal cancer (CRC) because precursor lesions, such as conventional adenomas or serrated polyps, are removed. Individuals with polypectomies are advised to undergo colonoscopy surveillance to prevent CRC. However, guidelines for surveillance intervals after diagnosis of a precursor lesion, particularly for individuals with serrated polyps, vary widely, and lack sufficient supporting evidence. Consequently, some high-risk patients do not receive enough surveillance and lower-risk subjects receive excessive surveillance.MethodsWe examined the association between findings from first endoscopy and CRC risk among 122,899 participants who underwent flexible sigmoidoscopy or colonoscopy in the Nurses' Health Study 1 (1990-2012), Nurses' Health Study 2 (1989-2013), or the Health Professionals Follow-up Study (1990-2012). Endoscopic findings were categorized as no polyp, conventional adenoma, or serrated polyp (hyperplastic polyp, traditional serrated adenoma, or sessile serrated adenoma, with or without cytological dysplasia). Conventional adenomas were classified as advanced (≥10 mm, high-grade dysplasia, or tubulovillous or villous histology) or nonadvanced, and serrated polyps were assigned to categories of large (≥10 mm) or small (<10 mm). We used a Cox proportional hazards regression model to calculate the hazard ratios (HRs) of CRC incidence, after adjusting for various potential risk factors.ResultsAfter a median follow-up period of 10 years, we documented 491 incident cases of CRC: 51 occurred in 6161 participants with conventional adenomas, 24 in 5918 participants with serrated polyps, and 427 in 112,107 participants with no polyp. Compared with participants with no polyp detected during initial endoscopy, the multivariable HR for incident CRC in individuals with an advanced adenoma was 4.07 (95% confidence interval [CI] 2.89-5.72) and the HR for CRC in individuals with a large serrated polyp was 3.35 (95% CI 1.37-8.15). In contrast, there was no significant increase in risk of CRC in patients with nonadvanced adenomas (HR 1.21; 95% CI 0.68-2.16, P = .52) or small serrated polyps (HR 1.25; 95% CI 0.76-2.08; P = .38).ConclusionsThese findings provide support for guidelines that recommend repeat lower endoscopy within 3 years of a diagnosis of advanced adenoma and large serrated polyps. In contrast, patients with nonadvanced adenoma or small serrated polyps may not require more intensive surveillance than patients without polyps.
| S-EPMC6954345 | biostudies-literature
Project description:The aim of the study was to compare the effects of vitamin D3 supplementation versus placebo on serum sex hormones in postmenopausal women completing a 12-month diet + exercise weight loss program.Two hundred eighteen overweight or obese women (50-75 y) with serum 25-hydroxyvitamin D at least 10 to less than 32?ng/mL ("insufficient") were randomized to either weight loss + 2,000?IU/day oral vitamin D3, or to weight loss + daily placebo. Serum sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone were measured by radioimmunoassay before randomization and at 12 months. Mean changes were compared between groups (intent-to-treat) using generalized estimating equations.The 12-month changes in sex hormone-binding globulin, estrone, total, free, and bioavailable estradiol, and testosterone did not differ between groups (all P?>?0.05). However, a greater increase in serum 25-hydroxyvitamin D was associated with a greater increase in sex hormone-binding globulin (Ptrend?=?0.01), and larger decreases in free and bioavailable estradiol (Ptrend?=?0.04, Ptrend?=?0.03, respectively). In post-hoc analyses, we compared women randomized to vitamin D whose serum 25-hydroxyvitamin D remained insufficient (n?=?38), to women who became replete (25-hydroxyvitamin D ?32?ng/mL; n?=?53). Replete women showed greater reductions in bioavailable estradiol (-1.8 vs -0.7?pg/mL), free testosterone (-0.8 vs -0.3?pg/mL), and bioavailable testosterone (-1.8 vs -0.6?ng/dL), and a greater increase in sex hormone-binding globulin (10.6 vs 4.7?nmol/L) (all P?<?0.05), even after adjusting for differences in total 12-month weight loss.Overall, 12-month changes in sex hormone did not differ between groups. However, vitamin D repletion was associated with greater reductions in sex hormones during weight loss, with a possible dose-dependent effect. Future studies should test higher doses and target circulating 25-hydroxyvitamin D levels when measuring such effects.
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