Endometriosis and Risk of Adverse Pregnancy Outcomes Farland, Leslie V; Prescott, Jennifer; Sasamoto, Naoko ...
Obstetrics and gynecology (New York. 1953),
2019-September, 2019-09-00, 20190901, Volume:
134, Issue:
3
Journal Article
Peer reviewed
Open access
OBJECTIVE:To investigate the relationship between endometriosis and adverse pregnancy outcomes.
METHODS:Women between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on ...pregnancies and reproductive health at baseline and every 2 years thereafter in the Nursesʼ Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman.
RESULTS:Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortionRR 1.40, 95% CI 1.31–1.49; ectopic pregnancyRR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45).
CONCLUSIONS:We observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.
BACKGROUND: Leukocyte telomere length is associated with diseases of aging, but there is limited knowledge of diet and lifestyle determinants. OBJECTIVE: The objective was to examine ...cross-sectionally the association between diet, body composition, and lifestyle factors on leukocyte telomere length in women. DESIGN: Leukocyte telomere length was measured by quantitative polymerase chain reaction in 2284 female participants from the Nurses' Health Study, who were selected as controls for an investigation of biological predictors of cancer. Diet, lifestyle, and anthropometric data were assessed by questionnaire. RESULTS: After multivariate adjustment, dietary fiber intake was positively associated with telomere length (z score), specifically cereal fiber, with an increase of 0.19 units between the lowest and highest quintiles (P = 0.007, P for trend = 0.03). Although total fat intake was not associated with telomere length, polyunsaturated fatty acid intake (-0.26 units, quintile 5 compared with quintile 1: P = 0.002, P for trend = 0.02), specifically linoleic acid intake, was inversely associated with telomere length after multivariate adjustment (-0.32 units; P = 0.001, P for trend = 0.05). Waist circumference was inversely associated with telomere length 0.15-unit difference in z score in a comparison of the highest (≥32 in, 81.28 cm) with the lowest (less-than or equal to28 in, 71.12 cm) category (P = 0.01, P for trend = 0.02) in the multivariate model. We found no association between telomere length and smoking, physical activity, or postmenopausal hormone use. CONCLUSION: Although the strength of the associations was modest in this population of middle- and older-age women, our results support the hypothesis that body composition and dietary factors are related to leukocyte telomere length, which is a potential biomarker of chronic disease risk.
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CMK, GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Telomere length is important in tumorigenesis. Using quantitative real-time PCR, we prospectively measured relative telomere length in a nested case–control study within the Nurses’ Health Study: 218 ...melanoma cases, 285 squamous-cell carcinoma (SCC) cases, 300 basal-cell carcinoma (BCC) cases, and 870 controls. We observed that shorter telomeres were associated with a decreased number of moles (P=0.002) and a decreased risk of melanoma. Women in the second and first quartiles, those with the shortest telomere length, had an odds ratio (OR) for melanoma of 0.54 (95% confidence interval (CI), 0.29–1.01) and 0.59 (95% CI, 0.31–1.13), respectively, compared with those in the fourth quartile (P, trend=0.09). There was no clear trend between telomere length and SCC risk. In contrast, we found that shorter telomere length was associated with an increased risk of BCC. Compared with those in the fourth quartile, women in the first quartile had an OR of 1.85 (95% CI, 0.94–3.62) (P, trend=0.09). The opposing associations observed should be interpreted with caution, and further research is needed to confirm these possible associations.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Whether a healthy lifestyle may be associated with longer telomere length is largely unknown.
To examine healthy lifestyle practices, which are primary prevention measures against major age-related ...chronic diseases, in relation to leukocyte telomere length.
Cross-sectional analysis in the Nurses' Health Study (NHS).
The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5-24.9 kg/m(2)), engaging in regular moderate or vigorous physical activities (≥150 minutes/week), drinking alcohol in moderation (1 drink/week to <2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest.
Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population) and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015) higher for women who had 1 to 5 low-risk factors, respectively.
Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abuse victimization in childhood is associated with a variety of age-related cardiometabolic diseases, but the mechanisms remain unknown. Telomeres, which form the protective caps at the ends of ...chromosomes, have been proposed as measures of biological age, and a growing body of research suggests that telomere attrition may help to explain relationships between stress and cardiometabolic degradation. We examined the association between childhood abuse victimization and leukocyte telomere length among 1,135 participants in the Nurses' Health Study II (NHSII).
The NHSII ascertained physical and sexual child abuse histories in 2001. Telomere length was measured in genomic DNA extracted from peripheral blood leukocytes collected between 1996 and 1999. The ratio of telomere repeat copy number to a single gene copy number (T/S) was determined by a modified version of the quantitative real-time PCR telomere assay. Telomere length was log-transformed and corrected for assay variation across batch. We regressed telomere length on childhood abuse exposure variables and covariates using linear regression.
We observed a reduction in telomere length associated with moderate physical abuse versus no physical abuse, but there was no evidence of a dose-response relationship for increased severity of physical abuse. No associations were noted for sexual abuse.
We found no evidence of an association between severity of childhood physical or sexual abuse and leukocyte telomere length in the NHSII.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Chronic psychological distress has been linked to shorter telomeres, an indication of accelerated aging. Yet, little is known about relations of anxiety to telomeres. We examined whether a typically ...chronic form of anxiety--phobic anxiety--is related to telomere length.
Relative telomere lengths (RTLs) in peripheral blood leukocytes were measured by quantitative real-time polymerase chain reaction among 5,243 women (aged 42-69 years) who: were participants in the Nurses' Health Study; were controls in prior case-control studies of telomeres and disease, or randomly selected healthy participants in a cognitive function sub-study; had completed the Crown-Crisp phobic index proximal to blood collection. Adjusted least-squares mean RTLs (z-scores) were calculated across phobic categories. Higher phobic anxiety was generally associated with lower RTLs (age-adjusted p-trend = 0.09); this association was similar after adjustment for confounders--paternal age-at-birth, smoking, body mass index (BMI) and physical activity (p-trend = 0.15). Notably, a threshold was identified. Among women with Crown-Crisp<6 points, the multivariable-adjusted least-squares mean RTL z-score = 0.02 standard units; however, among the most phobic women (Crown-Crisp ≥ 6), the multivariable-adjusted least-squares mean RTL z-score = -0.09 standard units (mean difference = -0.10 standard units; p = 0.02). The magnitude of this difference was comparable to that for women 6 years apart in age. Finally, effect modification by BMI, smoking and paternal age was observed: associations were stronger among highly phobic women with BMI ≥ 25 kg/m(2), without smoking history, or born to fathers aged ≥ 40 years.
In this large, cross-sectional study high phobic anxiety was associated with shorter telomeres. These results point toward prospective investigations relating anxiety to telomere length change.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
During breast cancer progression, a substantial increase in chromosomal aberrations is observed in the transition from ductal
hyperplasia to carcinoma in situ . Telomeres are essential structures to ...chromosomal integrity. Consequently, telomere dysfunction, which leads to genomic
instability, is hypothesized to play a causal role in the progression of breast cancer. However, the few epidemiologic studies
that have assessed the relationship between telomere length and breast cancer risk have been inconsistent. We used quantitative
real-time PCR to measure relative telomere length in genomic DNA extracted from peripheral blood leukocytes and examined its
association with postmenopausal breast cancer risk in 1,122 invasive breast cancer cases and 1,147 matched controls free of
diagnosed cancer nested within the prospective Nurses' Health Study. Our data show that relative telomere length was not associated
with a significant elevation in postmenopausal breast cancer risk below versus above median; odds ratio, 1.23; 95% confidence
interval, 0.94-1.60; P trend = 0.20. Estrone and estradiol hormone levels were significantly inversely associated with relative telomere length ( P = 0.02). Other established breast cancer risk factors such as family history of breast cancer and history of benign breast
disease were not associated with relative telomere length in separate linear regression models each adjusted for age and disease
status ( P ≥ 0.07). Our results provide little support for an important role of telomere length, as measured in peripheral blood leukocytes,
as a biomarker of breast cancer risk. (Cancer Epidemiol Biomarkers Prev 2009;18(4):1152–6)
Telomere function is essential to maintaining the physical integrity of linear chromosomes and healthy human aging. The probability of forming proper telomere structures depends on the length of the ...telomeric DNA tract. We attempted to identify common genetic variants associated with log relative telomere length using genome-wide genotyping data on 3,554 individuals from the Nurses' Health Study and the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial that took part in the National Cancer Institute Cancer Genetic Markers of Susceptibility initiative for breast and prostate cancer. After genotyping 64 independent SNPs selected for replication in additional Nurses' Health Study and Women's Genome Health Study participants, we did not identify genome-wide significant loci; however, we replicated the inverse association of log relative telomere length with the minor allele variant C of rs16847897 at the TERC locus (per allele β = -0.03, P = 0.003) identified by a previous genome-wide association study. We did not find evidence for an association with variants at the OBFC1 locus or other loci reported to be associated with telomere length. With this sample size we had >80% power to detect β estimates as small as ±0.10 for SNPs with minor allele frequencies of ≥0.15 at genome-wide significance. However, power is greatly reduced for β estimates smaller than ±0.10, such as those for variants at the TERC locus. In general, common genetic variants associated with telomere length homeostasis have been difficult to detect. Potential biological and technical issues are discussed.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aberrant signaling by the androgen receptor contributes to the initiation and progression of prostate cancer. The involvement of molecular chaperones in the processes of folding, activation, ...trafficking, and transcriptional activity of the androgen receptor provide different points along the signaling axis where regulation of androgen receptor activity can be hijacked to provide growth signals for clonal selection in cancer progression. Evidence exists of abnormal chaperone expression that could contribute to the upregulation of AR activity in prostate tumors. Regardless of whether chaperones are involved in the causation of prostate carcinogenesis, molecular chaperones provide therapeutic targets for the treatment of prostate cancer.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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