| 1. |
- Burke, Kristin E., et al.
(author)
-
Identification of Menopausal and Reproductive Risk Factors for Microscopic Colitis-Results From the Nurses' Health Study
- 2018
-
In: Gastroenterology. - : Saunders Elsevier. - 0016-5085 .- 1528-0012. ; 155:6, s. 1764-1775
-
Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: Microscopic colitis is a chronic inflammatory disorder of the colon primarily affecting postmenopausal women. However, the relation between hormonal determinants, including reproductive and menopausal factors, and risk of microscopic colitis has yet to be characterized.METHODS: We collected data from 227,766 women who participated in the Nurses' Health Study (NHS) and the NHSII without a baseline history of microscopic colitis. Reproductive and menopausal factors were assessed in 1988 in the NHS and 1989 in the NHSII and updated biennially. Cases of microscopic colitis were confirmed through review of pathology records. We used Cox proportional hazards modeling to estimate hazard ratios and 95% confidence intervals.RESULTS: Through 2014 in the NHS and 2015 in the NHSII, we confirmed 275 incident cases of microscopic colitis over 5,147,282 person-years. Compared with never use, current use of menopausal hormone therapy was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 2.64; 95% confidence interval 1.78-3.90). The risk increased with longer duration of use (P for trend < .0001) and decreased after discontinuation (P for trend = .002). The association did not differ according to disease subtype (P for heterogeneity = .34). Similarly, ever use of oral contraceptives was associated with increased risk of microscopic colitis (multivariable-adjusted hazard ratio 1.57; 95% confidence interval 1.16-2.13). There were no associations between age at menarche, parity, age at first birth, age at menopause, or menopause type and incident microscopic colitis.CONCLUSIONS: In 2 large prospective cohort studies, we observed an association between exogenous hormone use and incident microscopic colitis. Further studies are needed to determine the mechanisms underlying these associations.
|
|
| 2. |
- Jung, Seungyoun, et al.
(author)
-
Anti‐Müllerian hormone and risk of ovarian cancer in nine cohorts
- 2018
-
In: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 142:2, s. 262-270
-
Journal article (peer-reviewed)abstract
- Animal and experimental data suggest that anti‐Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case‐control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme‐linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable‐adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable‐adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59–1.67) (Ptrend: 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity: ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity: ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.
|
|
| 3. |
- Lu, Yingchang, et al.
(author)
-
A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.
- 2018
-
In: Cancer Research. - 0008-5472 .- 1538-7445. ; 78:18, s. 5419-5430
-
Journal article (peer-reviewed)abstract
- .AbstractLarge-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci. We used RNA sequencing data (68 normal ovarian tissue samples from 68 individuals and 6,124 cross-tissue samples from 369 individuals) and high-density genotyping data from European descendants of the Genotype-Tissue Expression (GTEx V6) project to build ovarian and cross-tissue models of genetically regulated expression using elastic net methods. We evaluated 17,121 genes for their cis-predicted gene expression in relation to EOC risk using summary statistics data from GWAS of 97,898 women, including 29,396 EOC cases. With a Bonferroni-corrected significance level of P < 2.2 × 10−6, we identified 35 genes, including FZD4 at 11q14.2 (Z = 5.08, P = 3.83 × 10−7, the cross-tissue model; 1 Mb away from any GWAS-identified EOC risk variant), a potential novel locus for EOC risk. All other 34 significantly associated genes were located within 1 Mb of known GWAS-identified loci, including 23 genes at 6 loci not previously linked to EOC risk. Upon conditioning on nearby known EOC GWAS-identified variants, the associations for 31 genes disappeared and three genes remained (P < 1.47 × 10−3). These data identify one novel locus (FZD4) and 34 genes at 13 known EOC risk loci associated with EOC risk, providing new insights into EOC carcinogenesis.Significance: Transcriptomic analysis of a large cohort confirms earlier GWAS loci and reveals FZD4 as a novel locus associated with EOC risk. Cancer Res; 78(18); 5419–30. ©2018 AACR.
|
|
