| 1. |
- Beal, Jacob, et al.
(author)
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Robust estimation of bacterial cell count from optical density
- 2020
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In: Communications Biology. - : Springer Science and Business Media LLC. - 2399-3642. ; 3:1
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Journal article (peer-reviewed)abstract
- Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data.
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| 2. |
- Hollestelle, Antoinette, et al.
(author)
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No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer
- 2016
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In: Gynecologic Oncology. - : Elsevier BV. - 0090-8258 .- 1095-6859. ; 141:2, s. 386-401
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Journal article (peer-reviewed)abstract
- Objective Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3′ UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. Methods Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). Results We found no association with risk of ovarian cancer (OR = 0.99, 95% CI 0.94-1.04, p = 0.74) or breast cancer (OR = 0.98, 95% CI 0.94-1.01, p = 0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR = 1.09, 95% CI 0.97-1.23, p = 0.14, breast cancer HR = 1.04, 95% CI 0.97-1.12, p = 0.27; BRCA2, ovarian cancer HR = 0.89, 95% CI 0.71-1.13, p = 0.34, breast cancer HR = 1.06, 95% CI 0.94-1.19, p = 0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR = 0.94, 95% CI 0.83-1.07, p = 0.38), breast cancer (HR = 0.96, 95% CI 0.87-1.06, p = 0.38), and all other previously-reported associations. Conclusions rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
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| 3. |
- Lawrenson, Kate, et al.
(author)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Journal article (peer-reviewed)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 4. |
- Bellenguez, Celine, et al.
(author)
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Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke
- 2012
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In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:3, s. 141-328
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Journal article (peer-reviewed)abstract
- Genetic factors have been implicated in stroke risk, but few replicated associations have been reported. We conducted a genome-wide association study (GWAS) for ischemic stroke and its subtypes in 3,548 affected individuals and 5,972 controls, all of European ancestry. Replication of potential signals was performed in 5,859 affected individuals and 6,281 controls. We replicated previous associations for cardioembolic stroke near PITX2 and ZFHX3 and for large vessel stroke at a 9p21 locus. We identified a new association for large vessel stroke within HDAC9 (encoding histone deacetylase 9) on chromosome 7p21.1 (including further replication in an additional 735 affected individuals and 28,583 controls) (rs11984041; combined P = 1.87 x 10(-11); odds ratio (OR) = 1.42, 95% confidence interval (CI) = 1.28-1.57). All four loci exhibited evidence for heterogeneity of effect across the stroke subtypes, with some and possibly all affecting risk for only one subtype. This suggests distinct genetic architectures for different stroke subtypes.
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| 5. |
- Fortner, Renée T., et al.
(author)
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Ovarian cancer risk factors by tumor aggressiveness : An analysis from the Ovarian Cancer Cohort Consortium
- 2019
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In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 145:1, s. 58-69
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Journal article (peer-reviewed)abstract
- Ovarian cancer risk factors differ by histotype; however, within subtype, there is substantial variability in outcomes. We hypothesized that risk factor profiles may influence tumor aggressiveness, defined by time between diagnosis and death, independent of histology. Among 1.3 million women from 21 prospective cohorts, 4,584 invasive epithelial ovarian cancers were identified and classified as highly aggressive (death in <1 year, n = 864), very aggressive (death in 1 to < 3 years, n = 1,390), moderately aggressive (death in 3 to < 5 years, n = 639), and less aggressive (lived 5+ years, n = 1,691). Using competing risks Cox proportional hazards regression, we assessed heterogeneity of associations by tumor aggressiveness for all cases and among serous and endometrioid/clear cell tumors. Associations between parity (phet = 0.01), family history of ovarian cancer (phet = 0.02), body mass index (BMI; phet ≤ 0.04) and smoking (phet < 0.01) and ovarian cancer risk differed by aggressiveness. A first/single pregnancy, relative to nulliparity, was inversely associated with highly aggressive disease (HR: 0.72; 95% CI [0.58-0.88]), no association was observed for subsequent pregnancies (per pregnancy, 0.97 [0.92-1.02]). In contrast, first and subsequent pregnancies were similarly associated with less aggressive disease (0.87 for both). Family history of ovarian cancer was only associated with risk of less aggressive disease (1.94 [1.47-2.55]). High BMI (≥35 vs. 20 to < 25 kg/m2 , 1.93 [1.46-2.56] and current smoking (vs. never, 1.30 [1.07-1.57]) were associated with increased risk of highly aggressive disease. Results were similar within histotypes. Ovarian cancer risk factors may be directly associated with subtypes defined by tumor aggressiveness, rather than through differential effects on histology. Studies to assess biological pathways are warranted.
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| 6. |
- Jennings, Eleanor, et al.
(author)
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From Highs to Lows : Changes in Dissolved Organic Carbon in a Peatland Catchment and Lake Following Extreme Flow Events
- 2020
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In: Water. - : MDPI AG. - 2073-4441. ; 12:10
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Journal article (peer-reviewed)abstract
- The concentration of dissolved organic carbon (DOC) in freshwater catchments has implications for carbon availability in downstream lakes and for water supplies. The links between catchment hydrology and stream and lake DOC concentrations are, however, still not fully understood. Much of the literature has been from catchments with organo-mineral soils, with fewer studies from upland peat sites. We used high-frequency fluorescence data, a proxy for DOC, to investigate 1. the relationship between stream discharge and concentration in a blanket peat catchment during extreme high flows and 2. the relationship between inflow and in-lake estimated DOC concentrations. We found that for approximately two thirds of extreme events, there was a decrease in stream DOC concentration (i.e., a dilution) on the rising limb rather than an increase (i.e., a flushing out of DOC from terrestrial stores). Flushing events dominated only in summer when concentrations in the stream were also increasing. In comparison to the stream, concentrations in the downstream lake were less variable, and peaks and troughs were damped and lagged. Replicating these patterns and processes in DOC models would be critical in order to provide appropriate simulations in response to shorter- and longer-term changes in climate, and thus inform future catchment and lake management.
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| 7. |
- Ose, Jennifer, et al.
(author)
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Androgens Are Differentially Associated with Ovarian Cancer Subtypes in the Ovarian Cancer Cohort Consortium
- 2017
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In: Cancer Research. - 0008-5472 .- 1538-7445. ; 77:14, s. 3951-3960
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Journal article (peer-reviewed)abstract
- Invasive epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. The etiology of EOC remains elusive; however, experimental and epidemiologic data suggest a role for hormone-related exposures in ovarian carcinogenesis and risk factor differences by histologic phenotypes and developmental pathways. Research on prediagnosis androgen concentrations and EOC risk has yielded inconclusive results, and analyses incorporating EOC subtypes are sparse. We conducted a pooled analysis of 7 nested case–control studies in the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis circulating androgens [testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate (DHEAS)], sex hormone binding globulin (SHBG), and EOC risk by tumor characteristics (i.e., histology, grade, and stage). The final study population included 1,331 EOC cases and 3,017 matched controls. Multivariable conditional logistic regression was used to assess risk associations in pooled individual data. Testosterone was positively associated with EOC risk (all subtypes combined, ORlog2 = 1.12; 95% confidence interval 1.02–1.24); other endogenous androgens and SHBG were not associated with overall risk. Higher concentrations of testosterone and androstenedione associated with an increased risk in endometrioid and mucinous tumors [e.g., testosterone, endometrioid tumors, ORlog2 = 1.40 (1.03–1.91)], but not serous or clear cell. An inverse association was observed between androstenedione and high grade serous tumors [ORlog2 = 0.76 (0.60–0.96)]. Our analyses provide further evidence for a role of hormone-related pathways in EOC risk, with differences in associations between androgens and histologic subtypes of EOC.
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| 8. |
- Ose, Jennifer, et al.
(author)
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Pre-diagnosis insulin-like growth factor-I and risk of epithelial invasive ovarian cancer by histological subtypes : A collaborative re-analysis from the Ovarian Cancer Cohort Consortium
- 2017
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In: Cancer Causes and Control. - : SPRINGER. - 0957-5243 .- 1573-7225. ; 28:5, s. 429-435
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Journal article (peer-reviewed)abstract
- Biologic evidence suggests that the Insulin-like growth factor (IGF)-family may be involved in the etiology of epithelial invasive ovarian cancer (EOC). However, prospective studies investigating the role of IGF-I in ovarian carcinogenesis have yielded conflicting results. We pooled and harmonized data from 6 case-control studies nested within the Ovarian Cancer Cohort Consortium to investigate the association between pre-diagnosis IGF-I concentrations and subsequent risk of EOC. We evaluated IGF-I concentrations and risk of EOC overall and by tumor subtype (defined by histology, grade, stage) in 1,270 cases and 2,907 matched controls. Multivariable conditional logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). Doubling of IGF-I concentration was associated with significantly lower risk of overall EOC [ORlog2 = 0.82; CI 0.72-0.93]. We observed no heterogeneity by tumor characteristics (e.g., histology, p (het) = 0.62), menopausal status at blood collection (p (het) = 0.79), or age at diagnosis (p (het) = 0.60). These results suggest that IGF-I concentrations are inversely associated with EOC risk, independent of histological phenotype. Future prospective research should consider potential mechanisms for this association, including, considering other members of the IGF-family to better characterize the role of IGF-signaling in the etiology of EOC.
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| 9. |
- Peres, Lauren C, et al.
(author)
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High Levels of C-Reactive Protein Are Associated with an Increased Risk of Ovarian Cancer : Results from the Ovarian Cancer Cohort Consortium
- 2019
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In: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 79:20, s. 5442-5451
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Journal article (peer-reviewed)abstract
- Growing epidemiologic evidence supports chronic inflammation as a mechanism of ovarian carcinogenesis. An association between a circulating marker of inflammation, C-reactive protein (CRP), and ovarian cancer risk has been consistently observed, yet, potential heterogeneity of this association by tumor and patient characteristics has not been adequately explored. In this study, we pooled data from case-control studies nested within six cohorts in the Ovarian Cancer Cohort Consortium (OC3) to examine the association between CRP and epithelial ovarian cancer risk overall, by histologic subtype and by participant characteristics. CRP concentrations were measured from prediagnosis serum or plasma in 1,091 cases and 1,951 controls. Multivariable conditional logistic regression was used to estimate ORs and 95% confidence intervals (CI). When CRP was evaluated using tertiles, no associations with ovarian cancer risk were observed. A 67% increased ovarian cancer risk was found for women with CRP concentrations >10 mg/L compared with <1 mg/L (OR = 1.67; 95% CI = 1.12-2.48). A CRP concentration >10 mg/L was positively associated with risk of mucinous (OR = 9.67; 95% CI = 1.10-84.80) and endometrioid carcinoma (OR = 3.41; 95% CI = 1.07-10.92), and suggestively positive, although not statistically significant, for serous (OR = 1.43; 95% CI = 0.82-2.49) and clear cell carcinoma (OR = 2.05; 95% CI = 0.36-11.57; P heterogeneity = 0.20). Heterogeneity was observed with oral contraceptive use (P interaction = 0.03), where the increased risk was present only among ever users (OR = 3.24; 95% CI = 1.62-6.47). This study adds to the existing evidence that CRP plays a role in ovarian carcinogenesis and suggests that inflammation may be particularly implicated in the etiology of endometrioid and mucinous carcinoma. SIGNIFICANCE: C-reactive protein is involved in ovarian carcinogenesis, and chronic inflammation may be particularly implicated in the etiology of mucinous and endometrioid carcinomas.
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| 10. |
- Rannikmaee, Kristiina, et al.
(author)
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Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease
- 2015
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In: Neurology. - 1526-632X. ; 84:9, s. 918-926
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Journal article (peer-reviewed)abstract
- Objectives:We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.Methods:We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).Results:Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.Conclusions:Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.
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| 11. |
- Ryder, Elizabeth, et al.
(author)
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Reply to a comment by Watras et al. (2014) on temperature compensation method for field measurements of CDOM fluorescence
- 2015
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In: Limnology and Oceanography. - : Wiley. - 1541-5856. ; 13:10, s. 527-528
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Journal article (peer-reviewed)abstract
- The recent comment by Watras et al. (2014) clarifies the calculation of the temperature correction coefficient (rho) in Watras et al. (2011). Based on this clarification, we accept that the equation to compensate for temperature quenching of chromophoric dissolved organic matter (CDOM) fluorescence presented in Ryder et al. (2012) and the equation proposed in Watras et al. (2011) are mathematically equivalent.
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| 12. |
- Ryder, Elizabeth, et al.
(author)
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Temperature quenching of CDOM fluorescence sensors : temporal and spatial variability in the temperature response and a recommended temperature correction equation
- 2012
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In: Limnology and Oceanography. - : Wiley. - 1541-5856. ; 10, s. 1004-1010
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Journal article (peer-reviewed)abstract
- Field-based instruments measuring chromophoric dissolved organic matter (CDOM) fluorescence are often used as a proxy for dissolved organic carbon concentrations in lakes and streams. CDOM fluorescence yield is, however, affected by water temperature at the time of measurement, a factor which varies on both diel and seasonal timescales. A temperature correction must therefore be applied to these data. We present data on temporal and site-specific variability in temperature quenching of CDOM fluorescence for water from a humic lake and one of its main inflows in the west of Ireland. In addition, we present a temperature compensation equation and show that this equation is an improvement on methods previously proposed.
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| 13. |
- Stegmayr, Bernd, 1949-, et al.
(author)
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Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis
- 2021
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In: Transfusion Medicine and Hemotherapy. - : S. Karger. - 1660-3796 .- 1660-3818. ; 48:4, s. 234-239
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Research review (peer-reviewed)abstract
- Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. Conclusion: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects. (c) 2021 S. Karger AG, Basel
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| 14. |
- Trudel-Fitzgerald, Claudia, et al.
(author)
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The Association of Work Characteristics With Ovarian Cancer Risk and Mortality
- 2017
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In: Psychosomatic Medicine. - : Lippincott Williams & Wilkins. - 0033-3174 .- 1534-7796. ; 79:9, s. 1059-1067
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Journal article (peer-reviewed)abstract
- Objective: Ovarian cancer (OvCA) is a leading cause of cancer death for women. Depression and social isolation have been associated with a higher OvCA risk and poorer survival, but other forms of chronic psychosocial stress, including work-related characteristics, remain understudied. Methods: Women from three prospective cohorts (Nurses' Health Study: n = 31,754; Nurses' Health Study II: n = 74,260; Northern Sweden Health and Disease Study: n(nested case-control study) = 196) completed a job questionnaire, assessing demand and control at work, social support provided by coworkers and supervisor, and job security. Multivariate Cox and conditional logistic regression models estimated hazard ratios (Nurses' Health Study/Nurses' Health Study II) and odd ratios (Northern Sweden Health and Disease Study) of OvCA risk and mortality among cases. Random coefficient models were used for meta-analyses. Results: There were 396 OvCA cases and 186 deaths during follow-up. Overall, job strain, strain chronicity, social support, and job security were not significantly associated with OvCA risk (e.g., pooled relative risk [RR](high demand/low control) = 1.06, confidence interval [CI] = 0.72-1.55) or mortality (e.g., pooled RRhigh demand/low control = 1.08, CI = 0.64-1.82). When considered individually, compared with low levels, only moderate levels of demand were associated with a reduced OvCA risk (pooled RR = 0.66, CI = 0.49-0.90). Social support provided by the coworker or the supervisor did not moderate the association of job strain with either OvCA risk or overall mortality. Conclusions: We did not observe clear associations between work characteristics and OvCA incidence or mortality, but further research with diverse populations is warranted.
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| 15. |
- Vrielink, Hans, et al.
(author)
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The world apheresis association registry, 2023 update
- 2023
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In: Transfusion and apheresis science. - : Elsevier. - 1473-0502 .- 1878-1683. ; 62:6
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Research review (peer-reviewed)abstract
- The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs).Material and Methods: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.orgResults: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018–2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0–94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%).Conclusion: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.
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| 16. |
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| 17. |
- Wentzensen, Nicolas, et al.
(author)
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Ovarian Cancer Risk Factors by Histologic Subtype : An Analysis From the Ovarian Cancer Cohort Consortium
- 2016
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In: Journal of Clinical Oncology. - : AMER SOC CLINICAL ONCOLOGY. - 0732-183X .- 1527-7755. ; 34:24, s. 2888-2898
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Journal article (peer-reviewed)abstract
- Purpose: An understanding of the etiologic heterogeneity of ovarian cancer is important for improving prevention, early detection, and therapeutic approaches. We evaluated 14 hormonal, reproductive, and lifestyle factors by histologic subtype in the Ovarian Cancer Cohort Consortium (OC3).Patients and Methods: Among 1.3 million women from 21 studies, 5,584 invasive epithelial ovarian cancers were identified (3,378 serous, 606 endometrioid, 331 mucinous, 269 clear cell, 1,000 other). By using competing-risks Cox proportional hazards regression stratified by study and birth year and adjusted for age, parity, and oral contraceptive use, we assessed associations for all invasive cancers by histology. Heterogeneity was evaluated by likelihood ratio test.Results: Most risk factors exhibited significant heterogeneity by histology. Higher parity was most strongly associated with endometrioid (relative risk [RR] per birth, 0.78; 95% CI, 0.74 to 0.83) and clear cell (RR, 0.68; 95% CI, 0.61 to 0.76) carcinomas (P value for heterogeneity [P-het] < .001). Similarly, age at menopause, endometriosis, and tubal ligation were only associated with endometrioid and clear cell tumors (P-het ≤ .01). Family history of breast cancer (P-het = .008) had modest heterogeneity. Smoking was associated with an increased risk of mucinous (RR per 20 pack-years, 1.26; 95% CI, 1.08 to 1.46) but a decreased risk of clear cell (RR, 0.72; 95% CI, 0.55 to 0.94) tumors (P-het = .004). Unsupervised clustering by risk factors separated endometrioid, clear cell, and low-grade serous carcinomas from high-grade serous and mucinous carcinomas.Conclusion: The heterogeneous associations of risk factors with ovarian cancer subtypes emphasize the importance of conducting etiologic studies by ovarian cancer subtypes. Most established risk factors were more strongly associated with nonserous carcinomas, which demonstrate challenges for risk prediction of serous cancers, the most fatal subtype.
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| 18. |
- Yang, Meng, et al.
(author)
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Prediagnosis leukocyte telomere length and risk of ovarian cancer
- 2016
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In: Clinical Cancer Research. - : American Association for Cancer Research. - 1078-0432 .- 1557-3265. ; 22
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Journal article (other academic/artistic)abstract
- Introduction: Ovarian cancer is characterized by substantial genomic instability. Telomeres, which protect the physical integrity of chromosomes, are shortened by each cell division, and evidence supports that longer telomeres may reduce genomic instability. While retrospective studies generally support an inverse association of telomere length and ovarian cancer risk, the measures of telomere length after diagnosis may be influenced by treatment. Therefore, we examined the relationship between leukocyte telomere length (LTL) assessed prior to diagnosis and risk of ovarian cancer in three prospective studies. Methods: We used buffy coat samples collected from healthy participants in the Nurses' Health Study (NHS), NHSII, and the Northern Sweden Health and Disease Study (NSHDS). Women who later developed ovarian cancer were matched to one or two controls on age, menopausal status, and date of blood collection. LTL was assessed using quantitative PCR-based assays in 5 batches with coefficients of variation of 10-15%. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression, based on study-specific quartiles in controls, for each study separately. We used fixed-effects models for meta-analysis. Multivariate models adjusted for oral contraceptive use, tubal ligation, family history of ovarian cancer, parity, smoking status, and body mass index. Results: In total, there were 487 cases and 810 controls across the three studies. The mean age at blood collection ranged from 45 (NHSII) to 57 (NHS) years. In unadjusted and multivariate models, we observed a suggestion of an inverse association between LTL and ovarian cancer risk in each study, although none of the trend tests were statistically significant. In a meta-analysis of the multivariate adjusted models, women in the longest versus shortest quartile of LTL had a non-significant 26% lower risk of ovarian cancer (OR=0.74; 95%CI=0.49-1.12; p-trend=0.33). Conclusion: In this first prospective study of telomere length and ovarian cancer risk, we observed that longer leukocyte telomere length was suggestively associated with lower ovarian cancer risk. Given that serous tumors are more likely to exhibit genomic instability, we are currently evaluating the association for this subtype as well as conducting pooled analyses with common quartile cut points across studies.
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| 19. |
- Yang, Meng, et al.
(author)
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Prediagnosis Leukocyte Telomere Length and Risk of Ovarian Cancer
- 2017
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 26:3, s. 339-345
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Journal article (peer-reviewed)abstract
- Background: The associations between telomere length and cancer risk are equivocal, and none have examined the association between prediagnosis leukocyte telomere length (LTL) and the risk of developing ovarian cancer. Methods: We prospectively measured LTL collected from 442 ovarian cancer cases and 727 controls in the Nurses' Health Studies and the Northern Sweden Health and Disease Study. Cases were matched to one or two controls on age, menopausal status, and date of blood collection. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression. Results: LTL was measured a median of 9.5 years before ovarian cancer diagnosis among cases. We observed a decreased risk of ovarian cancer with longer LTL. In multivariable models, women in the top quartile of LTL had an OR for ovarian cancer of 0.67 (95% CI, 0.46-0.97) compared with those in the bottom quartile. Inverse associations were stronger for nonserous cases (ORquartile (4 vs. quartile 1 of LTL) = 0.55, 95% CI, 0.33-0.94) and rapidly fatal cases (i.e., cases who died within 3 years of diagnosis; ORquartile 4 vs. quartile 1 of LTL = 0.55, 95% CI, 0.32-0.95). Conclusions: Our prospective findings suggest that longer circulating LTL may be associated with a lower ovarian cancer risk, especially for nonserous and rapidly fatal cases. The evaluation of LTL in relation to ovarian cancer risk by tumor subtypes is warranted in larger prospective studies. Impact: Prediagnosis LTL may reflect an early event in the ovarian cancer development and could serve as a biomarker to predict future risk.
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