Faculty Bibliography
Searched for:
in-biosketch:yes
person:jacqua02
Total Results:
333
Endogenous sex steroid hormones and risk of liver cancer among US men: Results from the Liver Cancer Pooling Project
BACKGROUND & AIMS/UNASSIGNED:Incidence rates of liver cancer in most populations are two to three times higher among men than women. The higher rates among men have led to the suggestion that androgens are related to increased risk whereas oestrogens are related to decreased risk. This hypothesis was investigated in the present study via a nested case-control analysis of pre-diagnostic sex steroid hormone levels among men in five US cohorts. METHODS/UNASSIGNED:Concentrations of sex steroid hormones and sex hormone-binding globulin were quantitated using gas chromatography-mass spectrometry and a competitive electrochemiluminescence immunoassay, respectively. Multivariable conditional logistic regression was used to calculate odds ratios (ORs) and 95% CIs for associations between hormones and liver cancer among 275 men who subsequently developed liver cancer and 768 comparison men. RESULTS/UNASSIGNED: = 1.77, 95% CI = 1.38-2.29), dihydrotestosterone (OR = 1.76, 95% CI = 1.21-2.57), oestrone (OR = 1.74, 95% CI = 1.08-2.79), total oestradiol (OR = 1.58, 95% CI=1.22-20.05), and sex hormone-binding globulin (OR = 1.63, 95% CI = 1.27-2.11) were associated with increased risk. Higher concentrations of dehydroepiandrosterone (DHEA), however, were associated with a 53% decreased risk (OR = 0.47, 95% CI = 0.33-0.68). CONCLUSIONS/UNASSIGNED:Higher concentrations of both androgens (testosterone, dihydrotestosterone) and their aromatised oestrogenic metabolites (oestrone, oestradiol) were observed among men who subsequently developed liver cancer compared with men who did not. As DHEA is an adrenal precursor of both androgens and oestrogens, these results may suggest that a lower capacity to convert DHEA to androgens, and their subsequent conversion to oestrogens, confers a lower risk of liver cancer, whereas a greater capacity to convert DHEA confers a greater risk. IMPACT AND IMPLICATIONS/UNASSIGNED:This study does not fully support the current hormone hypothesis as both androgen and oestrogen levels were associated with increased risk of liver cancer among men. The study also found that higher DHEA levels were associated with lower risk, thus suggesting the hypothesis that greater capacity to convert DHEA could be associated with increased liver cancer risk among men.
PMCID:10326694
PMID: 37425211
ISSN: 2589-5559
CID: 5537372
Goodness-of-fit two-phase sampling designs for time-to-event outcomes: a simulation study based on New York University Women's Health Study for breast cancer
BACKGROUND:Sub-cohort sampling designs such as a case-cohort study play a key role in studying biomarker-disease associations due to their cost effectiveness. Time-to-event outcome is often the focus in cohort studies, and the research goal is to assess the association between the event risk and risk factors. In this paper, we propose a novel goodness-of-fit two-phase sampling design for time-to-event outcomes when some covariates (e.g., biomarkers) can only be measured on a subgroup of study subjects. METHODS:Assuming that an external model, which can be the well-established risk models such as the Gail model for breast cancer, Gleason score for prostate cancer, and Framingham risk models for heart diseases, or built from preliminary data, is available to relate the outcome and complete covariates, we propose to oversample subjects with worse goodness-of-fit (GOF) based on an external survival model and time-to-event. With the cases and controls sampled using the GOF two-phase design, the inverse sampling probability weighting method is used to estimate the log hazard ratio of both incomplete and complete covariates. We conducted extensive simulations to evaluate the efficiency gain of our proposed GOF two-phase sampling designs over case-cohort study designs. RESULTS:Through extensive simulations based on a dataset from the New York University Women's Health Study, we showed that the proposed GOF two-phase sampling designs were unbiased and generally had higher efficiency compared to the standard case-cohort study designs. CONCLUSION:In cohort studies with rare outcomes, an important design question is how to select informative subjects to reduce sampling costs while maintaining statistical efficiency. Our proposed goodness-of-fit two-phase design provides efficient alternatives to standard case-cohort designs for assessing the association between time-to-event outcome and risk factors. This method is conveniently implemented in standard software.
PMCID:10199513
PMID: 37208600
ISSN: 1471-2288
CID: 5503692
Circulating vitamin D and breast cancer risk: an international pooling project of 17 cohorts
Laboratory and animal research support a protective role for vitamin D in breast carcinogenesis, but epidemiologic studies have been inconclusive. To examine comprehensively the relationship of circulating 25-hydroxyvitamin D [25(OH)D] to subsequent breast cancer incidence, we harmonized and pooled participant-level data from 10 U.S. and 7 European prospective cohorts. Included were 10,484 invasive breast cancer cases and 12,953 matched controls. Median age (interdecile range) was 57 (42-68) years at blood collection and 63 (49-75) years at breast cancer diagnosis. Prediagnostic circulating 25(OH)D was either newly measured using a widely accepted immunoassay and laboratory or, if previously measured by the cohort, calibrated to this assay to permit using a common metric. Study-specific relative risks (RRs) for season-standardized 25(OH)D concentrations were estimated by conditional logistic regression and combined by random-effects models. Circulating 25(OH)D increased from a median of 22.6 nmol/L in consortium-wide decile 1 to 93.2 nmol/L in decile 10. Breast cancer risk in each decile was not statistically significantly different from risk in decile 5 in models adjusted for breast cancer risk factors, and no trend was apparent (P-trend = 0.64). Compared to women with sufficient 25(OH)D based on Institute of Medicine guidelines (50- < 62.5 nmol/L), RRs were not statistically significantly different at either low concentrations (< 20 nmol/L, 3% of controls) or high concentrations (100- < 125 nmol/L, 3% of controls; ≥ 125 nmol/L, 0.7% of controls). RR per 25 nmol/L increase in 25(OH)D was 0.99 [95% confidence intervaI (CI) 0.95-1.03]. Associations remained null across subgroups, including those defined by body mass index, physical activity, latitude, and season of blood collection. Although none of the associations by tumor characteristics reached statistical significance, suggestive inverse associations were seen for distant and triple negative tumors. Circulating 25(OH)D, comparably measured in 17 international cohorts and season-standardized, was not related to subsequent incidence of invasive breast cancer over a broad range in vitamin D status.
PMID: 36593337
ISSN: 1573-7284
CID: 5409842
Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes
Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P < 5 × 10-8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10-9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P < 5 × 10-8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture.
PMID: 36273105
ISSN: 1476-5551
CID: 5359152
Neighborhood walkability and sex steroid hormone levels in women
BACKGROUND:Neighborhood walkability (NW) has been linked to increased physical activity, which in turn is associated with lower concentrations of sex hormones and higher concentration of SHBG in women. However, no study has directly examined the association of NW with female sex hormone levels. OBJECTIVE:We conducted a cross-sectional study to evaluate the association between NW and circulating levels of sex hormones and SHBG in pre- and post-menopausal women. METHODS:We included 797 premenopausal and 618 postmenopausal women from the New York University Women's Health Study (NYUWHS) who were healthy controls in previous nested case-control studies in which sex hormones (androstenedione, testosterone, DHEAS, estradiol and estrone) and SHBG had been measured in serum at enrollment. Baseline residential addresses were geo-coded and the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) was calculated. Generalized Estimating Equations were used to assess the association between BEH-NWI and sex hormone and SHBG concentrations adjusting for individual- and neighborhood-level factors. RESULTS:In premenopausal women, a one standard deviation (SD) increment in BEH-NWI was associated with a 3.5% (95% CI 0.9%-6.1%) lower DHEAS concentration. In postmenopausal women, a one SD increment in BEH-NWI was related to an 8.5% (95% CI 5.4%-11.5%) lower level of DHEAS, a 3.7% (95% CI 0.5%-6.8%) lower level of testosterone, a 1.8% (95% CI 0.5%-3.0%) lower level of estrone, and a 4.2% (95% CI 2.7%-5.7%) higher level of SHBG. However, the associations with respect to DHEAS and estrone became apparent only after adjusting for neighborhood-level variables. Sensitivity analyses using fixed effects meta-analysis and inverse probability weighting accounting for potential selection bias yielded similar results. CONCLUSION/CONCLUSIONS:Our findings suggest that NW is associated with lower concentrations of androgens and estrone, and increased SHBG, in postmenopausal women, and lower levels of DHEAS in premenopausal women.
PMID: 36088991
ISSN: 1096-0953
CID: 5332702
Cohort Profile: The Ovarian Cancer Cohort Consortium (OC3)
PMID: 34652432
ISSN: 1464-3685
CID: 5084952
International journal of environmental research & public health. 2022:19(9).DOI: 10.3390/ijerph19095104
Global DNA Methylation Profiles in Peripheral Blood of WTC-Exposed Community Members with Breast Cancer
Breast cancer represents the most common cancer diagnosis among World Trade Center (WTC)-exposed community members, residents, and cleanup workers enrolled in the WTC Environmental Health Center (WTC EHC). The primary aims of this study were (1) to compare blood DNA methylation profiles of WTC-exposed community members with breast cancer and WTC-unexposed pre-diagnostic breast cancer blood samples, and (2) to compare the DNA methylation differences among the WTC EHC breast cancer cases and WTC-exposed cancer-free controls. Gene pathway enrichment analyses were further conducted. There were significant differences in DNA methylation between WTC-exposed breast cancer cases and unexposed prediagnostic breast cancer cases. The top differentially methylated genes were Intraflagellar Transport 74 (IFT74), WD repeat-containing protein 90 (WDR90), and Oncomodulin (OCM), which are commonly upregulated in tumors. Probes associated with established tumor suppressor genes (ATM, BRCA1, PALB2, and TP53) were hypermethylated among WTC-exposed breast cancer cases compared to the unexposed group. When comparing WTC EHC breast cancer cases vs. cancer-free controls, there appeared to be global hypomethylation among WTC-exposed breast cancer cases compared to exposed controls. Functional pathway analysis revealed enrichment of several gene pathways in WTC-exposed breast cancer cases including endocytosis, proteoglycans in cancer, regulation of actin cytoskeleton, axon guidance, focal adhesion, calcium signaling, cGMP-PKG signaling, mTOR, Hippo, and oxytocin signaling. The results suggest potential epigenetic links between WTC exposure and breast cancer in local community members enrolled in the WTC EHC program.
PMCID:9105091
PMID: 35564499
ISSN: 1660-4601
CID: 5215082
Temporal reproducibility of IgG and IgM autoantibodies in serum from healthy women
Autoantibodies are present in healthy individuals and altered in chronic diseases. We used repeated samples collected from participants in the NYU Women's Health Study to assess autoantibody reproducibility and repertoire stability over a one-year period using the HuProt array. We included two samples collected one year apart from each of 46 healthy women (92 samples). We also included eight blinded replicate samples to assess laboratory reproducibility. A total of 21,211 IgG and IgM autoantibodies were interrogated. Of those, 86% of IgG (n = 18,303) and 34% of IgM (n = 7,242) autoantibodies showed adequate lab reproducibility (coefficient of variation [CV] < 20%). Intraclass correlation coefficients (ICCs) were estimated to assess temporal reproducibility. A high proportion of both IgG and IgM autoantibodies with CV < 20% (76% and 98%, respectively) showed excellent temporal reproducibility (ICC > 0.8). Temporal reproducibility was lower after using quantile normalization suggesting that batch variability was not an important source of error, and that normalization removed some informative biological information. To our knowledge this study is the largest in terms of sample size and autoantibody numbers to assess autoantibody reproducibility in healthy women. The results suggest that for many autoantibodies a single measurement may be used to rank individuals in studies of autoantibodies as etiologic markers of disease.
PMCID:9008031
PMID: 35418192
ISSN: 2045-2322
CID: 5201972
Risk Stratification for Early-Onset Colorectal Cancer Using a Combination of Genetic and Environmental Risk Scores: An International Multi-Center Study
BACKGROUND:Incidence of colorectal cancer (CRC) among individuals aged less than 50 years has been increasing. As screening guidelines lower the recommended age of screening initiation, concerns including the burden on screening capacity and costs have been recognized, suggesting that an individualized approach may be warranted. We developed risk prediction models for early-onset CRC that incorporate an environmental risk score (ERS), including 16 lifestyle and environmental factors, and a polygenic risk score (PRS), of 141 variants. METHODS:Relying on risk score weights for ERS and PRS derived from studies of CRC at all ages, we evaluated risks for early-onset CRC in 3,486 cases and 3,890 controls aged less than 50 years. Relative and absolute risks for early-onset CRC were assessed according to values of the ERS and PRS. The discriminatory performance of these scores was estimated using the covariate-adjusted area under the receiver operating characteristic curve. RESULTS:Increasing values of ERS and PRS were associated with increasing relative risks for early-onset CRC (odds ratio per standard deviation of ERS = 1.14, 95% confidence interval [CI] = 1.08, 1.20; odds ratio per standard deviation of PRS = 1.59, 95% CI = 1.51, 1.68), both contributing to case-control discrimination (area under the curve = 0.631, 95% CI = 0.615, 0.647). Based on absolute risks, we can expect 26 excess cases per 10,000 men and 21 per 10,000 women, among those scoring at the 90th percentile for both risk scores. CONCLUSIONS:Personal risk scores have the potential to identify individuals at differential relative and absolute risk for early-onset CRC. Improved discrimination may aid in targeted CRC screening of younger, high-risk individuals, potentially improving outcomes.
PMID: 35026030
ISSN: 1460-2105
CID: 5118962
Gut Microbiota and Subjective Memory Complaints in Older Women
BACKGROUND:Epidemiological studies that investigate alterations in gut microbial composition associated with cognitive dysfunction are limited. OBJECTIVE:To examine the association between the gut microbiota and subjective memory complaints (SMCs), a self-reported, validated indicator of cognitive dysfunction. METHODS:In this cross-sectional study of 95 older women selected from the New York University Women's Health Study (NYUWHS), we characterized the gut microbial composition using 16S rRNA gene sequencing. We estimated odds ratio (OR) from beta regression which approximates the ratio of mean relative abundances of individual bacterial taxon from phylum to genus levels by binary (2+ versus < 2) and continuous SMCs. RESULTS:Women reporting 2 or more SMCs had higher relative abundances of genus Holdemania and family Desulfovibrionaceae compared with those reporting one or no complaint. Compared with women with < 2 SMCs, the relative abundances of Holdemania and family Desulfovibrionaceae were 2.09 times (OR: 2.09, 95% confidence interval [CI]: 1.38-3.17) and 2.10 times (OR: 2.10, 95% CI: 1.43-3.09) higher in women with 2+ SMCs, respectively (false discovery rate (FDR)-adjusted p = 0.038 and 0.010, respectively). A dose-response association was observed for genus Sutterella and family Desulfovibrionaceae. Every one-unit increase in SMCs was associated with 25% and 27% higher relative abundances of Sutterella (OR: 1.25; 95% CI: 1.11-1.40) and Desulfovibrionaceae (OR: 1.27; 95% CI: 1.13-1.42), respectively (FDR-adjusted p = 0.018 and 0.006, respectively). CONCLUSION/CONCLUSIONS:Our findings support an association between alterations in the gut bacterial composition and cognitive dysfunction.
PMID: 35570486
ISSN: 1875-8908
CID: 5249152
