Publications by authors named "Tess V Clendenen"

28 Publications

  • Page 1 of 1

Neighborhood Walkability and Mortality in a Prospective Cohort of Women.

Epidemiology 2021 11;32(6):763-772

From the Division of Epidemiology, Department of Population Health, New York University Grossman School of Medicine, New York, NY.

Background: There is a paucity of prospective cohort studies evaluating neighborhood walkability in relation to the risk of death.

Methods: We geocoded baseline residential addresses of 13,832 women in the New York University Women's Health Study (NYUWHS) and estimated the Built Environment and Health Neighborhood Walkability Index (BEH-NWI) for each participant circa 1990. The participants were recruited from 1985 to 1991 in New York City and followed for an average of 27 years. We conducted survival analyses using Cox proportional hazards models to assess the association between neighborhood walkability and risk of death from any cause, obesity-related diseases, cardiometabolic diseases, and obesity-related cancers.

Results: Residing in a neighborhood with a higher neighborhood walkability score was associated with a lower mortality rate. Comparing women in the top versus the lowest walkability tertile, the hazards ratios (and 95% CIs) were 0.96 (0.93, 0.99) for all-cause, 0.91 (0.86, 0.97) for obesity-related disease, and 0.72 (0.62, 0.85) for obesity-related cancer mortality, respectively, adjusting for potential confounders at both the individual and neighborhood level. We found no association between neighborhood walkability and risk of death from cardiometabolic diseases. Results were similar in analyses censoring participants who moved during follow-up, using multiple imputation for missing covariates, and using propensity scores matching women with high and low neighborhood walkability on potential confounders. Exploratory analyses indicate that outdoor walking and average BMI mediated the association between neighborhood walkability and mortality.

Conclusion: Our findings are consistent with a protective role of neighborhood walkability in obesity-related mortality in women, particularly obesity-related cancer mortality.
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http://dx.doi.org/10.1097/EDE.0000000000001406DOI Listing
November 2021

Breast Cancer Risk Factors and Circulating Anti-Müllerian Hormone Concentration in Healthy Premenopausal Women.

J Clin Endocrinol Metab 2021 10;106(11):e4542-e4553

Department of Population Health, New York University School of Medicine, New York, NY, USA.

Context: We previously reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies.

Objective: This study assessed whether risk factors for breast cancer are correlates of AMH concentration.

Methods: This cross-sectional study included 3831 healthy premenopausal women (aged 21-57, 87% aged 35-49) from 10 cohort studies among the general population.

Results: Adjusting for age and cohort, AMH positively associated with age at menarche (P < 0.0001) and parity (P = 0.0008) and inversely associated with hysterectomy/partial oophorectomy (P = 0.0008). Compared with women of normal weight, AMH was lower (relative geometric mean difference 27%, P < 0.0001) among women who were obese. Current oral contraceptive (OC) use and current/former smoking were associated with lower AMH concentration than never use (40% and 12% lower, respectively, P < 0.0001). We observed higher AMH concentrations among women who had had a benign breast biopsy (15% higher, P = 0.03), a surrogate for benign breast disease, an association that has not been reported. In analyses stratified by age (<40 vs ≥40), associations of AMH with body mass index and OCs were similar in younger and older women, while associations with the other factors (menarche, parity, hysterectomy/partial oophorectomy, smoking, and benign breast biopsy) were limited to women ≥40 (P-interaction < 0.05).

Conclusion: This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and it suggests that most associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
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http://dx.doi.org/10.1210/clinem/dgab461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8530718PMC
October 2021

Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study.

Eur J Clin Nutr 2020 09 21;74(9):1306-1315. Epub 2020 Apr 21.

Departments of Population Health and Environmental Medicine, New York University School of Medicine, 650 First Avenue, New York, NY, 10016, USA.

Background/objectives: Folates found in natural foods are thought to protect against cancer. However, folic acid (FA), a synthetic form of folate used in supplements and fortified foods, may increase breast cancer risk if present in unmetabolized form (UMFA) in the circulation. This study examined the associations of serum UMFA and 5-methyltetrahydrofolate (5-mTHF), the predominant form of circulating folate, with breast cancer risk.

Subjects/methods: We conducted a nested case-control study in a prospective cohort. In total, 553 cases of invasive breast cancer, diagnosed before mandatory FA fortification of grain in the US in 1998, were individually-matched to 1059 controls. Serum UMFA and 5-mTHF were measured using liquid chromatography-tandem mass spectrometry in stored serum samples, and 5-mTHF was corrected for storage degradation.

Results: Serum UMFA was not associated with breast cancer risk: the percentage of women with detectable levels of UMFA was similar in cases and controls (18% and 20%, respectively; p = 0.46). Two tag-SNPs in the promoter region of the FA-metabolizing gene were also not associated with risk. There was a marginally significant inverse association of 5-mTHF with breast cancer risk (odds ratio for the highest vs. lowest quintile = 0.69, 95% CI = 0.49 to 0.97; p = 0.08).

Conclusions: Circulating UMFA was not associated with breast cancer risk. These results apply to countries without mandatory FA food fortification. Studies are needed in countries with mandatory fortification, where levels of UMFA are much higher than in our study.
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http://dx.doi.org/10.1038/s41430-020-0615-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508257PMC
September 2020

Reproductive and Hormonal Factors and Risk of Ovarian Cancer by Tumor Dominance: Results from the Ovarian Cancer Cohort Consortium (OC3).

Cancer Epidemiol Biomarkers Prev 2020 01 12;29(1):200-207. Epub 2019 Nov 12.

Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Background: Laterality of epithelial ovarian tumors may reflect the underlying carcinogenic pathways and origins of tumor cells.

Methods: We pooled data from 9 prospective studies participating in the Ovarian Cancer Cohort Consortium. Information on measures of tumor size or tumor dominance was extracted from surgical pathology reports or obtained through cancer registries. We defined dominant tumors as those restricted to one ovary or where the dimension of one ovary was at least twice as large as the other, and nondominant tumors as those with similar dimensions across the two ovaries or peritoneal tumors. Competing risks Cox models were used to examine whether associations with reproductive and hormonal risk factors differed by ovarian tumor dominance.

Results: Of 1,058 ovarian cancer cases with tumor dominance information, 401 were left-dominant, 363 were right-dominant, and 294 were nondominant. Parity was more strongly inversely associated with risk of dominant than nondominant ovarian cancer ( = 0.004). Ever use of oral contraceptives (OC) was associated with lower risk of dominant tumors, but was not associated with nondominant tumors ( = 0.01). Higher body mass index was associated with higher risk of left-dominant tumors, but not significantly associated with risk of right-dominant or nondominant tumors ( = 0.08).

Conclusions: These data suggest that reproductive and hormonal risk factors appear to have a stronger impact on dominant tumors, which may have an ovarian or endometriosis origin.

Impact: Examining the associations of ovarian cancer risk factors by tumor dominance may help elucidate the mechanisms through which these factors influence ovarian cancer risk.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0734DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954293PMC
January 2020

Breast cancer risk prediction in women aged 35-50 years: impact of including sex hormone concentrations in the Gail model.

Breast Cancer Res 2019 03 19;21(1):42. Epub 2019 Mar 19.

Department of Population Health, New York University School of Medicine, 650 First Avenue, New York, NY, 10016, USA.

Background: Models that accurately predict risk of breast cancer are needed to help younger women make decisions about when to begin screening. Premenopausal concentrations of circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and testosterone have been positively associated with breast cancer risk in prospective studies. We assessed whether adding AMH and/or testosterone to the Gail model improves its prediction performance for women aged 35-50.

Methods: In a nested case-control study including ten prospective cohorts (1762 invasive cases/1890 matched controls) with pre-diagnostic serum/plasma samples, we estimated relative risks (RR) for the biomarkers and Gail risk factors using conditional logistic regression and random-effects meta-analysis. Absolute risk models were developed using these RR estimates, attributable risk fractions calculated using the distributions of the risk factors in the cases from the consortium, and population-based incidence and mortality rates. The area under the receiver operating characteristic curve (AUC) was used to compare the discriminatory accuracy of the models with and without biomarkers.

Results: The AUC for invasive breast cancer including only the Gail risk factor variables was 55.3 (95% CI 53.4, 57.1). The AUC increased moderately with the addition of AMH (AUC 57.6, 95% CI 55.7, 59.5), testosterone (AUC 56.2, 95% CI 54.4, 58.1), or both (AUC 58.1, 95% CI 56.2, 59.9). The largest AUC improvement (4.0) was among women without a family history of breast cancer.

Conclusions: AMH and testosterone moderately increase the discriminatory accuracy of the Gail model among women aged 35-50. We observed the largest AUC increase for women without a family history of breast cancer, the group that would benefit most from improved risk prediction because early screening is already recommended for women with a family history.
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http://dx.doi.org/10.1186/s13058-019-1126-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6425605PMC
March 2019

Ovarian cancer risk factors by tumor aggressiveness: An analysis from the Ovarian Cancer Cohort Consortium.

Int J Cancer 2019 07 14;145(1):58-69. Epub 2019 Jan 14.

City of Hope, Duarte, CA.

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 (p = 0.01), family history of ovarian cancer (p = 0.02), body mass index (BMI; p ≤ 0.04) and smoking (p < 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/m , 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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http://dx.doi.org/10.1002/ijc.32075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488363PMC
July 2019

Authors' reply to: Anti-Müllerian hormone and breast cancer risk: is the correlation possibly associated with PCOS.

Int J Cancer 2019 01 26;144(1):210. Epub 2018 Oct 26.

Department of Population Health, New York University School of Medicine, New York, NY.

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http://dx.doi.org/10.1002/ijc.31728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6263028PMC
January 2019

Circulating Vitamin D and Colorectal Cancer Risk: An International Pooling Project of 17 Cohorts.

J Natl Cancer Inst 2019 02;111(2):158-169

Department of Health National Institute for Health and Welfare, Helsinki, Finland.

Background: Experimental and epidemiological studies suggest a protective role for vitamin D in colorectal carcinogenesis, but evidence is inconclusive. Circulating 25-hydroxyvitamin D (25(OH)D) concentrations that minimize risk are unknown. Current Institute of Medicine (IOM) vitamin D guidance is based solely on bone health.

Methods: We pooled participant-level data from 17 cohorts, comprising 5706 colorectal cancer case participants and 7107 control participants with a wide range of circulating 25(OH)D concentrations. For 30.1% of participants, 25(OH)D was newly measured. Previously measured 25(OH)D was calibrated to the same assay to permit estimating risk by absolute concentrations. Study-specific relative risks (RRs) for prediagnostic season-standardized 25(OH)D concentrations were calculated using conditional logistic regression and pooled using random effects models.

Results: Compared with the lower range of sufficiency for bone health (50-<62.5 nmol/L), deficient 25(OH)D (<30 nmol/L) was associated with 31% higher colorectal cancer risk (RR = 1.31, 95% confidence interval [CI] = 1.05 to 1.62); 25(OH)D above sufficiency (75-<87.5 and 87.5-<100 nmol/L) was associated with 19% (RR = 0.81, 95% CI = 0.67 to 0.99) and 27% (RR = 0.73, 95% CI = 0.59 to 0.91) lower risk, respectively. At 25(OH)D of 100 nmol/L or greater, risk did not continue to decline and was not statistically significantly reduced (RR = 0.91, 95% CI = 0.67 to 1.24, 3.5% of control participants). Associations were minimally affected when adjusting for body mass index, physical activity, or other risk factors. For each 25 nmol/L increment in circulating 25(OH)D, colorectal cancer risk was 19% lower in women (RR = 0.81, 95% CI = 0.75 to 0.87) and 7% lower in men (RR = 0.93, 95% CI = 0.86 to 1.00) (two-sided Pheterogeneity by sex = .008). Associations were inverse in all subgroups, including colorectal subsite, geographic region, and season of blood collection.

Conclusions: Higher circulating 25(OH)D was related to a statistically significant, substantially lower colorectal cancer risk in women and non-statistically significant lower risk in men. Optimal 25(OH)D concentrations for colorectal cancer risk reduction, 75-100 nmol/L, appear higher than current IOM recommendations.
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http://dx.doi.org/10.1093/jnci/djy087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376911PMC
February 2019

Circulating anti-Müllerian hormone and breast cancer risk: A study in ten prospective cohorts.

Int J Cancer 2018 06 8;142(11):2215-2226. Epub 2018 Feb 8.

Department of Population Health, New York University School of Medicine, New York, NY.

A strong positive association has been observed between circulating anti-Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case-control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme-linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (p across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31-1.94). Though the test for interaction was not statistically significant (p  = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: OR  = 1.96, 95% CI = 1.46-2.64, p <0.0001; ER+/PR-: OR  = 0.82, 95% CI = 0.40-1.68, p  = 0.51; ER-/PR+: OR  = 3.23, 95% CI = 0.48-21.9, p  = 0.26; ER-/PR-: OR  = 1.15, 95% CI = 0.63-2.09, p  = 0.60. The association was observed for both pre- (OR = 1.35, 95% CI = 1.05-1.73) and post-menopausal (OR  = 1.61, 95% CI = 1.03-2.53) breast cancer (p  = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.
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http://dx.doi.org/10.1002/ijc.31249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5922424PMC
June 2018

Ovarian Cancer Risk Factors by Histologic Subtype: An Analysis From the Ovarian Cancer Cohort Consortium.

J Clin Oncol 2016 08 20;34(24):2888-98. Epub 2016 Jun 20.

Nicolas Wentzensen, Britton Trabert, Amanda Black, Louise A. Brinton, Patricia Hartge, Catherine Schairer, and Hannah P. Yang, National Cancer Institute; Dale P. Sandler, National Institute of Environmental Health Science, Bethesda, MD; Elizabeth M. Poole, Julie Buring, I-Min Lee, and Shelley S. Tworoger, Brigham and Women's Hospital; Elizabeth M. Poole, Hans-Olov Adami, Julie Buring, I-Min Lee, and Shelley S. Tworoger, Harvard University, Boston, MA; Emily White and Ulrike Peters, Fred Hutchinson Cancer Research Center, Seattle, WA; Alan A. Arslan, Tess V. Clendenen, and Anne Zeleniuch-Jacquotte, New York University School of Medicine; Thomas Rohan, Albert Einstein College of Medicine, New York, NY; Alpa V. Patel, Susan M. Gapstur, and Mia M. Gaudet, American Cancer Society, Atlanta, GA; V. Wendy Setiawan, University of Southern California, Los Angeles; Leslie Bernstein and James V. Lacey Jr, City of Hope, Duarte, CA; Kala Visvanathan and Judith Hoffman-Bolton, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Elisabete Weiderpass and Inger T. Gram, University of Tromsø-The Arctic University of Norway, Tromsø; Elisabete Weiderpass, Cancer Registry of Norway, Oslo, Norway; Elisabete Weiderpass, Hans-Olov Adami, Louise K. Sjöholm, and Alicja Wolk, Karolinska Institute; Stockholm; Annika Idahl and Eva Lundin, Umeå University, Umeå, Sweden; Elisabete Weiderpass, Folkhälsan Research Center, Helsinki, Finland; Lesley M. Butler, University of Pittsburgh, Pittsburgh, PA; Saioa Chamosa, BioDonostia Research Institute, San Sebastian, Spain; Laure Dossus, French Institute of Health and Medical Research, Paris; Sabina Rinaldi, International Agency for Research on Cancer, Lyon, France; Renee Fortner and Rudolf Kaaks, German Cancer Research Center, Heidelberg, Germany; Michael Jones and Anthony Swerdlow, The Institute of Cancer Research; Melissa A. Merritt, Imperial College of London, London; Ruth Travis, University of Oxford, Oxford, United Kingdom; Victoria

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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http://dx.doi.org/10.1200/JCO.2016.66.8178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5012665PMC
August 2016

Premenopausal Circulating Androgens and Risk of Endometrial Cancer: results of a Prospective Study.

Horm Cancer 2016 06 29;7(3):178-87. Epub 2016 Feb 29.

Department of Population Health, Division of Epidemiology and Biostatistics, New York University School of Medicine, 650 1st Ave, New York, NY, 10016, USA.

Endometrial cancer risk is increased by estrogens unopposed by progesterone. In premenopausal women, androgen excess is often associated with progesterone insufficiency, suggesting that premenopausal androgen concentrations may be associated with risk. In a case-control study nested within three cohorts, we assessed the relationship between premenopausal androgens and risk of endometrial cancer (161 cases and 303 controls matched on age and date of blood donation). Testosterone, DHEAS, androstenedione, and SHBG were measured in serum or plasma. Free testosterone was calculated from testosterone and SHBG. We observed trends of increasing risk across tertiles of testosterone (ORT3-T1 = 1.59, 95 % CI = 0.96, 2.64, p = 0.08) and free testosterone (ORT3-T1 = 1.76, 95 % CI = 1.01, 3.07, p = 0.047), which were not statistically significant after adjustment for body mass index (BMI). There was no association for DHEAS, androstenedione, or SHBG. There were significant interactions by age at diagnosis (<55 years, n = 51 cases; ≥55 years, n = 110 cases). Among women who were ≥55 years of age (predominantly postmenopausal) at diagnosis, the BMI-adjusted OR was 2.08 (95 % CI = 1.25, 3.44, p = 0.005) for a doubling in testosterone and 1.55 (95 % CI = 1.04, 2.31, p = 0.049) for a doubling in free testosterone. There was no association among women aged <55 years at diagnosis, consistent with the only other prospective study to date. If pre- and post-menopausal concentrations of androgens are correlated, our observation of an association of premenopausal androgens with risk among women aged ≥55 years at diagnosis could be due to the effect on the endometrium of postmenopausal androgen-derived estrogens in the absence of progesterone, which is no longer secreted.
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http://dx.doi.org/10.1007/s12672-016-0258-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4860027PMC
June 2016

Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: A Nested Case-Control Study.

PLoS One 2015 21;10(10):e0140478. Epub 2015 Oct 21.

Department of Population Health, New York University School of Medicine, New York, New York, United States of America; New York University Cancer Institute, New York University School of Medicine, New York, New York, United States of America.

Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH)D concentration in GWAS were also associated with plasma 25(OH)D in our study (p-trend <0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH)D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0140478PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4619526PMC
June 2016

Genotyping of Single Nucleotide Polymorphisms in DNA Isolated from Serum Using Sequenom MassARRAY Technology.

PLoS One 2015 14;10(8):e0135943. Epub 2015 Aug 14.

Department of Population Health, New York University School of Medicine, New York, New York, United States of America; NYU Cancer Institute, New York University Langone Medical Center, New York, New York, United States of America.

Background: Large epidemiologic studies have the potential to make valuable contributions to the assessment of gene-environment interactions because they prospectively collected detailed exposure data. Some of these studies, however, have only serum or plasma samples as a low quantity source of DNA.

Methods: We examined whether DNA isolated from serum can be used to reliably and accurately genotype single nucleotide polymorphisms (SNPs) using Sequenom multiplex SNP genotyping technology. We genotyped 81 SNPs using samples from 158 participants in the NYU Women's Health Study. Each participant had DNA from serum and at least one paired DNA sample isolated from a high quality source of DNA, i.e. clots and/or cell precipitates, for comparison.

Results: We observed that 60 of the 81 SNPs (74%) had high call frequencies (≥95%) using DNA from serum, only slightly lower than the 85% of SNPs with high call frequencies in DNA from clots or cell precipitates. Of the 57 SNPs with high call frequencies for serum, clot, and cell precipitate DNA, 54 (95%) had highly concordant (>98%) genotype calls across all three sample types. High purity was not a critical factor to successful genotyping.

Conclusions: Our results suggest that this multiplex SNP genotyping method can be used reliably on DNA from serum in large-scale epidemiologic studies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135943PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537187PMC
May 2016

Intake of vitamins A, C, and E and folate and the risk of ovarian cancer in a pooled analysis of 10 cohort studies.

Cancer Causes Control 2015 Sep 14;26(9):1315-27. Epub 2015 Jul 14.

CRCHUM (Centre de recherche du CHUM) and Department of Social and Preventive Medicine, Université de Montréal, 850 Saint-Denis Street, 2nd Floor, Montreal, QC, H2X 0A9, Canada,

Purpose: Vitamins A, C, and E and folate have anticarcinogenic properties and thus might protect against cancer. Few known modifiable risk factors for ovarian cancer exist. We examined the associations between dietary and total (food and supplemental) vitamin intake and the risk of invasive epithelial ovarian cancer.

Methods: The primary data from 10 prospective cohort studies in North America and Europe were analyzed. Vitamin intakes were estimated from validated food frequency questionnaires in each study. Study-specific relative risks (RRs) were estimated using the Cox proportional hazards model and then combined using a random-effects model.

Results: Among 501,857 women, 1,973 cases of ovarian cancer occurred over a median follow-up period of 7-16 years across studies. Dietary and total intakes of each vitamin were not significantly associated with ovarian cancer risk. The pooled multivariate RRs [95% confidence intervals (CIs)] for incremental increases in total intake of each vitamin were 1.02 (0.97-1.07) for vitamin A (increment: 1,300 mcg/day), 1.01 (0.99-1.04) for vitamin C (400 mg/day), 1.02 (0.97-1.06) for vitamin E (130 mg/day), and 1.01 (0.96-1.07) for folate (250 mcg/day). Multivitamin use (vs. nonuse) was not associated with ovarian cancer risk (pooled multivariate RR = 1.00, 95% CI 0.89-1.12). Associations did not vary substantially by study, or by subgroups of the population. Greater vitamin intakes were associated with modestly higher risks of endometrioid tumors (n = 156 cases), but not with other histological types.

Conclusion: These results suggest that consumption of vitamins A, C, and E and folate during adulthood does not play a major role in ovarian cancer risk.
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http://dx.doi.org/10.1007/s10552-015-0626-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4907363PMC
September 2015

Partially Linear Single Index Cox Regression Model in Nested Case-Control Studies.

Comput Stat Data Anal 2013 Nov;67:199-212

Department of Statistics, North Carolina State University, Raleigh, USA.

The nested case-control (NCC) design is widely used in epidemiologic studies as a cost-effective subcohort sampling method to study the association between a disease and its potential risk factors. NCC data are commonly analyzed using Thomas' partial likelihood approach under the Cox proportional hazards model assumption. However, the linear modeling form in the Cox model may be insufficient for practical applications, especially when there are a large number of risk factors under investigation. In this paper, we consider a partially linear single index proportional hazard model, which includes a linear component for covariates of interest to yield easily interpretable results and a nonparametric single index component to adjust for multiple confounders effectively. We propose to approximate the nonparametric single index function by polynomial splines and estimate the parameters of interest using an iterative algorithm based on the partial likelihood. Asymptotic properties of the resulting estimators are established. The proposed methods are evaluated using simulations and applied to an NCC study of ovarian cancer.
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http://dx.doi.org/10.1016/j.csda.2013.05.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719588PMC
November 2013

Evaluation of the kinetic properties of background parenchymal enhancement throughout the phases of the menstrual cycle.

Radiology 2013 Aug 8;268(2):356-65. Epub 2013 May 8.

Department of Radiology, Center for Biomedical Imaging, New York University School of Medicine, 660 First Ave, 4th Floor, New York, NY 10016, USA.

Purpose: To develop and apply a semiautomatic method of segmenting fibroglandular tissue to quantify magnetic resonance (MR) imaging contrast material-enhancement kinetics of breast background parenchyma (BP) and lesions throughout the phases of the menstrual cycle in women with benign and malignant lesions.

Materials And Methods: The institutional review board approved this retrospective HIPAA-compliant study, and informed consent was waived. From December 2008 to August 2011, 58 premenopausal women who had undergone contrast material-enhanced MR imaging and MR imaging-guided biopsy were identified. The longest time from the start of the last known period was 34 days. One lesion per patient (37 benign and 21 malignant) was analyzed. The patient groups were stratified according to the week of the menstrual cycle when MR imaging was performed. A method based on principal component analysis (PCA) was applied for quantitative analysis of signal enhancement in the BP and lesions by using the percentage of slope and percentage of enhancement. Linear regression and the Mann-Whitney U test were used to assess the association between the kinetic parameters and the week of the menstrual cycle.

Results: In the women with benign lesions, percentages of slope and enhancement for both BP and lesions during week 2 were significantly (P < .05) lower than those in week 4. Percentage of enhancement in the lesion in week 2 was lower than that in week 3 (P < .05). The MR images of women with malignant lesions showed no significant difference between the weeks for any of the parameters. There was a strong positive correlation between lesion and BP percentage of slope (r = 0.72) and between lesion and BP percentage of enhancement (r = 0.67) in the benign group. There was also a significant (P = .03) difference in lesion percentage of slope between the benign and malignant groups at week 2.

Conclusion: The PCA-based method can quantify contrast enhancement kinetics of BP semiautomatically, and kinetics of BP and lesions vary according to the week of the menstrual cycle in benign but not in malignant lesions.
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http://dx.doi.org/10.1148/radiol.13121101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721056PMC
August 2013

Estimation and selection of complex covariate effects in pooled nested case-control studies with heterogeneity.

Biostatistics 2013 Sep 30;14(4):682-94. Epub 2013 Apr 30.

Departments of Population Health and Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.

A major challenge in cancer epidemiologic studies, especially those of rare cancers, is observing enough cases. To address this, researchers often join forces by bringing multiple studies together to achieve large sample sizes, allowing for increased power in hypothesis testing, and improved efficiency in effect estimation. Combining studies, however, renders the analysis difficult owing to the presence of heterogeneity in the pooled data. In this article, motivated by a collaborative nested case-control (NCC) study of ovarian cancer in three cohorts from United States, Sweden, and Italy, we investigate the use of penalty regularized partial likelihood estimation in the context of pooled NCC studies to achieve two goals. First, we propose an adaptive group lasso (gLASSO) penalized approach to simultaneously identify important variables and estimate their effects. Second, we propose a composite agLASSO penalized approach to identify variables with heterogeneous effects. Both methods are readily implemented with the group coordinate gradient decent algorithm and shown to enjoy the oracle property. We conduct simulation studies to evaluate the performance of our proposed approaches in finite samples under various heterogeneity settings, and apply them to the pooled ovarian cancer study.
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http://dx.doi.org/10.1093/biostatistics/kxt015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3841381PMC
September 2013

Circulating levels of 25-hydroxyvitamin D and risk of breast cancer: a nested case-control study.

Breast Cancer Res 2013 Feb 26;15(1):R15. Epub 2013 Feb 26.

Introduction: Experimental evidence suggests a protective role for circulating 25-hydroxyvitamin D (25(OH)D) in breast cancer development, but the results of epidemiological studies have been inconsistent.

Methods: We conducted a case-control study nested within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Mammary Screening Cohort. Blood samples were collected at enrollment, and women were followed up for breast cancer ascertainment. In total, 1,585 incident breast cancer cases were individually-matched to 2,940 controls. Of these subjects, 678 cases and 1,208 controls contributed two repeat blood samples, at least one year apart. Circulating levels of 25(OH)D were measured, and multivariate odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.

Results: No association was observed between circulating levels of 25(OH)D and overall breast cancer risk (multivariate-adjusted model OR = 0.94, 95% CI = 0.76-1.16 for the highest vs. lowest quintile, ptrend = 0.30). The temporal reliability of 25(OH)D measured in repeat blood samples was high (intraclass correlation coefficients for season-adjusted 25(OH)D > 0.70). An inverse association between 25(OH)D levels and breast cancer risk was observed among women who were ≤ 45 years of age (ORQ5-Q1 = 0.48, 95% CI = 0.30-0.79, ptrend = 0.01) or premenopausal at enrollment (ORQ5-Q1 = 0.67, 95% CI = 0.48-0.92, ptrend = 0.03).

Conclusions: Circulating 25(OH)D levels were not associated with breast cancer risk overall, although we could not exclude the possibility of a protective effect in younger women. Recommendations regarding vitamin D supplementation should be based on considerations other than breast cancer prevention.
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http://dx.doi.org/10.1186/bcr3390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3672761PMC
February 2013

Circulating prolactin levels and risk of epithelial ovarian cancer.

Cancer Causes Control 2013 Apr 3;24(4):741-8. Epub 2013 Feb 3.

Department of Population Health, New York University School of Medicine, New York, NY, USA.

Purpose: Indirect evidence from experimental and epidemiological studies suggests that prolactin may be involved in ovarian cancer development. However, the relationship between circulating prolactin levels and risk of ovarian cancer is unknown.

Methods: We conducted a nested case-control study of 230 cases and 432 individually matched controls within three prospective cohorts to evaluate whether pre-diagnostic circulating prolactin is associated with subsequent risk of ovarian cancer. We also assessed whether lifestyle and reproductive factors are associated with circulating prolactin among controls.

Results: Prolactin levels were significantly lower among post- versus pre-menopausal women, parous versus nulliparous women, and past versus never users of oral contraceptives in our cross-sectional analysis of controls. In our nested case-control study, we observed a non-significant positive association between circulating prolactin and ovarian cancer risk (OR(Q4vsQ1) 1.56, 95 % CI 0.94, 2.63, p trend 0.15). Our findings were similar in multivariate-adjusted models and in the subgroup of women who donated blood ≥5 years prior to diagnosis. We observed a significant positive association between prolactin and risk for the subgroup of women with BMI ≥25 kg/m(2) (OR(Q4vsQ1) 3.10, 95 % CI 1.39, 6.90), but not for women with BMI <25 kg/m(2) (OR(Q4vsQ1) 0.81, 95 % CI 0.40, 1.64).

Conclusions: Our findings suggest that prolactin may be associated with increased risk of ovarian cancer, particularly in overweight/obese women. Factors associated with reduced risk of ovarian cancer, such as parity and use of oral contraceptives, were associated with lower prolactin levels, which suggests that modulation of prolactin may be a mechanism underlying their association with risk.
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http://dx.doi.org/10.1007/s10552-013-0156-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3602319PMC
April 2013

Comparison of 3-point Dixon imaging and fuzzy C-means clustering methods for breast density measurement.

J Magn Reson Imaging 2013 Aug 4;38(2):474-81. Epub 2013 Jan 4.

New York University School of Medicine, Department of Environmental Medicine, Division of Epidemiology, New York, NY 10016, USA.

Purpose: To assess two methods of fat and fibroglandular tissue (FGT) segmentation for measuring breast MRI FGT volume and FGT%, the volume percentage of FGT in the breast, in longitudinal studies.

Materials And Methods: Nine premenopausal women provided one MRI per week for 4 weeks during a natural menstrual cycle for a total of 36 datasets. We compared a fuzzy c-means (FC) and a 3-point Dixon segmentation method for estimation of changes in FGT volume and FGT% across the menstrual cycle. We also assessed whether differences due to changes in positioning each week could be minimized by coregistration, i.e., the application of the breast boundary selected at one visit to images obtained at other visits.

Results: FC and Dixon FGT volume were highly correlated (r = 0.93, P < 0.001), as was FC and Dixon FGT% (r = 0.86, P = 0.01), although Dixon measurements were on average 10-20% higher. Although FGT measured by both methods showed the expected pattern of increase during the menstrual cycle, the magnitude, and for one woman the direction, of change varied according to the method used. Measurements of FGT for coregistered images were in close agreement with those for which the boundaries were determined independently.

Conclusion: The method of segmentation of fat and FGT tissue may have an impact on the results of longitudinal studies of changes in breast MRI FGT.
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http://dx.doi.org/10.1002/jmri.24002DOI Listing
August 2013

Magnetic resonance imaging (MRI) of hormone-induced breast changes in young premenopausal women.

Magn Reson Imaging 2013 Jan 13;31(1):1-9. Epub 2012 Aug 13.

New York University School of Medicine, Department of Environmental Medicine, Divison of Epidemiology, New York, NY 10016, USA.

Objectives: We conducted a pilot study to identify whether MRI parameters are sensitive to hormone-induced changes in the breast during the natural menstrual cycle and whether changes could also be observed during an oral contraceptive (OC) cycle.

Materials And Methods: The New York University Langone Medical Center Institutional Review Board approved this HIPAA-compliant prospective study. All participants provided written informed consent. Participants were aged 24-31 years.We measured several non-contrast breast MRI parameters during each week of a single menstrual cycle (among 9 women) and OC cycle (among 8 women). Hormones were measured to confirm ovulation and classify menstrual cycle phase among naturally cycling women and to monitor OC compliance among OC users. We investigated how the non-contrast MRI parameters of breast fibroglandular tissue (FGT), apparent diffusion coefficient (ADC), magnetization transfer ratio (MTR), and transverse relaxation time (T2) varied over the natural and the OC cycles.

Results: We observed significant increases in MRI FGT% and ADC in FGT, and longer T2 in FGT in the luteal vs. follicular phase of the menstrual cycle. We did not observe any consistent pattern of change for any of the MRI parameters among women using OCs.

Conclusions: MRI is sensitive to hormone-induced breast tissue changes during the menstrual cycle. Larger studies are needed to assess whether MRI is also sensitive to the effects of exogenous hormones, such as various OC formulations, on the breast tissue of young premenopausal women.
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http://dx.doi.org/10.1016/j.mri.2012.06.022DOI Listing
January 2013

Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.

Cancer Epidemiol 2012 Oct 25;36(5):445-52. Epub 2012 May 25.

Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.

Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk.

Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts).

Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol.

Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.
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http://dx.doi.org/10.1016/j.canep.2012.04.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663487PMC
October 2012

Factors associated with inflammation markers, a cross-sectional analysis.

Cytokine 2011 Dec 19;56(3):769-78. Epub 2011 Oct 19.

Department of Environmental Medicine, Division of Epidemiology, New York University School of Medicine, New York, NY, USA.

Epidemiological studies have reported associations between circulating inflammation markers and risk of chronic diseases. It is of interest to examine whether risk factors for these diseases are associated with inflammation. We conducted a cross-sectional analysis to evaluate whether reproductive and lifestyle factors and circulating vitamin D were associated with inflammation markers, including C-reactive protein, cytokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα), and cytokine modulators (IL-1RA, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1/R2), among 616 healthy women. We confirmed associations of several inflammation markers with age and BMI. We also observed significantly higher levels of certain inflammation markers in postmenopausal vs. premenopausal women (TNFα, sIL-1RII, sIL-2Ra), with increasing parity (IL-12p40), and with higher circulating 25(OH) vitamin D (IL-13) and lower levels among current users of non-steroidal anti-inflammatory drugs (NSAIDs) (IL-1β, IL-2, IL-10, IL-12p70, and IL-12p40), current smokers (IL-4, IL-13, IL-12p40), and women with a family history of breast or ovarian cancer (IL-4, IL-10, IL-13). Our findings suggest that risk factors for chronic diseases (age, BMI, menopausal status, parity, NSAID use, family history of breast and ovarian cancer, and smoking) are associated with inflammation markers in healthy women.
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http://dx.doi.org/10.1016/j.cyto.2011.09.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245985PMC
December 2011

Circulating inflammation markers and risk of epithelial ovarian cancer.

Cancer Epidemiol Biomarkers Prev 2011 May 5;20(5):799-810. Epub 2011 Apr 5.

Department of Environmental Medicine, Division of Epidemiology, New York University School of Medicine, New York, NY, USA.

Background: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer.

Methods: We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer.

Results: We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98-2.52, P = 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95-2.38, P = 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03-2.58, P = 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02-2.51, P = 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90-2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors.

Conclusions And Impact: This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.
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http://dx.doi.org/10.1158/1055-9965.EPI-10-1180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089656PMC
May 2011

Temporal reliability of cytokines and growth factors in EDTA plasma.

BMC Res Notes 2010 Nov 13;3:302. Epub 2010 Nov 13.

Department of Environmental Medicine, New York University Langone Medical Center, New York, NY, USA.

Background: Cytokines are involved in the development of chronic diseases, including cancer. It is important to evaluate the temporal reproducibility of cytokines in plasma prior to conducting epidemiologic studies utilizing these markers.

Findings: We assessed the temporal reliability of CRP, 22 cytokines and their soluble receptors (IL-1α, IL-1β, IL-1RA, IL-2, sIL-2R, IL-4, IL-5, IL-6, sIL-6R, IL-7, IL-8, IL-10, IL-12p40, IL-12p70, IL-13, IL-15, IL-17, TNFα, sTNF-R1, sTNF-R2, IFNα, IFNγ) and eight growth factors (GM-CSF, EGF, bFGF, G-CSF, HGF, VEGF, EGFR, ErbB2) in repeated EDTA plasma samples collected an average of two years apart from 18 healthy women (age range: 42-62) enrolled in a prospective cohort study. We also estimated the correlation between serum and plasma biomarker levels using 18 paired clinical samples from postmenopausal women (age range: 75-86).Twenty-six assays were able to detect their analytes in at least 70% of samples. Of those 26 assays, we observed moderate to high intra-class correlation coefficients (ICCs)(ranging from 0.53-0.89) for 22 assays, and low ICCs (0-0.47) for four assays. Serum and plasma levels were highly correlated (r > 0.6) for most markers, except for seven assays (r < 0.5).

Conclusions: For 22 of the 31 biomarkers, a single plasma measurement is a reliable estimate of a woman's average level over a two-year period.
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http://dx.doi.org/10.1186/1756-0500-3-302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2997094PMC
November 2010

Circulating vitamin d and risk of epithelial ovarian cancer.

J Oncol 2009 27;2009:672492. Epub 2009 Aug 27.

Department of Environmental Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.

We conducted a nested case-control study within two prospective cohorts, the New York University Women's Health Study and the Northern Sweden Health and Disease Study, to examine the association between prediagnostic circulating levels of 25-hydroxy vitamin D (25(OH)D) and the risk of subsequent invasive epithelial ovarian cancer (EOC). The 25(OH)D levels were measured in serum or plasma from 170 incident cases of EOC and 373 matched controls. Overall, circulating 25(OH)D levels were not associated with the risk of EOC in combined cohort analysis: adjusted OR for the top tertile versus the reference tertile, 1.09 (95% CI, 0.59-2.01). In addition, there was no evidence of an interaction effect between VDR SNP genotype or haplotype and circulating 25(OH)D levels in relation to ovarian cancer risk, although more complex gene-environment interactions may exist.
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http://dx.doi.org/10.1155/2009/672492DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2735000PMC
July 2013

Postmenopausal levels of endogenous sex hormones and risk of colorectal cancer.

Cancer Epidemiol Biomarkers Prev 2009 Jan;18(1):275-81

Division of Epidemiology, Department of Environmental Medicine, New York University School of Medicine, 650 First Avenue, 5th Floor, New York, NY 10016-3240, USA.

Observational epidemiologic studies and randomized trials have reported a protective effect of oral hormonal replacement therapy on risk of colorectal cancer. Only one previous prospective study, the Women's Health Initiative Observational Study, has reported on the relationship between endogenous hormones and incident colorectal cancer. Contrary to expectation, the investigators found that women with higher circulating estradiol levels were at increased risk of developing colorectal cancer. We conducted a case-control study nested within the New York University Women's Health Study prospective cohort to evaluate the association between endogenous levels of estrone, estradiol, and sex hormone-binding globulin (SHBG) with risk of colorectal cancer. We measured hormones and SHBG in serum samples collected at enrollment from a total of 148 women who subsequently developed colorectal cancer and 293 matched controls. Circulating estrone levels were positively associated with risk of colorectal cancer: The odds ratio for the highest versus lowest quartile of estrone was 1.8 (95% confidence interval, 1.0-3.3). We found a nonsignificant inverse association between SHBG and colorectal cancer, which disappeared after adjusting for body mass index. We did not find an association between estradiol and colorectal cancer risk, but we cannot rule out a potential association because of substantial laboratory error in the measurement. Our results suggest that endogenous estrone is associated with increased risk of colorectal cancer in postmenopausal women.
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http://dx.doi.org/10.1158/1055-9965.EPI-08-0777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2682428PMC
January 2009

Vitamin D receptor polymorphisms and risk of epithelial ovarian cancer.

Cancer Lett 2008 Feb;260(1-2):209-15

Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA.

The vitamin D receptor (VDR) is a critical mediator of the cellular effects of vitamin D. The associations between four common VDR polymorphisms (BSMI, APAI, TAQI, and FOKI) and risk of epithelial ovarian cancer (EOC) were assessed in a case-control study nested within two prospective cohorts. One hundred seventy incident cases of EOC and 323 individually matched controls were genotyped. Overall, no associations were observed in genotype analyses. Haplotypes combining three SNPs in high linkage disequilibrium (BSMI, APAI, and TAQI) were also not associated with risk. These observations do not support a role for BSMI, APAI, TAQI, and FOKI polymorphisms in epithelial ovarian cancer in a predominantly Caucasian population.
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http://dx.doi.org/10.1016/j.canlet.2007.11.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2259240PMC
February 2008
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