Person: Prescott, Jennifer
Loading...
Email Address
AA Acceptance Date
Birth Date
Research Projects
Organizational Units
Job Title
Last Name
Prescott
First Name
Jennifer
Name
Prescott, Jennifer
13 results
Search Results
Now showing 1 - 10 of 13
Publication Exome-Wide Association Study of Endometrial Cancer in a Multiethnic Population(Public Library of Science, 2014) Chen, Maxine M.; Crous-Bou, Marta; Setiawan, Veronica W.; Prescott, Jennifer; Olson, Sara H.; Wentzensen, Nicolas; Black, Amanda; Brinton, Louise; Chen, Chu; Chen, Constance; Cook, Linda S.; Doherty, Jennifer; Friedenreich, Christine M.; Hankinson, Susan; Hartge, Patricia; Henderson, Brian E.; Hunter, David; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Orlow, Irene; Petruzella, Stacey; Polidoro, Silvia; Pooler, Loreall; Rebbeck, Timothy R.; Risch, Harvey; Sacerdote, Carlotta; Schumacher, Frederick; Sheng, Xin; Shu, Xiao-ou; Weiss, Noel S.; Xia, Lucy; Van Den Berg, David; Yang, Hannah P.; Yu, Herbert; Chanock, Stephen; Haiman, Christopher; Kraft, Phillip; De Vivo, ImmaculataEndometrial cancer (EC) contributes substantially to total burden of cancer morbidity and mortality in the United States. Family history is a known risk factor for EC, thus genetic factors may play a role in EC pathogenesis. Three previous genome-wide association studies (GWAS) have found only one locus associated with EC, suggesting that common variants with large effects may not contribute greatly to EC risk. Alternatively, we hypothesize that rare variants may contribute to EC risk. We conducted an exome-wide association study (EXWAS) of EC using the Infinium HumanExome BeadChip in order to identify rare variants associated with EC risk. We successfully genotyped 177,139 variants in a multiethnic population of 1,055 cases and 1,778 controls from four studies that were part of the Epidemiology of Endometrial Cancer Consortium (E2C2). No variants reached global significance in the study, suggesting that more power is needed to detect modest associations between rare genetic variants and risk of EC.Publication Telomere Length and the Risk of Cutaneous Malignant Melanoma in Melanoma-Prone Families with and without CDKN2A Mutations(Public Library of Science, 2013) Burke, Laura S.; Hyland, Paula L.; Pfeiffer, Ruth M.; Prescott, Jennifer; Wheeler, William; Mirabello, Lisa; Savage, Sharon A.; Burdette, Laurie; Yeager, Meredith; Chanock, Stephen; De Vivo, Immaculata; Tucker, Margaret A.; Goldstein, Alisa M.; Yang, Xiaohong R.Introduction: Recent evidence suggests a link between constitutional telomere length (TL) and cancer risk. Previous studies have suggested that longer telomeres were associated with an increased risk of melanoma and larger size and number of nevi. The goal of this study was to examine whether TL modified the risk of melanoma in melanoma-prone families with and without CDKN2A germline mutations. Materials and Methods We measured TL in blood DNA in 119 cutaneous malignant melanoma (CMM) cases and 208 unaffected individuals. We also genotyped 13 tagging SNPs in TERT. Results: We found that longer telomeres were associated with an increased risk of CMM (adjusted OR = 2.81, 95% CI = 1.02–7.72, P = 0.04). The association of longer TL with CMM risk was seen in CDKN2A- cases but not in CDKN2A+ cases. Among CMM cases, the presence of solar injury was associated with shorter telomeres (P = 0.002). One SNP in TERT, rs2735940, was significantly associated with TL (P = 0.002) after Bonferroni correction. Discussion Our findings suggest that TL regulation could be variable by CDKN2A mutation status, sun exposure, and pigmentation phenotype. Therefore, TL measurement alone may not be a good marker for predicting CMM risk.Publication Surrogates of Long-Term Vitamin D Exposure and Ovarian Cancer Risk in Two Prospective Cohort Studies(MDPI, 2013) Prescott, Jennifer; Bertrand, Kimberly; Poole, Elizabeth M.; Rosner, Bernard; Tworoger, ShelleyExperimental evidence and ecologic studies suggest a protective role of vitamin D in ovarian carcinogenesis. However, epidemiologic studies using individual level data have been inconsistent. We evaluated ultraviolet (UV)-B radiation, vitamin D intake, and predicted plasma 25-hydroxyvitamin D [25(OH)D] levels as long-term surrogates of vitamin D exposure within the Nurses’ Health Study (NHS) and NHSII. We estimated incidence rate ratios (RRs) and 95% confidence intervals (CIs) for risk of overall ovarian cancer and by histologic subtype using Cox proportional hazards models. Between 1976 and 2010 in NHS and 1989 and 2011 in NHSII, we identified a total of 1,225 incident epithelial ovarian cancer cases (NHS: 970, NHSII: 255) over 4,628,648 person-years of follow-up. Cumulative average UV-B exposure was not associated with ovarian cancer risk in NHS (Ptrend = 0.08), but was associated with reduced risk in NHSII (highest vs. lowest category RR = 0.67; 95% CI: 0.50, 0.89; Ptrend < 0.01). When stratified by histologic subtype, UV-B flux was positively associated with risk of serous tumors in NHS (Ptrend < 0.01), but inversely associated in NHSII (Ptrend = 0.01). Adjusted for confounders, ovarian cancer risk was not associated with vitamin D intake from food or supplements or with predicted 25(OH)D levels. Our study does not strongly support a protective role for vitamin D in ovarian cancer risk.Publication Genome-wide association study of endometrial cancer in E2C2(Springer Berlin Heidelberg, 2013) De Vivo, Immaculata; Prescott, Jennifer; Setiawan, Veronica Wendy; Olson, Sara H.; Wentzensen, Nicolas; Attia, John; Black, Amanda; Brinton, Louise; Chen, Chu; Turman, Constance; Cook, Linda S.; Crous-Bou, Marta; Doherty, Jennifer; Dunning, Alison M.; Easton, Douglas F.; Friedenreich, Christine M.; Garcia-Closas, Montserrat; Gaudet, Mia M.; Haiman, Christopher; Hankinson, Susan; Hartge, Patricia; Henderson, Brian E.; Holliday, Elizabeth; Horn-Ross, Pamela L.; Hunter, David; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Long, Jirong; Lu, Lingeng; Magliocco, Anthony M.; McEvoy, Mark; O’Mara, Tracy A.; Orlow, Irene; Painter, Jodie N.; Pooler, Loreall; Rastogi, Radhai; Rebbeck, Timothy R.; Risch, Harvey; Sacerdote, Carlotta; Schumacher, Fredrick; Scott, Rodney J.; Sheng, Xin; Shu, Xiao-ou; Spurdle, Amanda B.; Thompson, Deborah; VanDen Berg, David; Weiss, Noel S.; Xia, Lucy; Xiang, Yong-Bing; Yang, Hannah P.; Yu, Herbert; Zheng, Wei; Chanock, Stephen; Kraft, PhillipEndometrial cancer (EC), a neoplasm of the uterine epithelial lining, is the most common gynecological malignancy in developed countries and the fourth most common cancer among US women. Women with a family history of EC have an increased risk for the disease, suggesting that inherited genetic factors play a role. We conducted a two-stage genome-wide association study of Type I EC. Stage 1 included 5,472 women (2,695 cases and 2,777 controls) of European ancestry from seven studies. We selected independent single-nucleotide polymorphisms (SNPs) that displayed the most significant associations with EC in Stage 1 for replication among 17,948 women (4,382 cases and 13,566 controls) in a multiethnic population (African America, Asian, Latina, Hawaiian and European ancestry), from nine studies. Although no novel variants reached genome-wide significance, we replicated previously identified associations with genetic markers near the HNF1B locus. Our findings suggest that larger studies with specific tumor classification are necessary to identify novel genetic polymorphisms associated with EC susceptibility. Electronic supplementary material The online version of this article (doi:10.1007/s00439-013-1369-1) contains supplementary material, which is available to authorized users.Publication Body Mass Index Genetic Risk Score and Endometrial Cancer Risk(Public Library of Science, 2015) Prescott, Jennifer; Setiawan, Veronica W.; Wentzensen, Nicolas; Schumacher, Fredrick; Yu, Herbert; Delahanty, Ryan; Bernstein, Leslie; Chanock, Stephen J.; Chen, Chu; Cook, Linda S.; Friedenreich, Christine; Garcia-Closas, Monserrat; Haiman, Christopher A.; Le Marchand, Loic; Liang, Xiaolin; Lissowska, Jolanta; Lu, Lingeng; Magliocco, Anthony M.; Olson, Sara H.; Risch, Harvey A.; Shu, Xiao-Ou; Ursin, Giske; Yang, Hannah P.; Kraft, Phillip; De Vivo, ImmaculataGenome-wide association studies (GWAS) have identified common variants that predispose individuals to a higher body mass index (BMI), an independent risk factor for endometrial cancer. Composite genotype risk scores (GRS) based on the joint effect of published BMI risk loci were used to explore whether endometrial cancer shares a genetic background with obesity. Genotype and risk factor data were available on 3,376 endometrial cancer case and 3,867 control participants of European ancestry from the Epidemiology of Endometrial Cancer Consortium GWAS. A BMI GRS was calculated by summing the number of BMI risk alleles at 97 independent loci. For exploratory analyses, additional GRSs were based on subsets of risk loci within putative etiologic BMI pathways. The BMI GRS was statistically significantly associated with endometrial cancer risk (P = 0.002). For every 10 BMI risk alleles a woman had a 13% increased endometrial cancer risk (95% CI: 4%, 22%). However, after adjusting for BMI, the BMI GRS was no longer associated with risk (per 10 BMI risk alleles OR = 0.99, 95% CI: 0.91, 1.07; P = 0.78). Heterogeneity by BMI did not reach statistical significance (P = 0.06), and no effect modification was noted by age, GWAS Stage, study design or between studies (P≥0.58). In exploratory analyses, the GRS defined by variants at loci containing monogenic obesity syndrome genes was associated with reduced endometrial cancer risk independent of BMI (per BMI risk allele OR = 0.92, 95% CI: 0.88, 0.96; P = 2.1 x 10−5). Possessing a large number of BMI risk alleles does not increase endometrial cancer risk above that conferred by excess body weight among women of European descent. Thus, the GRS based on all current established BMI loci does not provide added value independent of BMI. Future studies are required to validate the unexpected observed relation between monogenic obesity syndrome genetic variants and endometrial cancer risk.Publication Evidence of Differential Effects of Vitamin D Receptor Variants on Epithelial Ovarian Cancer Risk by Predicted Vitamin D Status(Frontiers Media S.A., 2014) Prescott, Jennifer; Bertrand, Kimberly; Reid, Brett M.; Permuth-Wey, Jennifer; De Vivo, Immaculata; Cramer, Daniel; Terry, Kathryn; Tworoger, ShelleyIntroduction: Experimental studies suggest vitamin D inhibits ovarian carcinogenesis. Yet, epidemiologic studies of ovarian cancer risk and lifestyle correlates of vitamin D status, plasma 25-hydroxyvitamin D [25(OH)D], or vitamin D receptor (VDR) variants have been inconsistent. Objective: To evaluate VDR genetic associations by high vs. low predicted 25(OH)D, scores derived from known determinants of plasma 25(OH)D. To assess ovarian cancer associations with variants identified in genome-wide association studies (GWAS) of plasma 25(OH)D. Methods: We genotyped up to seven VDR and eight 25(OH)D GWAS variants in the Nurses’ Health Studies (562 cases, 1,553 controls) and New England Case–Control study (1,821 cases, 1,870 controls). We estimated haplotype scores using expectation-maximization-based algorithms. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CI). We combined study results using DerSimonian and Laird meta-analysis. Results: Ovarian cancer risk increased per A allele of rs7975232 (VDR; OR = 1.12, 95% CI = 1.01–1.25) among all women. When stratified by predicted 25(OH)D, ovarian cancer was associated with rs731236 (VDR; per C allele OR = 1.31) and rs7975232 (OR = 1.38) among women with high predicted 25(OH)D, but not among women with low levels (P ≤ 0.009). We also observed heterogeneity by predicted 25(OH)D for the ovarian cancer association with VDR 3′ end haplotypes (P = 0.009). Of 25(OH)D-associated GWAS loci, rs7041 was associated with reduced ovarian cancer risk (per T allele OR = 0.92, 95% CI = 0.85-0.99), which did not differ by predicted 25(OH)D status. Conclusion: Our study suggests an influence of VDR 3′ end variants on ovarian cancer risk may be observed in women with high predicted 25(OH)D, which remained even after taking multiple comparisons into consideration. Future studies are needed to confirm our results and explore further the relation between vitamin D exposure, genetic variants, and ovarian cancer risk.Publication Mediterranean diet and telomere length in Nurses’ Health Study: population based cohort study(BMJ Publishing Group Ltd., 2014) Crous-Bou, Marta; Fung, Teresa; Prescott, Jennifer; Julin, Bettina; Du, Mengmeng; Sun, Qi; Rexrode, Kathryn; Hu, Frank; De Vivo, ImmaculataObjective: To examine whether adherence to the Mediterranean diet was associated with longer telomere length, a biomarker of aging. Design: Population based cohort study. Setting: Nurses’ Health Study, an ongoing prospective cohort study of 121 700 nurses enrolled in 1976; in 1989-90 a subset of 32 825 women provided blood samples. Participants: 4676 disease-free women from nested case-control studies within the Nurses’ Health Study with telomere length measured who also completed food frequency questionnaires. Main outcome measure Association between relative telomere lengths in peripheral blood leukocytes measured by quantitative real time polymerase chain reaction and Alternate Mediterranean Diet score calculated from self reported dietary data. Results: Greater adherence to the Mediterranean diet was associated with longer telomeres after adjustment for potential confounders. Least squares mean telomere length z scores were −0.038 (SE 0.035) for the lowest Mediterranean diet score groups and 0.072 (0.030) for the highest group (P for trend=0.004). Conclusion: In this large study, greater adherence to the Mediterranean diet was associated with longer telomeres. These results further support the benefits of adherence to the Mediterranean diet for promoting health and longevity.Publication Childhood Physical and Sexual Abuse History and Leukocyte Telomere Length among Women in Middle Adulthood(Public Library of Science, 2015) Mason, Susan M.; Prescott, Jennifer; Tworoger, Shelley; DeVivo, Immaculata; Rich-Edwards, JanetObjective: Abuse victimization in childhood is associated with a variety of age-related cardiometabolic diseases, but the mechanisms remain unknown. Telomeres, which form the protective caps at the ends of chromosomes, have been proposed as measures of biological age, and a growing body of research suggests that telomere attrition may help to explain relationships between stress and cardiometabolic degradation. We examined the association between childhood abuse victimization and leukocyte telomere length among 1,135 participants in the Nurses’ Health Study II (NHSII). Methods: The NHSII ascertained physical and sexual child abuse histories in 2001. Telomere length was measured in genomic DNA extracted from peripheral blood leukocytes collected between 1996 and 1999. The ratio of telomere repeat copy number to a single gene copy number (T/S) was determined by a modified version of the quantitative real-time PCR telomere assay. Telomere length was log-transformed and corrected for assay variation across batch. We regressed telomere length on childhood abuse exposure variables and covariates using linear regression. Results: We observed a reduction in telomere length associated with moderate physical abuse versus no physical abuse, but there was no evidence of a dose-response relationship for increased severity of physical abuse. No associations were noted for sexual abuse. Conclusions: We found no evidence of an association between severity of childhood physical or sexual abuse and leukocyte telomere length in the NHSII.Publication Healthy Lifestyle and Leukocyte Telomere Length in U.S. Women(Public Library of Science, 2012) Sun, Qi; Shi, Ling; Prescott, Jennifer; Chiuve, Stephanie; Hu, Frank; De Vivo, Immaculata; Stampfer, Meir; Franks, Paul W.; Manson, JoAnn; Rexrode, KathrynContext: Whether a healthy lifestyle may be associated with longer telomere length is largely unknown. Objectives: To examine healthy lifestyle practices, which are primary prevention measures against major age-related chronic diseases, in relation to leukocyte telomere length. Design and Setting Cross-sectional analysis in the Nurses' Health Study (NHS). Participants: The population consisted of 5,862 women who participated in multiple prospective case-control studies within the NHS cohort. Z scores of leukocyte telomere length were derived within each case-control study. Based on prior work, we defined low-risk or healthy categories for five major modifiable factors assessed in 1988 or 1990: non-current smoking, maintaining a healthy body weight (body mass index in 18.5–24.9 kg/m\(^2\)), engaging in regular moderate or vigorous physical activities (\(\geq\)150 minutes/week), drinking alcohol in moderation (1 drink/week to <2 drinks/day), and eating a healthy diet (Alternate Healthy Eating Index score in top 50%). We calculated difference (%) of the z scores contrasting low-risk groups with reference groups to evaluate the association of interest. Results: Although none of the individual low-risk factors was significantly associated with larger leukocyte telomere length z scores, we observed a significant, positive relationship between the number of low-risk factors and the z scores. In comparison with women who had zero low-risk factors (1.9% of the total population) and were, therefore, considered the least healthy group, the leukocyte telomere length z scores were 16.4%, 22.1%, 28.7%, 22.6%, and 31.2% (P for trend = 0.015) higher for women who had 1 to 5 low-risk factors, respectively. Conclusions: Adherence to a healthy lifestyle, defined by major modifiable risk factors, was associated with longer telomere length in leukocytes.Publication Genome-Wide Association Study of Circulating Estradiol, Testosterone, and Sex Hormone-Binding Globulin in Postmenopausal Women(Public Library of Science, 2012) Prescott, Jennifer; Thompson, Deborah J.; Kraft, Peter; Chanock, Stephen J.; Audley, Tina; Brown, Judith; Leyland, Jean; Folkerd, Elizabeth; Doody, Deborah; Hankinson, Susan; Hunter, David; Jacobs, Kevin B.; Dowsett, Mitch; Cox, David G.; Easton, Douglas F.; De Vivo, ImmaculataGenome-wide association studies (GWAS) have successfully identified common genetic variants that contribute to breast cancer risk. Discovering additional variants has become difficult, as power to detect variants of weaker effect with present sample sizes is limited. An alternative approach is to look for variants associated with quantitative traits that in turn affect disease risk. As exposure to high circulating estradiol and testosterone, and low sex hormone-binding globulin (SHBG) levels is implicated in breast cancer etiology, we conducted GWAS analyses of plasma estradiol, testosterone, and SHBG to identify new susceptibility alleles. Cancer Genetic Markers of Susceptibility (CGEMS) data from the Nurses’ Health Study (NHS), and Sisters in Breast Cancer Screening data were used to carry out primary meta-analyses among ∼1600 postmenopausal women who were not taking postmenopausal hormones at blood draw. We observed a genome-wide significant association between SHBG levels and rs727428 (joint \(\beta\) = -0.126; joint P = 2.09×10–16), downstream of the SHBG gene. No genome-wide significant associations were observed with estradiol or testosterone levels. Among variants that were suggestively associated with estradiol (P<10–5), several were located at the CYP19A1 gene locus. Overall results were similar in secondary meta-analyses that included ∼900 NHS current postmenopausal hormone users. No variant associated with estradiol, testosterone, or SHBG at P<10–5 was associated with postmenopausal breast cancer risk among CGEMS participants. Our results suggest that the small magnitude of difference in hormone levels associated with common genetic variants is likely insufficient to detectably contribute to breast cancer risk.