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Neighborhood Walkability and Mortality in a Prospective Cohort of Women

India-Aldana, Sandra; Rundle, Andrew G; Zeleniuch-Jacquotte, Anne; Quinn, James W; Kim, Byoungjun; Afanasyeva, Yelena; Clendenen, Tess V; Koenig, Karen L; Liu, Mengling; Neckerman, Kathryn M; Thorpe, Lorna E; Chen, Yu
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.
PMID: 34347687
ISSN: 1531-5487
CID: 5039302

Breast cancer risk factors and circulating anti-Müllerian hormone concentration in healthy premenopausal women

Clendenen, Tess V; Ge, Wenzhen; Koenig, Karen L; Afanasyeva, Yelena; Agnoli, Claudia; Bertone-Johnson, Elizabeth; Brinton, Louise A; Darvishian, Farbod; Dorgan, Joanne F; Eliassen, A Heather; Falk, Roni T; Hallmans, Göran; Hankinson, Susan E; Hoffman-Bolton, Judith; Key, Timothy J; Krogh, Vittorio; Nichols, Hazel B; Sandler, Dale P; Schoemaker, Minouk J; Sluss, Patrick M; Sund, Malin; Swerdlow, Anthony J; Visvanathan, Kala; Liu, Mengling; Zeleniuch-Jacquotte, Anne
CONTEXT/BACKGROUND:In a previous study we reported that anti-Müllerian hormone (AMH), a marker of ovarian reserve, is positively associated with breast cancer risk, consistent with other studies. OBJECTIVE:Assess whether risk factors for breast cancer are correlates of AMH concentration. DESIGN/METHODS:Cross-sectional. PARTICIPANTS/METHODS:3831 healthy premenopausal women (aged 21-57, 87% aged 35-49). SETTING/METHODS:Ten cohort studies, general population. RESULTS:Adjusting for age and cohort, we observed positive associations of AMH with age at menarche (p<0.0001) and parity (p=0.0008), and an inverse association with hysterectomy/partial oophorectomy (p=0.0008). Compared to women of normal weight (BMI 18.5-24.9 kg/m 2, AMH was lower (relative geometric mean difference 27%, p<0.0001) among women who were obese (BMI>30). Current oral contraceptive 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/≥40), associations of AMH with BMI and oral contraceptives 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/CONCLUSIONS:This is the largest study of AMH and breast cancer risk factors among women from the general population (not presenting with infertility), and suggests that most of the associations are limited to women over 40, who are approaching menopause and whose AMH concentration is declining.
PMID: 34157104
ISSN: 1945-7197
CID: 4918342

Hepcidin-regulating iron metabolism genes and pancreatic ductal adenocarcinoma: a pathway analysis of genome-wide association studies

Julián-Serrano, Sachelly; Yuan, Fangcheng; Wheeler, William; Benyamin, Beben; Machiela, Mitchell J; Arslan, Alan A; Beane-Freeman, Laura E; Bracci, Paige M; Duell, Eric J; Du, Mengmeng; Gallinger, Steven; Giles, Graham G; Goodman, Phyllis J; Kooperberg, Charles; Marchand, Loic Le; Neale, Rachel E; Shu, Xiao-Ou; Van Den Eeden, Stephen K; Visvanathan, Kala; Zheng, Wei; Albanes, Demetrius; Andreotti, Gabriella; Ardanaz, Eva; Babic, Ana; Berndt, Sonja I; Brais, Lauren K; Brennan, Paul; Bueno-de-Mesquita, Bas; Buring, Julie E; Chanock, Stephen J; Childs, Erica J; Chung, Charles C; Fabiánová, Eleonora; Foretová, Lenka; Fuchs, Charles S; Gaziano, J Michael; Gentiluomo, Manuel; Giovannucci, Edward L; Goggins, Michael G; Hackert, Thilo; Hartge, Patricia; Hassan, Manal M; Holcátová, Ivana; Holly, Elizabeth A; Hung, Rayjean I; Janout, Vladimir; Kurtz, Robert C; Lee, I-Min; Malats, Núria; McKean, David; Milne, Roger L; Newton, Christina C; Oberg, Ann L; Perdomo, Sandra; Peters, Ulrike; Porta, Miquel; Rothman, Nathaniel; Schulze, Matthias B; Sesso, Howard D; Silverman, Debra T; Thompson, Ian M; Wactawski-Wende, Jean; Weiderpass, Elisabete; Wenstzensen, Nicolas; White, Emily; Wilkens, Lynne R; Yu, Herbert; Zeleniuch-Jacquotte, Anne; Zhong, Jun; Kraft, Peter; Li, Dounghui; Campbell, Peter T; Petersen, Gloria M; Wolpin, Brian M; Risch, Harvey A; Amundadottir, Laufey T; Klein, Alison P; Yu, Kai; Stolzenberg-Solomon, Rachael Z
BACKGROUND:Epidemiological studies have suggested positive associations for iron and red meat intake with risk of pancreatic ductal adenocarcinoma (PDAC). Inherited pathogenic variants in genes involved in the hepcidin-regulating iron metabolism pathway are known to cause iron overload and hemochromatosis. OBJECTIVES/OBJECTIVE:The objective of this study was to determine whether common genetic variation in the hepcidin-regulating iron metabolism pathway is associated with PDAC. METHODS:We conducted a pathway analysis of the hepcidin-regulating genes using single nucleotide polymorphism (SNP) summary statistics generated from 4 genome-wide association studies in 2 large consortium studies using the summary data-based adaptive rank truncated product method. Our population consisted of 9253 PDAC cases and 12,525 controls of European descent. Our analysis included 11 hepcidin-regulating genes [bone morphogenetic protein 2 (BMP2), bone morphogenetic protein 6 (BMP6), ferritin heavy chain 1 (FTH1), ferritin light chain (FTL), hepcidin (HAMP), homeostatic iron regulator (HFE), hemojuvelin (HJV), nuclear factor erythroid 2-related factor 2 (NRF2), ferroportin 1 (SLC40A1), transferrin receptor 1 (TFR1), and transferrin receptor 2 (TFR2)] and their surrounding genomic regions (±20 kb) for a total of 412 SNPs. RESULTS:The hepcidin-regulating gene pathway was significantly associated with PDAC (P = 0.002), with the HJV, TFR2, TFR1, BMP6, and HAMP genes contributing the most to the association. CONCLUSIONS:Our results support that genetic susceptibility related to the hepcidin-regulating gene pathway is associated with PDAC risk and suggest a potential role of iron metabolism in pancreatic carcinogenesis. Further studies are needed to evaluate effect modification by intake of iron-rich foods on this association.
PMID: 34258619
ISSN: 1938-3207
CID: 4938492

Prolactin and Risk of Epithelial Ovarian Cancer

Hathaway, Cassandra A; Rice, Megan S; Townsend, Mary K; Hankinson, Susan E; Arslan, Alan A; Buring, Julie E; Hallmans, Goran; Idahl, Annika; Kubzansky, Laura D; Lee, I-Min; Lundin, Eva A; Sluss, Patrick M; Zeleniuch-Jacquotte, Anne; Tworoger, Shelley S
BACKGROUND:Prolactin is synthesized in the ovaries and may play a role in ovarian cancer etiology. One prior prospective study observed a suggestive positive association between prolactin levels and risk of ovarian cancer. METHODS:We conducted a pooled case-control study of 703 cases and 864 matched controls nested within five prospective cohorts. We used unconditional logistic regression to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association between prolactin and ovarian cancer risk. We examined heterogeneity by menopausal status at blood collection, body mass index (BMI), age, and histotype. RESULTS:Among women with known menopausal status, we observed a positive trend in the association between prolactin and ovarian cancer risk (ptrend=0.045; OR, quartile 4 vs. 1=1.34; 95% CI=0.97-1.85), but no significant association was observed for premenopausal or postmenopausal women individually (corresponding OR=1.38; 95%CI=0.74-2.58; ptrend=0.32 and OR=1.41; 95% CI=0.93-2.13; ptrend=0.08, respectively; pheterogeneity=0.91). In stratified analyses, we observed a positive association between prolactin and risk for women with BMI {greater than or equal to}25 kg/m2, but not BMI <25 kg/m2 (corresponding OR=2.68; 95% CI=1.56-4.59; ptrend<0.01 and OR=0.90; 95% CI=0.58-1.40; ptrend=0.98, respectively; pheterogeneity<0.01). Associations did not vary by age, postmenopausal hormone therapy use, histotype, or time between blood draw and diagnosis. CONCLUSIONS:We found a trend between higher prolactin levels and increased ovarian cancer risk, especially among women with a BMI >=25 kg/m2. IMPACT/CONCLUSIONS:This work supports a previous study linking higher prolactin with ovarian carcinogenesis in a high adiposity setting. Future work is needed to understand the mechanism underlying this association.
PMID: 34244157
ISSN: 1538-7755
CID: 4938022

Dairy foods, calcium, and risk of breast cancer overall and for subtypes defined by estrogen receptor status: a pooled analysis of 21 cohort studies

Wu, You; Huang, Ruyi; Wang, Molin; Bernstein, Leslie; Bethea, Traci N; Chen, Chu; Chen, Yu; Eliassen, A Heather; Freedman, Neal D; Gaudet, Mia M; Gierach, Gretchen L; Giles, Graham G; Krogh, Vittorio; Larsson, Susanna C; Liao, Linda M; McCullough, Marjorie L; Miller, Anthony B; Milne, Roger L; Monroe, Kristine R; Neuhouser, Marian L; Palmer, Julie R; Prizment, Anna; Reynolds, Peggy; Robien, Kim; Rohan, Thomas E; Sandin, Sven; Sawada, Norie; Sieri, Sabina; Sinha, Rashmi; Stolzenberg-Solomon, Rachael Z; Tsugane, Shoichiro; van den Brandt, Piet A; Visvanathan, Kala; Weiderpass, Elisabete; Wilkens, Lynne R; Willett, Walter C; Wolk, Alicja; Zeleniuch-Jacquotte, Anne; Ziegler, Regina G; Smith-Warner, Stephanie A
BACKGROUND:Epidemiologic studies examining the relations between dairy product and calcium intakes and breast cancer have been inconclusive, especially for tumor subtypes. OBJECTIVE:To evaluate the associations between intakes of specific dairy products and calcium and risk of breast cancer overall and for subtypes defined by estrogen receptor (ER) status. METHOD/METHODS:We pooled the individual-level data of over 1 million women who were followed for a maximum of 8-20 years across studies. Associations were evaluated for dairy product and calcium intakes and risk of incident invasive breast cancer overall (n = 37,861 cases) and by subtypes defined by ER status. Study-specific multivariable hazard ratios (HRs) were estimated and then combined using random-effects models. RESULTS:Overall, no clear association was observed between the consumption of specific dairy foods, dietary (from foods only) calcium, and total (from foods and supplements) calcium, and risk of overall breast cancer. Although each dairy product showed a null or very weak inverse association with risk of overall breast cancer (P, test for trend >0.05 for all), differences by ER status were suggested for yogurt and cottage/ricotta cheese with associations observed for ER-negative tumors only (pooled HR = 0.90, 95% CI: 0.83, 0.98 comparing ≥60 g/d with <1 g/d of yogurt and 0.85, 95% CI: 0.76, 0.95 comparing ≥25 g/d with <1 g/d of cottage/ricotta cheese). Dietary calcium intake was only weakly associated with breast cancer risk (pooled HR = 0.98, 95% CI: 0.97, 0.99 per 350 mg/d). CONCLUSION/CONCLUSIONS:Our study shows that adult dairy or calcium consumption is unlikely to associate with a higher risk of breast cancer and that higher yogurt and cottage/ricotta cheese intakes were inversely associated with the risk of ER-negative breast cancer, a less hormonally dependent subtype with poor prognosis. Future studies on fermented dairy products, earlier life exposures, ER-negative breast cancer, and different racial/ethnic populations may further elucidate the relation.
PMID: 33964859
ISSN: 1938-3207
CID: 4866972

Epidemiology of 40 blood biomarkers of one-carbon metabolism, vitamin status, inflammation, and renal and endothelial function among cancer-free older adults

Zahed, Hana; Johansson, Mattias; Ueland, Per M; Midttun, Øivind; Milne, Roger L; Giles, Graham G; Manjer, Jonas; Sandsveden, Malte; Langhammer, Arnulf; Sørgjerd, Elin Pettersen; Grankvist, Kjell; Johansson, Mikael; Freedman, Neal D; Huang, Wen-Yi; Chen, Chu; Prentice, Ross; Stevens, Victoria L; Wang, Ying; Le Marchand, Loic; Wilkens, Lynne R; Weinstein, Stephanie J; Albanes, Demetrius; Cai, Qiuyin; Blot, William J; Arslan, Alan A; Zeleniuch-Jacquotte, Anne; Shu, Xiao-Ou; Zheng, Wei; Yuan, Jian-Min; Koh, Woon-Puay; Visvanathan, Kala; Sesso, Howard D; Zhang, Xuehong; Gaziano, J Michael; Fanidi, Anouar; Muller, David; Brennan, Paul; Guida, Florence; Robbins, Hilary A
Imbalances of blood biomarkers are associated with disease, and biomarkers may also vary non-pathologically across population groups. We described variation in concentrations of biomarkers of one-carbon metabolism, vitamin status, inflammation including tryptophan metabolism, and endothelial and renal function among cancer-free older adults. We analyzed 5167 cancer-free controls aged 40-80 years from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). Centralized biochemical analyses of 40 biomarkers in plasma or serum were performed. We fit multivariable linear mixed effects models to quantify variation in standardized biomarker log-concentrations across four factors: age, sex, smoking status, and body mass index (BMI). Differences in most biomarkers across most factors were small, with 93% (186/200) of analyses showing an estimated difference lower than 0.25 standard-deviations, although most were statistically significant due to large sample size. The largest difference was for creatinine by sex, which was - 0.91 standard-deviations lower in women than men (95%CI - 0.98; - 0.84). The largest difference by age was for total cysteine (0.40 standard-deviation increase per 10-year increase, 95%CI 0.36; 0.43), and by BMI was for C-reactive protein (0.38 standard-deviation increase per 5-kg/m2 increase, 95%CI 0.34; 0.41). For 31 of 40 markers, the mean difference between current and never smokers was larger than between former and never smokers. A statistically significant (p < 0.05) association with time since smoking cessation was observed for 8 markers, including C-reactive protein, kynurenine, choline, and total homocysteine. We conclude that most blood biomarkers show small variations across demographic characteristics. Patterns by smoking status point to normalization of multiple physiological processes after smoking cessation.
PMCID:8257595
PMID: 34226613
ISSN: 2045-2322
CID: 4933002

Smoking modifies pancreatic cancer risk loci on 2q21.3

Mocci, Evelina; Kundu, Prosenjit; Wheeler, William; Arslan, Alan A; Beane Freeman, Laura E; Bracci, Paige M; Brennan, Paul; Canzian, Federico; Du, Mengmeng; Gallinger, Steven; Giles, Graham G; Goodman, Phyllis J; Kooperberg, Charles; Le Marchand, Loic; Neale, Rachel E; Shu, Xiao-Ou; Visvanathan, Kala; White, Emily; Zheng, Wei; Albanes, Demetrius; Andreotti, Gabriella; Babic, Ana; Bamlet, William R; Berndt, Sonja I; Blackford, Amanda L; Bueno-de-Mesquita, Bas; Buring, Julie E; Campa, Daniele; Chanock, Stephen J; Childs, Erica J; Duell, Eric J; Fuchs, Charles S; Gaziano, J Michael; Giovannucci, Edward L; Goggins, Michael G; Hartge, Patricia; Hassan, Manal M; Holly, Elizabeth A; Hoover, Robert N; Hung, Rayjean J; Kurtz, Robert C; Lee, I-Min; Malats, Nuria; Milne, Roger L; Ng, Kimmie; Oberg, Ann L; Panico, Salvatore; Peters, Ulrike; Porta, Miquel; Rabe, Kari G; Riboli, Elio; Rothman, Nathaniel; Scelo, Ghislaine; Sesso, Howard D; Silverman, Debra T; Stevens, Victoria L; Strobel, Oliver; Thompson, Ian M; Tjonneland, Anne; Trichopoulou, Antonia; Van Den Eeden, Stephen K; Wactawski-Wende, Jean; Wentzensen, Nicolas; Wilkens, Lynne R; Yu, Herbert; Yuan, Fangcheng; Zeleniuch-Jacquotte, Anne; Amundadottir, Laufey T; Li, Donghui; Jacobs, Eric J; Petersen, Gloria M; Wolpin, Brian M; Risch, Harvey A; Kraft, Peter; Chatterjee, Nilanjan; Klein, Alison P; Stolzenberg-Solomon, Rachael Z
Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine if there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P-values < 5 x 10-8 were considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region which included 45 significantly associated SNPs, was rs1818613 (per allele OR in never smokers 0.87, 95% CI 0.82-0.93; former smokers 1.00, 95 CI 0.91-1.07; current smokers 1.25, 95%CI 1.12-1.40, interaction P-value=3.08x10-9). Examination of the Genotype-Tissue Expression Project data demonstrated an expression quantitative trait locus in this region for TMEM163 and CCNT2 in several tissue types. Colocalization analysis supported a shared SNP, rs842357, in high LD with rs1818613 (r2=0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings.
PMID: 33574088
ISSN: 1538-7445
CID: 4780022

Prediagnostic antibody responses to Fusobacterium nucleatum proteins are not associated with risk of colorectal cancer in a large United States consortium

Lo, Chun-Han; Blot, William J; Teras, Lauren R; Visvanathan, Kala; Le Marchand, Loic; Haiman, Christopher A; Chen, Yu; Sesso, Howard D; Wassertheil-Smoller, Sylvia; Tinker, Lesley F; Peek, Richard M; Potter, John D; Cover, Timothy L; Zeleniuch-Jacquotte, Anne; Berndt, Sonja I; Waterboer, Tim; Epplein, Meira; Butt, Julia; Song, Mingyang
BACKGROUND:The association between prediagnostic antibody responses to Fusobacterium nucleatum (F. nucleatum) and subsequent risk of colorectal cancer (CRC) is not established. METHODS:We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States. RESULTS:Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared to White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and CRC risk. CONCLUSIONS:Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of CRC. IMPACT/CONCLUSIONS:Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue samples.
PMID: 33737297
ISSN: 1538-7755
CID: 4818082

Nongenetic Determinants of Risk for Early-Onset Colorectal Cancer

Archambault, Alexi N; Lin, Yi; Jeon, Jihyoun; Harrison, Tabitha A; Bishop, D Timothy; Brenner, Hermann; Casey, Graham; Chan, Andrew T; Chang-Claude, Jenny; Figueiredo, Jane C; Gallinger, Steven; Gruber, Stephen B; Gunter, Marc J; Hoffmeister, Michael; Jenkins, Mark A; Keku, Temitope O; Marchand, Loïc Le; Li, Li; Moreno, Victor; Newcomb, Polly A; Pai, Rish; Parfrey, Patrick S; Rennert, Gad; Sakoda, Lori C; Sandler, Robert S; Slattery, Martha L; Song, Mingyang; Win, Aung Ko; Woods, Michael O; Murphy, Neil; Campbell, Peter T; Su, Yu-Ru; Zeleniuch-Jacquotte, Anne; Liang, Peter S; Du, Mengmeng; Hsu, Li; Peters, Ulrike; Hayes, Richard B
Background/UNASSIGNED:Incidence of early-onset (younger than 50 years of age) colorectal cancer (CRC) is increasing in many countries. Thus, elucidating the role of traditional CRC risk factors in early-onset CRC is a high priority. We sought to determine whether risk factors associated with late-onset CRC were also linked to early-onset CRC and whether association patterns differed by anatomic subsite. Methods/UNASSIGNED:Using data pooled from 13 population-based studies, we studied 3767 CRC cases and 4049 controls aged younger than 50 years and 23 437 CRC cases and 35 311 controls aged 50 years and older. Using multivariable and multinomial logistic regression, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) to assess the association between risk factors and early-onset CRC and by anatomic subsite. Results/UNASSIGNED: = .04). Conclusion/UNASSIGNED:In this large study, we identified several nongenetic risk factors associated with early-onset CRC, providing a basis for targeted identification of those most at risk, which is imperative in mitigating the rising burden of this disease.
PMCID:8134523
PMID: 34041438
ISSN: 2515-5091
CID: 4888152

Pregnancy Outcomes and Risk of Endometrial Cancer: A Pooled Analysis of Individual Participant Data in the Epidemiology of Endometrial Cancer Consortium

Jordan, Susan J; Na, Renhua; Weiderpass, Elisabete; Adami, Hans-Olov; Anderson, Kristin E; van den Brandt, Piet A; Brinton, Louise A; Chen, Chu; Cook, Linda S; Doherty, Jennifer A; Du, Mengmeng; Friedenreich, Christine M; Gierach, Gretchen L; Goodman, Marc T; Krogh, Vittorio; Levi, Fabio; Lu, Lingeng; Miller, Anthony B; McCann, Susan E; Moysich, Kirsten B; Negri, Eva; Olson, Sara H; Petruzella, Stacey; Palmer, Julie R; Parazzini, Fabio; Pike, Malcolm C; Prizment, Anna E; Rebbeck, Timothy R; Reynolds, Peggy; Ricceri, Fulvio; Risch, Harvey A; Rohan, Thomas E; Sacerdote, Carlotta; Schouten, Leo J; Serraino, Diego; Setiawan, Veronica W; Shu, Xiao-Ou; Sponholtz, Todd R; Spurdle, Amanda B; Stolzenberg-Solomon, Rachael Z; Trabert, Britton; Wentzensen, Nicolas; Wilkens, Lynne R; Wise, Lauren A; Yu, Herbert; La Vecchia, Carlo; De Vivo, Immaculata; Xu, Wanghong; Zeleniuch-Jacquotte, Anne; Webb, Penelope M
A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16,986 women with endometrial cancer and 39,538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (OR) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR=0.59, 95% confidence interval (CI) 0.56-0.63). The risk reduction appeared greatest for the first full-term pregnancy (OR=0.78, 95%CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR=0.20, 95%CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
PMID: 33105052
ISSN: 1097-0215
CID: 4646372