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1. Characterizing a Clinical Trial – Representative, Real-World Population with Heart Failure with Reduced Ejection Fraction

Author

Wells QS, Farber-Eger E, Lipworth L, Dluzniewski P, Dent R, Umeijiego J, and Cohen SS

Subjects
heart failure, reduced ejection fraction, real world evidence, electronic health record, Infectious and parasitic diseases, RC109-216
Abstract

Quinn S Wells,1,2 Eric Farber-Eger,1,2 Loren Lipworth,2,3 Paul Dluzniewski,4 Ricardo Dent,4 John Umeijiego,4 Sarah S Cohen3,5 1Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; 2Vanderbilt Translational and Clinical Cardiovascular Research Center (VTRACC), Vanderbilt University Medical Center, Nashville, TN, USA; 3Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA; 4Center for Observational Research, Amgen, Inc., Thousand Oaks, CA, USA; 5Epidstrategies, A Division of Toxstrategies, Inc., Cary, NC, USACorrespondence: Sarah S Cohen Tel +1 919-885-0548Email scohen@epidstrategies.comPurpose: Given known differences between real-world and clinical trial populations, we characterized demographics, clinical characteristics, and outcomes using real-world (RW) data for patients with heart failure with reduced ejection fraction (HFrEF), including those similar to subjects enrolled in an HFrEF clinical trial to better understand patient populations that could benefit from novel therapies.Patients and Methods: Using Vanderbilt University Medical Center electronic health records (2006– 2019), two RW cohorts of HFrEF patients were identified. The “Clinical Cohort” was based on a validated HFrEF algorithm and left ventricular ejection fraction (LVEF) ≤ 40%. The “GALACTIC-HF-like Cohort” mirrored enrollment requirements of the GALACTIC-HF clinical trial including hospitalizations, medications, laboratory values, and LVEF ≤ 35%.Results: Median age at index for the Clinical Cohort (N = 3954) and GALACTIC-HF-like Cohort (N = 1541) were 65 and 61 years, respectively; both were 67% male and 80% white. Over half had coronary artery disease (55% Clinical vs 64% GALACTIC-HF-like); hypercholesterolemia was common (69% Clinical vs 74% GALACTIC-HF-like). Chronic kidney disease (31 vs 21%), atrial fibrillation (32 vs 29%), and cardiac resynchronization or implantable cardioverter defibrillator (26 vs 23%) were higher in the GALACTIC-HF-like Cohort. ACE inhibitor use was high in both groups but more common in the GALACTIC-HF-like Cohort (71% and 82%, respectively). Beta-blockers or loop diuretics were used by > 90% of both cohorts. HF hospitalization rates were 261 (95% CI 224, 297) per 1000 person-years in Clinical versus 523 (484, 562) in GALACTIC-HF-like Cohort (median follow-up of 2.9 and 4.2 years, respectively).Conclusion: Approximately 40% of RW HFrEF patients met criteria for the GALACTIC-HF trial. While findings of ongoing clinical trials may be directly generalizable to this sizable proportion of patients, future trials should examine whether the majority of patients with lower prevalence of comorbidities and rate of HF hospitalization could benefit from emerging HF treatments.Keywords: heart failure, reduced ejection fraction, real-world evidence, electronic health record

Published
2022

2. Cross-Cancer Genome-Wide Association Study of Endometrial Cancer and Epithelial Ovarian Cancer Identifies Genetic Risk Regions Associated with Risk of Both Cancers.

Author

Glubb D.M., Thompson D.J., Aben K.K.H., Alsulimani A., Amant F., Annibali D., Attia J., Barricarte A., Beckmann M.W., Berchuck A., Bermisheva M., Bernardini M.Q., Bischof K., Bjorge L., Bodelon C., Brand A.H., Brenton J.D., Brinton L.A., Bruinsma F., Buchanan D.D., Burghaus S., Butzow R., Cai H., Carney M.E., Chanock S.J., Chen C., Chen X.Q., Chen Z., Cook L.S., Cunningham J.M., De Vivo I., deFazio A., Doherty J.A., Dork T., du Bois A., Dunning A.M., Durst M., Edwards T., Edwards R.P., Ekici A.B., Ewing A., Fasching P.A., Ferguson S., Flanagan J.M., Fostira F., Fountzilas G., Friedenreich C.M., Gao B., Gaudet M.M., Gawelko J., Gentry-Maharaj A., Giles G.G., Glasspool R., Goodman M.T., Gronwald J., Harris H.R., Harter P., Hein A., Heitz F., Hildebrandt M.A.T., Hillemanns P., Hogdall E., Hogdall C.K., Holliday E.G., Huntsman D.G., Huzarski T., Jakubowska A., Jensen A., Jones M.E., Karlan B.Y., Karnezis A., Kelley J.L., Khusnutdinova E., Killeen J.L., Kjaer S.K., Klapdor R., Kobel M., Konopka B., Konstantopoulou I., Kopperud R.K., Koti M., Kraft P., Kupryjanczyk J., Lambrechts D., Larson M.C., Le Marchand L., Lele S., Lester J., Li A.J., Liang D., Liebrich C., Lipworth L., Lissowska J., Lu L., Lu K.H., Macciotta A., Mattiello A., May T., McAlpine J.N., McGuire V., McNeish I.A., Menon U., Modugno F., Moysich K.B., Nevanlinna H., Odunsi K., Olsson H., Orsulic S., Osorio A., Palli D., Park-Simon T.-W., Pearce C.L., Pejovic T., Permuth J.B., Podgorska A., Ramus S.J., Rebbeck T.R., Riggan M.J., Risch H.A., Rothstein J.H., Runnebaum I.B., Scott R.J., Sellers T.A., Senz J., Setiawan V.W., Siddiqui N., Sieh W., Spiewankiewicz B., Sutphen R., Swerdlow A.J., Szafron L.M., Teo S.H., Thompson P.J., Thomsen L.C.V., Titus L., Tone A., Tumino R., Turman C., Vanderstichele A., Edwards D.V., Vergote I., Vierkant R.A., Wang Z., Wang-Gohrke S., Webb P.M., White E., Whittemore A.S., Winham S.J., Wu X., Wu A.H., Yannoukakos D., Spurdle A.B., O'Mara T.A., Glubb D.M., Thompson D.J., Aben K.K.H., Alsulimani A., Amant F., Annibali D., Attia J., Barricarte A., Beckmann M.W., Berchuck A., Bermisheva M., Bernardini M.Q., Bischof K., Bjorge L., Bodelon C., Brand A.H., Brenton J.D., Brinton L.A., Bruinsma F., Buchanan D.D., Burghaus S., Butzow R., Cai H., Carney M.E., Chanock S.J., Chen C., Chen X.Q., Chen Z., Cook L.S., Cunningham J.M., De Vivo I., deFazio A., Doherty J.A., Dork T., du Bois A., Dunning A.M., Durst M., Edwards T., Edwards R.P., Ekici A.B., Ewing A., Fasching P.A., Ferguson S., Flanagan J.M., Fostira F., Fountzilas G., Friedenreich C.M., Gao B., Gaudet M.M., Gawelko J., Gentry-Maharaj A., Giles G.G., Glasspool R., Goodman M.T., Gronwald J., Harris H.R., Harter P., Hein A., Heitz F., Hildebrandt M.A.T., Hillemanns P., Hogdall E., Hogdall C.K., Holliday E.G., Huntsman D.G., Huzarski T., Jakubowska A., Jensen A., Jones M.E., Karlan B.Y., Karnezis A., Kelley J.L., Khusnutdinova E., Killeen J.L., Kjaer S.K., Klapdor R., Kobel M., Konopka B., Konstantopoulou I., Kopperud R.K., Koti M., Kraft P., Kupryjanczyk J., Lambrechts D., Larson M.C., Le Marchand L., Lele S., Lester J., Li A.J., Liang D., Liebrich C., Lipworth L., Lissowska J., Lu L., Lu K.H., Macciotta A., Mattiello A., May T., McAlpine J.N., McGuire V., McNeish I.A., Menon U., Modugno F., Moysich K.B., Nevanlinna H., Odunsi K., Olsson H., Orsulic S., Osorio A., Palli D., Park-Simon T.-W., Pearce C.L., Pejovic T., Permuth J.B., Podgorska A., Ramus S.J., Rebbeck T.R., Riggan M.J., Risch H.A., Rothstein J.H., Runnebaum I.B., Scott R.J., Sellers T.A., Senz J., Setiawan V.W., Siddiqui N., Sieh W., Spiewankiewicz B., Sutphen R., Swerdlow A.J., Szafron L.M., Teo S.H., Thompson P.J., Thomsen L.C.V., Titus L., Tone A., Tumino R., Turman C., Vanderstichele A., Edwards D.V., Vergote I., Vierkant R.A., Wang Z., Wang-Gohrke S., Webb P.M., White E., Whittemore A.S., Winham S.J., Wu X., Wu A.H., Yannoukakos D., Spurdle A.B., and O'Mara T.A.

Abstract

BACKGROUND: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers. METHOD(S): Using LDScore regression, we explored the genetic correlation between endometrial cancer and ovarian cancer. To identify loci associated with the risk of both cancers, we implemented a pipeline of statistical genetic analyses (i.e., inverse-variance meta-analysis, colocalization, and M-values) and performed analyses stratified by subtype. Candidate target genes were then prioritized using functional genomic data. RESULT(S): Genetic correlation analysis revealed significant genetic correlation between the two cancers (rG = 0.43, P = 2.66 x 10-5). We found seven loci associated with risk for both cancers (PBonferroni < 2.4 x 10-9). In addition, four novel subgenome-wide regions at 7p22.2, 7q22.1, 9p12, and 11q13.3 were identified (P < 5 x 10-7). Promoter-associated HiChIP chromatin loops from immortalized endometrium and ovarian cell lines and expression quantitative trait loci data highlighted candidate target genes for further investigation. CONCLUSION(S): Using cross-cancer GWAS meta-analysis, we have identified several joint endometrial and ovarian cancer risk loci and candidate target genes for future functional analysis. IMPACT: Our research highlights the shared genetic relationship between endometrial cancer and ovarian cancer. Further studies in larger sample sets are required to confirm our findings.Copyright ©2020 American Association for Cancer Research.

Published
2022

3. A prospective study of statin use and mortality among 67,385 blacks and whites in the Southeastern United States

Author

Lipworth L, Fazio S, Kabagambe EK, Munro HM, Nwazue VC, Tarone RE, McLaughlin JK, Blot WJ, and Sampson UKA

Subjects
Infectious and parasitic diseases, RC109-216
Abstract

Loren Lipworth,1 Sergio Fazio,1,2 Edmond K Kabagambe,1 Heather M Munro,3 Victor C Nwazue,1 Robert E Tarone,3 Joseph K McLaughlin,3 William J Blot,1,3 Uchechukwu KA Sampson1,2,41Department of Medicine, Vanderbilt University Medical Center, 2Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA; 3International Epidemiology Institute, Rockville, MD, USA; 4Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN, USAPurpose: The primary objective of this study is to examine the race-specific associations between statin use and overall mortality, as well as cardiovascular and cancer mortality, among blacks and whites in the Southeastern United States (US). Little is known about these associations in blacks.Patients and methods: The Southern Community Cohort Study is an ongoing, prospective cohort study, which enrolled from 2002 through 2009 nearly 86,000 participants aged 40–79 years. We used Cox regression models to estimate race-specific hazard ratios (HRs) and 95% confidence intervals (CI) for overall and cause-specific mortality associated with statin use based on self-reported hypercholesterolemia and treatment at cohort entry. Mean age at cohort entry was 51.4 years in blacks (n=48,825) and 53.5 years in whites (n=18,560). Sixty-one percent of participants were women. Whites were more likely to have self-reported hypercholesterolemia (40% versus 27%, P0.05 for race and sex interaction). Statin use was not associated with cancer mortality overall or in subgroup analyses.Conclusion: Regardless of race or sex, self-reported statin use was linked to reduced all-cause and cardiovascular disease mortality. However, factors contributing to the modestly lower statin use and markedly lower prevalence of self-reported hypercholesterolemia among blacks remain to be determined.Keywords: statins, disparities, hypercholesteromia, undertreatment, underdiagnosis, mortality

Published
2013

9. Genome-wide association study identifies multiple risk loci for renal cell carcinoma

Author

Scelo, G, Purdue, MP, Brown, KM, Johansson, M, Wang, Z, Eckel-Passow, JE, Ye, Y, Hoffman, JN, Choi, J, Foll, M, Gaborieau, V, Machiela, MJ, Colli, LM, Li, P, Sampson, JN, Abedi-Ardekani, B, Besse, C, Blanche, H, Boland, A, Burdette, L, Charbrier, A, Durand, G, Le Calvez-Kelm, F, Prokhortchouk, E, Robinot, N, Skyrabin, KG, Wozniak, MB, Yeager, M, Basta-Jovanovich, G, Dzamic, Z, Foretova, L, Holcatova, I, Janout, V, Mates, D, Mukeriya, A, Rascu, S, Zaridze, D, Bencko, V, Cybulski, C, Fabianova, E, Jinga, V, Lissowska, J, Lubinski, J, Navratilova, M, Rudnai, P, Szeszenia-Dabrowska, N, Benhamou, S, Cancel-Tassin, G, Cussenot, O, Baglietto, L, Boeing, H, Khaw, K-T, Weiderpass, E, Ljungberg, B, Sitaram, RT, Bruinsma, F, Jordan, SJ, Severi, G, Winship, I, Hveem, K, Vatten, LJ, Fletcher, T, Koppova, K, Larsson, SC, Wolk, A, Banks, RE, Selby, PJ, Easton, DF, Pharoah, P, Andreotti, G, Beane Freeman, LE, Koutros, S, Albanes, D, Mannisto, S, Weinstein, S, Clark, PE, Edwards, TL, Lipworth, L, Gapstur, SM, Stevens, VL, Carol, H, Freedman, ML, Pomerantz, MM, Cho, E, Kraft, P, Preston, MA, Wilson, KM, Gaziano, JM, Sesso, HD, Black, A, Freedman, ND, Huang, WY, Anema, JG, Kahnoski, RJ, Lane, BR, Noyes, SL, Petillo, D, Teh, BT, Peters, U, White, E, Anderson, GL, Johnson, L, Luo, J, Buring, J, Lee, I-M, Chow, W-H, Moore, LE, Wood, C, Eisen, T, Henrion, M, Larkin, J, Barman, P, Leibovich, BC, Choueiri, TK, Lathrop, GM, Rothman, N, Deleuze, J-F, McKay, JD, Parker, AS, Wu, X, Houlston, RS, Brennan, P, and Chanock, SJ

Abstract

Previous genome-wide association studies (GWAS) have identified six risk loci for renal cell carcinoma (RCC). We conducted a meta-analysis of two new scans of 5,198 cases and 7,331 controls together with four existing scans, totalling 10,784 cases and 20,406 controls of European ancestry. Twenty-four loci were tested in an additional 3,182 cases and 6,301 controls. We confirm the six known RCC risk loci and identify seven new loci at 1p32.3 (rs4381241, P=3.1 × 10−10), 3p22.1 (rs67311347, P=2.5 × 10−8), 3q26.2 (rs10936602, P=8.8 × 10−9), 8p21.3 (rs2241261, P=5.8 × 10−9), 10q24.33-q25.1 (rs11813268, P=3.9 × 10−8), 11q22.3 (rs74911261, P=2.1 × 10−10) and 14q24.2 (rs4903064, P=2.2 × 10−24). Expression quantitative trait analyses suggest plausible candidate genes at these regions that may contribute to RCC susceptibility.

Published
2017

10. Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Author

Phelan, C. (Catherine), Kuchenbaecker, K.B. (Karoline), Tyrer, J.P. (Jonathan P.), Kar, S.P. (Siddhartha P.), Lawrenson, K. (Kate), Winham, S.J. (Stacey J.), Dennis, J. (Joe), Pirie, A. (Ailith), Riggan, M.J. (Marjorie J.), Chornokur, G. (Ganna), Earp, M.A. (Madalene A.), Lyra, P.C. (Paulo C.), Lee, J.M. (Janet M.), Coetzee, S. (Simon), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Soucy, P. (Penny), Dicks, E. (Ed), Lee, A. (Andrew), Barrowdale, D. (Daniel), Lecarpentier, J. (Julie), Leslie, G. (Goska), Aalfs, C.M. (Cora), Aben, K.K.H. (Katja), Adams, M. (Marcia), Adlard, J.W. (Julian), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N. (Natalia), Aravantinos, G. (Gerasimos), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita), Azzollini, J., Balmana, J. (Judith), Banerjee, S. (Susana), Barjhoux, L. (Laure), Barkardottir, R.B. (Rosa B.), Bean, Y. (Yukie), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Bernardini, M.Q. (Marcus Q.), Birrer, M.J. (Michael J.), Bjorge, L. (Line), Black, A., Blankstein, K. (Kenneth), Blok, M.J. (Marinus), Bodelon, C. (Clara), Bogdanova, N. (Natalia), Bojesen, A. (Anders), Bonanni, B. (Bernardo), Borg, Å. (Åke), Bradbury, A.R. (Angela R.), Brenton, J.D. (James D.), Brewer, C. (Carole), Brinton, L.A. (Louise), Broberg, P. (Per), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buecher, B. (Bruno), Butzow, R. (Ralf), Buys, S.S. (Saundra), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Cannioto, R. (Rikki), Carney, M.E. (Michael), Cescon, T. (Terence), Chan, S. (Salina), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, X.Q. (Xiao Qing), Chiew, Y.-E. (Yoke-Eng), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K. (Kathleen), Conner, T. (Thomas), Cook, L.S. (Linda S.), Cook, J. (Jackie), Cramer, D.W. (Daniel), Cunningham, J.M. (Julie), D'Aloisio, A.A. (Aimee A.), Daly, M.B. (Mary), Damiola, F. (Francesca), Damirovna, S.D. (Sakaeva Dina), Dansonka-Mieszkowska, A. (Agnieszka), Dao, F. (Fanny), Davidson, R. (Rosemarie), DeFazio, A. (Anna), Delnatte, C.D. (Capucine), Doheny, K.F. (Kimberly), Díez, O. (Orland), Ding, Y.C. (Yuan Chun), Doherty, J.A. (Jennifer), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dossus, L. (Laure), Duran, M. (Mercedes), Dürst, M. (Matthias), Dworniczak, B. (Bernd), Eccles, D. (Diana), Edwards, T. (Todd), Eeles, R. (Rosalind), Eilber, U. (Ursula), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S. (Steve), Elvira, M. (Mingajeva), Eng, K.H. (Kevin H.), Engel, C. (Christoph), Evans, D.G. (Gareth), Fasching, P.A. (Peter), Ferguson, S. (Sarah), Ferrer, S.F., Flanagan, J.M. (James), Fogarty, Z.C. (Zachary C.), Fortner, R.T. (Renée T.), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), García, M.J. (María J.), Garcia-Barberan, V. (Vanesa), Gehrig, P.A. (Paola A.), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham G.), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Radice, P. (Paolo), Goranova, T. (Teodora), Gore, M. (Martin), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Gruber, S.B. (Stephen), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hamann, U. (Ute), Hansen, T.V.O. (Thomas V.O.), Harrington, P.A. (Patricia A.), Harris, H.R. (Holly), Hauke, J. (Jan), Hein, A. (Alexander), Henderson, A. (Alex), Hildebrandt, M.A.T. (Michelle A.T.), Hillemanns, P. (Peter), Hodgson, S. (Shirley), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans B. L.), Holland, H. (Helene), Hooning, M.J. (Maartje J.), Hosking, K. (Karen), Huang, R.-Y. (Ruea-Yea), Hulick, P.J. (Peter), Hung, J. (Jillian), Hunter, D.J. (David J.), Huntsman, D.G. (David G.), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Iversen, E. (Erik), Izatt, L. (Louise), Izquierdo, A. (A.), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Jernetz, M. (Mats), Jensen, A. (Allan), Jensen, U.B., John, E.M. (Esther), Johnatty, S.E. (Sharon), Jones, M.E. (Michael E.), Kannisto, P. (Päivi), Karlan, B.Y. (Beth), Karnezis, A. (Anthony), Kast, K. (Karin), Kennedy, C.J. (Catherine J.), Khusnutdinova, E.K. (Elza), Kiemeney, L.A.L.M. (Bart), Kiiski, J.I. (Johanna I.), Kim, S.-W. (Sung-Won), Kjaer, M. (Michael), Köbel, M. (Martin), Kopperud, R.K. (Reidun K.), Kruse, T.A. (Torben), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Larrañaga, N. (Nerea), Larson, M.C. (Melissa), Lazaro, C. (Conxi), Le, N.D. (Nhu D.), Le Marchand, L. (Loic), Lee, J.W. (Jong Won), Lele, S.B. (Shashikant B.), Leminen, A. (Arto), Leroux, D. (Dominique), Lester, J. (Jenny), Lesueur, F. (Fabienne), Levine, D.A. (Douglas), Liang, D. (Dong), Liebrich, C. (Clemens), Lilyquist, J. (Jenna), Lipworth, L. (Loren), Lissowska, J. (Jolanta), Lu, K.H. (Karen), Lubinski, J. (Jan), Luccarini, C. (Craig), Lundvall, L. (Lene), Mai, P.L. (Phuong), Mendoza-Fandiño, G. (Gustavo), Manoukian, S. (Siranoush), Massuger, L.F. (Leon), May, T. (Taymaa), Mazoyer, S. (Sylvie), McAlpine, J.N. (Jessica N.), McGuire, V. (Valerie), McLaughlin, J. (John), McNeish, I. (Iain), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Merritt, M.A. (Melissa A.), Milne, R.L. (Roger), Mitchell, G. (Gillian), Modugno, F. (Francesmary), Moes-Sosnowska, J. (Joanna), Moffitt, M. (Melissa), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Mulligan, A.M. (Anna Marie), Musinsky, J. (Jacob), Nathanson, K.L. (Katherine), Nedergaard, L. (Lotte), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Olah, E. (Edith), Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Ong, K.-R. (Kai-Ren), Onland-Moret, N.C. (Charlotte), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Palli, D. (Domenico), Papi, L. (Laura), Park-Simon, T.-W., Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Søkilde), Peeters, P.H.M., Peissel, B. (Bernard), Peixoto, A. (Ana), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa M.), Permuth, J.B. (Jennifer B.), Peterlongo, P. (Paolo), Pezzani, L. (Lidia), Pfeiler, G. (Georg), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm), Piskorz, A.M. (Anna M.), Poblete, S.R. (Samantha R.), Pócza, T. (Tímea), Poole, E.M. (Elizabeth M.), Poppe, B. (Bruce), Porteous, M.E. (Mary), Prieur, F. (Fabienne), Prokofyeva, D. (Darya), Pugh, E. (Elizabeth), Pujana, M.A. (Miquel Angel), Pujol, P. (Pascal), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rice, P. (Patricia), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rodríguez-Antona, C. (Cristina), Romm, J. (Jane), Rookus, M.A. (Matti), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salvesen, H.B. (Helga), Sandler, D.P. (Dale P.), Schoemaker, M.J. (Minouk J.), Senter, L. (Leigha), Setiawan, V.W. (V. Wendy), Severi, G. (Gianluca), Sharma, P. (Priyanka), Shelford, T. (Tameka), Siddiqui, N. (Nadeem), Side, L. (Lucy), Sieh, W. (Weiva), Singer, C.F. (Christian), Sobol, H. (Hagay), Song, H. (Honglin), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Steinemann, D. (Doris), Stoppa-Lyonnet, D. (Dominique), Sucheston-Campbell, L.E. (Lara E.), Sukiennicki, G. (Grzegorz), Sutphen, R. (Rebecca), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Szafron, L. (Lukasz), Tan, Y.Y. (Yen Y.), Taylor, J.A. (Jack A.), Tea, M.-K., Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn L.), Thompson, P.J. (Pamela J.), Thomsen, L.C.V. (Liv Cecilie Vestrheim), Thull, D.L. (Darcy L.), Tihomirova, L. (Laima), Tinker, A.V. (Anna V.), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda Ewart), Tone, A. (Alicia), Trabert, B. (Britton), Travis, S.P.L. (Simon), Trichopoulou, A. (Antonia), Tung, N. (Nadine), Tworoger, S. (Shelley), Van Altena, A.M. (Anne M.), Van Den Berg, D. (David), Van Der Hout, A.H. (Annemarie H.), Luijt, R.B. (Rob) van der, Van Heetvelde, M. (Mattias), Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vanderstichele, A. (Adriaan), Varon-Mateeva, R. (Raymonda), Vega, A. (Ana), Edwards, D.V. (Digna Velez), Vergote, I., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vratimos, A. (Athanassios), Walker, L.J. (Lisa), Walsh, C. (Christine), Wand, D. (Dorothea), Wang-Gohrke, S. (Shan), Wappenschmidt, B. (Barbara), Webb, P.M. (Penelope M.), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wijnen, J.T. (Juul), Wilkens, L.R. (Lynne), Wolk, K. (Kerstin), Woo, M. (Michelle), Wu, X. (Xifeng), Wu, A.H. (Anna), Yang, H.P. (Hannah), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Narod, S.A. (Steven A.), Easton, D.F. (Douglas), Amos, W., Schildkraut, J.M. (Joellen), Ramus, S.J. (Susan), Ottini, L. (Laura), Goodman, M.T. (Marc), Park, S.K. (Sue K.), Kelemen, L.E. (Linda), Risch, H. (Harvey), Thomassen, M. (Mads), Offit, K. (Kenneth), Simard, J. (Jacques), Schmutzler, R.K. (Rita), Hazelett, D. (Dennis), Monteiro, A.N.A. (Alvaro N.), Couch, F.J. (Fergus), Berchuck, A. (Andrew), Chenevix-Trench, G. (Georgia), Goode, E.L. (Ellen), Sellers, T.F., Gayther, S.A. (Simon), Antoniou, A.C. (Antonis), Pharoah, P.D.P. (Paul), Phelan, C. (Catherine), Kuchenbaecker, K.B. (Karoline), Tyrer, J.P. (Jonathan P.), Kar, S.P. (Siddhartha P.), Lawrenson, K. (Kate), Winham, S.J. (Stacey J.), Dennis, J. (Joe), Pirie, A. (Ailith), Riggan, M.J. (Marjorie J.), Chornokur, G. (Ganna), Earp, M.A. (Madalene A.), Lyra, P.C. (Paulo C.), Lee, J.M. (Janet M.), Coetzee, S. (Simon), Beesley, J. (Jonathan), McGuffog, L. (Lesley), Soucy, P. (Penny), Dicks, E. (Ed), Lee, A. (Andrew), Barrowdale, D. (Daniel), Lecarpentier, J. (Julie), Leslie, G. (Goska), Aalfs, C.M. (Cora), Aben, K.K.H. (Katja), Adams, M. (Marcia), Adlard, J.W. (Julian), Andrulis, I.L. (Irene), Anton-Culver, H. (Hoda), Antonenkova, N. (Natalia), Aravantinos, G. (Gerasimos), Arnold, N. (Norbert), Arun, B.K. (Banu), Arver, B. (Brita), Azzollini, J., Balmana, J. (Judith), Banerjee, S. (Susana), Barjhoux, L. (Laure), Barkardottir, R.B. (Rosa B.), Bean, Y. (Yukie), Beckmann, M.W. (Matthias), Beeghly-Fadiel, A. (Alicia), Benítez, J. (Javier), Bermisheva, M. (Marina), Bernardini, M.Q. (Marcus Q.), Birrer, M.J. (Michael J.), Bjorge, L. (Line), Black, A., Blankstein, K. (Kenneth), Blok, M.J. (Marinus), Bodelon, C. (Clara), Bogdanova, N. (Natalia), Bojesen, A. (Anders), Bonanni, B. (Bernardo), Borg, Å. (Åke), Bradbury, A.R. (Angela R.), Brenton, J.D. (James D.), Brewer, C. (Carole), Brinton, L.A. (Louise), Broberg, P. (Per), Brooks-Wilson, A. (Angela), Bruinsma, F. (Fiona), Brunet, J. (Joan), Buecher, B. (Bruno), Butzow, R. (Ralf), Buys, S.S. (Saundra), Caldes, T. (Trinidad), Caligo, M.A. (Maria A.), Campbell, I. (Ian), Cannioto, R. (Rikki), Carney, M.E. (Michael), Cescon, T. (Terence), Chan, S. (Salina), Chang-Claude, J. (Jenny), Chanock, S.J. (Stephen), Chen, X.Q. (Xiao Qing), Chiew, Y.-E. (Yoke-Eng), Chiquette, J. (Jocelyne), Chung, W. (Wendy), Claes, K. (Kathleen), Conner, T. (Thomas), Cook, L.S. (Linda S.), Cook, J. (Jackie), Cramer, D.W. (Daniel), Cunningham, J.M. (Julie), D'Aloisio, A.A. (Aimee A.), Daly, M.B. (Mary), Damiola, F. (Francesca), Damirovna, S.D. (Sakaeva Dina), Dansonka-Mieszkowska, A. (Agnieszka), Dao, F. (Fanny), Davidson, R. (Rosemarie), DeFazio, A. (Anna), Delnatte, C.D. (Capucine), Doheny, K.F. (Kimberly), Díez, O. (Orland), Ding, Y.C. (Yuan Chun), Doherty, J.A. (Jennifer), Domchek, S.M. (Susan), Dorfling, C.M. (Cecilia), Dörk, T. (Thilo), Dossus, L. (Laure), Duran, M. (Mercedes), Dürst, M. (Matthias), Dworniczak, B. (Bernd), Eccles, D. (Diana), Edwards, T. (Todd), Eeles, R. (Rosalind), Eilber, U. (Ursula), Ejlertsen, B. (Bent), Ekici, A.B. (Arif), Ellis, S. (Steve), Elvira, M. (Mingajeva), Eng, K.H. (Kevin H.), Engel, C. (Christoph), Evans, D.G. (Gareth), Fasching, P.A. (Peter), Ferguson, S. (Sarah), Ferrer, S.F., Flanagan, J.M. (James), Fogarty, Z.C. (Zachary C.), Fortner, R.T. (Renée T.), Fostira, F. (Florentia), Foulkes, W.D. (William D.), Fountzilas, G. (George), Fridley, B.L. (Brooke), Friebel, M.O.W. (Mark ), Friedman, E. (Eitan), Frost, D. (Debra), Ganz, P.A. (Patricia), Garber, J. (Judy), García, M.J. (María J.), Garcia-Barberan, V. (Vanesa), Gehrig, P.A. (Paola A.), Gentry-Maharaj, A. (Aleksandra), Gerdes, A-M. (Anne-Marie), Giles, G.G. (Graham G.), Glasspool, R. (Rosalind), Glendon, G. (Gord), Godwin, A.K. (Andrew K.), Radice, P. (Paolo), Goranova, T. (Teodora), Gore, M. (Martin), Greene, M.H. (Mark H.), Gronwald, J. (Jacek), Gruber, S.B. (Stephen), Hahnen, E. (Eric), Haiman, C.A. (Christopher), Håkansson, N. (Niclas), Hamann, U. (Ute), Hansen, T.V.O. (Thomas V.O.), Harrington, P.A. (Patricia A.), Harris, H.R. (Holly), Hauke, J. (Jan), Hein, A. (Alexander), Henderson, A. (Alex), Hildebrandt, M.A.T. (Michelle A.T.), Hillemanns, P. (Peter), Hodgson, S. (Shirley), Høgdall, C.K. (Claus), Høgdall, E. (Estrid), Hogervorst, F.B.L. (Frans B. L.), Holland, H. (Helene), Hooning, M.J. (Maartje J.), Hosking, K. (Karen), Huang, R.-Y. (Ruea-Yea), Hulick, P.J. (Peter), Hung, J. (Jillian), Hunter, D.J. (David J.), Huntsman, D.G. (David G.), Huzarski, T. (Tomasz), Imyanitov, E.N. (Evgeny), Isaacs, C. (Claudine), Iversen, E. (Erik), Izatt, L. (Louise), Izquierdo, A. (A.), Jakubowska, A. (Anna), James, P. (Paul), Janavicius, R. (Ramunas), Jernetz, M. (Mats), Jensen, A. (Allan), Jensen, U.B., John, E.M. (Esther), Johnatty, S.E. (Sharon), Jones, M.E. (Michael E.), Kannisto, P. (Päivi), Karlan, B.Y. (Beth), Karnezis, A. (Anthony), Kast, K. (Karin), Kennedy, C.J. (Catherine J.), Khusnutdinova, E.K. (Elza), Kiemeney, L.A.L.M. (Bart), Kiiski, J.I. (Johanna I.), Kim, S.-W. (Sung-Won), Kjaer, M. (Michael), Köbel, M. (Martin), Kopperud, R.K. (Reidun K.), Kruse, T.A. (Torben), Kupryjanczyk, J. (Jolanta), Kwong, A. (Ava), Laitman, Y. (Yael), Lambrechts, D. (Diether), Larrañaga, N. (Nerea), Larson, M.C. (Melissa), Lazaro, C. (Conxi), Le, N.D. (Nhu D.), Le Marchand, L. (Loic), Lee, J.W. (Jong Won), Lele, S.B. (Shashikant B.), Leminen, A. (Arto), Leroux, D. (Dominique), Lester, J. (Jenny), Lesueur, F. (Fabienne), Levine, D.A. (Douglas), Liang, D. (Dong), Liebrich, C. (Clemens), Lilyquist, J. (Jenna), Lipworth, L. (Loren), Lissowska, J. (Jolanta), Lu, K.H. (Karen), Lubinski, J. (Jan), Luccarini, C. (Craig), Lundvall, L. (Lene), Mai, P.L. (Phuong), Mendoza-Fandiño, G. (Gustavo), Manoukian, S. (Siranoush), Massuger, L.F. (Leon), May, T. (Taymaa), Mazoyer, S. (Sylvie), McAlpine, J.N. (Jessica N.), McGuire, V. (Valerie), McLaughlin, J. (John), McNeish, I. (Iain), Meijers-Heijboer, E.J. (Hanne), Meindl, A. (Alfons), Menon, U. (Usha), Mensenkamp, A.R. (Arjen R.), Merritt, M.A. (Melissa A.), Milne, R.L. (Roger), Mitchell, G. (Gillian), Modugno, F. (Francesmary), Moes-Sosnowska, J. (Joanna), Moffitt, M. (Melissa), Montagna, M. (Marco), Moysich, K.B. (Kirsten), Mulligan, A.M. (Anna Marie), Musinsky, J. (Jacob), Nathanson, K.L. (Katherine), Nedergaard, L. (Lotte), Ness, R.B. (Roberta), Neuhausen, S.L. (Susan), Nevanlinna, H. (Heli), Niederacher, D. (Dieter), Nussbaum, R. (Robert), Odunsi, K. (Kunle), Olah, E. (Edith), Olopade, O.I. (Olofunmilayo), Olsson, H. (Håkan), Olswold, C. (Curtis), O'Malley, D.M. (David M.), Ong, K.-R. (Kai-Ren), Onland-Moret, N.C. (Charlotte), Orr, N. (Nick), Orsulic, S. (Sandra), Osorio, A. (Ana), Palli, D. (Domenico), Papi, L. (Laura), Park-Simon, T.-W., Paul, J. (James), Pearce, C.L. (Celeste), Pedersen, I.S. (Inge Søkilde), Peeters, P.H.M., Peissel, B. (Bernard), Peixoto, A. (Ana), Pejovic, T. (Tanja), Pelttari, L.M. (Liisa M.), Permuth, J.B. (Jennifer B.), Peterlongo, P. (Paolo), Pezzani, L. (Lidia), Pfeiler, G. (Georg), Phillips, K.-A. (Kelly-Anne), Piedmonte, M. (Marion), Pike, M.C. (Malcolm), Piskorz, A.M. (Anna M.), Poblete, S.R. (Samantha R.), Pócza, T. (Tímea), Poole, E.M. (Elizabeth M.), Poppe, B. (Bruce), Porteous, M.E. (Mary), Prieur, F. (Fabienne), Prokofyeva, D. (Darya), Pugh, E. (Elizabeth), Pujana, M.A. (Miquel Angel), Pujol, P. (Pascal), Rantala, J. (Johanna), Rappaport-Fuerhauser, C. (Christine), Rennert, G. (Gad), Rhiem, K. (Kerstin), Rice, P. (Patricia), Richardson, A.L. (Andrea), Robson, M. (Mark), Rodriguez, G.C. (Gustavo), Rodríguez-Antona, C. (Cristina), Romm, J. (Jane), Rookus, M.A. (Matti), Rossing, M.A. (Mary Anne), Rothstein, J.H. (Joseph H.), Rudolph, A. (Anja), Runnebaum, I.B. (Ingo), Salvesen, H.B. (Helga), Sandler, D.P. (Dale P.), Schoemaker, M.J. (Minouk J.), Senter, L. (Leigha), Setiawan, V.W. (V. Wendy), Severi, G. (Gianluca), Sharma, P. (Priyanka), Shelford, T. (Tameka), Siddiqui, N. (Nadeem), Side, L. (Lucy), Sieh, W. (Weiva), Singer, C.F. (Christian), Sobol, H. (Hagay), Song, H. (Honglin), Southey, M.C. (Melissa), Spurdle, A.B. (Amanda), Stadler, Z. (Zsofia), Steinemann, D. (Doris), Stoppa-Lyonnet, D. (Dominique), Sucheston-Campbell, L.E. (Lara E.), Sukiennicki, G. (Grzegorz), Sutphen, R. (Rebecca), Sutter, C. (Christian), Swerdlow, A.J. (Anthony ), Szabo, C. (Csilla), Szafron, L. (Lukasz), Tan, Y.Y. (Yen Y.), Taylor, J.A. (Jack A.), Tea, M.-K., Teixeira, P.J., Teo, S.-H. (Soo-Hwang), Terry, K.L. (Kathryn L.), Thompson, P.J. (Pamela J.), Thomsen, L.C.V. (Liv Cecilie Vestrheim), Thull, D.L. (Darcy L.), Tihomirova, L. (Laima), Tinker, A.V. (Anna V.), Tischkowitz, M. (Marc), Tognazzo, S. (Silvia), Toland, A.E. (Amanda Ewart), Tone, A. (Alicia), Trabert, B. (Britton), Travis, S.P.L. (Simon), Trichopoulou, A. (Antonia), Tung, N. (Nadine), Tworoger, S. (Shelley), Van Altena, A.M. (Anne M.), Van Den Berg, D. (David), Van Der Hout, A.H. (Annemarie H.), Luijt, R.B. (Rob) van der, Van Heetvelde, M. (Mattias), Van Nieuwenhuysen, E. (Els), Rensburg, E.J. (Elizabeth) van, Vanderstichele, A. (Adriaan), Varon-Mateeva, R. (Raymonda), Vega, A. (Ana), Edwards, D.V. (Digna Velez), Vergote, I., Vierkant, R.A. (Robert), Vijai, J. (Joseph), Vratimos, A. (Athanassios), Walker, L.J. (Lisa), Walsh, C. (Christine), Wand, D. (Dorothea), Wang-Gohrke, S. (Shan), Wappenschmidt, B. (Barbara), Webb, P.M. (Penelope M.), Weinberg, C.R. (Clarice R.), Weitzel, J.N. (Jeffrey), Wentzensen, N. (N.), Whittemore, A.S. (Alice), Wijnen, J.T. (Juul), Wilkens, L.R. (Lynne), Wolk, K. (Kerstin), Woo, M. (Michelle), Wu, X. (Xifeng), Wu, A.H. (Anna), Yang, H.P. (Hannah), Yannoukakos, D. (Drakoulis), Ziogas, A. (Argyrios), Zorn, K.K. (Kristin K.), Narod, S.A. (Steven A.), Easton, D.F. (Douglas), Amos, W., Schildkraut, J.M. (Joellen), Ramus, S.J. (Susan), Ottini, L. (Laura), Goodman, M.T. (Marc), Park, S.K. (Sue K.), Kelemen, L.E. (Linda), Risch, H. (Harvey), Thomassen, M. (Mads), Offit, K. (Kenneth), Simard, J. (Jacques), Schmutzler, R.K. (Rita), Hazelett, D. (Dennis), Monteiro, A.N.A. (Alvaro N.), Couch, F.J. (Fergus), Berchuck, A. (Andrew), Chenevix-Trench, G. (Georgia), Goode, E.L. (Ellen), Sellers, T.F., Gayther, S.A. (Simon), Antoniou, A.C. (Antonis), and Pharoah, P.D.P. (Paul)

Abstract

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.

Published
2017
Full Text
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12. RetroSpective cohort stUdy of PD-L1 expression in REcurrent and/or MEtastatic squamous cell carcinoma of the head and neck (SUPREME-HN)

Author

Pai, S., primary, Cohen, E.E., additional, Lin, D., additional, Fountzilas, G., additional, Kim, E.S., additional, Mehlhorn, H., additional, Baste, N., additional, Clayburgh, D., additional, Lipworth, L., additional, Resteghini, C., additional, Shara, N., additional, Fujii, T., additional, Zhang, J., additional, Stokes, M., additional, Lawrence, D., additional, Khaliq, A., additional, Melillo, G., additional, and Shire, N., additional

Published
2017
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13. Bladder cancer mortality of workers exposed to aromatic amines: A 58-year follow-up

Author

Pira, E., Piolatto, G., Negri, E., Romano, C., Boffetta, P., Lipworth, L., McLaughlin, J. K., La Vecchia, C., NEGRI, EVA VANNA LORENZA, Pira, E., Piolatto, G., Negri, E., Romano, C., Boffetta, P., Lipworth, L., McLaughlin, J.K., and La Vecchia, C.

Subjects
Adult, Male, Cancer Research, medicine.medical_specialty, aromatic amine, Risk Factors, Occupational Exposure, medicine, Odds Ratio, follow-up, Humans, Amines, Aged, Gynecology, Aged, 80 and over, Bladder cancer, Obstetrics, business.industry, Mortality rate, Absolute risk reduction, Cancer, Odds ratio, Middle Aged, medicine.disease, mortality, Confidence interval, Occupational Diseases, Standardized mortality ratio, Oncology, Italy, Urinary Bladder Neoplasms, Cohort, Carcinogens, Female, business, worker
Abstract

We previously investigated bladder cancer risk in a cohort of dyestuff workers who were heavily exposed to aromatic amines from 1922 through 1972. We updated the follow-up by 14 years (through 2003) for 590 exposed workers to include more than 30 years of follow-up since last exposure to aromatic amines. Expected numbers of deaths from bladder cancer and other causes were computed by use of national mortality rates from 1951 to 1980 and regional mortality rates subsequently. There were 394 deaths, compared with 262.7 expected (standardized mortality ratio = 1.50, 95% confidence interval = 1.36 to 1.66). Overall, 56 deaths from bladder cancer were observed, compared with 3.4 expected (standardized mortality ratio = 16.5, 95% confidence interval = 12.4 to 21.4). The standardized mortality ratio for bladder cancer increased with younger age at first exposure and increasing duration of exposure. Although the standardized mortality ratio for bladder cancer steadily decreased with time since exposure stopped, the absolute risk remained approximately constant at 3.5 deaths per 1000 man-years up to 29 years after exposure stopped. Excess risk was apparent 30 years or more after last exposure. © 2010 The Author. Published by Oxford University Press. All rights reserved.

Published
2010

14. Authors' Response

Author

Mclaughlin, J. K., Lipworth, L., Tarone, R. E., Vecchia, C. L., Blot, W. J., Boffetta, P., Mclaughlin, J.K., Lipworth, L., Tarone, R.E., Vecchia, C.L., Blot, W.J., and Boffetta, P.

Subjects
Epidemiology, Response, General Medicine, Author
Abstract

Authors’ Response From JOSEPH K MCLAUGHLIN,1,2 LOREN LIPWORTH,1,2 ROBERT E TARONE,1,2 CARLO LA VECCHIA,3,4 WILLIAM J BLOT1,2 and PAOLO BOFFETTA5

Published
2009

15. Energy intake during pregnancy in relation to offspring gender by maternal height

Author

Lagiou, P. Samoli, E. Lipworth, L. Lagiou, A. Fang, F. Rossi, M. Xu, B. Yu, G.-P. Adami, H.-O. Hsieh, C.-C. Trichopoulos, D.

Abstract

Male newborns are somewhat heavier than female ones and it has been reported, in a Caucasian population, that mothers carrying boys have higher energy intake during pregnancy compared to those carrying girls. In the context of a prospective study comprising 150 Caucasian women in Boston, USA and 243 Asian women in Shanghai China, energy intake at the second trimester of pregnancy was estimated based on center-specific food frequency questionnaires. There was a significant interaction (P = 0.01) of maternal height with offspring gender with respect to maternal daily energy intake. Among taller women, male gender of the offspring was associated with higher maternal energy intake (difference 341 kcal/day, 95% Confidence Interval 77-604; P = 0.01), whereas among shorter women, no significant association existed between offspring gender and maternal daily energy intake (difference -213 kcal/day, 95% Confidence Interval -479 to 54; P = 0.12). Our findings indicate that the higher somatic growth potential of boys in intrauterine life is realized only when there are no constrains imposed by maternal anthropometry and it is, then, associated with higher maternal energy intake during pregnancy. © 2010 Springer Science+Business Media B.V.

Published
2011

16. Maternal and cord blood hormone levels in the United States and China and the intrauterine origin of breast cancer

Author

Lagiou, P. Samoli, E. Okulicz, W. Xu, B. Lagiou, A. Lipworth, L. Georgila, C. Vatten, L. Adami, H.O. Trichopoulos, D. Hsieh, C.C.

Abstract

Background: Breast cancer is less common in China than in the United States and perinatal characteristics predict breast cancer risk in the offspring. We determined levels of pregnancy hormones in Boston and Shanghai to identify those possibly involved in the intrauterine origin of breast cancer. Participants and methods: We compared maternal and cord blood levels of estradiol, estriol, testosterone, progesterone, prolactin, insulin-like growth factors (IGF) 1 and 2, insulin-like growth factor-binding protein 3, adiponectin and sex hormone-binding globulin (SHBG) in 241 Caucasian and 295 Chinese women. Results: In both centers, hormone levels at the 16th were predictive of those at the 27th gestational week, but there was little correlation between maternal and cord blood levels. In cord blood, we found significantly (P < 0.01) higher levels of estradiol (44.2%), testosterone (54.5%), IGF-2 (22.7%) and strikingly SHBG (104.6%) in Shanghai women, whereas the opposite was true for IGF-1 (236.8%). Conclusions: Taking into account the current understanding of the plausible biological role of the examined endocrine factors, those likely to be involved in the intrauterine origin of breast cancer are SHBG and IGF-2, with higher cord blood levels among Chinese, and IGF-1, with higher cord blood levels among Caucasian women. © The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.

Published
2011

17. Vitamin D intake and breast cancer risk: a case-control study in Italy

Author

Rossi, M. McLaughlin, J. K. Lagiou, P. Bosetti, C. and Talamini, R. Lipworth, L. Giacosa, A. Montella, M. and Franceschi, S. Negri, E. La Vecchia, C.

Abstract

Background: Vitamin D has been suggested to play a protective role against several cancers, including breast cancer. Patients and methods: We used data from a case-control study conducted in Italy from 1991 to 1994 to study the relation between dietary intake of vitamin D and breast cancer risk. Subjects were 2569 women with incident, histologically confirmed breast cancer and 2588 hospital controls. Odds ratios (ORs) and 95% confidence intervals (CIs) according to deciles of vitamin D intake were estimated by multiple logistic regression models. Results: After allowance for major risk factors for breast cancer and dietary covariates including calcium and energy intake, there was no association with vitamin D up to the seventh decile. Thereafter, the OR declined, so that the overall trend was statistically significantly inverse. The OR for subjects in the three highest deciles of consumption compared with those in the lowest ones combined was 0.79 (95% CI 0.70-0.90). Intake of vitamin D > 3.57 mu g or 143 IU appeared to have a protective effect against breast cancer. The inverse association was consistent across strata of menopausal status. Conclusions: This study adds to the existing evidence that vitamin D intake in inversely associated with breast cancer risk.

Published
2009

18. Insulin-like growth factor levels in cord blood, birth weight and breast cancer risk

Author

Lagiou, P. Hsieh, C.C. Lipworth, L. Samoli, E. Okulicz, W. Troisi, R. Xu, B. Hall, P. Ekbom, A. Adami, H.O. Trichopoulos, D.

Abstract

Breast cancer incidence and birth weight are higher among Caucasian than Asian women, and birth size has been positively associated with breast cancer risk. Pregnancy hormone levels, however, have been generally lower in Caucasian than Asian women. We studied components of the insulin-like growth factor (IGF) system in cord blood from 92 singleton babies born in Boston, USA, and 110 born in Shanghai, China, in 1994-1995. Cord blood IGF-1 was significantly higher among Caucasian compared with Chinese babies (P10 6). The opposite was noted for IGF-2 (P10 4). IGF-1 was significantly positively associated with birth weight and birth length in Boston, but not Shanghai. In contrast, stronger positive, though statistically non-significant, associations of IGF-2 with birth size were only evident in Shanghai. The associations of birth weight and birth length were positive and significant in taller women (for IGF-1 in Boston P0.003 and 0.03, respectively; for IGF-2 in Shanghai P0.05 and 0.04, respectively), among whom maternal anthropometry does not exercise strong constraints in foetal growth. The documentation of higher cord blood levels of IGF-1, a principal growth hormone that does not cross the placenta, among Caucasian than in Asian newborns is concordant with breast cancer incidence in these populations. © 2009 Cancer Research UK.

Published
2009

19. Dietary glycemic load and hepatocellular carcinoma with or without chronic hepatitis infection

Author

Rossi, M. Lipworth, L. Dal Maso, L. Talamini, R. and Montella, M. Polesel, J. McLaughlin, J. K. Parpinel, M. and Franceschi, S. Lagiou, P. La Vecchia, C.

Subjects
digestive system diseases
Abstract

Patients and methods: We conducted a hospital-based case-control study in Italy in 1999-2002, including 185 HCC cases and 412 controls who answered a validated food frequency questionnaire and provided blood samples. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were computed using unconditional multiple logistic regression. Results: We observed a positive association between GL and HCC overall, with an OR of 3.02 (95% CI 1.49-6.12) for the highest quintile of GL compared with the lowest and a significant trend. The OR among HCC cases with evidence of chronic infection with HBV and/or HCV was 3.25 (95% CI 1.46-7.22), while the OR among those with no evidence of infection was 2.45 (95% CI 0.69-8.64), with no significant trend. The association was not explained by the presence of cirrhosis or diabetes. Conclusions: High dietary GL is associated with increased risk for HCC. The positive association was most pronounced among HCC cases with HBV and/or HCV markers.

Published
2009

21. A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark

Author

Peter Jepsen, Mette Vinther Skriver, Floyd, A. K., Lipworth, L., Schønheyder, H. C., and Henrik Toft Sørensen

Subjects
Denmark, Infant, Newborn, Pregnancy Outcome, Abnormalities, Drug-Induced, Amoxicillin, Penicillins, Infant, Low Birth Weight, Cohort Studies, Obstetric Labor, Premature, Short Reports, Pregnancy, Risk Factors, Case-Control Studies, Prenatal Exposure Delayed Effects, Humans, Female, Pregnancy Complications, Infectious, Fetal Death, Follow-Up Studies
Abstract

Amoxicillin is a widely used penicillin, but data on its safety in pregnancy are limited. We examined the association between amoxicillin exposure during pregnancy and birth weight, preterm delivery, congenital malformations, perinatal death, and spontaneous abortion.We identified all primiparous women with a live birth, or a stillbirth after the 28th gestational week, from 1 January 1991-31 December 2000 in the County of North Jutland, Denmark. Data on prescriptions for amoxicillin and outcome were obtained from population-based registries. Using a follow-up and a case-control design, we compared pregnancy outcomes between women who had been prescribed amoxicillin during pregnancy and those who had not, adjusting for available potentially confounding factors.We identified 401 primiparous women who redeemed a prescription for amoxicillin during their pregnancy. The control group consisted of 10 237 primiparous women who did not redeem any prescriptions from 3 months before pregnancy until the end of pregnancy. The adjusted mean birth weight of children born to amoxicillin-exposed mothers was 57 g [95% confidence interval (CI) 9, 105] higher than that of children born to controls. Odds ratios among amoxicillin-exposed relative to controls were: low birth weight 0.63 (95% CI 0.26, 1.53), preterm delivery 0.77 (95% CI 0.49, 1.21), congenital malformation 1.16 (95% CI 0.54, 2.50), and spontaneous abortion 0.89 (95% CI 0.66, 1.18). We did not observe any cases of perinatal death in the amoxicillin-exposed women.We did not find any increased risk of adverse pregnancy outcome associated with amoxicillin exposure during pregnancy, but additional studies are warranted.

Published
2003

22. Maternal and gestational correlates of pregnancy prolactin and growth hormone in USA and China

Author

Xu, B Lipworth, L Wide, L Wuu, J Yu, SZ Lagiou, P and Kuper, H Hankinson, SE Carlstrom, K Adami, HO and Trichopoulos, D Hsieh, CC

Abstract

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other. (C) 2003 Lippincott Williams Wilkins.

Published
2003

24. Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China

Author

Wuu, J Hellerstein, S Lipworth, L Wide, L Xu, B Yu, GP Kuper, H Lagiou, P Hankinson, SE Ekbom, A and Carlstrom, K Trichopoulos, D Adami, HO Hsieh, CC

Subjects
reproductive and urinary physiology, hormones, hormone substitutes, and hormone antagonists
Abstract

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics. (C) 2002 Lippincott Williams Wilkins.

Published
2002

25. Diet and overall survival in elderly people.

Author

Gnardellis C., Vassilakou T., Lagiou P., Polychronopoulos E., Kouris-Blazos A., Wahlqvist M.L., Lipworth L., Trichopoulos D., Trichopoulou A., Gnardellis C., Vassilakou T., Lagiou P., Polychronopoulos E., Kouris-Blazos A., Wahlqvist M.L., Lipworth L., Trichopoulos D., and Trichopoulou A.

Abstract

Objective - To assess the influence of a specific dietary pattern on overall survival. Design - Cohort study. Setting - Three rural Greek villages, the data from which were collected as part of an international cross cultural study of food habits in later life. Subjects - 182 elderly residents of the three villages. Main outcome measure - Overall mortality. Results - Diet was assessed with a validated extensive semiquantitative questionnaire on food intake. A one unit increase in diet score, devised a priori on the basis of eight component characteristics of the traditional common diet in the Mediterranean region, was associated with a significant 17% reduction in overall mortality (95% confidence interval 1% to 31%). Conclusion - A diet meeting currently understood health criteria does predict survival among people.

Published
2012

26. Energy intake and monounsaturated fat in relation to bone mineral density among women and men in Greece

Author

Trichopoulou, A Georgiou, E Bassiakos, Y Lipworth, L and Lagiou, P Proukakis, C Trichopoulos, D

Abstract

Background. Several variables have been established as risk factors for osteoporosis: it is more common among women and the gender difference increases with age and with years since menopause. Estrogens, androgens, physical activity, and body mass index have been previously shown to be positively associated with bone mineral density and inversely with risk for fractures. Methods. To assess the effect on bone mineral content of energy-generating nutrients, healthy men (n = 36) and women (n = 118) ages 25-69 years were interviewed among visitors and staff of the University of Athens Department of Medical Physics. Bone mineral density (BMD) was measured by single photon absorptiometry. Results. Demographic and lifestyle variables were not significantly related to BMD in this study, although the patterns were consistent with those previously reported by other investigators. Total energy intake, which also reflects energy expenditure through physical activity, was positively associated with BMD among both men (P = 0.003) and women (P = 0.04). After adjustment for nonnutritional variables and energy intake, monounsaturated fat, which in the Greek population is mostly derived from olive oil, was associated with BMD. The association was positive among both men (P = 0.01) and women (P = 0.03). There was evidence for an inverse association between carbohydrate intake and BMD, but the association was significant only with respect to mono- and disaccharides. Conclusions. In this population, consumption of monounsaturated fat and physical activity were predictive of bone mineral density, but larger studies are needed. (C) 1997 Academic Press.

Published
1997

27. Serum steroids in relation to prostate cancer risk in a case-control study (Greece)

Author

Signorello, LB Tzonou, A Mantzoros, CS Lipworth, L and Lagiou, P Hsieh, CC Stampfer, M Trichopoulos, D

Subjects
hormones, hormone substitutes, and hormone antagonists
Abstract

Blood samples were collected from 52 incident cases of histologically confirmed prostate cancer and 52 age- and town of residence-matched healthy controls in Athens, Greece. Samples were analyzed blindly in Boston, Massachusetts (USA) for testosterone (T), estradiol (E2), sex hormone-binding globulin (SHBG), and dihydrotestosterone (DHT). The data were modeled using multiple logistic regression with adjustment for age, height, body mass index (wt/ht(2)), years of schooling, and mutually among hormones. DHT was associated inversely, significantly, and strongly with the risk of prostate cancer, whereas T was associated marginally positively, and E2 was associated nonsignificantly inversely with the disease. No association was observed in this study with respect to SHBG.

Published
1997

28. History of breast-feeding in relation to breast cancer risk: a review of the epidemiologic literature.

Author

Lipworth L, Bailey LR, Trichopoulos D, Lipworth, L, Bailey, L R, and Trichopoulos, D

Abstract

The purpose of this review is to critically evaluate the collective epidemiologic evidence that a history of breast-feeding may decrease the risk of breast cancer. Original data for inclusion were identified through a MEDLINE(R) search of the English language literature from 1966 through 1998. To date, virtually all epidemiologic data regarding breast-feeding and breast cancer risk are derived from case-control studies, which vary according to classification of breast-feeding history. Overall, the evidence with respect to "ever" breast-feeding remains inconclusive, with results indicating either no association or a rather weak protective effect against breast cancer. An inverse association between increasing cumulative duration of breast-feeding and breast cancer risk among parous women has been reported in some, but not all, studies; the failure to detect an association in some Western populations may be due to the low prevalence of prolonged breast-feeding. It appears that the protective effect, if any, of long-term breast-feeding is stronger among, or confined to, premenopausal women. It has been hypothesized that an apparently protective effect of breast-feeding may be due to elevated breast cancer risk among women who discontinue breast-feeding or who take medication to suppress lactation; however, the evidence is limited and should be interpreted with caution. The biology underlying a protective effect of breast-feeding and why this should be restricted to premenopausal women remain unknown, although several mechanisms have been postulated (hormonal changes, such as reduced estrogen; removal of estrogens through breast fluid; excretion of carcinogens from breast tissue through breast-feeding; physical changes in the mammary epithelial cells, reflecting maximal differentiation; and delay of the re-establishment of ovulation). While breast-feeding is a potentially modifiable behavior, the practical implication of reduced breast cancer risk among premenopausal women with prolonged durations of breast-feeding may be of marginal importance, particularly in Western societies. [ABSTRACT FROM AUTHOR]

Published
2000
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29. A case-control study of lactation and cancer of the breast

Author

Katsouyanni, K Lipworth, L Trichopoulou, A Samoli, E and Stuver, S Trichopoulos, D

Abstract

We have examined the relation of lactation, by total duration, with breast cancer risk among pre- and post-menopausal women. In a hospital-based case-control study conducted in Athens (1989-91), involving 820 patients with confirmed breast cancer and 795 orthopaedic patient controls and 753 hospital visitor controls, logistic regression was used to analyse the data controlling for demographic, nutritional and reproductive factors, including parity and age at any birth. Among post-menopausal women, there was no association between breastfeeding and breast cancer risk, but among premenopausal women those who had breastfed for greater than or equal to 24 months had an odds ratio of 0.50 (95% confidence interval 0.23 - 1.41). A reduction of the odds ratio was also evident among premenopausal women who had breastfed between 12 and 23 months (odds ratio 0.70; 95% confidence interval 0.34-1.60). In conjunction with several other recent reports these results support the hypothesis that breastfeeding of prolonged duration may reduce the risk of breast cancer among premenopausal women but not among post-menopausal women. The biology underlying this different effect remains unknown, and the practical implication of the finding is of marginal importance.

Published
1996

30. Life-style factors and medical conditions in relation to esophageal cancer by histologic type in a low-risk population

Author

Garidou, A Tzonou, A Lipworth, L Signorello, LB and Kalapothaki, V Trichopoulos, D

Abstract

A case-control study of esophageal cancer was conducted in Athens, Greece, during the 3-year period 1989-1991. Cases were 43 patients with incident esophageal squamous-cell carcinoma and 56 patients with incident esophageal adenocarcinoma hospitalized in any one of the 9 major hospitals in Athens, whereas controls were 200 injury patients admitted to the only Athens accident hospital. The data were analyzed by modeling through multiple logistic regression. Tobacco smoking and alcohol drinking were associated with both histologic types, but the odds ratios were generally lower than those observed in several other investigations. It may be that the high consumption of vegetables and fruits by the Greek population cushions the deleterious effect of tobacco, while the intake of ethanol in the form of wine during meals reduces the impact of this substance on the esophageal mucosa. A preference for very hot temperature for beverages and food was associated with significant elevation of the odds ratio to about 1.8 for esophageal cancer in general. There was non-significant evidence in our data to support earlier reports that aspirin intake may reduce the risk of cancer of the esophagus. Overall, we found no striking difference in the risk profile of the 2 histologic types of esophageal cancer. (C) 1996 Wiley-Liss, Inc.

Published
1996

31. Dietary factors and the risk of endometrial cancer: A case-control study in Greece

Author

Tzonou, A Lipworth, L Kalandidi, A Trichopoulou, A and Gamatsi, I Hsieh, CC Notara, V Trichopoulos, D

Abstract

In a hospital-based case-control study of endometrial cancer undertaken in Athens (1992-94), 145 women residents of Greater Athens with confirmed cancer of the endometrium were compared with 298 control patients Kith orthopaedic diseases. Personal interviews were conducted in the hospital setting, and diet was assessed using a validated semiquantitative food frequency questionnaire. Nutrient intakes for individuals were calculated by multiplying the nutrient intake of a typical portion size for each specified food item by the frequency at which the food was consumed per month and summing these estimates For all food items. Data were modelled through logistic regression, controlling for demographic, reproductive and somatometric risk factors for endometrial cancer as well as for total energy intake. No macronutrient was significantly associated with endometrial cancer risk, but increasing intake of monounsaturated fat, mostly olive oil, by about one standard deviation was associated with a 26% risk reduction (odds ratio=0.74; 95% confidence interval 0.54-1.03). Among micronutrients, only calcium intake was significantly inversely associated with endometrial cancer risk, whereas there was evidence against retinol and zinc imparting protection against the disease. With respect to food groups, there was weak and non-significant evidence that vegetables are protective, whereas consumption of pulses was positively associated with disease possibly because they contribute substantially in Greece to energy intake in excess of physical activity-dependent requirements.

Published
1996

32. Epithelial, possibly precancerous, lesions of the lung in relation to smoking, passive smoking, and socio-demographic variables

Author

Agapitos, E Mollo, F Tomatis, L Katsouyanni, K Lipworth, L Delsedime, L Kalandidi, A Karakatsani, A Riboli, E and Saracci, R Trichopoulos, D

Abstract

We have undertaken an autopsy-based study to evaluate the etiologic importance of active and passive smoking, as well as socio-demographic variables, in the development of pathologic precursors of lung cancer. Lung specimens were taken at autopsy from 531 persons who had died within four hours from a cause other than respiratory or cancer in Athens (Greece) or the surrounding area. Specimens were examined blindly for basal cell hyperplasia, squamous cell metaplasia, cell atypia and mucous cell metaplasia, i.e., pathological entities considered as epithelial, possibly precancerous, lesions (EPPL). Interviews were conducted with next of kin of the deceased. Suitable autopsy specimens as well as completed interviews were eventually available for 275 subjects. EPPL score was regressed on the available independent variables. EPPL score was higher among active smokers than among nonsmokers, while ex-smokers occupied an intermediate position. Conditional on smoking habits, EPPL score was higher among women than among men and higher among manual than among non-manual workers, in agreement with the corresponding patterns with respect to lung cancer. Nonsmoking women married to ever smokers had significantly higher EPPL score than those married to never smokers. The overall findings of this study suggest that EPPL is a valuable indicator of lung cancer risk and that exposure to environmental tobacco smoke is associated with higher EPPL levels and therefore with higher lung cancer risk.

Published
1996

33. ORAL-CONTRACEPTIVES, MENOPAUSAL ESTROGENS, AND THE RISK OF BREAST-CANCER - A CASE-CONTROL STUDY IN GREECE

Author

LIPWORTH, L KATSOUYANNI, K STUVER, S SAMOLI, E and HANKINSON, SE TRICHOPOULOS, D

Abstract

In a hospital-based case-control study in Athens, we examined the association between the use of oral contraceptives and menopausal estrogens and the risk of breast cancer. Eight hundred and twenty patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to the cases by age and interviewer. The data were modeled through logistic regression, controlling for demographic and reproductive variables. Odds ratio patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not elevated among ever-users of oral contraceptives, regardless of age at diagnosis of breast cancer, duration of oral contraceptive use or timing of use in relation to first full-term pregnancy. Among peri- and post-menopausal women who ever used menopausal estrogens, with never-users as the baseline, a statistically significant elevated odds ratio was found after adjusting for age at menopause. (C) 1995 Wiley-Liss, Inc.

Published
1995

35. DIET AND OVERALL SURVIVAL IN ELDERLY PEOPLE

Author

TRICHOPOULOU, A KOURISBLAZOS, A WAHLQVIST, ML GNARDELLIS, C and LAGIOU, P POLYCHRONOPOULOS, E VASSILAKOU, T LIPWORTH, L and TRICHOPOULOS, D

Abstract

Objective-To assess the influence of a specific dietary pattern on overall survival. Design-Cohort study. Setting-Three rural Greek villages, the data from which were collected as part of an international cross cultural study of food habits in later life. Subjects-182 elderly residents of the three villages. Main outcome measure-Overall mortality. Results-Diet was assessed with a validated extensive semiquantitative questionnaire on food intake. A one unit increase in diet score, devised a priori on the basis of eight component characteristics of the traditional common diet in the Mediterranean region, was associated with a significant 17% reduction in overall mortality (95% confidence interval 1% to 31%). Conclusion-A diet meeting currently understood health criteria does predict survival among people.

Published
1995

36. ABORTION AND THE RISK OF BREAST-CANCER - A CASE-CONTROL STUDY IN GREECE

Author

LIPWORTH, L KATSOUYANNI, K EKBOM, A MICHELS, KB and TRICHOPOULOS, D

Subjects
reproductive and urinary physiology
Abstract

We have examined the association between induced or spontaneous abortion and breast cancer risk in Greece. In a hospital-based case-control study in Athens, 820 patients with confirmed breast cancer were compared with 795 orthopedic patient controls and 753 healthy visitor controls, matched to cases by age and interviewer. Logistic regression was used to analyze the data, controlling for demographic, reproductive and nutritional variables. Odds ratio (OR) patterns were similar for the 2 control series, which were therefore combined to increase precision of the estimates. The risk for breast cancer was not increased for women who had a history of abortion, compared to nulliparous women with no history of abortion. Thus ORs and 95% confidence intervals were for nulliparous women with spontaneous abortion, 1.17 (0.64-2.13); for nulliparous women with induced abortion, 0.98 (0.56-1.73); for parous women with no abortion, 0.56 (0.31-1.01); for parous women with spontaneous abortion, 0.61 (0.33-1.14) and for parous women with induced abortion, 0.99 (0.56-1.74). When the analysis was restricted to parous women, using parous women with no history of abortion as the baseline, ORs and 95% confidence intervals were for induced abortion before first full-term pregnancy, 2.06 (1.45-2.90); for induced abortion after first full-term pregnancy, 1.59 (1.24-2.04) and for spontaneous abortion, 1.10 (0.82-1.40). Our findings suggest that an interrupted pregnancy does not impart the long-term protective effect of a full-term pregnancy attributable to terminal differentiation. (C) 1995 Wiley-Liss, Inc.

Published
1995

38. Maternal and gestational correlates of pregnancy prolactin and growth hormone in USA and China

Author

Xu, B., Lipworth, L., Wide, Leif, Wuu, J., Yu, S.Z., Lagiou, P., Kuper, H., Hankinson, S.E., Carlström, K., Adami, Hans-Olov, Trichopoulos, D., Hsieh, C.C., Xu, B., Lipworth, L., Wide, Leif, Wuu, J., Yu, S.Z., Lagiou, P., Kuper, H., Hankinson, S.E., Carlström, K., Adami, Hans-Olov, Trichopoulos, D., and Hsieh, C.C.

Abstract

The objective of this study is to determine correlates of prolactin and growth hormone levels among pregnant women in the USA and China. We studied 304 pregnant Caucasian and 335 pregnant Chinese women. Levels of prolactin and growth hormone were measured at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Both growth hormone and, to a lesser extent, prolactin were inversely associated with pregnancy weight and body mass index, history of a previous live birth and newborn size, whereas educated women had higher levels of both hormones. Growth hormone levels were lower in women who gained more weight, smoked and had nausea and vomiting during pregnancy, whereas prolactin increased with longer total gestation. We found robust associations between maternal and newborn characteristics on the one hand and prolactin and growth hormone during pregnancy on the other.

Published
2003

39. Correlates of pregnancy oestrogen, progesterone and sex hormone-binding globulin in the USA and China

Author

Wuu, J., Hellerstein, S., Lipworth, L., Wide, Leif, Xu, B., Yu, G-P., Kuper, H., Lagiou, P., Hankinson, S.E., Ekbom, A., Carlström, K., Trichopoulos, D., Adami, Hans-Olov, Hsieh, C-C., Wuu, J., Hellerstein, S., Lipworth, L., Wide, Leif, Xu, B., Yu, G-P., Kuper, H., Lagiou, P., Hankinson, S.E., Ekbom, A., Carlström, K., Trichopoulos, D., Adami, Hans-Olov, and Hsieh, C-C.

Abstract

The objective of this study is to examine perinatal correlates of oestradiol (E2), oestriol (E3), progesterone and sex hormone-binding globulin (SHBG) among pregnant women in the USA and China. Three hundred and four Caucasian women in Boston and 335 Chinese women in Shanghai were studied. Levels of E2, E3, progesterone and SHBG were measured in maternal blood at weeks 16 and 27 of gestation, and correlated with maternal, gestational and perinatal characteristics. Height, weight and body mass index (BMI) before pregnancy is inversely associated with E2 and SHBG, whereas E3 is inversely associated with height and progesterone is inversely associated with weight and BMI. A previous live birth is associated with lower E2 and SHBG in the index pregnancy. Total gestation duration is inversely associated with E2, E3 and progesterone, whereas weight gain during pregnancy is inversely associated with progesterone and SHBG. In the US, pregnancies with female fetuses are characterized by significantly reduced progesterone. Pregnancy hormones are associated with several maternal, gestational and neonatal characteristics.

Published
2002

46. Acetaminophen, aspirin, and chronic renal failure.

Author

Fored, C M, Ejerblad, E, Lindblad, P, Fryzek, J P, Dickman, P W, Signorello, L B, Lipworth, L, Elinder, C G, Blot, W J, McLaughlin, J K, Zack, M M, Nyren, O, Fored, C M, Ejerblad, E, Lindblad, P, Fryzek, J P, Dickman, P W, Signorello, L B, Lipworth, L, Elinder, C G, Blot, W J, McLaughlin, J K, Zack, M M, and Nyren, O

Published
2001

47. Acetaminophen, aspirin, and chronic renal failure

Author

Fored, C. M., Ejerblad, E., Lindblad, Per, Fryzek, J. P., Dickman, P. W., Signorello, L. B., Lipworth, L., Elinder, C. G., Blot, W. J., McLaughlin, J. K., Zack, M. M., Nyren, O., Fored, C. M., Ejerblad, E., Lindblad, Per, Fryzek, J. P., Dickman, P. W., Signorello, L. B., Lipworth, L., Elinder, C. G., Blot, W. J., McLaughlin, J. K., Zack, M. M., and Nyren, O.

Abstract

Background: Several epidemiologic studies have demonstrated an association between heavy consumption of nonnarcotic analgesics and the occurrence of chronic renal failure, but it is unclear which is the cause and which is the effect. Methods: In a nationwide, population-based, case-control study of early-stage chronic renal failure in Sweden, face-to-face interviews were conducted with 926 patients with newly diagnosed renal failure and 998 control subjects, of whom 918 and 980, respectively, had complete data. We used logistic-regression models to estimate the relative risks of disease-specific types of chronic renal failure associated with the use of various analgesics. Results: Aspirin and acetaminophen were used regularly by 37 percent and 25 percent, respectively, of the patients with renal failure and by 19 percent and 12 percent, respectively, of the controls. Regular use of either drug in the absence of the other was associated with an increase by a factor of 2.5 in the risk of chronic renal failure from any cause. The relative risks rose with increasing cumulative lifetime doses, rose more consistently with acetaminophen use than with aspirin use, and were increased for most disease-specific types of chronic renal failure. When we disregarded the recent use of analgesics, which could have occurred in response to antecedents of renal disease, the associations were only slightly attenuated. Conclusions: Our results are consistent with the existence of exacerbating effects of acetaminophen and aspirin on chronic renal failure. However, we cannot rule out the possibility of bias due to the triggering of analgesic consumption by predisposing conditions.

Published
2001
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49. Characteristics of women with cosmetic breast augmentation surgery compared with breast reduction surgery patients and women in the general population of Sweden

Author

Fryzek, J.P., Weiderpass, Elisabete, Signorello, L.B., Hakelius, Lars, Lipworth, L., Blot, W.J., McLaughlin, J.K., Nyrén, O., Fryzek, J.P., Weiderpass, Elisabete, Signorello, L.B., Hakelius, Lars, Lipworth, L., Blot, W.J., McLaughlin, J.K., and Nyrén, O.

Abstract

To determine whether women with cosmetic breast implants have distinct demographic, lifestyle, and reproductive characteristics that put them at increased risk for subsequent morbidity, the authors compared 1,369 such women to 2,211 women who had undergone breast reduction surgery, and to a random sample of 49,262 women from the general population of Sweden. Information was collected through self-administered questionnaires, and comparisons were made using the prevalence odds ratio. Women with cosmetic breast implants were significantly (p <0.05) more likely to be current smokers, have a lower body mass index, have had a prematurely terminated pregnancy (induced abortion or miscarriage), and have had fewer live births than either women who underwent breast reduction or women from the general population. Type of implant (silicone gel or saline) did not modify the associations. Regardless of the comparison group used, studies of the health effects of breast implants need to consider that women who undergo cosmetic breast implantation have certain distinct characteristics.

Published
2000

50. Maternal pregnancy hormone levels in an area with a high incidence (Boston, USA) and in an area with a low incidence (Shanghai, China) of breast cancer

Author

Lipworth, L., Hsieh, C-Ce., Wide, Leif, Ekbom, A., Yu, S-Z., Yu, G-P., Xu, B., Hellerstein, S., Carlstrom, K., Trichopoulos, D., Adami, Hans-Olov, Lipworth, L., Hsieh, C-Ce., Wide, Leif, Ekbom, A., Yu, S-Z., Yu, G-P., Xu, B., Hellerstein, S., Carlstrom, K., Trichopoulos, D., and Adami, Hans-Olov

Abstract

Characteristics probably associated with the fetal hormonal milieu have recently been shown to increase (birth size indicators, prematurity, neonatal jaundice) or decrease (pregnancy toxaemia) breast cancer risk in the female offspring. However, it is unknown whether differences in pregnancy hormone levels may contribute to the marked geographical variation in breast cancer incidence. We have compared, in a highly standardized manner, pregnancy hormone levels in a population with high incidence and one with low incidence of breast cancer. Three hundred and four pregnant Caucasian women in Boston and 334 pregnant Chinese women in Shanghai were enrolled from March 1994 to October 1995. Levels of oestradiol, oestriol, prolactin, progesterone, human growth hormone, albumin and sex hormone-binding globulin were measured in maternal blood at weeks 16 and 27 of gestation and compared between the two study sites using non-parametric Wilcoxon's rank-sum test. Demographical, anthropometrical and pregnancy characteristics were ascertained through interview, and relevant variables concerning delivery and the newborn were abstracted from medical records and paediatric charts. During the first visit, median serum levels of all studied hormones were statistically significant, and in most instances substantially, higher among Chinese women, who have a low incidence of breast cancer, compared with American women, who have a high incidence of breast cancer. An analogous pattern was evident during the second visit, although the relative differences tended to be smaller. Further research is needed to identify lifestyle or other exogenous determinants of pregnancy hormone levels, as well as possible mechanisms by which they may influence carcinogenic processes in the breast and possibly other organs.

Published
1999
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