58 results on '"Yu-Tang Gao"'
Search Results
2. Author Correction: Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
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Ceres Fernandez-Rozadilla, Maria Timofeeva, Zhishan Chen, Philip Law, Minta Thomas, Stephanie Schmit, Virginia Díez-Obrero, Li Hsu, Juan Fernandez-Tajes, Claire Palles, Kitty Sherwood, Sarah Briggs, Victoria Svinti, Kevin Donnelly, Susan Farrington, James Blackmur, Peter Vaughan-Shaw, Xiao-ou Shu, Jirong Long, Qiuyin Cai, Xingyi Guo, Yingchang Lu, Peter Broderick, James Studd, Jeroen Huyghe, Tabitha Harrison, David Conti, Christopher Dampier, Mathew Devall, Fredrick Schumacher, Marilena Melas, Gad Rennert, Mireia Obón-Santacana, Vicente Martín-Sánchez, Ferran Moratalla-Navarro, Jae Hwan Oh, Jeongseon Kim, Sun Ha Jee, Keum Ji Jung, Sun-Seog Kweon, Min-Ho Shin, Aesun Shin, Yoon-Ok Ahn, Dong-Hyun Kim, Isao Oze, Wanqing Wen, Keitaro Matsuo, Koichi Matsuda, Chizu Tanikawa, Zefang Ren, Yu-Tang Gao, Wei-Hua Jia, John Hopper, Mark Jenkins, Aung Ko Win, Rish Pai, Jane Figueiredo, Robert Haile, Steven Gallinger, Michael Woods, Polly Newcomb, David Duggan, Jeremy Cheadle, Richard Kaplan, Timothy Maughan, Rachel Kerr, David Kerr, Iva Kirac, Jan Böhm, Lukka-Pekka Mecklin, Pekka Jousilahti, Paul Knekt, Lauri Aaltonen, Harri Rissanen, Eero Pukkala, Johan Eriksson, Tatiana Cajuso, Ulrika Hänninen, Johanna Kondelin, Kimmo Palin, Tomas Tanskanen, Laura Renkonen-Sinisalo, Brent Zanke, Satu Männistö, Demetrius Albanes, Stephanie Weinstein, Edward Ruiz-Narvaez, Julie Palmer, Daniel Buchanan, Elizabeth Platz, Kala Visvanathan, Cornelia Ulrich, Erin Siegel, Stefanie Brezina, Andrea Gsur, Peter Campbell, Jenny Chang-Claude, Michael Hoffmeister, Hermann Brenner, Martha Slattery, John Potter, Konstantinos Tsilidis, Matthias Schulze, Marc Gunter, Neil Murphy, Antoni Castells, Sergi Castellví-Bel, Leticia Moreira, Volker Arndt, Anna Shcherbina, Mariana Stern, Bens Pardamean, Timothy Bishop, Graham Giles, Melissa Southey, Gregory Idos, Kevin McDonnell, Zomoroda Abu-Ful, Joel Greenson, Katerina Shulman, Flavio Lejbkowicz, Kenneth Offit, Yu-Ru Su, Robert Steinfelder, Temitope Keku, Bethany van Guelpen, Thomas Hudson, Heather Hampel, Rachel Pearlman, Sonja Berndt, Richard Hayes, Marie Elena Martinez, Sushma Thomas, Douglas Corley, Paul Pharoah, Susanna Larsson, Yun Yen, Heinz-Josef Lenz, Emily White, Li Li, Kimberly Doheny, Elizabeth Pugh, Tameka Shelford, Andrew Chan, Marcia Cruz-Correa, Annika Lindblom, David Hunter, Amit Joshi, Clemens Schafmayer, Peter Scacheri, Anshul Kundaje, Deborah Nickerson, Robert Schoen, Jochen Hampe, Zsofia Stadler, Pavel Vodicka, Ludmila Vodickova, Veronika Vymetalkova, Nickolas Papadopoulos, Chistopher Edlund, William Gauderman, Duncan Thomas, David Shibata, Amanda Toland, Sanford Markowitz, Andre Kim, Stephen Chanock, Franzel van Duijnhoven, Edith Feskens, Lori Sakoda, Manuela Gago-Dominguez, Alicja Wolk, Alessio Naccarati, Barbara Pardini, Liesel FitzGerald, Soo Chin Lee, Shuji Ogino, Stephanie Bien, Charles Kooperberg, Christopher Li, Yi Lin, Ross Prentice, Conghui Qu, Stéphane Bézieau, Catherine Tangen, Elaine Mardis, Taiki Yamaji, Norie Sawada, Motoki Iwasaki, Christopher Haiman, Loic Le Marchand, Anna Wu, Chenxu Qu, Caroline McNeil, Gerhard Coetzee, Caroline Hayward, Ian Deary, Sarah Harris, Evropi Theodoratou, Stuart Reid, Marion Walker, Li Yin Ooi, Victor Moreno, Graham Casey, Stephen Gruber, Ian Tomlinson, Wei Zheng, Malcolm Dunlop, Richard Houlston, and Ulrike Peters
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Global Nutrition ,Wereldvoeding ,Nutrition and Disease ,Voeding en Ziekte ,Genetics ,Life Science ,VLAG - Abstract
In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article.
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- 2023
3. Development and external validation of a breast cancer absolute risk prediction model in Chinese population
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Yu-Tang Gao, Zheng Bian, Dezheng Huo, Ling Yang, Yiping Chen, Yizhen Hu, Liming Li, Zhengming Chen, Junshi Chen, Huaidong Du, Peng Liang, Yu Guo, Wei Zheng, Yong-Bing Xiang, Canqing Yu, Yuting Han, Xiao-Ou Shu, Jun Lv, Wanqing Wen, Hong Guo, Fangyuan Zhao, and Group, China Kadoorie Biobank Collaborative
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Adult ,China ,Global health ,Breast Neoplasms ,Absolute risk ,Risk Assessment ,03 medical and health sciences ,Breast cancer ,0302 clinical medicine ,Asian People ,Risk Factors ,Prediction model ,Humans ,Medicine ,Prospective Studies ,Prospective cohort study ,Survival rate ,RC254-282 ,Aged ,030304 developmental biology ,0303 health sciences ,Models, Statistical ,business.industry ,Proportional hazards model ,Incidence ,Absolute risk reduction ,Reproducibility of Results ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Cancer ,Middle Aged ,medicine.disease ,Confidence interval ,Area Under Curve ,030220 oncology & carcinogenesis ,Relative risk ,Women's Health ,Female ,business ,Research Article ,Demography - Abstract
BackgroundsIn contrast to developed countries, breast cancer in China is characterized by a rapidly escalating incidence rate in the past two decades, lower survival rate, and vast geographic variation. However, there is no validated risk prediction model in China to aid early detection yet.MethodsA large nationwide prospective cohort, China Kadoorie Biobank (CKB), was used to evaluate relative and attributable risks of invasive breast cancer. A total of 300,824 women free of any prior cancer were recruited during 2004–2008 and followed up to Dec 31, 2016. Cox models were used to identify breast cancer risk factors and build a relative risk model. Absolute risks were calculated by incorporating national age- and residence-specific breast cancer incidence and non-breast cancer mortality rates. We used an independent large prospective cohort, Shanghai Women’s Health Study (SWHS), with 73,203 women to externally validate the calibration and discriminating accuracy.ResultsDuring a median of 10.2 years of follow-up in the CKB, 2287 cases were observed. The final model included age, residence area, education, BMI, height, family history of overall cancer, parity, and age at menarche. The model was well-calibrated in both the CKB and the SWHS, yielding expected/observed (E/O) ratios of 1.01 (95% confidence interval (CI), 0.94–1.09) and 0.94 (95% CI, 0.89–0.99), respectively. After eliminating the effect of age and residence, the model maintained moderate but comparable discriminating accuracy compared with those of some previous externally validated models. The adjusted areas under the receiver operating curve (AUC) were 0.634 (95% CI, 0.608–0.661) and 0.585 (95% CI, 0.564–0.605) in the CKB and the SWHS, respectively.ConclusionsBased only on non-laboratory predictors, our model has a good calibration and moderate discriminating capacity. The model may serve as a useful tool to raise individuals’ awareness and aid risk-stratified screening and prevention strategies.
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- 2021
4. Association between type 2 diabetes and risk of cancer mortality: a pooled analysis of over 771,000 individuals in the Asia Cohort Consortium
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Shoichiro Tsugane, Eiko Saito, Keiko Wada, Seiki Kanemura, Manami Inoue, Ichiro Tsuji, Woon-Puay Koh, Minkyo Song, Paolo Boffetta, Yong-Bing Xiang, Fen Wu, Habibul Ahsan, Hidemi Ito, Wei Zheng, Yoon Ok Ahn, Hung N. Luu, Myung Hee Shin, Mangesh S. Pednekar, San Lin You, Kee Seng Chia, Wen-Harn Pan, Chisato Nagata, Prakash C. Gupta, Keun-Young Yoo, Yasutake Tomata, Kemmyo Sugiyama, Keitaro Matsuo, Daehee Kang, You-Lin Qiao, Yumi Sugawara, Yingsong Lin, John D. Potter, Renwei Wang, Norie Sawada, Hui Cai, Akiko Tamakoshi, Yu-Tang Gao, Sue K. Park, Yu Chen, Jian-Min Yuan, Xiao-Ou Shu, and Chen, Y. and Wu, F. and Saito, E. and Lin, Y. and Song, M. and Luu, H.N. and Gupta, P.C. and Sawada, N. and Tamakoshi, A. and Shu, X.-O. and Koh, W.-P. and Xiang, Y.-B. and Tomata, Y. and Sugiyama, K. and Park, S.K. and Matsuo, K. and Nagata, C. and Sugawara, Y. and Qiao, Y.-L. and You, S.-L. and Wang, R. and Shin, M.-H. and Pan, W.-H. and Pednekar, M.S. and Tsugane, S. and Cai, H. and Yuan, J.-M. and Gao, Y.-T. and Tsuji, I. and Kanemura, S. and Ito, H. and Wada, K. and Ahn, Y.-O. and Yoo, K.-Y. and Ahsan, H. and Chia, K.S. and Boffetta, P. and Zheng, W. and Inoue, M. and Kang, D. and Potter, J.D.
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Male ,Endocrinology, Diabetes and Metabolism ,Type 2 diabetes ,Gastroenterology ,gallbladder cancer ,0302 clinical medicine ,Neoplasms ,Surveys and Questionnaires ,cancer mortality ,thyroid cancer ,South Asian ,Surveys and Questionnaire ,030212 general & internal medicine ,East Asian ,pathophysiology ,Randomized Controlled Trials as Topic ,education.field_of_study ,adult ,kidney cancer ,ovary cancer ,Middle Aged ,prostate cancer ,medicine.anatomical_structure ,priority journal ,030220 oncology & carcinogenesis ,Hypertension ,Cohort ,Female ,Human ,medicine.medical_specialty ,Asia ,non insulin dependent diabetes mellitu ,cohort analysi ,Population ,colorectal cancer ,lymphoma ,malignant neoplasm ,bile duct cancer ,Article ,liver cancer ,03 medical and health sciences ,breast cancer ,pancreas cancer ,Internal medicine ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Meta-analysi ,education ,Exercise ,Cervix ,Aged ,Asian ,business.industry ,questionnaire ,Gallbladder ,disease association ,Cancer ,Asia Cohort Consortium ,medicine.disease ,major clinical study ,mortality ,Obesity ,endometrium cancer ,Diabetes Mellitus, Type 2 ,Neoplasm ,randomized controlled trial (topic), Aged ,business - Abstract
Aims/hypothesis: The aims of the study were to evaluate the association between type 2 diabetes and the risk of death from any cancer and specific cancers in East and South Asians. Methods: Pooled analyses were conducted of 19 prospective population-based cohorts included in the Asia Cohort Consortium, comprising data from 658,611 East Asians and 112,686 South Asians. HRs were used to compare individuals with diabetes at baseline with those without diabetes for the risk of death from any cancer and from site-specific cancers, including cancers of the oesophagus, stomach, colorectum, colon, rectum, liver, bile duct, pancreas, lung, breast, endometrium, cervix, ovary, prostate, bladder, kidney and thyroid, as well as lymphoma and leukaemia. Results: During a mean follow-up of 12.7 years, 37,343 cancer deaths (36,667 in East Asians and 676 in South Asians) were identified. Baseline diabetes status was statistically significantly associated with an increased risk of death from any cancer (HR 1.26; 95% CI 1.21, 1.31). Significant positive associations with diabetes were observed for cancers of the colorectum (HR 1.41; 95% CI 1.26, 1.57), liver (HR 2.05; 95% CI 1.77, 2.38), bile duct (HR 1.41; 95% CI 1.04, 1.92), gallbladder (HR 1.33; 95% CI 1.10, 1.61), pancreas (HR 1.53; 95% CI 1.32, 1.77), breast (HR 1.72; 95% CI 1.34, 2.19), endometrium (HR 2.73; 95% CI 1.53, 4.85), ovary (HR 1.60; 95% CI 1.06, 2.42), prostate (HR 1.41; 95% CI 1.09, 1.82), kidney (HR 1.84; 95% CI 1.28, 2.64) and thyroid (HR 1.99; 95% CI 1.03, 3.86), as well as lymphoma (HR 1.39; 95% CI 1.04, 1.86). Diabetes was not statistically significantly associated with the risk of death from leukaemia and cancers of the bladder, cervix, oesophagus, stomach and lung. Conclusions/interpretation: Diabetes was associated with a 26% increased risk of death from any cancer in Asians. The pattern of associations with specific cancers suggests the need for better control (prevention, detection, management) of the growing epidemic of diabetes (as well as obesity), in order to reduce cancer mortality. © 2017, Springer-Verlag Berlin Heidelberg.
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- 2017
5. Age at menarche and age at natural menopause in East Asian women: a genome-wide association study
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Ben Zhang, Ji Yeob Choi, Jirong Long, Xingwang Ye, Yiqin Wang, Sue K. Park, Seokang Chung, Jiajun Shi, Huaixing Li, Daehee Kang, Dong Young Noh, Wanqing Wen, Xiao-Ou Shu, Xu Lin, Ying Zheng, Yu-Tang Gao, Yong-Bing Xiang, Qiuyin Cai, and Wei Lu
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0301 basic medicine ,China ,Aging ,Genotype ,media_common.quotation_subject ,Locus (genetics) ,Fertility ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Risk Factors ,medicine ,Humans ,Aged ,media_common ,Genetic association ,Menarche ,Genetics ,Korea ,030219 obstetrics & reproductive medicine ,Age Factors ,Correction ,General Medicine ,Middle Aged ,medicine.disease ,Genetic architecture ,Menopause ,030104 developmental biology ,Genetic Loci ,Linear Models ,Female ,Geriatrics and Gerontology ,Genome-Wide Association Study ,Demography - Abstract
Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a reduced span of fertility and risk for several age-related diseases including breast, endometrial and ovarian cancer, cardiovascular disease, and osteoporosis. To identify novel genetic loci for AM or ANM in East Asian women and to replicate previously identified loci primarily in women of European ancestry by genome-wide association studies (GWASs), we conducted a two-stage GWAS. Stage I aimed to discover promising novel AM and ANM loci using GWAS data of 8073 women from Shanghai, China. The Stage II replication study used the data from another Chinese GWAS (n = 1230 for AM and n = 1458 for ANM), a Korean GWAS (n = 4215 for AM and n = 1739 for ANM), and de novo genotyping of 2877 additional Chinese women. Previous GWAS-identified loci for AM and ANM were also evaluated. We identified two suggestive menarcheal age loci tagged by rs79195475 at 10q21.3 (beta = −0.118 years, P = 3.4 × 10−6) and rs1023935 at 4p15.1 (beta = −0.145 years, P = 4.9 × 10−6) and one menopausal age locus tagged by rs3818134 at 22q12.2 (beta = −0.276 years, P = 8.8 × 10−6). These suggestive loci warrant a further validation in independent populations. Although limited by low statistical power, we replicated 19 of the 98 menarche loci and 5 of the 20 menopause loci previously identified in women of European ancestry in East Asian women, suggesting a shared genetic architecture for these two traits across populations.
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- 2016
6. Association between genetic risk score for telomere length and risk of breast cancer
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Jirong Long, Xiao-Ou Shu, Hung N. Luu, Qiuyin Cai, Yu-Tang Gao, Wei Zheng, Ying Zheng, and Wanqing Wen
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Adult ,0301 basic medicine ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Genome-wide association study ,Logistic regression ,Polymorphism, Single Nucleotide ,Article ,White People ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Asian People ,Internal medicine ,Epidemiology ,Ethnicity ,Humans ,Medicine ,Genetic Predisposition to Disease ,Allele ,Alleles ,Hematology ,business.industry ,Genetic Variation ,Middle Aged ,Telomere ,medicine.disease ,030104 developmental biology ,Risk factors for breast cancer ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Breast Cancer Genetics ,business ,Genome-Wide Association Study - Abstract
While leukocyte telomere length (TL) has been associated with breast cancer risk, limited information is available regarding the role of genetically-determined TL on breast cancer risk. We investigated whether aggregated TL-associated variants are associated with the risk of breast cancer in 2,865 breast cancer cases and 2,285 controls from the Shanghai Breast Cancer Genetics Study. Six genetic variants, identified through a genome-wide association study (GWAS) of TL in European-ancestry participants, were included in the study. A separate sample [n = 1,536, from the Shanghai Women’s Health Study (SWHS), for whom information on both phenotypical leukocyte TL and genetic information was collected] was used to evaluate the association of six variants with TL in Asians. Three genetic risk scores (GRSs), based on the number of alleles associated with shorter TL that each individual carries for the six variants, were derived for the study: un-weighted, internally weighted (from the SWHS), and externally weighted (from the European-ancestry GWAS study), and evaluated for their association with breast cancer risk by applying logistic regression analysis. Both internally and externally weighted GRSs were significantly associated with a decreased risk of breast cancer (OR 0.83, 95 % CI 0.72–0.95 and OR 0.84, 95 % CI 0.74–0.96, respectively, for tertile 3 vs. tertile 1). Non-genetic risk factors for breast cancer (i.e., age, years of menstruation/reproduction, oral contraceptive usage, and BMI) did not modify the association between GRSs and the risk of breast cancer. Our results suggest that short TL, determined by genetic factors, may be associated with a reduced susceptibility to breast cancer.
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- 2016
7. Body mass index and lung cancer risk: a pooled analysis based on nested case-control studies from four cohort studies
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Gary E. Goodman, Lesley M. Butler, Paolo Vineis, Woon-Puay Koh, Mattias Johansson, Isabelle Stücker, Harinakshi Sanikini, Jian-Min Yuan, Chu Chen, Annika Steffen, Rayjean J. Hung, Matt J. Barnett, Yu-Tang Gao, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Duke-NUS Medical School [Singapore], Saw Swee Hock School of Public Health, National University of Singapore (NUS), Department of Epidemiology, Shanghai Cancer Institute, School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Epidemiology and Biostatistics [Imperial College London], Imperial College London, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], This work was supported by the Fondation de France and Ecole doctarale de Sante Publique (ED420). The EPIC study has been supported by the Europe Against Cancer Program of the European Commission. The SCHS and SCS were supported by NCI, NIH grants U01-CA63673, UM1-CA167462 and R01-CA111703. The CARET was supported by the National Institute of Health (U01 CA63673) and the Fred Hutchinson Cancer Research Center, Seattle, WA., BMC, BMC, and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,Cancer Research ,Lung Neoplasms ,[SDV]Life Sciences [q-bio] ,Overweight ,Body Mass Index ,0302 clinical medicine ,Risk Factors ,030212 general & internal medicine ,2. Zero hunger ,Smoking ,Middle Aged ,3. Good health ,[SDV] Life Sciences [q-bio] ,Oncology ,030220 oncology & carcinogenesis ,MENDELIAN RANDOMIZATION ,Female ,Lung cancer ,medicine.symptom ,Underweight ,Life Sciences & Biomedicine ,Research Article ,Cohort study ,Adult ,medicine.medical_specialty ,HYPOXIA-INDUCIBLE FACTOR ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,SECULAR TRENDS ,03 medical and health sciences ,[SDV.CAN] Life Sciences [q-bio]/Cancer ,Internal medicine ,Genetics ,medicine ,Humans ,Oncology & Carcinogenesis ,Obesity ,METAANALYSIS ,Aged ,Science & Technology ,HISTOLOGIC TYPE ,business.industry ,MORTALITY ,Case-control study ,Odds ratio ,medicine.disease ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Case-Control Studies ,Nested case-control study ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,WEIGHT ,SINGAPORE CHINESE HEALTH ,business ,1112 Oncology And Carcinogenesis ,Body mass index - Abstract
Background Obesity has been proposed as a potential protective factor against lung cancer. We examined the association between BMI and lung cancer risk in a pooled analysis based on nested case-control studies from four cohort studies. Methods A case-control study was nested within four cohorts in USA, Europe, China and Singapore that included 4172 cases and 8471 control subjects. BMI at baseline was calculated as weight in kilograms divided by height in meters squared (kg/m2), and classified into 4 categories: underweight (BMI
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- 2018
8. Genome-wide significant risk associations for mucinous ovarian carcinoma
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Jenny Lester, Arif B. Ekici, Xiao-Ou Shu, Georgia Chenevix-Trench, Julie M. Cunningham, Catherine M. Phelan, Tassja J. Spindler, Shelley S. Tworoger, Allan Jensen, Diana Eccles, Wei Zheng, Satoyo Hosono, Svend Aage Engelholm, Linda S. Cook, Thomas A. Sellers, John R. McLaughlin, Matthias W. Beckmann, Elizabeth M. Poole, Ignace Vergote, Francesmary Modugno, Jennifer A. Doherty, Sandrina Lambrechts, Lara Sucheston, Wang Gohrke Shan, Rosalind Glasspool, Barry P. Rosen, Pamela J. Thompson, Christine Walsh, Camilla Krakstad, Jennifer Permuth-Wey, Hoda Anton-Culver, Ralf Bützow, Ed Dicks, Yin Ling Woo, Honglin Song, Qiyuan Li, Leon F.A.G. Massuger, Yurii B. Shvetsov, Joellen M. Schildkraut, Xiaoqing Chen, Hannah P. Yang, Graham G. Giles, Sara H. Olson, Edwin S. Iversen, Claus Høgdall, Jacek Grownwald, Fiona Bruinsma, Peter Hillemanns, Iwona K. Rzepecka, Douglas T. Easton, Robert P. Edwards, Lynne R. Wilkens, Yukie Bean, Y. Ann Chen, Jonathan Tyrer, Tanja Pejovic, Patricia Harrington, Iain A. McNeish, Steven A. Narod, Joanna Moes-Sosnowska, Hanis Nazihah Hasmad, Ji-Heui Seo, Line Bjørge, Peter A. Fasching, Daniel W. Cramer, Florian Heitz, Beth Y. Karlan, Cezary Cybulski, Simon A. Gayther, Jolanta Kupryjanczyk, Nhu D. Le, Alexander Hein, Soo Hwang Teo, Nicolas Wentzensen, Valerie McGuire, Michelle A.T. Hildebrandt, Argyrios Ziogas, Heli Nevanlinna, Karen H. Lu, Diether Lambrechts, Kirsten B. Moysich, Jonathan Beesley, Kate Lawrenson, Ian G. Campbell, Andrew Berchuck, Philipp Harter, Lene Lundvall, Sandra Orsulic, Kathryn L. Terry, Jolanta Lissowska, Helen Baker, Matthew L. Freedman, Linda E. Kelemen, Maria Bisogna, Celeste Leigh Pearce, Ira Schwaab, Elisa V. Bandera, Kristine G. Wicklund, Arto Leminen, Nadeem Siddiqui, Joseph H. Rothstein, Melissa Kellar, Matthias Dürst, Harvey A. Risch, Włodzimierz Sawicki, Katja K.H. Aben, Alice S. Whittemore, Kunle Odunsi, Shashi Lele, Noor Azmi Mat Adenan, Susanne K. Kjaer, Robert A. Vierkant, Jan Lubinski, Natalia Bogdanova, Helga B. Salvesen, Anja Rudolph, Els Van Nieuwenhuysen, Irene Orlow, Joe Dennis, Ingvild L. Tangen, Estrid Høgdall, Alice W. Lee, Roberta B. Ness, James Paul, Malcolm C. Pike, Rachel Palmieri Weber, Anna H. Wu, Agnieszka Dansonka-Mieszkowska, Melissa C. Southey, Natalia Antonenkova, Anne M. van Altena, Xifeng Wu, Keitaro Matsuo, Anna Jakubowska, Paul D.P. Pharoah, Weiva Sieh, Lambertus A. Kiemeney, Lotte Nedergaard, Ursula Eilber, Janet M. Lee, Zhihua Chen, Andreas du Bois, Joseph L. Kelley, Aleksandra Gentry-Maharaj, Jenny Chang-Claude, Ellen L. Goode, Bu Tian Ji, Liisa M. Pelttari, Usha Menon, Dong Liang, Yu-Tang Gao, Brooke L. Fridley, Mary Anne Rossing, Thilo Dörk, Douglas A. Levine, Louise A. Brinton, Marc T. Goodman, Angela Brooks-Wilson, Ingo B. Runnebaum, Karen Carty, and Susan J. Ramus
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Green Fluorescent Proteins ,Molecular Sequence Data ,Quantitative Trait Loci ,Single-nucleotide polymorphism ,Genome-wide association study ,Quantitative trait locus ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Cell Line, Tumor ,Ovarian carcinoma ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic Association Studies ,030304 developmental biology ,Genetic association ,Cell Nucleus ,Homeodomain Proteins ,Ovarian Neoplasms ,0303 health sciences ,Base Sequence ,Reverse Transcriptase Polymerase Chain Reaction ,medicine.disease ,Adenocarcinoma, Mucinous ,Neoplasm Proteins ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,3. Good health ,Gene Expression Regulation, Neoplastic ,Microscopy, Fluorescence ,Chromosomes, Human, Pair 2 ,Urological cancers Radboud Institute for Health Sciences [Radboudumc 15] ,030220 oncology & carcinogenesis ,Expression quantitative trait loci ,Cancer research ,Adenocarcinoma ,Female ,Ovarian cancer ,Genome-Wide Association Study - Abstract
Genome-wide association studies have identified several risk associations for ovarian carcinomas (OC) but not for mucinous ovarian carcinomas (MOC). Genotypes from OC cases and controls were imputed into the 1000 Genomes Project reference panel. Analysis of 1,644 MOC cases and 21,693 controls identified three novel risk associations: rs752590 at 2q13 (P = 3.3 × 10−8), rs711830 at 2q31.1 (P = 7.5 × 10−12) and rs688187 at 19q13.2 (P = 6.8 × 10−13). Expression Quantitative Trait Locus (eQTL) analysis in ovarian and colorectal tumors (which are histologically similar to MOC) identified significant eQTL associations for HOXD9 at 2q31.1 in ovarian (P = 4.95 × 10−4, FDR = 0.003) and colorectal (P = 0.01, FDR = 0.09) tumors, and for PAX8 at 2q13 in colorectal tumors (P = 0.03, FDR = 0.09). Chromosome conformation capture analysis identified interactions between the HOXD9 promoter and risk SNPs at 2q31.1. Overexpressing HOXD9 in MOC cells augmented the neoplastic phenotype. These findings provide the first evidence for MOC susceptibility variants and insights into the underlying biology of the disease.
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- 2015
9. Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer
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Vesa Kataja, Aida Karina Dieffenbach, Chia-Ni Hsiung, Catherine S. Healey, Gie Hooi Tan, Soo Hwang Teo, Domenico Palli, Frederik Marme, Katri Pylkäs, Roger L. Milne, Jaana M. Hartikainen, Gord Glendon, Susan L. Slager, Chen-Yang Shen, Fredrick R. Schumacher, Daniel F. Schmidt, Suleeporn Sangrajrang, Kee Seng Chia, Lorna Gibson, Pascal Guénel, Alice S. Whittemore, Jenny Chang-Claude, Yu Tang Gao, Hidemi Ito, Simon S. Cross, Sofia Khan, Marie Sanchez, Daniel Vincent, Daniel Herrero, Nicola Miller, Antoinette Hollestelle, Caroline M. Seynaeve, Christopher A. Haiman, Hermann Brenner, Kay-Tee Khaw, Loris Bernard, Habibul Ahsan, Melissa C. Southey, David Van Den Berg, Martha J. Shrubsole, Daniel O. Stram, William Blot, Mel Maranian, Robert Winqvist, Keitaro Matsuo, John W. M. Martens, Heli Nevanlinna, Mia M. Gaudet, Anna Jakubowska, Christine D. Berg, Paul D.P. Pharoah, Jacques Simard, Manjeet K. Bolla, Dieter Flesch-Janys, Mark S. Goldberg, Paul Brennan, Ching Wan Chan, Sune F. Nielsen, Sara Lindström, Mitul Shah, Matthias W. Beckmann, Craig Luccarini, Jonathan Beesley, Kyriaki Michailidou, Paolo Peterlongo, Marc J. Gunter, Anna González-Neira, Ji Yeob Choi, Per Hall, Sarah Stewart-Brown, Keith Humphreys, Hui Cai, Kathleen E. Malone, Elinor J. Sawyer, Louise A. Brinton, Marjanka K. Schmidt, Xiao-Ou Shu, Barbara Perkins, Lotte Maxild Mortensen, Chiu-Chen Tseng, Hanne Meijers-Heijboer, Minouk J. Schoemaker, Keun-Young Yoo, Julia A. Knight, Alan Ashworth, Stig E. Bojesen, Kamila Czene, Artitaya Lophatananon, Graham G. Giles, S. Ahmed, Kazuo Tajima, Douglas F. Easton, Maria Kabisch, Arja Jukkola-Vuorinen, Wei Lu, Peter A. Fasching, Irene L. Andrulis, Clare Turnbull, Caroline Baynes, Christine B. Ambrosone, Jan Lubinski, Muriel A. Adank, A. Meindl, Taru A. Muranen, Siranoush Manoukian, Susan M. Gapstur, Natalia Bogdanova, Alexander Hein, Annika Lindblom, Nazneen Rahman, Annegien Broeks, Lothar Haeberle, Federico Canzian, G Pita, Ming-Feng Hou, Hiroji Iwata, Drakoulis Yannoukakos, Diana Torres, Vessela N. Kristensen, Peter Devilee, Qiuyin Cai, Christi J Asperen, John L. Hopper, Diether Lambrechts, Michael Lush, Hans Wildiers, Joe Dennis, Sandra L. Halverson, Carl Blomqvist, Erik Van Limbergen, Malin Sund, Daehee Kang, Grethe I. Grenaker Alnæs, Marilie D. Gammon, Ursula Eilber, Ian Tomlinson, Thérèse Truong, Amanda E. Toland, Anna Marie Mulligan, Kirsimari Aaltonen, Olivia Fletcher, Jonine D. Figueroa, Angela Cox, Pei Ei Wu, Maartje J. Hooning, Catriona McLean, Georgia Chenevix-Trench, Pornthep Siriwanarangsan, Malcolm W.R. Reed, Emily Hallberg, Sara Margolin, Volker Arndt, Montserrat Garcia-Closas, Francois Bacot, Rita K. Schmutzler, Julian Peto, David J. Hunter, Thomas Brüning, Katarzyna Jaworska, Christof Sohn, Børge G. Nordestgaard, Enes Makalic, Hatef Darabi, Barbara Burwinkel, Petra P.H. Peeters, J. Margriet Collée, Rongxi Yang, Robert N. Hoover, Eiliv Lund, Fergus J. Couch, Ute Hamann, Jirong Long, Wei Zheng, Sabine Behrens, Giske Ursin, Muhammad G. Kibriya, Claire Mulot, Laure Dossus, Helen Tsimiklis, Tomasz Huzarski, Peter Kraft, Anja Rudolph, Arto Mannermaa, Alison M. Dunning, Lisa B. Signorello, Valerie Gaborieau, Kenneth Muir, Anthony J. Swerdlow, Javier Benitez, Judith S. Brand, Sander Canisius, Hoda Anton-Culver, Veli-Matti Kosma, Thilo Dörk, Sten Cornelissen, Christa Stegmaier, Cheng Har Yip, Brian E. Henderson, Harald Surowy, Jingmei Li, Nur Aishah Taib, W. Ryan Diver, Carmel Apicella, Janet E. Olson, Kristiina Aittomäki, Celine M. Vachon, Regina M. Santella, Dimitrios Trichopoulos, Jianjun Liu, Nick Orr, Martine Dumont, Christian Sutter, Sue K. Park, Mikael Hartman, Susan L. Neuhausen, Hui Miao, M. Pilar Zamora, Anna H. Wu, Rob B. van der Luijt, Isabel dos-Santos-Silva, Graham Casey, Henrik Flyger, M. Rosario Alonso, Nuria Álvarez, Michael J. Kerin, Loic Le Marchand, Jose Ignacio Arias Perez, Mikael Eriksson, Esther M. John, Quinten Waisfisz, Qin Wang, Daniel C. Tessier, Paolo Radice, Robert A.E.M. Tollenaar, James McKay, Silje Nord, Hiltrud Brauch, José María Huerta, Stephen J. Chanock, Mervi Grip, Patrick Neven, Senno Verhoef, Clinical Genetics, Obstetrics & Gynecology, Medical Oncology, Cardiothoracic Surgery, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Khaw, Kay-Tee [0000-0002-8802-2903], Pharoah, Paul [0000-0001-8494-732X], Dunning, Alison [0000-0001-6651-7166], Easton, Douglas [0000-0003-2444-3247], Apollo - University of Cambridge Repository, Human genetics, and CCA - Oncogenesis
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Breast Neoplasms ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Research Support ,Polymorphism, Single Nucleotide ,N.I.H ,Cohort Studies ,brca1 ,Breast cancer ,Research Support, N.I.H., Extramural ,Meta-Analysis as Topic ,SDG 3 - Good Health and Well-being ,common variants ,Journal Article ,estrogen ,chek2-asterisk-1100delc ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,1000 Genomes Project ,Non-U.S. Gov't ,genotype imputation ,risk ,Genetic association ,Research Support, Non-U.S. Gov't ,Chromatin binding ,Extramural ,Cancer ,Microarray Analysis ,confer susceptibility ,medicine.disease ,3. Good health ,ovarian-cancer ,Genetic Loci ,Case-Control Studies ,alleles ,Female ,Imputation (genetics) ,Genome-Wide Association Study ,metaanalysis - Abstract
Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1. ispartof: Nature Genetics vol:47 issue:4 pages:373-80 ispartof: location:United States status: published
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- 2015
10. Interactions between household air pollution and GWAS-identified lung cancer susceptibility markers in the Female Lung Cancer Consortium in Asia (FLCCA)
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Jen Yu Hung, Laurie Burdette, Chih Yi Chen, Jiucun Wang, Yu-Tang Gao, Keitaro Matsuo, Pan-Chyr Yang, Yi-Long Wu, Yuh Min Chen, Chao A. Hsiung, Chong-Jen Yu, Sonja I. Berndt, Reury Perng Perng, Kuan-Yu Chen, Maria Pik Wong, Baosen Zhou, Chien-Jen Chen, Tangchun Wu, Dara Lu, Stephen J. Chanock, Wei Jie Seow, Joseph F. Fraumeni, Zhaoming Wang, Wei Wu, Ying Hsiang Chen, Neil E. Caporaso, Maria Teresa Landi, Chien Chung Lin, Zhihua Yin, Minsun Song, Nathaniel Rothman, Xiao-Ou Shu, Nilanjan Chatterjee, Fang Yu Tsai, Yao Jen Li, Qing Lan, Li Jin, Chung Hsing Chen, I. Shou Chang, Dongxin Lin, Yun-Chul Hong, Hongbing Shen, Ming Shyan Huang, H. Dean Hosgood, Kexin Chen, Adeline Seow, Tsung-Ying Yang, Christopher Kim, Qincheng He, Qiuyin Cai, Chen Wu, Yi Song Chen, Gee-Chen Chang, Yong-Bing Xiang, Wei Zheng, Peng Guan, Chih-Liang Wang, Ying-Huang Tsai, Meredith Yeager, Li Hsin Chien, Min-Ho Shin, Wu Chou Su, Kun-Chieh Chen, Wong Ho Chow, Bryan A. Bassig, and Chin-Fu Hsiao
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Adult ,Genetic Markers ,Risk ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Single-nucleotide polymorphism ,Genome-wide association study ,Adenocarcinoma ,Biology ,Polymorphism, Single Nucleotide ,Article ,Internal medicine ,Genetic variation ,TP63 ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Lung cancer ,Genetics (clinical) ,Carcinogen ,Aged ,Air Pollutants ,Middle Aged ,medicine.disease ,Lung cancer susceptibility ,Air Pollution, Indoor ,Case-Control Studies ,Female ,Gene-Environment Interaction ,Genome-Wide Association Study - Abstract
We previously carried out a multi-stage genome-wide association study (GWAS) on lung cancer among never smokers in the Female Lung Cancer Consortium in Asia (FLCCA) (6,609 cases, 7,457 controls) that identified novel susceptibility loci at 10q25.2, 6q22.2, and 6p21.32, and confirmed two previously identified loci at 5p15.33 and 3q28. Household air pollution (HAP) attributed to solid fuel burning for heating and cooking, is the leading cause of the overall disease burden in Southeast Asia, and is known to contain lung carcinogens. To evaluate the gene–HAP interactions associated with lung cancer in loci independent of smoking, we analyzed data from studies participating in FLCCA with fuel use information available (n = 3; 1,731 cases; 1,349 controls). Coal use was associated with a 30 % increased risk of lung cancer (OR 1.3, 95 % CI 1.0–1.6). Among the five a priori SNPs identified by our GWAS, two showed a significant interaction with coal use (HLA Class II rs2395185, p = 0.02; TP63 rs4488809 (rs4600802), p = 0.04). The risk of lung cancer associated with coal exposure varied with the respective alleles for these two SNPs. Our observations provide evidence that genetic variation in HLA Class II and TP63 may modify the association between HAP and lung cancer risk. The roles played in the cell cycle and inflammation pathways by the proteins encoded by these two genes provide biological plausibility for these interactions; however, additional replication studies are needed in other non-smoking populations.
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- 2015
11. Genome-wide association analysis in East Asians identifies breast cancer susceptibility loci at 1q32.1, 5q14.3 and 15q26.1
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Siew-Kee Low, Wei Lu, Min Ho Park, Yoshio Kasuga, Jiemin Liao, Sei Hyun Ahn, Ji Yeob Choi, Hyuna Sung, Michiaki Kubo, Bingshan Li, Kyota Ashikawa, Yanfeng Zhang, Hidemi Ito, Koichi Matsuda, Chen-Yang Shen, Ryan J. Delahanty, Bu Tian Ji, Yu-Tang Gao, Han Sung Kang, Yusuke Nakamura, Motoki Iwasaki, Hiroji Iwata, Chia-Ni Hsiung, Mi Kyung Kim, Ying Zheng, Ellen P S Man, Daehee Kang, Ui-Soon Khoo, Soo Hwang Teo, Xiao-Ou Shu, Yong-Bing Xiang, Wanqing Wen, Jiajun Shi, Wei Zheng, Chun Li, Shoichiro Tsugane, Keitaro Matsuo, Hui Miao, Peter B. Kang, Pei-Ei Wu, Qiuyin Cai, Sue K. Park, Kelvin Y.K. Chan, Dong-Young Noh, Jirong Long, Shivaani Mariapun, Ben Zhang, Sun-Seog Kweon, Atsushi Takahashi, Mikael Hartman, and Min-Ho Shin
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Adult ,Risk ,Breast Neoplasms ,Genome-wide association study ,Biology ,White People ,Article ,Breast cancer ,Asian People ,Genetics ,medicine ,Genome-Wide Association Analysis ,Humans ,Genetic Predisposition to Disease ,skin and connective tissue diseases ,Genetic association ,Chromosomes, Human, Pair 15 ,Asia, Eastern ,Case-control study ,Middle Aged ,medicine.disease ,3. Good health ,Chromosomes, Human, Pair 1 ,Genetic Loci ,Case-Control Studies ,Susceptibility locus ,Chromosomes, Human, Pair 5 ,Female ,Genome-Wide Association Study - Abstract
In a three-stage genome-wide association study among East Asian women including 22,780 cases and 24,181 controls, we identified three novel genetic loci associated with breast cancer risk, including rs4951011 at 1q32.1 (in intron 2 of the ZC3H11A gene, P = 8.82 × 10−9), rs10474352 at 5q14.3 (near the ARRDC3 gene, P = 1.67 × 10−9), and rs2290203 at 15q26.1 (in intron 14 of the PRC1 gene, P = 4.25 × 10−8). These associations were replicated in European-ancestry populations including 16,003 cases and 41,335 controls (P = 0.030, 0.004, and 0.010, respectively). Data from the ENCODE project suggest that variants rs4951011 and rs10474352 may be located in an enhancer region and transcription factor binding sites, respectively. This study provides additional insights into the genetics and biology of breast cancer.
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- 2014
12. Large-scale genetic study in East Asians identifies six new loci associated with colorectal cancer risk
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Atsushi Takahashi, Gong Yang, Fredrick R. Schumacher, Yoon Ok Ahn, Jirong Long, Yong-Bing Xiang, Stephanie L. Stenzel, Dong Hyun Kim, Zhi Zhong Pan, Ben Zhang, Yan Guo, Yanfeng Zhang, Bingshan Li, Wanqing Wen, Wei Hua Jia, Sang-Hee Cho, Ji Won Park, Yu-Tang Gao, Satoyo Hosono, Chun Li, Qiuyin Cai, Yi Xin Zeng, Jiajun Shi, Wei Zheng, Martha L. Slattery, Min-Ho Shin, Sun Ha Jee, Michiaki Kubo, Bu Tian Ji, Aesun Shin, Jae Hwan Oh, Jenny Chang-Claude, Fumihiko Matsuda, Xiao-Ou Shu, Jin Young Jeong, Koichi Matsuda, Soriul Kim, Graham Casey, Hong Lan Li, Hyeong Rok Kim, Andrew T. Chan, Stephen B. Gruber, Zefang Ren, Sun-Seog Kweon, and Keitaro Matsuo
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Male ,Risk ,China ,Genotype ,Colorectal cancer ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Article ,Metastasis ,03 medical and health sciences ,Delta-5 Fatty Acid Desaturase ,0302 clinical medicine ,Asian People ,Japan ,Polymorphism (computer science) ,Republic of Korea ,Genetic variation ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Neoplasm Metastasis ,030304 developmental biology ,0303 health sciences ,Gene Expression Profiling ,Case-control study ,Chromosome Mapping ,Computational Biology ,Genetic Variation ,medicine.disease ,3. Good health ,Genetic Loci ,Case-Control Studies ,030220 oncology & carcinogenesis ,Female ,Colorectal Neoplasms ,TCF7L2 ,Genome-Wide Association Study - Abstract
Known genetic loci explain only a small proportion of the familial relative risk of colorectal cancer (CRC). We conducted a genome-wide association study of CRC in East Asians with 14,963 cases and 31,945 controls and identified 6 new loci associated with CRC risk (P = 3.42 × 10(-8) to 9.22 × 10(-21)) at 10q22.3, 10q25.2, 11q12.2, 12p13.31, 17p13.3 and 19q13.2. Two of these loci map to genes (TCF7L2 and TGFB1) with established roles in colorectal tumorigenesis. Four other loci are located in or near genes involved in transcriptional regulation (ZMIZ1), genome maintenance (FEN1), fatty acid metabolism (FADS1 and FADS2), cancer cell motility and metastasis (CD9), and cell growth and differentiation (NXN). We also found suggestive evidence for three additional loci associated with CRC risk near genome-wide significance at 8q24.11, 10q21.1 and 10q24.2. Furthermore, we replicated 22 previously reported CRC-associated loci. Our study provides insights into the genetic basis of CRC and suggests the involvement of new biological pathways.
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- 2014
13. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
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Tazeen H. Jafar, Lars Lind, Peter Almgren, Wendy Winckler, Eitaro Nakashima, Young Min Cho, Annette Peters, Rona J. Strawbridge, Ananda R. Wickremasinghe, Katharine R. Owen, Lee-Ming Chuang, Tien-Jyun Chang, Graeme I. Bell, James B. Meigs, Bill Musk, Timo A. Lakka, Elin Grundberg, Wei Lu, Sarah Edkins, George Dedoussis, Weiping Jia, Danish Saleheen, Suthesh Sivapalaratnam, Maria Samuel, Tien Yin Wong, Lu Qi, Pierre Fontanillas, Momoko Horikoshi, Jirong Long, Abdul Basit, Anubha Mahajan, Andrew T. Hattersley, Markus M. Nöthen, Denis Rybin, Inger Njølstad, S. Krithika, Miguel Cruz, Delilah Zabaneh, Leena Peltonen, Jasmina Kravic, Sangsoo Kim, David Couper, Lori L. Bonnycastle, Heather M. Stringham, Yi-Cheng Chang, Paul Elliott, Eric J.G. Sijbrands, Nita G. Forouhi, Alena Stančáková, Ghazala Mirza, Robert W. Lawrence, Ruth J. F. Loos, Norman Klopp, Shiro Maeda, Martina Müller-Nurasyid, Jer-Yuarn Wu, Jianjun Liu, Kee Seng Chia, Elodie Eury, Loukianos S. Rallidis, Timothy M. Frayling, Ken Yamamoto, David Altshuler, Gunnar Sigurosson, Harald Grallert, Jackie F. Price, Barbara Thorand, Jouko Saramies, Malene M. Kristensen, Sonali Pechlivanis, Inês Barroso, Jong-Young Lee, Melissa Parkin, Josée Dupuis, Stéphane Lobbens, Jesús Kumate, Elena Tremoli, Sudhir Kowlessur, Xueling Sim, Norihiro Kato, Philippe Froguel, Kathleen Stirrups, Eero Lindholm, Alex S. F. Doney, Andres Metspalu, Yu-Tang Gao, Roman Wennauer, Xiao-Ou Shu, Marilyn C. Cornelis, Veikko Salomaa, Nanette R. Lee, Johanna Kuusisto, Caroline S. Fox, Man Li, James Scott, Wing-Yee So, Andrew R. Wood, Inga Prokopenko, Oddgeir L. Holmen, Tin Aung, Ryoichi Takayanagi, Chen Suo, Hara Kazuo, Carl G. P. Platou, Ann M. Kelly, Teresa Ferreira, Karl-Heinz Jöckel, Wei-Yen Lim, James F. Wilson, Tom Forsén, Qi Sun, Valur Emilsson, Gonçalo R. Abecasis, Fan Zhang, Timo Saaristo, Harry Campbell, Ying Wu, Mark Seielstad, Wei Zheng, Han Chen, Stavroula Kanoni, Yuqian Bao, Jose C. Florez, Wan Ting Tay, Ronald C. WMa, Gerald Steinbach, Min Jin Go, Rong Zhang, Junbin Liang, Vasiliki Lagou, Leif Groop, Emil Rehnberg, Nabi Shah, Weihua Zhang, Yun Li, Bengt Sennblad, Olle Melander, Nancy L. Pedersen, Muhammed Islam, Jaakko Tuomilehto, Young Jin Kim, Richard N. Bergman, Juliana C.N. Chan, Eleftheria Zeggini, Andrew D. Johnson, Kees Hovingh, Joban Sehmi, Rainer Rauramaa, Satu Männistö, Reedik Mägi, Samuel Liju, Mingyu Yang, Ayellet V. Segrè, Noël P. Burtt, Mozhgan Dorkhan, Beverley Balkau, Neelam Hassanali, Hyun Min Kang, Fabrizio Veglia, Eeva Korpi-Hyövälti, Loic Yengo, Elizabeth J. Rossin, Angela Silveira, Maggie C.Y. Ng, Yuan-Tsong Chen, Anders Hamsten, David R. Matthews, Mark J. Caulfield, Emmi Tikkanen, Tanya M. Teslovich, John R. B. Perry, Karen L. Mohlke, Sarah E. Hunt, Soo Heon Kwak, Jorge Escobedo, Christopher J. Groves, Ulf de Faire, Jeremy B M Jowett, Gudmar Thorleifsson, Michael Roden, Evelin Mihailov, Viswanathan Mohan, Craig L. Hanis, Thomas WMühleisen, Congrong Wang, Sonia Shah, Kyle J. Gaulton, Jaspal S. Kooner, Jiro Nakamura, Mustafa Atalay, Linda S. Adair, S Wiltshire, Tõnu Esko, Anna Jonsson, Antigone S. Dimas, Karin Leander, Li Ching Chang, George B. Grant, Bo Isomaa, Anne U. Jackson, Claudia Langenberg, Kristian Hveem, Yoon Shin Cho, Astradur B. Hreidarsson, Xu Wang, Keizo Ohnaka, Alexandra C. Nica, Simon D. Rees, Pau Navarro, Sekar Kathiresan, Rob M. van Dam, Zafar I. Hydrie, Bok Ghee Han, Francis S. Collins, Fuu Jen Tsai, Unnur Thorsteinsdottir, Ross M. Fraser, Caroline Hayward, Cornelia M. van Duijn, Samuli Ripatti, Mieke D. Trip, Hyung Lae Kim, Rafn Benediktsson, Candace Guiducci, Bruna Gigante, Kyong Soo Park, Wen Hong L. Kao, Tom Wilsgaard, Leena Kinnunen, John Danesh, Alan James, Alan R. Shuldiner, Mitsuhiro Yokota, Jen Mai Lee, Kari Stefansson, Erik Ingelsson, Colin N. A. Palmer, David J. Hunter, Paul Zimmet, Manickam Chidambaram, Sirkka Keinänen-Kiukaanniemi, Laura J. Scott, Susanne Moebus, Benjamin F. Voight, Wolfgang Rathmann, Hassan Khan, Thomas Illig, Prasad Katulanda, Christian Gieger, Andrew D. Morris, Yik Ying Teo, Andrew P. Morris, Venkatesan Radha, N. William Rayner, Johan G. Eriksson, Christian Dina, Igor Rudan, Sailaja Vedantam, Cheng Hu, James S. Pankow, Ann-Christine Syvänen, Karl Gertow, Valeriya Lyssenko, Guillaume Charpentier, Albert Hofman, Chiea Chuen Khor, Joseph Trakalo, Peter Kraft, Takashi Kadowaki, Qiuyin Cai, John C. Chambers, André G. Uitterlinden, Simon C. Potter, Nicholas J. Wareham, Soumya Raychaudhuri, Jian'an Luan, Tiinamaija Tuomi, Anthony H. Barnett, Juha Saltevo, Robert A. Scott, Valgerdur Steinthorsdottir, Peng Keat Ng, Mark I. McCarthy, Åsa K. Hedman, Kerrin S. Small, Julia Meyer, Frank B. Hu, Cecilia M. Lindgren, Jennifer E. Below, Nancy J. Cox, Jennie Hui, Andrew Crenshaw, Latonya F. Been, Nam H. Cho, Janani Pinidiyapathirage, A. Samad Shera, Bernhard OBoehm, Jason Carey, Augustine Kong, Twee Hee Ong, Philippe M. Frossard, Donald W. Bowden, Toshimasa Yamauchi, Steve E. Humphries, Cordelia Langford, Xinzhong Li, Hiroshi Ikegami, Stéphane Cauchi, Ching-Ti Liu, Michael Boehnke, Peter M. Nilsson, Debashish Das, John Beilby, Robin Young, Christian Herder, Asif Rasheed, Neil Robertson, Raimund Erbel, Fumihiko Takeuchi, Markku Laakso, Esteban J. Parra, Panos Deloukas, Eric Boerwinkle, Adan Valladares-Salgado, Chien-Hsiun Chen, Kay-Tee Khaw, Damiano Baldassarre, Ashok Kumar, E. Shyong Tai, Peter S. Chines, Dharambir KSanghera, Peter Donnelly, [ 1 ] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England [ 2 ] Natl Inst Hlth, Ctr Genome Sci, Gangoe Myeon, Yeonje Ri, South Korea [ 3 ] Univ London Imperial Coll Sci Technol & Med, London, England [ 4 ] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA [ 5 ] Univ Oxford, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX1 2JD, England [ 6 ] NHLBI, Framingham Heart Study, Framingham, MA USA [ 7 ] Wake Forest Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA [ 8 ] Wake Forest Sch Med, Ctr Diabet Res, Winston Salem, NC USA [ 9 ] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London, England [ 10 ] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England [ 11 ] Ctr Noncommunicable Dis Pakistan, Karachi, Pakistan [ 12 ] Natl Univ Singapore, Dept Epidemiol & Publ Hlth, Singapore 117548, Singapore [ 13 ] Wellcome Trust Sanger Inst, Cambridge, England [ 14 ] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA [ 15 ] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA [ 16 ] Lund Univ, Scania Univ Hosp, Dept Clin Sci Malmo, Ctr Diabet, Malmo, Sweden [ 17 ] Univ Eastern Finland, Inst Biomed, Kuopio, Finland [ 18 ] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore, Singapore [ 19 ] Natl Univ Singapore, Dept Ophthalmol, Singapore 117548, Singapore [ 20 ] IRCCS, Ctr Cardiol Monzino, Milan, Italy [ 21 ] Univ Milan, Dept Pharmacol Sci, Milan, Italy [ 22 ] INSERM, Ctr Rech Epidemiol & Sante Populat CESP, U1018, Villejuif, France [ 23 ] Univ Paris 11, UMRS 1018, Villejuif, France [ 24 ] Shanghai Jiao Tong Univ, Affiliated Peoples Hosp 6, Dept Endocrinol & Metab, Shanghai Key Lab Diabet Mellitus,Shanghai Diabet, Shanghai 200030, Peoples R China [ 25 ] Univ Birmingham, Coll Med & Dent Sci, Birmingham, W Midlands, England [ 26 ] Heart England Natl Hlth Serv NHS Fdn Trust, Ctr Biomed Res, Birmingham, W Midlands, England [ 27 ] Univ Cambridge, Addenbrookes Hosp, Metab Res Labs, Inst Metab Sci, Cambridge CB2 2QQ, England [ 28 ] Addenbrookes Hosp, Inst Metab Sci, Cambridge Biomed Res Ctr, Natl Inst Hlth Res, Cambridge, England [ 29 ] Baqai Inst Diabetol & Endocrinol, Karachi, Pakistan [ 30 ] Univ Oklahoma, Hlth Sci Ctr, Coll Med, Dept Pediat,Sect Genet, Oklahoma City, OK 73190 USA [ 31 ] Sir Charles Gairdner Hosp, Busselton Populat Med Res Inst, Nedlands, WA 6009, Australia [ 32 ] Queen Elizabeth II Med Ctr, PathWest Lab Med Western Australia, Nedlands, WA, Australia [ 33 ] Univ Western Australia, Sch Pathol & Lab Med, Nedlands, WA 6009, Australia [ 34 ] Univ Chicago, Dept Med, Chicago, IL 60637 USA [ 35 ] Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA [ 36 ] Univ Iceland, Fac Med, Reykjavik, Iceland [ 37 ] Landspitali Univ Hosp, Reykjavik, Iceland [ 38 ] Cedars Sinai Med Ctr, Diabet & Obes Res Inst, Los Angeles, CA 90048 USA [ 39 ] Univ Med Ctr Ulm, Div Endocrinol & Diabet, Dept Internal Med, Ulm, Germany [ 40 ] Nanyang Technol Univ, Lee Kong Chian LKC Sch Med, Singapore 639798, Singapore [ 41 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 42 ] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA [ 43 ] NHGRI, NIH, Bethesda, MD 20892 USA [ 44 ] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA [ 45 ] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37212 USA [ 46 ] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland [ 47 ] Univ Edinburgh, Western Gen Hosp, MRC, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland [ 48 ] CNRS, Unite Mixte Rech UMR 8199, Inst Biol, Lille, France [ 49 ] Univ Lille 2, Inst Pasteur, Lille, France [ 50 ] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England [ 51 ] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Barts & London Genome Ctr, London, England [ 52 ] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China [ 53 ] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan [ 54 ] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan [ 55 ] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France [ 56 ] China Med Univ, Sch Chinese Med, Taichung, Taiwan [ 57 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA [ 58 ] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore [ 59 ] Indian Council Med Res, Adv Ctr Genom Diabet, Madras Diabet Res Fdn, Dept Mol Genet, Madras, Tamil Nadu, India [ 60 ] Ajou Univ, Sch Med, Dept Prevent Med, Suwon 441749, South Korea [ 61 ] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea [ 62 ] Natl Taiwan Univ, Sch Med, Grad Inst Clin Med, Taipei 10764, Taiwan [ 63 ] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA [ 64 ] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA [ 65 ] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore [ 66 ] Ealing Hosp NHS Trust, Southall, Middx, England [ 67 ] Karolinska Inst, Inst Environm Med, Divis Cardiovasc Epidemiol, S-10401 Stockholm, Sweden [ 68 ] Harokopio Univ, Dept Dietet Nutr, Athens, Greece [ 69 ] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland [ 70 ] Biomed Sci Res Ctr Alexander Fleming, Vari, Greece [ 71 ] INSERM, UMR 1087, Nantes, France [ 72 ] CNRS, UMR 6291, Nantes, France [ 73 ] Univ Nantes, Nantes, France [ 74 ] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Diabet Res Ctr, Dundee, Scotland [ 75 ] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland [ 76 ] Univ Oxford, Dept Stat, Oxford OX1 3TG, England [ 77 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands [ 78 ] Netherlands Consortium Healthy Ageing, Netherland Genom Initiat, Rotterdam, Netherlands [ 79 ] Ctr Med Syst Biol, Rotterdam, Netherlands [ 80 ] Univ London Imperial Coll Sci Technol & Med, MRC, Hlth Protect Agcy, Ctr Environm & Hlth, London, England [ 81 ] Iceland Heart Assoc, Kopavogur, Iceland [ 82 ] Univ Duisburg Essen, Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, Essen, Germany [ 83 ] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland [ 84 ] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland [ 85 ] Univ Helsinki, Gen Hosp, Unit Gen Practice, Helsinki, Finland [ 86 ] Folkhalsan Res Ctr, Helsinki, Finland [ 87 ] Inst Mexicano Seguro Social, Hosp Gen Reg 1, Unidad Invest Epidemiol Clin, Mexico City, DF, Mexico [ 88 ] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia [ 89 ] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia [ 90 ] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA [ 91 ] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA [ 92 ] Harvard Univ, Sch Med, Dept Med, Boston, MA USA [ 93 ] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA [ 94 ] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA [ 95 ] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England [ 96 ] Vaasa Hlth Care Ctr, Vaasa, Finland [ 97 ] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA [ 98 ] Harvard Univ, Sch Med, Boston, MA USA [ 99 ] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England [ 100 ] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China [ 101 ] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden [ 102 ] Karolinska Univ, Hosp Solna, Ctr Mol Med, Stockholm, Sweden [ 103 ] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany [ 104 ] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany [ 105 ] Univ Munich, Clin Cooperat Grp Diabet, Munich, Germany [ 106 ] Helmholtz Zentrum Muenchen, Munich, Germany [ 107 ] Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Munich, Germany [ 108 ] German Ctr Diabet Res DZD, Neuherberg, Germany [ 109 ] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England [ 110 ] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan [ 111 ] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England [ 112 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany [ 113 ] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway [ 114 ] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands [ 115 ] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA [ 116 ] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia [ 117 ] UCL, Inst Cardiovasc Sci, London, England [ 118 ] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA [ 119 ] Kinki Univ, Sch Med, Dept Diabet Endocrinol & Metab, Osaka 589, Japan [ 120 ] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany [ 121 ] Univ Uppsala Hosp, Dept Mol Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden [ 122 ] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan [ 123 ] Dept Social Serv & Hlth Care, Pietarsaari, Finland [ 124 ] Aga Khan Univ, Dept Med, Karachi, Pakistan [ 125 ] Queen Elizabeth II Med Ctr, West Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia [ 126 ] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia [ 127 ] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany [ 128 ] Heart & Diabet Inst, Baker Int Diabet Inst IDI, Melbourne, Australia [ 129 ] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA [ 130 ] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA [ 131 ] Natl Ctr Global Hlth & Med, Res Inst, Shinjuku Ku, Tokyo, Japan [ 132 ] Univ Colombo, Dept Clin Med, Diabet Res Unit, Colombo, Sri Lanka [ 133 ] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland [ 134 ] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland [ 135 ] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore [ 136 ] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul, South Korea [ 137 ] Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea [ 138 ] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland [ 139 ] deCODE Genet, Reykjavik, Iceland [ 140 ] South Ostrobothnia Cent Hosp, Seinajoki, Finland [ 141 ] Minist Hlth, Port Louis, Mauritius [ 142 ] Univ Toronto, Dept Anthropol, Mississauga, ON L5L 1C6, Canada [ 143 ] Fdn IMSS, Mexico City, DF, Mexico [ 144 ] Univ Eastern Finland, Dept Med, Kuopio, Finland [ 145 ] Kuopio Univ Hosp, SF-70210 Kuopio, Finland [ 146 ] Kuopio Res Inst Exercise Med, Kuopio, Finland [ 147 ] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia [ 148 ] Univ San Carlos, Off Populat Studies Fdn Inc, Cebu, Philippines [ 149 ] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England [ 150 ] Univ N Carolina, Dept Genet, Chapel Hill, NC USA [ 151 ] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA [ 152 ] Beijing Genom Inst, Shenzhen, Peoples R China [ 153 ] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden [ 154 ] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA [ 155 ] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY USA [ 156 ] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA [ 157 ] Shanghai Inst Prevent Med, Shanghai, Peoples R China [ 158 ] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA [ 159 ] Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India [ 160 ] Univ Bonn, Inst Human Genet, Bonn, Germany [ 161 ] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany [ 162 ] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany [ 163 ] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany [ 164 ] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia [ 165 ] Nagoya Univ, Grad Sch Med, Div Endocrinol & Diabet, Dept Internal Med, Nagoya, Aichi 4648601, Japan [ 166 ] Chubu Rosai Hosp, Dept Endocrinol & Diabet, Nagoya, Aichi, Japan [ 167 ] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway [ 168 ] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Higashi Ku, Fukuoka 812, Japan [ 169 ] Churchill Hosp, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford OX3 7LJ, England [ 170 ] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA [ 171 ] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, World Class Univ Program, Seoul, South Korea [ 172 ] Seoul Natl Univ, Coll Med, Seoul, South Korea [ 173 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 174 ] Inst Mol Med Finland FIMM, Helsinki, Finland [ 175 ] Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany [ 176 ] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka [ 177 ] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway [ 178 ] Univ Gen Hosp Attikon, Athens, Greece [ 179 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany [ 180 ] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland [ 181 ] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA [ 182 ] Partners Ctr Personalized Genom Med, Boston, MA USA [ 183 ] Univ Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany [ 184 ] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany [ 185 ] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA [ 186 ] MIT, Boston, MA USA [ 187 ] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA [ 188 ] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA [ 189 ] Finnish Diabet Assoc, Tampere, Finland [ 190 ] Pirkanmaa Hosp Dist, Tampere, Finland [ 191 ] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland [ 192 ] South Karelia Cent Hosp, Lappeenranta, Finland [ 193 ] UCL, Dept Genet Evolut & Environm, Genet Inst, London, England [ 194 ] Diabet Assoc Pakistan, Karachi, Pakistan [ 195 ] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA [ 196 ] Baltimore Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA [ 197 ] Univ Maryland, Sch Med, Program Personalised & Genom Med, Baltimore, MD 21201 USA [ 198 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 199 ] Univ Ulm, Dept Clin Chem, D-89069 Ulm, Germany [ 200 ] Univ Ulm, Cent Lab, D-89069 Ulm, Germany [ 201 ] Uppsala Univ, Dept Med Sci, Uppsala, Sweden [ 202 ] Kyushu Univ, Grad Sch Med Sci, Dept Internal Med & Bioregulatory Sci, Higashi Ku, Fukuoka 812, Japan [ 203 ] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland [ 204 ] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain [ 205 ] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria [ 206 ] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia [ 207 ] IMSS, Ctr Med Nacl Siglo 21, Hosp Especialidades, Unidad Invest Med Bioquim, Mexico City, DF, Mexico [ 208 ] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA [ 209 ] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia [ 210 ] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 812, Japan [ 211 ] Univ Lille 1, Math Lab, CNRS UMR 8524, MODAL Team,INRIA Lille Nord Europe, F-59655 Villeneuve Dascq, France [ 212 ] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan [ 213 ] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA [ 214 ] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA [ 215 ] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA [ 216 ] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA [ 217 ] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA [ 218 ] Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea [ 219 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 220 ] Imperial Coll Healthcare NHS Trust, London, England [ 221 ] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA [ 222 ] Blood Syst Res Inst, San Francisco, CA USA [ 223 ] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore [ 224 ] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore [ 225 ] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore [ 226 ] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore [ 227 ] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England, Obstetrics & Gynecology, Radiology & Nuclear Medicine, Surgery, Epidemiology, Dermatology, Internal Medicine, Medical Microbiology & Infectious Diseases, Medical Research Council (MRC), National Institute for Health Research, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, and Cardiology
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CHROMATIN ,endocrine system diseases ,South Asian Type 2 Diabetes (SAT2D) Consortium ,SCALE ASSOCIATION ANALYSIS ,Medizin ,LOCI ,Genome-wide association study ,VARIANTS ,0302 clinical medicine ,Risk Factors ,IMPUTATION ,Glucose homeostasis ,11 Medical and Health Sciences ,Genetics & Heredity ,Genetics ,0303 health sciences ,IDENTIFY ,Hispanic or Latino ,3. Good health ,MAP ,POPULATIONS ,Medical genetics ,Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium ,Hispanic Americans ,Life Sciences & Biomedicine ,Asian Continental Ancestry Group ,medicine.medical_specialty ,European Continental Ancestry Group ,TRANSETHNIC METAANALYSIS ,030209 endocrinology & metabolism ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,Sykursýki ,03 medical and health sciences ,Asian People ,SDG 3 - Good Health and Well-being ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium ,Alleles ,030304 developmental biology ,Genetic association ,Science & Technology ,DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium ,Mexican American Type 2 Diabetes (MAT2D) Consortium ,06 Biological Sciences ,Arfgengi ,Genetic architecture ,INDIVIDUALS ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,GLUCOSE-HOMEOSTASIS ,ASSOCIATION ANALYSES ,Imputation (genetics) ,Developmental Biology ,Genome-Wide Association Study - Abstract
To access publisher's full text version of this article click on the hyperlink at the bottom of the page To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. Canadian Institutes of Health Research Medical Research Council UK G0601261 Mexico Convocatoria SSA/IMMS/ISSSTE-CONACYT 2012-2 clave 150352 IMSS R-2011-785-018 CONACYT Salud-2007-C01-71068 US National Institutes of Health DK062370 HG000376 DK085584 DK085545 DK073541 DK085501 Wellcome Trust WT098017 WT090532 WT090367 WT098381 WT081682 WT085475 info:eu-repo/grantAgreement/EC/FP7/201413
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- 2014
14. Prediction of breast cancer risk based on common genetic variants in women of East Asian ancestry
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Hidemi Ito, Ji Yeob Choi, Douglas F. Easton, Keitaro Matsuo, Paul D.P. Pharoah, Joe Dennis, Daehee Kang, Xingyi Guo, Yong-Bing Xiang, Ying Zheng, Montserrat Garcia-Closas, Chen-Yang Shen, Paul Brennan, Chiu-Chen Tseng, Manjeet K. Bolla, Wanqing Wen, Qiuyin Cai, Soo Hwang Teo, Jacques Simard, Kyriaki Michailidou, Wei Zheng, Xiao-Ou Shu, Per Hall, Yu-Tang Gao, Hui Miao, Qin Wang, Anna H. Wu, Jirong Long, Cheng Har Yip, Artitaya Lophatananon, Suleeporn Sangrajrang, Alison M. Dunning, Kenneth Muir, Shou-Tung Chen, Mikael Hartman, Dennis, Joe [0000-0003-4591-1214], Wang, Jean [0000-0002-9139-0627], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Easton, Douglas [0000-0003-2444-3247], and Apollo - University of Cambridge Repository
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0301 basic medicine ,Oncology ,Genome-wide association study ,Bioinformatics ,0302 clinical medicine ,Risk Factors ,Surgical oncology ,Odds Ratio ,skin and connective tissue diseases ,Medicine(all) ,Research Support, Non-U.S. Gov't ,Methodology for SNP data analysis ,3. Good health ,Population Surveillance ,030220 oncology & carcinogenesis ,Female ,Risk assessment ,Algorithms ,Research Article ,Asian Continental Ancestry Group ,medicine.medical_specialty ,Asia ,Breast Neoplasms ,Single-nucleotide polymorphism ,Risk Assessment ,03 medical and health sciences ,Breast cancer ,Asian People ,Research Support, N.I.H., Extramural ,Prediction model ,Internal medicine ,Journal Article ,medicine ,Humans ,Genetic Predisposition to Disease ,Statistical methods in genetics ,Genetic Association Studies ,Genetic association ,Models, Statistical ,business.industry ,Case-control study ,Genetic Variation ,Odds ratio ,medicine.disease ,030104 developmental biology ,Case-Control Studies ,business ,Breast cancer risk ,Research Support, U.S. Gov't, Non-P.H.S ,Genome-Wide Association Study - Abstract
Background Approximately 100 common breast cancer susceptibility alleles have been identified in genome-wide association studies (GWAS). The utility of these variants in breast cancer risk prediction models has not been evaluated adequately in women of Asian ancestry. Methods We evaluated 88 breast cancer risk variants that were identified previously by GWAS in 11,760 cases and 11,612 controls of Asian ancestry. SNPs confirmed to be associated with breast cancer risk in Asian women were used to construct a polygenic risk score (PRS). The relative and absolute risks of breast cancer by the PRS percentiles were estimated based on the PRS distribution, and were used to stratify women into different levels of breast cancer risk. Results We confirmed significant associations with breast cancer risk for SNPs in 44 of the 78 previously reported loci at P
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- 2016
15. Genome-wide association analyses in east Asians identify new susceptibility loci for colorectal cancer
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Ji Won Park, Yu-Tang Gao, Ben Zhang, Honglan Li, Qiuyin Cai, Satoyo Hosono, Jae Hwan Oh, Ryan J. Delahanty, Graham Casey, Jiajun Shi, Wei Zheng, Yong-Bing Xiang, Aesun Shin, Yi Xin Zeng, Ulrike Peters, Dong Hyun Kim, Zefang Ren, Gong Yang, Fumihiko Matsuda, Keitaro Matsuo, Eun Jung Park, Jin Young Jeong, Yoon-Ok Ahn, Jaeseong Jo, Xiao-Ou Shu, Zhi Zhong Pan, Jirong Long, Bu Tian Ji, Sun Ha Jee, Wanqing Wen, and Wei Hua Jia
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Genotype ,Colorectal cancer ,Population ,Chromosomes, Human, Pair 20 ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Genome ,White People ,Article ,03 medical and health sciences ,0302 clinical medicine ,Asian People ,Polymorphism (computer science) ,Odds Ratio ,Genetics ,medicine ,Cyclin D2 ,Humans ,Genetic Predisposition to Disease ,education ,030304 developmental biology ,Principal Component Analysis ,0303 health sciences ,education.field_of_study ,Chromosomes, Human, Pair 12 ,Asia, Eastern ,Genome, Human ,Odds ratio ,medicine.disease ,Human genetics ,3. Good health ,Genetics, Population ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 5 ,Colorectal Neoplasms ,Genome-Wide Association Study - Abstract
To identify new genetic factors for colorectal cancer (CRC), we conducted a genome-wide association study in east Asians. By analyzing genome-wide data in 2,098 cases and 5,749 controls, we selected 64 promising SNPs for replication in an independent set of samples, including up to 5,358 cases and 5,922 controls. We identified four SNPs with association P values of 8.58 × 10(-7) to 3.77 × 10(-10) in the combined analysis of all east Asian samples. Three of the four were replicated in a study conducted in 26,060 individuals of European descent, with combined P values of 1.22 × 10(-10) for rs647161 (5q31.1), 6.64 × 10(-9) for rs2423279 (20p12.3) and 3.06 × 10(-8) for rs10774214 (12p13.32 near the CCND2 gene), derived from meta-analysis of data from both east Asian and European-ancestry populations. This study identified three new CRC susceptibility loci and provides additional insight into the genetics and biology of CRC.
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- 2012
16. Dietary B vitamin and methionine intakes and lung cancer risk among female never smokers in China
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Xiao-Ou Shu, Yu-Tang Gao, Honglan Li, Alicia Beeghly-Fadiel, Wei Zheng, Martha J. Shrubsole, Gong Yang, Bu Tian Ji, Wong Ho Chow, Qiuyin Cai, and Yumie Takata
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China ,Cancer Research ,Pathology ,medicine.medical_specialty ,Lung Neoplasms ,Physiology ,Riboflavin ,medicine.disease_cause ,Article ,Cohort Studies ,chemistry.chemical_compound ,Methionine ,Risk Factors ,Surveys and Questionnaires ,Humans ,Medicine ,Prospective Studies ,Registries ,Vitamin B12 ,Prospective cohort study ,Lung cancer ,business.industry ,Incidence ,Smoking ,Middle Aged ,medicine.disease ,respiratory tract diseases ,B vitamins ,Oncology ,chemistry ,Vitamin B Complex ,Female ,business ,Carcinogenesis ,Niacin - Abstract
B vitamins and methionine have been postulated to have potential effects on carcinogenesis; however, findings from previous epidemiologic studies on B vitamins, methionine, and lung cancer risk are inconsistent. We investigated associations of dietary intakes of B vitamins (i.e., riboflavin, niacin, vitamin B6, folate, and vitamin B12) and methionine with lung cancer risk among female never smokers.The Shanghai Women's Health Study, a population-based, prospective cohort study, included 74,941 women. During a median follow-up of 11.2 years, 428 incident lung cancer cases accrued among 71,267 women with no history of smoking or cancer at baseline. Baseline dietary intakes were derived from a validated, interviewer-administered food frequency questionnaire. Cancer incidence and vital status were ascertained through annual linkage to the Shanghai Cancer Registry and Shanghai Vital Statistics Registry databases and through biennial in-person follow-ups with participants. Adjusted hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox regression.Dietary riboflavin intake was inversely associated with lung cancer risk (HR = 0.62; 95 % CI = 0.43-0.89; p trend = 0.03 for the highest quartile compared with the lowest). A higher than median intake of methionine was associated with lower risk of lung cancer (HR = 0.78; 95 % CI = 0.60-0.99); however, there was no dose-response relation. Intakes of other B vitamins were not associated with lung cancer risk.Our study suggests that dietary riboflavin intake may be inversely associated with lung cancer risk among female never smokers, which warrants further investigation.
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- 2012
17. Cancer incidence in urban Shanghai, 1973-2010: an updated trend and age-period-cohort effects
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Fan Wu, Yu-Tang Gao, Fan Jin, Chunxiao Wu, Weijian Zhong, Ying Zheng, Yong-Bing Xiang, Zhezhou Huang, Wei Lu, and Pingping Bao
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Adult ,Male ,China ,Cancer Research ,medicine.medical_specialty ,Urban Population ,Shanghai ,03 medical and health sciences ,0302 clinical medicine ,Surgical oncology ,Neoplasms ,Genetics ,medicine ,Humans ,030212 general & internal medicine ,Lung cancer ,Cervix ,Gynecology ,business.industry ,Gallbladder ,Stomach ,Incidence (epidemiology) ,Age Factors ,Cancer ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Age-period-cohort analysis ,030220 oncology & carcinogenesis ,Female ,Liver cancer ,business ,Time trend ,Cancer incidence ,Research Article ,Demography - Abstract
Background To provide a comprehensive overview of temporal trends in cancer incidence during 1973–2010 in urban Shanghai. Methods The estimated annual percent changes (EAPCs) for the whole period and for the time segments in age-standardized incidence rates (ASR) were evaluated with Joinpoint analysis. Age-period-cohort (APC) models were modeled to examine the effects of age, period and birth cohort on cancer incidence. Results The overall ASR decreased slightly and significantly in males (EAPC of −0.41) but increased significantly in females (EAPC of 0.57) during 1973–2010 in urban Shanghai. The incidence trend was not linear and varied by time segments. During the most recent 10 years (2001–2010), the ASR in males decreased by 1.65 % per year and stabilized in females. Incidence rates continued to decline during 1973–2010 for esophagus, stomach, and liver cancer in both sexes, as well as male lung cancer and cervix cancer. It should be noted that it was the first time to document a significant decline in lung cancer incidence among males during 1973–2010 with EAPC of −0.58 %, and a notable upward for cervix cancer since 1996 with EAPC of 8.94 %. Unfavorable trends in incidence were observed for the most common cancer sites in the 38 years period: colorectum, gallbladder & biliary tract, pancreas, kidney, bladder, brain & central nervous system (CNS), thyroid, non-Hodgkin’s lymphoma (NHL), prostate, female breast, corpus uteri, and ovary. APC analysis showed age, period and birth cohort yielded different effects by cancer sites. Conclusions The observed trends primarily reflect dramatic changes in socioeconomic development and lifestyles in urban Shanghai over the past four decades.
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- 2016
18. Induction and inhibition of the pan-nuclear gamma-H2AX response in resting human peripheral blood lymphocytes after X-ray irradiation
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Yu-Tang Gao, Quanfu Li, Yaping Zhang, Jian-She Wang, Hao Chen, Xuxia Zhang, J. Li, Lifeng Yin, and Defang Ding
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0301 basic medicine ,Cancer Research ,TUNEL assay ,DNA damage ,Immunology ,Cell Biology ,Biology ,Molecular biology ,Article ,Staining ,Ionizing radiation ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,Apoptosis ,030220 oncology & carcinogenesis ,Mitogen-activated protein kinase ,Chromosome instability ,biology.protein ,Phosphorylation - Abstract
Human peripheral blood lymphocytes (HPBLs) are one of the most sensitive cells to ionizing radiation (IR) in the human body, and IR-induced DNA damage and functional impairment of HPBLs are the adverse consequences of IR accidents and major side effects of radiotherapy. Phosphorylated H2AX (γH2AX) is a sensitive marker for DNA double-strand breaks, but the role and regulation of the pan-nuclear γH2AX response in HPBLs after IR remain unclear. We herein demonstrated that the pan-nuclear γH2AX signals were increased in a time- and dose-dependent manner, colocalized with >94% of TUNEL apoptotic staining, and displayed a typical apoptotic pattern in resting HPBLs after low LET X-ray IR. In addition, the X-irradiation-induced pan-nuclear p-ATM and p-DNA-PKcs responses also occurred in resting HPBLs, and were colocalized with 92–95% of TUNEL staining and 97–98% of the pan-nuclear γH2AX signals, respectively, with a maximum at 6 h post irradiation, but disappeared at 24 h post irradiation. Moreover, ATM/DNA-PKcs inhibitor KU55933, p53 inhibitor PFT-μ and pan-caspase inhibitor ZVAD-fmk significantly decreased X-irradiation-induced pan-nuclear γH2AX signals and TUNEL staining, protected HPBLs from apoptosis, but decreased the proliferative response to mitogen in X-irradiated HPBLs. Notably, whereas both KU55933 and PFT-μ increased the IR-induced chromosome breaks and mis-repair events through inhibiting the formation of p-ATM, p-DNA-PKcs and γH2AX foci in X-irradiated HPBLs, the ZVAD-fmk did not increase the IR-induced chromosomal instability. Taken together, our data indicate that pan-nuclear γH2AX response represents an apoptotic signal that is triggered by the transient pan-nuclear ATM and DNA-PKcs activation, and mediated by p53 and pan-caspases in X-irradiated HPBLs, and that caspase inhibitors are better than ATM/DNA-PKcs inhibitors and p53 inhibitors to block pan-nuclear γH2AX response/apoptosis and protect HPBLs from IR.
- Published
- 2016
19. Genome-wide association study of glioma and meta-analysis
- Author
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Joseph L. Wiemels, Ching C. Lau, Sanjay Shete, Alicja Wolk, Tania Carreón, Patricia Hartge, Melissa L. Bondy, Ulrike Peters, Graham G. Giles, Mark P. Purdue, Victoria L. Stevens, Brooke L. Fridley, Wei Zheng, Matthew L. Kosel, Joseph F. Fraumeni, Avima M. Ruder, Anders Ahlbom, Meredith Yeager, Martha S. Linet, Meir J. Stampfer, Sarah Fleming, Richard S. Houlston, Gianluca Severi, Melissa Z. Braganza, Anthony J. Swerdlow, Zhaoming Wang, Yong-Bing Xiang, Stephen J. Chanock, Victor Enciso-Mora, Nilanjan Chatterjee, Maria Feychting, Howard D. Sesso, Kala Visvanathan, Loic Le Marchand, Laura E. Beane Freeman, Anne Zeleniuch-Jacquotte, Margaret Wrensch, Preetha Rajaraman, Judith Hoffman-Bolton, Julie E. Buring, Roger Henriksson, Xiao-Ou Shu, Terri Rice, Nathaniel Rothman, Dominique S. Michaud, J. Michael Gaziano, Ulrika Andersson, Robert N. Hoover, Mary Ann Butler, Paul A. Decker, Sophia S. Wang, Robert B. Jenkins, John K. Wiencke, Cari M. Kitahara, Matthias Simon, Yuanyuan Xiao, Daniel H. Lachance, Peter D. Inskip, Marc Sanson, Beatrice Melin, Susan M. Gapstur, Emily White, Stefan Lonn, Mark Lathrop, Chenwei Liu, Christoffer Johansen, Roberta McKean-Cowdin, Göran Hallmans, Yu-Tang Gao, and Demetrius Albanes
- Subjects
Male ,Population ,Single-nucleotide polymorphism ,Genome-wide association study ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Article ,Cohort Studies ,Paediatrics and Reproductive Medicine ,Rare Diseases ,Complementary and Alternative Medicine ,Clinical Research ,Glioma ,Genetics ,medicine ,Humans ,2.1 Biological and endogenous factors ,Polymorphism ,Aetiology ,education ,Telomerase ,Genetics (clinical) ,Aged ,Cyclin-Dependent Kinase Inhibitor p15 ,Cancer ,Genetic association ,Genetics & Heredity ,education.field_of_study ,Brain Neoplasms ,Prevention ,Human Genome ,DNA Helicases ,Neurosciences ,Case-control study ,Single Nucleotide ,Middle Aged ,medicine.disease ,Brain Disorders ,Brain Cancer ,Case-Control Studies ,Cohort ,Female ,Glioblastoma ,Genome-Wide Association Study ,Cohort study - Abstract
Gliomas account for approximately 80% of all primary malignant brain tumors and, despite improvements in clinical care over the last 20years, remain among the most lethal tumors, underscoring the need for gaining new insights that could translate into clinical advances. Recent genome-wide association studies (GWAS) have identified seven new susceptibility regions. We conducted a new independent GWAS of glioma using 1,856 cases and 4,955 controls (from 14 cohort studies, 3 case-control studies, and 1 population-based case-only study) and found evidence of strong replication for three of the seven previously reported associations at 20q13.33 (RTEL), 5p15.33 (TERT), and 9p21.3 (CDKN2BAS), and consistent association signals for the remaining four at 7p11.2 (EGFR both loci), 8q24.21 (CCDC26) and 11q23.3 (PHLDB1). The direction and magnitude of the signal were consistent for samples from cohort and case-control studies, but the strength of the association was more pronounced for loci rs6010620 (20q,13.33; RTEL) and rs2736100 (5p15.33, TERT) in cohort studies despite the smaller number of cases in this group, likely due to relatively more higher grade tumors being captured in the cohort studies. We further examined the 85 most promising single nucleotide polymorphism (SNP) markers identified in our study in three replication sets (5,015 cases and 11,601 controls), but no new markers reached genome-wide significance. Our findings suggest that larger studies focusing on novel approaches as well as specific tumor subtypes or subgroups will be required to identify additional common susceptibility loci for glioma risk.
- Published
- 2012
20. Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia
- Author
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Chih Yi Chen, Biyun Qian, Jeong Seon Ryu, Sung Ick Cha, Wen Chang Wang, Dianke Yu, Zhenhong Zhao, Xueying Zhao, Yu Fang Chiu, Jae Sook Sung, Chih-Liang Wang, Ying-Huang Tsai, Chao A. Hsiung, Jeff Yuenger, Bryan A. Bassig, Yeul Hong Kim, Joseph F. Fraumeni, Reury Perng Perng, Zhang Huan, Jin Hee Kim, Chien Chung Lin, Kyoung Mu Lee, Jiucun Wang, Chin-Fu Hsiao, Ming Shyan Huang, Hu Wei, Stephen J. Chanock, Wen Tan, Liming Huang, Kyong Hwa Park, Zhihua Yin, Xiaoling Zhu, Nathaniel Rothman, Hongyan Chen, Joohyun Kim, Chen Wu, Jen Yu Hung, Fang Yu Tsai, Yangwu Ren, Qing Lan, Qiuyin Cai, Kexin Chen, Tsung-Ying Yang, Margaret A. Tucker, Sook Whan Sung, Chong-Jen Yu, Adeline Seow, Xuelian Li, Wong Ho Chow, Jun Suk Kim, Kuan-Yu Chen, Ju Yeon Park, Chien-Jen Chen, Wu Chou Su, Yong-Bing Xiang, Wei Zheng, Li Jin, Wei Wu, Ying Hsiang Chen, Amy Hutchinson, Kun-Chieh Chen, Neil E. Caporaso, Xiao-Ou Shu, Yen Li Lo, Yu Tang Gao, Tae Hoon Jung, In San Kim, H. Dean Hosgood, Meredith Yeager, Daru Lu, Yuh Min Chen, Gee-Chen Chang, Jae Yong Park, Dongxin Lin, Yun-Chul Hong, Chang Ho Kim, Nilanjan Chatterjee, Baosen Zhou, Yao Jen Li, I. Shou Chang, Young Tae Kim, Pan-Chyr Yang, Maria Teresa Landi, and Ying Chen
- Subjects
Risk ,Oncology ,medicine.medical_specialty ,Asia ,Lung Neoplasms ,Genotype ,Adenocarcinoma of Lung ,Genome-wide association study ,Single-nucleotide polymorphism ,Adenocarcinoma ,Biology ,Polymorphism, Single Nucleotide ,Article ,Internal medicine ,Genetic variation ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele ,Lung cancer ,Genetics (clinical) ,Squamous-cell carcinoma of the lung ,Tumor Suppressor Proteins ,Smoking ,Case-control study ,Genetic Variation ,medicine.disease ,Case-Control Studies ,Immunology ,Carcinoma, Squamous Cell ,Female ,Genome-Wide Association Study ,Transcription Factors - Abstract
A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.
- Published
- 2012
21. Replication study for reported SNP associations with breast cancer survival
- Author
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Alicia Beeghly-Fadiel, Wei Zheng, Xiao-Ou Shu, Ying Zheng, Yu-Tang Gao, Jirong Long, Kai Gu, Zhi Chen, Qiuyin Cai, Wei Lu, and Hui Cai
- Subjects
Adult ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,Genotype ,Breast Neoplasms ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Disease-Free Survival ,Linkage Disequilibrium ,Article ,Cohort Studies ,Young Adult ,Breast cancer ,Internal medicine ,medicine ,Humans ,SNP ,Prospective Studies ,Young adult ,Stage (cooking) ,skin and connective tissue diseases ,Prospective cohort study ,Alleles ,Aged ,Neoplasm Staging ,Case-control study ,General Medicine ,Middle Aged ,Prognosis ,medicine.disease ,Matrix Metalloproteinase 8 ,Receptors, Estrogen ,Case-Control Studies ,Matrix Metalloproteinase 7 ,Immunology ,Female ,Receptors, Progesterone ,Follow-Up Studies - Abstract
Nine previously reported associations between single nucleotide polymorphisms (SNPs) and breast cancer outcomes from the Shanghai Breast Cancer Study (Stage 1) were further evaluated in relation to disease-free survival (DFS) and overall survival (OS) among 5,192 additional breast cancer patients (Stage 2).Hazard ratios (HR) and 95% confidence intervals (CI) were calculated by proportional hazards regression in models adjusted for age, disease stage, estrogen and progesterone receptor status, and treatment regimens.Two SNPs had generally consistent results and significant associations with OS in combined analyses. Compared to women with MMP7 rs11225297 AA genotypes, OS was moderately better for women with AT genotypes (HR: 0.8, 95% CI: 0.7-1.0) and much better for women with TT genotypes (HR: 0.4, 95% CI: 0.2-0.8). Compared to women with MMP8 rs11225395 CC genotypes, OS was slightly better for women with CT genotypes (HR: 0.9, 95% CI: 0.7-1.1) and moderately better for women with TT genotypes (HR: 0.6, 95% CI: 0.4-0.9). Joint analysis showed significant dose-response relationships with increasing numbers of rare alleles for both OS (p0.001) and DFS (p = 0.001).A functional variant in MMP8 and a SNP in high linkage disequilibrium with a functional variant in MMP7 were significantly associated with breast cancer survival in a large two-stage survival study among Chinese women. This supports the hypothesis that SNPs in matrix metalloproteinase genes may influence breast cancer prognosis; additional research on these and other SNPs in genes important in metastasis, angiogenesis, and the regulation of the tumor microenvironment is warranted.
- Published
- 2012
22. Blood leukocyte Alu and LINE-1 methylation and gastric cancer risk in the Shanghai Women's Health Study
- Author
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Nathanial Rothman, Andrea A. Baccarelli, Hong Lan Li, Wong-Ho Chow, Yu-Tang Gao, Lifang Hou, Gong Yang, Bu Tian Ji, Xiao-Ou Shu, Kelly J. Yu, Wei Zheng, and Letizia Tarantini
- Subjects
Adult ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,Alu element ,Health Promotion ,Biology ,Alu Elements ,Risk Factors ,Stomach Neoplasms ,Internal medicine ,Leukocytes ,medicine ,Humans ,Prospective Studies ,Registries ,Prospective cohort study ,Aged ,DNA methylation ,gastric cancer ,Case-control study ,Cancer ,DNA, Neoplasm ,Methylation ,Odds ratio ,Middle Aged ,medicine.disease ,Long Interspersed Nucleotide Elements ,Case-Control Studies ,Immunology ,Women's Health ,Female ,leukocyte ,DNA hypomethylation - Abstract
BACKGROUND: Recent data suggest a link between blood leukocyte DNA methylation, and cancer risk. However, reports on DNA methylation from a prospective study are unavailable for gastric cancer. METHODS: We explored the association between methylation in pre-diagnostic blood leukocyte DNA and gastric cancer risk in a case–control study nested in the prospective Shanghai Women’s Health Study cohort. Incident gastric cancer cases (n ¼192) and matched controls (n ¼384) were included in the study. Methylation of Alu and long interspersed nucleotide elements (LINE)-1 were evaluated using bisulphite pyrosequencing. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated from logistic regression adjusting for potential confounders. RESULTS: Alu methylation was inversely associated with gastric cancer risk, mainly among cases diagnosed one or more years after blood collection. After excluding cases diagnosed during the first year of follow-up, the ORs for the third, second, and first quartiles of Alu methylation compared with the highest quartile were 2.43 (1.43–4.13), 1.47(0.85–2.57), and 2.22 (1.28–3.84), respectively. This association appeared to be modified by dietary intake, particularly isoflavone. In contrast, LINE-1 methylation levels were not associated with gastric cancer risk. CONCLUSION: Evidence from this prospective study is consistent with the hypothesis that DNA hypomethylation in blood leukocytes may be related to cancer risk, including risk of gastric cancer.
- Published
- 2011
23. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians
- Author
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Bok Ghee Han, Congrong Wang, Wing-Yee So, Ying Wu, Rong Zhang, Xueling Sim, Norihiro Kato, Eitaro Nakashima, Qiuyin Cai, Tien-Jyun Chang, Jiro Nakamura, Wei Lu, Mark Seielstad, Yu-Tang Gao, Juliana C.N. Chan, Fumihiko Takeuchi, Jer-Yuarn Wu, Lee-Ming Chuang, Young Min Cho, Hyung Lae Kim, Yik Ying Teo, Andrew P. Morris, Nam H. Cho, Daniel P.K. Ng, Rick Twee-Hee Ong, Cheng Hu, Kyong Soo Park, Sangsoo Kim, Shiro Maeda, Toshimasa Yamauchi, Fuu Jen Tsai, Yoon Shin Cho, Hiroshi Ikegami, Ronald C.W. Ma, Jirong Long, Ken Yamamoto, Yi-Cheng Chang, Xiao-Ou Shu, Karen L. Mohlke, Wei Zheng, Mitsuhiro Yokota, Soo Heon Kwak, Yuan-Tsong Chen, Chien Hsiun Chen, Linda S. Adair, Yun Li, Nanette R. Lee, Young-Jin Kim, Jeannette Lee, Li Ching Chang, Keizo Ohnaka, Ryoichi Takayanagi, Min Jin Go, Wan Ting Tay, Jianjun Liu, Tin Aung, Jong-Young Lee, Hara Kazuo, Yuqian Bao, Weiping Jia, Tien Yin Wong, E. Shyong Tai, Takashi Kadowaki, Mark I. McCarthy, Åsa K. Hedman, and Frank B. Hu
- Subjects
Genetics ,endocrine system ,education.field_of_study ,endocrine system diseases ,PEPD ,Population ,Case-control study ,Genome-wide association study ,Type 2 diabetes ,Biology ,medicine.disease ,Polymorphism (computer science) ,Diabetes mellitus ,medicine ,education ,Genetic association - Abstract
We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
- Published
- 2011
24. Metabolic syndrome and insulin resistance in relation to biliary tract cancer and stone risks: a population-based study in Shanghai, China
- Author
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B. H. Zhang, Fatma M. Shebl, Yu-Tang Gao, Tamra E. Meyer, Asif Rashid, Bingsheng Wang, Tian Quan Han, Ming-Chang Shen, Kai Yu, Frank Z. Stanczyk, Gabriella Andreotti, and Ann W. Hsing
- Subjects
Male ,China ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,Population ,biliary tract cancers ,Gallstones ,Gastroenterology ,Insulin resistance ,insulin resistance ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,Gallbladder cancer ,education ,Metabolic Syndrome ,education.field_of_study ,Biliary tract neoplasm ,business.industry ,medicine.disease ,Biliary Tract Neoplasms ,Oncology ,Biliary tract ,Case-Control Studies ,Female ,Metabolic syndrome ,business ,biliary stones - Abstract
Background: Serum lipids, diabetes, and obesity, individual components of metabolic syndrome, are associated with biliary tract cancer and stone risk, but the associations of metabolic syndrome or insulin resistance with biliary tract cancers and stones are not well studied. Methods: In this population-based case-control study in Shanghai, China (627 biliary tract cancers, 1037 biliary stones, and 959 controls), metabolic syndrome was defined as the presence of any three of the five components, including high waist circumference, high triglycerides, low high-density lipoprotein cholesterol (HDL), high blood pressure, and diabetes. Insulin resistance and β-cell function were assessed, using homeostasis assessment models. Results: Metabolic syndrome was significantly associated with gallbladder cancer (odds ratio (OR)=2.75, 95% confidence interval (95% CI)=1.82–4.15) and biliary stones (OR=1.64, 95% CI=1.24–2.16), with a significant dose effect with increasing number of metabolic syndrome components (P trend
- Published
- 2011
25. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma
- Author
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Stephen J. Chanock, Chaoyu Wang, Zhaoming Wang, Nan Hu, Woon-Puay Koh, Carol Giffen, Ze Zhong Tang, Margaret A. Tucker, Ti Ding, Jin-Hu Fan, Joseph F. Fraumeni, Neal D. Freedman, Yu-Tang Gao, Philip R. Taylor, William Wheeler, Meredith Yeager, Yong-Bing Xiang, Sanford M. Dawsey, Jeff Yuenger, Maxwell P. Lee, Kevin B. Jacobs, Kai Yu, Xiao-Ou Shu, Wei Zheng, Mitchell H. Gail, Wong Ho Chow, Linda M. Dong, Jian-Min Yuan, You-Lin Qiao, Laurie Burdett, Christian C. Abnet, Alisa M. Goldstein, and Amy Hutchinson
- Subjects
0303 health sciences ,PLCE1 ,Esophageal disease ,Cancer ,Locus (genetics) ,Biology ,medicine.disease ,Bioinformatics ,3. Good health ,03 medical and health sciences ,0302 clinical medicine ,Gene mapping ,030220 oncology & carcinogenesis ,Genetics ,medicine ,Carcinoma ,Cancer research ,Adenocarcinoma ,Stomach cancer ,030304 developmental biology - Abstract
Christian Abnet and colleagues report genome-wide association studies for gastric adenocarcinoma and esophageal squamous cell carcinoma in a Chinese population. They identified a new shared risk locus in the PLCE1 gene at 10q23.
- Published
- 2010
26. Diabetes in relation to biliary tract cancer and stones: a population-based study in Shanghai, China
- Author
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Jr Jf Fraumeni, Fatma M. Shebl, B. H. Zhang, Bingsheng Wang, Ming-Chang Shen, Qizhai Li, Kai Yu, Tian Quan Han, Yu-Tang Gao, Aw Hsing, Asif Rashid, and Gabriella Andreotti
- Subjects
Adult ,Male ,China ,Cancer Research ,medicine.medical_specialty ,Short Communication ,Population ,biliary tract cancers ,Gallstones ,Gastroenterology ,Body Mass Index ,Bile duct cancer ,Diabetes Complications ,Blood serum ,Risk Factors ,Internal medicine ,Diabetes mellitus ,Humans ,Medicine ,education ,Aged ,education.field_of_study ,Biliary tract neoplasm ,Biliary tract cancer ,diabetes ,business.industry ,Middle Aged ,medicine.disease ,Biliary Tract Neoplasms ,Oncology ,population characteristics ,Female ,Gallbladder Neoplasms ,mediation modelling ,Lipoproteins, HDL ,business ,human activities ,Body mass index ,geographic locations ,biliary stones - Abstract
Background: Biliary tract cancers are rare but fatal malignancies. Diabetes has been related to biliary stones, but its association with biliary tract cancers is less conclusive. Methods: In a population-based case–control study of 627 cancers, 1037 stones, and 959 controls in Shanghai, China, we examined the association between diabetes and the risks of biliary tract cancer and stones, as well as the effect of potential mediating factors, including serum lipids and biliary stones (for cancer), contributing to the causal pathway from diabetes to biliary diseases. Results: Independent of body mass index (BMI), diabetes was significantly associated with gallbladder cancer and biliary stones ((odds ratio (OR) (95% confidence interval)=2.6 (1.5–4.7) and 2.0 (1.2–3.3), respectively). Biliary stones and low serum levels of high-density lipoprotein (HDL) were significant mediators of the diabetes effect on gallbladder cancer risk, accounting for 60 and 17% of the diabetes effect, respectively. High-density lipoprotein was also a significant mediator of the diabetes effect on biliary stones, accounting for 18% of the diabetes effect. Conclusions: Independent of BMI, diabetes is a risk factor for gallbladder cancer, but its effect is mediated in part by biliary stones and serum HDL levels, suggesting that gallbladder cancer risk may be reduced by controlling diabetes, stones, and HDL levels.
- Published
- 2010
27. E-cadherin polymorphisms and breast cancer susceptibility: a report from the Shanghai Breast Cancer Study
- Author
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Wei Zheng, Sandra L. Deming, Yu-Tang Gao, Alicia Beeghly-Fadiel, Ying Zheng, Jirong Long, Xiao-Ou Shu, Wei Lu, and Qiuyin Cai
- Subjects
Adult ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,CDH1 ,Breast cancer ,Risk Factors ,Internal medicine ,Genotype ,Genetic variation ,medicine ,Humans ,Genetic Predisposition to Disease ,Aged ,Cadherin ,Case-control study ,Cancer ,Middle Aged ,Cadherins ,medicine.disease ,Postmenopause ,Premenopause ,Case-Control Studies ,Immunology ,biology.protein ,Female - Abstract
The epithelial transmembrane glycoprotein E-cadherin (CDH1) is necessary for intercellular adhesion, cell signaling, and maintenance of cellular differentiation; reduced expression contributes to cell proliferation, invasion, and cancer progression. Functional or potentially functional single nucleotide polymorphisms (SNPs) in E-cadherin have been previously identified and evaluated in relation to cancer risk; however, studies on breast cancer have been sparse. Forty-six SNPs were genotyped to capture genetic variation of the CDH1 gene among 2,290 Phase 1 and 1,944 Phase 2 participants of the Shanghai Breast Cancer Study (SBCS), a large, population-based, case-control study. No overall associations between E-cadherin SNPs and breast cancer risk were observed. When stratified by menopausal status, associations that were consistent between Phases 1 and 2 and significant when data from both phases were combined were observed for several SNPs. Although none of these associations retained statistical significance after correcting for the total number of polymorphisms evaluated, this study suggests that genetic variation in CDH1 may be associated with breast cancer risk, and that this relationship may vary by menopausal status.
- Published
- 2009
28. Genome-wide association study identifies a new breast cancer susceptibility locus at 6q25.1
- Author
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Jirong Long, Kai Gu, Chun Li, Qiuyin Cai, Wei Lu, Yu-Tang Gao, Wei Zheng, Alecia M. Fair, Yong Bin Xiang, Xiao-Ou Shu, Shawn Levy, Sandra L. Deming, Jonathan L. Haines, Wanqing Wen, and Ying Zheng
- Subjects
Adult ,Linkage disequilibrium ,Quantitative Trait Loci ,Breast Neoplasms ,Genome-wide association study ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Gene Frequency ,Risk Factors ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Allele frequency ,030304 developmental biology ,0303 health sciences ,Estrogen Receptor alpha ,Cancer ,Middle Aged ,medicine.disease ,3. Good health ,TOX3 ,Case-Control Studies ,030220 oncology & carcinogenesis ,Chromosomes, Human, Pair 6 ,Female ,Breast disease ,Genome-Wide Association Study - Abstract
A genome-wide association study was conducted among Chinese women to identify risk variants for breast cancer. By analyzing 607,728 SNPs in 1505 cases and 1522 controls, we selected 29 promising SNPs for a fast-track replication in an independent set of 1554 cases and 1576 controls. Four replicated loci were further investigated in a third set of samples including 3472 cases and 900 controls. SNP rs2046210 at 6q25.1, located upstream of the estrogen receptor 1 gene (ESR1), exhibited strong and consistent association with breast cancer across all three stages. Adjusted odds ratio (95% CI) were 1.36 (1.24–1.49) and 1.59 (1.40–1.82), respectively, for genotypes A/G and A/A versus G/G (P for trend, 2.0×10−15) in the pooled analysis of samples from all three stages. A similar, although weaker, association was also found in an independent study including 1591 cases and 1466 controls of European ancestry (Ptrend, 0.01). These results provide strong evidence implicating 6q25.1 as a susceptibility locus for breast cancer.
- Published
- 2009
29. Body size and the risk of biliary tract cancer: a population-based study in China
- Author
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Yu-Tang Gao, Tian Quan Han, Ann W. Hsing, Ming-Chang Shen, Bingsheng Wang, Lori C. Sakoda, Jinbo Chen, and Asif Rashid
- Subjects
Adult ,Male ,obesity ,China ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,Population ,body mass index ,waist-to-hip ratio ,digestive system ,Gastroenterology ,Bile duct cancer ,03 medical and health sciences ,0302 clinical medicine ,biliary tract cancer ,Internal medicine ,medicine ,Body Size ,Humans ,Risk factor ,education ,Aged ,030304 developmental biology ,2. Zero hunger ,0303 health sciences ,education.field_of_study ,Bladder cancer ,Bile duct ,business.industry ,Gallbladder ,Ampulla of Vater ,Gallstones ,Middle Aged ,medicine.disease ,digestive system diseases ,3. Good health ,Biliary Tract Neoplasms ,medicine.anatomical_structure ,Oncology ,Case-Control Studies ,Population Surveillance ,030220 oncology & carcinogenesis ,Female ,gallstones ,business - Abstract
Though obesity is an established risk factor for gall bladder cancer, its role in cancers of the extrahepatic bile ducts and ampulla of Vater is less clear, as also is the role of abdominal obesity. In a population-based case-control study of biliary tract cancer in Shanghai, China, odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for biliary tract cancer in relation to anthropometric measures, including body mass index (BMI) at various ages and waist-to-hip ratio (WHR), adjusting for age, sex, and education. The study included 627 patients with biliary tract cancer (368 gall bladder, 191 bile duct, 68 ampulla of Vater) and 959 healthy subjects randomly selected from the population. A higher BMI at all ages, including early adulthood (ages 20-29 years), and a greater WHR were associated with an increased risk of gall bladder cancer. A high usual adult BMI (or=25) was associated with a 1.6-fold risk of gall bladder cancer (95% CI 1.2-2.1, P for trend0.001). Among subjects without gallstones, BMI was also positively associated with gall bladder cancer risk. Regardless of BMI levels, increasing WHR was associated with an excess risk of gall bladder cancer risk, with those having a high BMI (or=25) and a high WHR (0.90) having the highest risk of gall bladder cancer (OR=12.6, 95% CI 4.8-33.2), relative to those with a low BMI and WHR. We found no clear risk patterns for cancers of the bile duct and ampulla of Vater. These results suggest that both overall and abdominal obesity, including obesity in early adulthood, are associated with an increased risk of gall bladder cancer. The increasing prevalence of obesity and cholesterol stones in Shanghai seems at least partly responsible for the rising incidence of gall bladder cancer in Shanghai.
- Published
- 2008
30. Joint effects of body size, energy intake, and physical activity on breast cancer risk
- Author
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Aesun Shin, Charles E. Matthews, Yu-Tang Gao, Wei Lu, Wei Zheng, Xiao-Ou Shu, and Kai Gu
- Subjects
Cancer Research ,medicine.medical_specialty ,Time Factors ,Antineoplastic Agents ,Breast Neoplasms ,Motor Activity ,Mastectomy, Segmental ,Breast cancer ,Internal medicine ,Nitriles ,medicine ,Body Size ,Humans ,Risk factor ,Aged ,Aged, 80 and over ,Cancer prevention ,Aromatase Inhibitors ,Obstetrics ,business.industry ,Cancer ,Odds ratio ,Middle Aged ,Triazoles ,Anthropometry ,medicine.disease ,Neoadjuvant Therapy ,Postmenopause ,Treatment Outcome ,Endocrinology ,Receptors, Estrogen ,Oncology ,Letrozole ,Female ,Breast disease ,Energy Intake ,Energy Metabolism ,business ,Body mass index - Abstract
To evaluate the joint effect of body size, energy intake, and physical activity on breast cancer risk, we analyzed information on body weight history, energy intake, anthropometric measurements, and physical activity patterns in a population based case-control study. Included in this analysis were 3,458 incidence breast cancer cases and 3,474 age-frequency matched controls from the Shanghai Breast Cancer Study. High weight, height, body mass index, waist-to-hip ratio, and weight gain showed stronger associations with breast cancer risk in postmenopausal women than premenopausal women. High total physical activity was inversely associated with postmenopausal breast cancer risk (p for trend=0.026) and premenopausal breast cancer (p for trend=0.059). The odds ratios for women with a high waist-to-hip ratio (or=0.84) and low total physical activity (or=10.9 MET-h/day) had the highest risk for breast cancer (OR=2.7, 95% CI: 1.4-4.9 for postmenopausal women, OR=2.1, 95% CI: 1.5-3.1 for premenopausal women) compared to their counterpart with low waist-to-hip ratio (0.76) and high total physical activity (20.5 MET-h/day). We did not find a statistically significant multiplicative interaction between body size, caloric intake and total physical activity on breast cancer risk.
- Published
- 2008
31. Circulating transforming growth factor-β-1 and breast cancer prognosis: results from the Shanghai Breast Cancer Study
- Author
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Jinghuan Zi, Yu-Tang Gao, Ana M. Grau, Wanqing Wen, Denise S. Ramroopsingh, Xiao-Ou Shu, Qiuyin Cai, and Wei Zheng
- Subjects
Adult ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,Population ,Breast Neoplasms ,Disease-Free Survival ,Article ,Transforming Growth Factor beta1 ,Breast cancer ,Median follow-up ,Internal medicine ,medicine ,Humans ,Protein Isoforms ,education ,Proportional Hazards Models ,education.field_of_study ,business.industry ,Proportional hazards model ,Hazard ratio ,Case-control study ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Treatment Outcome ,Endocrinology ,Case-Control Studies ,Multivariate Analysis ,Female ,Breast disease ,business - Abstract
INTRODUCTION: Studies investigating the prognostic effect of circulating TGF-β-1 in breast cancer have given inconsistent findings. The purpose of this study is to evaluate whether circulating transforming growth factor beta 1 (TGF-β-1) is associated with overall and disease-free survival in a cohort of recently diagnosed breast cancer patients. METHODS: We measured TGF-β-1 levels in plasma samples of breast cancer patients in the Shanghai Breast Cancer Study, a population-based case–control study. We evaluated the relationship between TGF-β-1 levels and overall and disease-free survival. The median follow up time was 7.2 years. RESULTS: We observed that, compared with the patients with the lowest quartile of plasma TGF-β-1, patients with the highest quartile of plasma TGF-β-1 had significantly worse overall survival with hazards ratio (HR) = 2.78, with 95% confidence interval (CI): 1.34–5.79 and disease-free survival with HR = 2.49, 95% CI: 1.15–5.41, while the patients with the second and third quartiles of plasma TGF-β-1 did not have significantly different overall and disease-free breast cancer survival. The shape of association between plasma TGF-β-1 levels and breast cancer survival appears to be nonlinear. Stratified analysis by stage of disease did not appreciably change the association pattern. CONCLUSIONS: We conclude that the relationship between circulating levels of TGF-β-1 and prognosis in breast cancer is complex and nonlinear. High levels of TGF-β-1 are associated with worse survival independent of stage of disease.
- Published
- 2007
32. Gallstones and the risk of biliary tract cancer: a population-based study in China
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Yu-Tang Gao, Asif Rashid, Jinbo Chen, Ming-Chang Shen, B. H. Zhang, Shelley Niwa, Tian-Quan Han, Bingsheng Wang, Lori C. Sakoda, J. F. Fraumeni, and Ann W. Hsing
- Subjects
Male ,China ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,Gallstones ,Gastroenterology ,Bile duct cancer ,Bile Acids and Salts ,cholecystitis ,Risk Factors ,biliary tract cancer ,Internal medicine ,Odds Ratio ,medicine ,Humans ,Gallbladder cancer ,Biliary Tract ,Aged ,Bile duct ,business.industry ,Gallbladder ,Ampulla of Vater ,Bilirubin ,Organ Size ,Middle Aged ,medicine.disease ,Biliary Tract Neoplasms ,Cholesterol ,medicine.anatomical_structure ,Oncology ,Biliary tract ,Population Surveillance ,Cholecystitis ,Female ,business - Abstract
We conducted a population-based study of 627 patients with biliary tract cancers (368 of gallbladder, 191 bile duct, and 68 ampulla of Vater), 1037 with biliary stones, and 959 healthy controls randomly selected from the Shanghai population, all personally interviewed. Gallstone status was based on information from self-reports, imaging procedures, surgical notes, and medical records. Among controls, a transabdominal ultrasound was performed to detect asymptomatic gallstones. Gallstones removed from cancer cases and gallstone patients were classified by size, weight, colour, pattern, and content of cholesterol, bilirubin, and bile acids. Of the cancer patients, 69% had gallstones compared with 23% of the population controls. Compared with subjects without gallstones, odds ratios associated with gallstones were 23.8 (95% confidence interval (CI), 17.0–33.4), 8.0 (95% CI 5.6–11.4), and 4.2 (95% CI 2.5–7.0) for cancers of the gallbladder, extrahepatic bile ducts, and ampulla of Vater, respectively, persisting when restricted to those with gallstones at least 10 years prior to cancer. Biliary cancer risks were higher among subjects with both gallstones and self-reported cholecystitis, particularly for gallbladder cancer (OR=34.3, 95% CI 19.9–59.2). Subjects with bile duct cancer were more likely to have pigment stones, and with gallbladder cancer to have cholesterol stones (P
- Published
- 2007
33. ERBB2 genetic polymorphism and breast cancer risk in Chinese women: a population-based case-control study
- Author
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Yinghao Su, Xiao-Ou Shu, Yu-Tang Gao, Wei Lu, Shizhen Emily Wang, Wei Zheng, Hui Cai, Qiuyin Cai, and Shimian Qu
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Article ,Breast cancer ,Internal medicine ,Genotype ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic variability ,skin and connective tissue diseases ,Genotyping ,Polymorphism, Genetic ,business.industry ,Case-control study ,Cancer ,Odds ratio ,Genes, erbB-2 ,Middle Aged ,medicine.disease ,Endocrinology ,Case-Control Studies ,Female ,Breast disease ,business - Abstract
A polymorphism at codon 655 (ATC/isoleucine to GTC/valine [Ile(655)Val], rs1801200) in the transmembrane domain-coding region of human ERBB2 gene has been previously evaluated for its association with breast cancer risk with mixed results. We evaluated this polymorphism in association with breast cancer in a group of women who participated in a large-scale, population-based, case-control study of breast cancer in Shanghai, China, followed by an in vitro analysis of the function of this polymorphism. Genomic DNA from 3,012 patients with breast cancer and 3,004 healthy controls was examined for the Ile(655)Val polymorphism using a TaqMan genotyping method. Adjusted odds ratios (OR) were derived from multiple logistic regression. In vitro analyses were carried out to examine whether the Ile(655)Val polymorphism affect ERBB2 expression and the activity of its downstream targets. Approximately 2% of study subjects carry the Val/Val genotype. Compared with women with the Ile/Ile (76%) genotype, women who had the Ile/Val (22%) or Val/Val genotype did not have an elevated risk of breast cancer. Stratified analyses by age and menopausal status revealed no apparent association with this polymorphism in any subgroups of women. In a serious of biochemical analyses, we found that the Ile(655)Val substitution did not alter ErbB2 and its downstream signaling molecule activity. These study results suggest that Ile(655)Val polymorphism of the ERBB2 gene do not alter its activity and may not be associated with increased breast cancer risk among Chinese women.
- Published
- 2007
34. Impacts of weight change on prehypertension in middle-aged and elderly women
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Yu-Tang Gao, Xianglan Zhang, Gong Yang, Honglan Li, Xiao-Ou Shu, and Wei Zheng
- Subjects
Adult ,China ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Medicine (miscellaneous) ,Blood Pressure ,Weight Gain ,Prehypertension ,Weight loss ,Internal medicine ,Weight Loss ,medicine ,Humans ,Aged ,Nutrition and Dietetics ,business.industry ,Weight change ,Odds ratio ,Middle Aged ,medicine.disease ,Obesity ,Middle age ,Endocrinology ,Blood pressure ,Hypertension ,Female ,medicine.symptom ,Epidemiologic Methods ,business ,Weight gain ,Demography - Abstract
Individuals with prehypertension, a new blood pressure category defined as systolic blood pressure of 120-139 mm Hg and/or diastolic blood pressure of 80-89 mm Hg, are at an increased risk for heart diseases and are strongly recommended to practice lifestyle changes, including weight control. Data on impacts of long-term weight change on prehypertension are sparse.To evaluate the association between weight change since age 20 and prehypertension risk.In this cross-sectional analysis of 36 075 non-hypertensive women aged 40-70 years, information on weight history was collected at enrollment in the Shanghai Women's Health Study; blood pressures were measured 2-3 years later by medical professionals. The odds ratios (ORs) of prehypertension were calculated for women who gained or lost weight since age 20 compared with those with stable weight (gain or loss5 kg), adjusting for age, lifestyle factors, sodium intake and body mass index at age 20.A total of 47% of the study participants (n=16 981) had prehypertension. For a 6- to 10-kg gain, the OR (95% CI) was 1.36 (1.28-1.45); for 11- to 15-kg gain, 1.64 (1.54-1.75); for 16- to 20-kg gain, 2.32 (2.14-2.51); for 21- to 25-kg gain, 2.91 (2.60-3.26); and for a gain25 kg; 3.65 (3.13-4.26). While for a 6- to 10-kg loss and a loss10 kg, the respective ORs were 0.76 (0.67-0.87) and 0.47 (0.38-0.59). The increase in prehypertension risk associated with each 1-kg gain was similar to that associated with a 1-year increase in age. Although weight gain during early adulthood appeared to have a more pronounced effect on the risk of prehypertension, weight gain later in life also contributed significantly to an elevated risk.Weight gain since age 20 substantially increases risk for prehypertension in non-hypertensive individuals, while weight loss significantly lowers the risk, emphasizing the importance of weight control throughout adulthood in preventing hypertension.
- Published
- 2007
35. Role of TGF-β1 and its receptors in breast carcinogenesis: Evaluation of gene expression patterns and clinical implications
- Author
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Harold I. Moses, Aesun Shin, Yu-Tang Gao, Xiao-Ou Shu, Wenjing Wang, Qiuyin Cai, Wei Zheng, Wei Lu, and Zefang Ren
- Subjects
Breast cancer ,Cytokine ,medicine.medical_treatment ,Gene expression ,Immunology ,Cancer research ,medicine ,Breast carcinogenesis ,Biology ,Receptor ,medicine.disease ,Earth-Surface Processes ,Transforming growth factor - Abstract
Objective Transforming growth factor β1 (TGF-β1) is a multifunctional cytokine that may play an important role in tumor development and progression.
- Published
- 2007
36. Quantitative analysis of mitochondrial DNA 4977-bp deletion in sporadic breast cancer and benign breast diseases
- Author
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Chuanzhong Ye, Xiao-Ou Shu, Wanqing Wen, Qiuyin Cai, Wei Zheng, Yu-Tang Gao, Regina Courtney, and Larry Pierce
- Subjects
Cancer Research ,Mitochondrial DNA ,Pathology ,medicine.medical_specialty ,DNA Mutational Analysis ,Breast Neoplasms ,Biology ,medicine.disease_cause ,DNA, Mitochondrial ,Sensitivity and Specificity ,Article ,law.invention ,Breast Diseases ,Breast cancer ,law ,medicine ,Humans ,skin and connective tissue diseases ,Polymerase chain reaction ,Sequence Deletion ,Mutation ,Reverse Transcriptase Polymerase Chain Reaction ,Cancer ,Histology ,Middle Aged ,medicine.disease ,Oncology ,Female ,Breast disease ,Carcinogenesis - Abstract
The mitochondrial DNA (mtDNA) 4977-bp deletion (DeltamtDNA(4977) mutation) is one of the most frequently observed mtDNA mutations in human tissues and may play a role in carcinogenesis. Only a few studies have evaluated DeltamtDNA(4977) mutation in breast cancer tissue, and the findings have been inconsistent, which may be due to methodological differences. In this study, we developed a quantitative real-time PCR assay to assess the level of the DeltamtDNA(4977) mutation in tumor tissue samples from 55 primary breast cancer patients and 21 patients with benign breast disease (BBD). The DeltamtDNA(4977) mutation was detected in all of the samples with levels varying from 0.000149% to 7.0%. The DeltamtDNA(4977) mutation levels were lower in tumor tissues than in adjacent normal tissues in both breast cancer and BBD subjects. The differences, however, were not statistically significant. No significant difference between breast cancer and BBD patients was found in the DeltamtDNA(4977) mutation levels of tumor tissues and adjacent normal tissues. The DeltamtDNA(4977) mutation levels were not significantly associated with clinicopathological characteristics (age, histology, tumor stage, and ER/PR status) in breast cancer or BBD patients. These results do not support the notion that the mitochondrial DNA 4977-bp deletion plays a major role in breast carcinogenesis.
- Published
- 2007
37. Two-stage case-control study of common ATM gene variants in relation to breast cancer risk
- Author
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Yu-Tang Gao, Xiao-Ou Shu, Kai Gu, Qi Dai, Wei Zheng, Chuanzhong Ye, Ying Zheng, Wei Lu, and Qiuyin Cai
- Subjects
Adult ,Oncology ,Cancer Research ,medicine.medical_specialty ,Breast Neoplasms ,Cell Cycle Proteins ,Single-nucleotide polymorphism ,Ataxia Telangiectasia Mutated Proteins ,Protein Serine-Threonine Kinases ,Biology ,Polymorphism, Single Nucleotide ,Risk Assessment ,Gene Expression Regulation, Enzymologic ,Breast cancer ,Asian People ,Gene Frequency ,Risk Factors ,Internal medicine ,Genotype ,Odds Ratio ,medicine ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Allele frequency ,Genetics ,Tumor Suppressor Proteins ,Case-control study ,Reproducibility of Results ,Cancer ,Odds ratio ,Middle Aged ,medicine.disease ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Case-Control Studies ,Female - Abstract
The ataxia telangiectasia mutated (ATM) gene is a tumor suppressor gene that plays a critical role in cell cycle arrest, apoptosis, and DNA repair. We evaluated two reported nonsynonymous SNPs (rs1800054 and rs1800058) and three additional common gene variants (rs664143, rs228589, rs1003623) in the ATM gene in relation to breast cancer risk. A two-stage case-control study, using data from the Shanghai Breast Cancer Study, was conducted in which all SNPs were screened in the stage I study, including 1,123 cases and 1,232 controls. Any promising associations were re-evaluated in the stage II study, including 2,003 cases and 1,918 controls. In the stage I study, with the exception of rs1003623, no apparent association was found for any other SNPs with breast cancer risk. For the rs1003623, the T allele was associated with an increased breast cancer risk among postmenopausal women with odds ratios (ORs) of 1.4 (95% Confidence Intervals (CIs) = 1.0-1.9) for the CT and 1.6 (95% CIs = 1.0-2.4) for the TT, (P for trend = 0.03). This association, however, was not replicated in the stage II study, suggesting that the positive association identified in stage I for rs1003623 may be due to chance. Our study reveals no apparent association of common ATM variants with breast cancer risk and underscores the importance of replication using independent samples to reduce type I errors in association studies of low-penetrance genetic factors.
- Published
- 2007
38. Pre-diagnostic cruciferous vegetables intake and lung cancer survival among Chinese women
- Author
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Qi-Jun Wu, Yu-Tang Gao, Gong Yang, Jing Gao, Wei Zheng, Xiao-Ou Shu, Yong-Bing Xiang, Honglan Li, and Jing Wang
- Subjects
Adult ,China ,medicine.medical_specialty ,Pathology ,Lung Neoplasms ,Article ,Cohort Studies ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Interquartile range ,Surveys and Questionnaires ,Internal medicine ,Vegetables ,medicine ,Humans ,Prospective Studies ,Lung cancer ,Prospective cohort study ,Life Style ,Aged ,030304 developmental biology ,0303 health sciences ,Multidisciplinary ,Proportional hazards model ,Cruciferous vegetables ,business.industry ,Hazard ratio ,Middle Aged ,medicine.disease ,Diet ,3. Good health ,Quartile ,030220 oncology & carcinogenesis ,Female ,business ,Cohort study - Abstract
No study to date has prospectively evaluated the association between pre-diagnostic cruciferous vegetables intake and lung cancer survival among women. This analysis included 547 incident lung cancer cases identified from the Shanghai Women’s Health Study (SWHS) during the follow-up period of 1997-2011. Dietary intake was assessed for all SWHS participants at enrollment and reassessed 2-3 years later. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) with adjustment for potential confounders. Of the 547 lung cancer patients, 412 patients died during the follow-up. A total of 393 (95.4%) deaths from lung cancer were documented with median survival time of 10.3 months (interquartile range, 3.6-21.1 months). High cruciferous vegetables intake was significantly associated with improved lung cancer-specific survival after adjusting for all nonclinical prognostic factors (n = 547, HR = 0.69; 95%CI = 0.49-0.95; P trend = 0.02) for the highest versus lowest quartile. A slightly stronger association of cruciferous vegetables intake with lung cancer-specific survival was observed in analyses restricted to patients with known clinical prognostic factors (n = 331, HR = 0.63; 95%CI = 0.41-0.97; P trend = 0.03) or never smokers (n = 308, HR = 0.58; 95%CI = 0.37-0.91; P trend = 0.02). In conclusion, pre-diagnostic cruciferous vegetables intake is associated with better survival of lung cancer in Chinese women.
- Published
- 2015
39. Genetic variation in IGF1, IGF-1R, IGFALS, and IGFBP3 in breast cancer survival among Chinese women: a report from the Shanghai Breast Cancer Study
- Author
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Xiao-Ou Shu, Yu-Tang Gao, Qiuyin Cai, Zefang Ren, Sandra L. Deming, Wanqing Wen, and Wei Zheng
- Subjects
Adult ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,IGFBP3 ,Breast Neoplasms ,Single-nucleotide polymorphism ,Disease-Free Survival ,Receptor, IGF Type 1 ,Breast cancer ,Internal medicine ,Genotype ,Humans ,Medicine ,Insulin-Like Growth Factor I ,Glycoproteins ,business.industry ,Proportional hazards model ,Hazard ratio ,Case-control study ,Genetic Variation ,Cancer ,Middle Aged ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Insulin-Like Growth Factor Binding Protein 3 ,Treatment Outcome ,Endocrinology ,Case-Control Studies ,Female ,Carrier Proteins ,business - Abstract
Disruption of the balance of IGF (Insulin like growth factor) pathway constituents has been implicated in the etiology and progression of breast and other cancers. We hypothesized that genetic polymorphisms in IGF system members may be associated with breast cancer survival and evaluated this hypothesis in a cohort of 1,455 women diagnosed with breast cancer between 1996 and 1998 in Shanghai, China. Nineteen functional or potentially functional polymorphisms were evaluated in the IGF-1, IGF-1R, IGFALS, and IGFBP3 genes. Disease recurrence and vital status were obtained with a median follow-up time of 7.1 years. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Overall, no significant association was noted between any of the 19 polymorphisms and survival. However, subgroup analyses demonstrated apparent interactions between menopausal status and survival for several (Single nucleotide polymorphism) SNPs in the IGF-1R and IGFBP3 genes. Carriers of the A/G or G/G genotypes (rs951715) in the IGF-1R gene had an increased risk of death among post-menopausal women (HR = 1.7, 95% CI = 1.1-2.7). Significant associations with breast cancer survival in pre-menopausal women were found for two IGFBP3 polymorphisms (rs2854744 and rs3110697), with an additional polymorphism (rs6413441) reaching borderline significance (P = 0.05). Hazard ratios for overall survival among pre-menopausal women were 1.5 (95% CI = 1.1-2.0) for the C/T-T/T genotypes (rs3110697), 1.4 (95% CI = 1.0-1.9) for the A/C-C/C genotypes (rs2854744), and 1.4 (95% CI = 1.0-1.9) for the N/A-A/A genotypes (rs6413441). Taken together, these data suggest that polymorphisms in the IGF-1R and IGFBP3 genes may be associated with altered survival among subgroups of breast cancer patients defined by menopausal status.
- Published
- 2006
40. Animal food intake and cooking methods in relation to endometrial cancer risk in Shanghai
- Author
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Z.-X. Ruan, Wanghong Xu, Qi Dai, Yu-Tang Gao, Wei Zheng, Yong-Bing Xiang, J.-R. Cheng, Xiao-Ou Shu, and Genming Zhao
- Subjects
Adult ,China ,Cancer Research ,medicine.medical_specialty ,Meat ,Epidemiology ,dietary factor ,Animal food ,Population ,03 medical and health sciences ,0302 clinical medicine ,Risk Factors ,Environmental health ,medicine ,Humans ,Cooking ,030212 general & internal medicine ,Risk factor ,education ,Aged ,2. Zero hunger ,Gynecology ,education.field_of_study ,business.industry ,Endometrial cancer ,Confounding ,Case-control study ,food and beverages ,case–control study ,Odds ratio ,Middle Aged ,medicine.disease ,Diet ,Endometrial Neoplasms ,3. Good health ,Oncology ,Quartile ,Case-Control Studies ,030220 oncology & carcinogenesis ,endometrial cancer ,Female ,business - Abstract
We evaluated animal food intake and cooking methods in relation to endometrial cancer risk in a population-based case-control study in Shanghai, China. A validated food frequency questionnaire was used to collect the usual dietary habits of 1204 cases and 1212 controls aged 30-69 years between 1997 and 2003. Statistical analyses were based on an unconditional logistic regression model adjusting for potential confounders. High intake of meat and fish was associated with an increased risk of endometrial cancer, with adjusted odds ratios for the highest vs the lowest quartile groups being 1.7 (95% confidence interval: 1.3-2.2) and 2.4 (1.8-3.1), respectively. The elevated risk was observed for all types of meat and fish intake. Intake of eggs and milk was not related to risk. Cooking methods and doneness levels for meat and fish were not associated with risk, nor did they modify the association with meat and fish consumption. Our study suggests that animal food consumption may play an important role in the aetiology of endometrial cancer, but cooking methods have minimal influence on risk among Chinese women.
- Published
- 2006
41. A case–control study in Shanghai of fruit and vegetable intake and endometrial cancer
- Author
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Xiao-Ou Shu, Wanghong Xu, Yong-Bing Xiang, Meng-Hua Tao, J.-R. Cheng, Yu-Tang Gao, Z X Ruan, and Wei Zheng
- Subjects
vegetables ,Adult ,China ,Cancer Research ,medicine.medical_specialty ,Epidemiology ,Population ,03 medical and health sciences ,0302 clinical medicine ,Environmental health ,medicine ,Humans ,030212 general & internal medicine ,education ,Legume ,2. Zero hunger ,Gynecology ,education.field_of_study ,business.industry ,Incidence ,Endometrial cancer ,Incidence (epidemiology) ,Case-control study ,fruit ,Middle Aged ,medicine.disease ,Diet ,Endometrial Neoplasms ,3. Good health ,Trend analysis ,Oncology ,Quartile ,Case-Control Studies ,030220 oncology & carcinogenesis ,endometrial cancer ,Female ,business - Abstract
In a population-based case–control study of 832 incident endometrial cancer cases and 846 frequency-matched controls among Chinese women in Shanghai, using a validated food-frequency questionnaire, dietary habits were estimated by in-person interviews. Total vegetable consumption was inversely associated with endometrial cancer risk (highest quartile vs lowest: OR=0.69, 95% CI 0.50–0.96). The risk was reduced with increasing intake of dark green/dark yellow vegetables (trend test, P=0.02), fresh legumes (trend test, P
- Published
- 2005
42. MTHFR genotypes and breast cancer survival after surgery and chemotherapy: a report from the Shanghai Breast Cancer Study
- Author
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Hui Cai, Martha J. Shrubsole, Zhi Xian Ruan, Wei Zheng, Yu-Tang Gao, Qi Niu, Qiuyin Cai, and Xiao-Ou Shu
- Subjects
Adult ,China ,Cancer Research ,medicine.medical_specialty ,Genotype ,Breast Neoplasms ,Cohort Studies ,Breast cancer ,Predictive Value of Tests ,Risk Factors ,medicine ,Humans ,Methylenetetrahydrofolate Reductase (NADPH2) ,Survival analysis ,Neoplasm Staging ,Polymorphism, Genetic ,biology ,Proportional hazards model ,business.industry ,Hazard ratio ,Cancer ,Middle Aged ,medicine.disease ,Survival Analysis ,Surgery ,Oncology ,Methylenetetrahydrofolate reductase ,Cohort ,biology.protein ,Female ,business - Abstract
Methylenetetrahydrofolate reductase (MTHFR) regulates the intracellular folates pool for DNA synthesis and methylation. Sequence variations in MTHFR (nucleotides 677 (C--T) and 1298 (A--C)) result in allozymes with decreased activity. The 677TT genotype is associated with increased toxicity of methotrexate and increased clinical response to 5-fluorouracil in treatment of cancers including breast cancer. We evaluated MTHFR genotypes and breast cancer survival in a cohort of 1067 Chinese women diagnosed with breast cancer between 1996 and 1998 who received surgery and chemotherapy. Life table method was used to calculate 5-year survival rates. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) after adjusting for potential confounding factors. Median follow-up time was 5.2 years; 5-year survival was 84.6%. Sixty-six percent carried a 677T allele and 31% carried a 1298 C allele. We found that overall 5-year breast cancer survival did not differ significantly across all genotypes (85.3% for 677 CC and 83.8% for 677TT; 83.8% for 1298 AA and 79.1% for 1298 CC). However, carrying the 677T allele was associated with non-significant increased risk of death for subjects with late stage disease (stages III-IV) (HR=1.80, 95% CI: 0.79-4.14 for TT vs. CC, p for trend=0.15), particularly among those who had survived past the second year (HR=2.97, 95% CI: 1.10-7.98, p for trend=0.04). The A1298C genotypes were not significantly associated with risk of death. This study suggests that the MTHFR C677T polymorphisms may affect long-term survival from advanced breast cancer.
- Published
- 2005
43. The Long-Term Impact of Medical and Socio-Demographic Factors on the Quality of Life of Breast Cancer Survivors Among Chinese Women
- Author
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Hui Cai, Xiao-Ou Shu, Zhi-Xian Ruan, Wanqing Wen, Yu-Tang Gao, Wei Zheng, Yong Cui, and Fan Jin
- Subjects
Adult ,Gerontology ,China ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,Psychological intervention ,Breast Neoplasms ,Disease ,Education ,Breast cancer ,Quality of life ,medicine ,Humans ,Survivors ,education ,Aged ,education.field_of_study ,business.industry ,Public health ,Social Support ,Middle Aged ,medicine.disease ,humanities ,Radiation therapy ,Oncology ,Case-Control Studies ,Income ,Quality of Life ,Marital status ,Female ,Neoplasm Recurrence, Local ,business ,Needs Assessment - Abstract
Quality of life (QOL) has become an integral part of the modern assessment of cancer treatment in Western society. However, little is known about the QOL of Chinese breast cancer survivors. To evaluate the long-term impact of medical and socio-demographic factors on survivors' QOL, we conducted a population-based study of 1065 breast cancer survivors in Shanghai, China. The mean age at diagnosis was 48.1 years and the median survival time was 4.3 years for the study participants. The Generic Quality of Life Inventory was used to assess survivors' QOL. Multiple linear regression models were employed to analyze the associations of QOL outcomes with socio-demographic and medical factors. The results revealed that recurrence status, time since diagnosis, marital status, income and education all had an independent, significant association with overall QOL and differential domains of QOL. Age at diagnosis exhibited a dual effect on QOL, positively associated with material well-being and negatively associated with physical well-being. Stage of disease was only associated with social well-being, while the type of surgery was related to material well-being alone. No associations between QOL and chemotherapy or radiotherapy were found. Further, analyses by survival intervals suggested a domain-specific order of recovery of QOL after cancer treatment. These results fill gaps in the limited literature, and provide valuable information for physicians to target the specific needs of Chinese women with breast cancer, choose appropriate interventions at the optimal time, and develop strategies accordingly in terms of improvement of patient's QOL.
- Published
- 2004
44. Variation in nutrient intakes among women in Shanghai, China
- Author
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Fan Jin, Hui Cai, Dake Liu, James R. Hébert, Yu-Tang Gao, Xiao-Ou Shu, Wei Zheng, and Gong Yang
- Subjects
Adult ,Gerontology ,China ,medicine.medical_specialty ,Population ,Large population ,Medicine (miscellaneous) ,Diet Surveys ,Sensitivity and Specificity ,Cohort Studies ,Chine ,Nutrient ,Surveys and Questionnaires ,Environmental health ,Vegetables ,Epidemiology ,medicine ,Humans ,Shanghai china ,education ,Aged ,education.field_of_study ,Nutrition and Dietetics ,business.industry ,Reproducibility of Results ,Middle Aged ,Diet ,Calibration ,Mental Recall ,Population study ,Female ,Seasons ,business ,Cohort study - Abstract
Background: In 1997, we launched a large population-based cohort study, the Shanghai Women Health Study (SWHS), to investigate diet in relation to cancer risk among 74 943 Chinese women. Simultaneously, a dietary calibration study was conducted among 200 SWHS participants with biweekly 24-h dietary recall (24HDR) over a 1-y period in order to evaluate the validity and reliability of the SWHS food frequency questionnaire (FFQ). Objective: The objectives of the current study were to evaluate the nature and magnitude of variances for intake of 26 nutrients among SWHS participants, and to estimate the number of 24HDR needed for estimate intake of the 26 nutrients examined in the study population. Design: In all, 1-y biweekly 24HDR collected from 200 healthy, free-living women aged between 40 and 70 y, who participated in the SWHS dietary calibration study, was analyzed by mixed effects model and ratios of within-individual and between-individual dietary intake variances ( w2/ b2) were estimated. Results: In agreement with reports from studies conducted in the US, we found that within-individual variances were larger than between-individual variances in dietary intake of most nutrients. The sum of all other variation (eg, weekday and weekend, seasonal, interviewer) accounted for less than 5% of total variation. Ratios of within- to between-individual variances (for log transformed data) ranged from 1.05 (carbohydrate) to 2.79 (fat) for macronutrient intake, 1.74 (niacin) to 8.48 (δ-tocopherol) for vitamin intake, and 1.35 (phosphorus) to 5.59 (sodium) for mineral intake. Conclusions: The results of this study suggest that within- and between-individual differences in nutrient intake are the major sources of variation in this population of adult Chinese women. Cultural practices as well as seasonal supply and consumption patterns of vegetable intake are likely the major contributors to the variation. Implications of these results are discussed. Sponsorship: This study is supported by the NIH grant R01CA70867.
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- 2004
45. Physical Activity, Body Size, and Estrogen Metabolism in Women
- Author
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Yu-Tang Gao, Jay H. Fowke, Christopher Longcope, Xiao-Ou Shu, Wei Zheng, James R. Hébert, Charles E. Matthews, H. Leon Bradlow, Fan Jin, and Qi Dai
- Subjects
China ,Cancer Research ,medicine.medical_specialty ,medicine.drug_class ,Cross-sectional study ,Breast Neoplasms ,Enzyme-Linked Immunosorbent Assay ,Estrone ,Urine ,Body Mass Index ,chemistry.chemical_compound ,Breast cancer ,Internal medicine ,medicine ,Humans ,Exercise ,Aged ,business.industry ,Estrogens ,Middle Aged ,Anthropometry ,medicine.disease ,Obesity ,Cross-Sectional Studies ,Endocrinology ,Adipose Tissue ,Oncology ,chemistry ,Estrogen ,North America ,Recreation ,Regression Analysis ,Female ,business ,Body mass index - Abstract
Objectives: Physical activity has demonstrable effects on estrogen levels in pre- and postmenopausal women. Increased oxidation of estrone to 2-hydroxyestrone (2HE) relative to 16α-hydroxyestrone (16HE) has been hypothesized to reduce breast cancer risk, but little is known about the effect of physical activity and body size in relation to the ratio of 2HE and 16HE in women. We examined these relationships in cross-sectional analyses of 157 North American and Chinese women. Methods: Physical activity was assessed using validated questionnaires. Adiposity was assessed as body mass index (BMI, kg/m2) and by anthropometric methods (% body fat). Estrone metabolites, 2HE and 16HE, were determined from urine via ELISA. Results: Regression analyses on the 2HE/16HE ratio revealed an interaction between leisure-time physical activities and adiposity in both North American and Chinese women (p≤ 0.05). Women reporting low levels of leisure-time physical activity who had higher BMI levels had 2HE/16HE ratios that were lower than their lean counterparts. In contrast, women with higher BMI levels that were physically active maintained higher 2HE/16HE ratios. Conclusion: These findings suggest that physical activity participation has the potential to modify the adverse effect of increased adiposity on estrogen metabolism in North American and Chinese women.
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- 2004
46. Use of complementary and alternative medicine by Chinese women with breast cancer
- Author
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Zhi-Xian Ruan, Yu-Tang Gao, Wei Zheng, Fan Jin, Xiao-Ou Shu, Yong Cui, and Wanqing Wen
- Subjects
Adult ,Complementary Therapies ,China ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Population ,MEDLINE ,Breast Neoplasms ,Traditional Chinese medicine ,Metastasis ,Breast cancer ,Internal medicine ,medicine ,Acupuncture ,Humans ,education ,Motivation ,education.field_of_study ,Traditional medicine ,business.industry ,Cancer ,Middle Aged ,medicine.disease ,Radiation therapy ,Socioeconomic Factors ,Oncology ,Case-Control Studies ,Female ,business ,Attitude to Health ,Drugs, Chinese Herbal ,Phytotherapy - Abstract
The use of complementary and alternative medicine (CAM) has been rapidly increasing among cancer patients. The aim of this study is to evaluate the prevalence and patterns of CAM use, particularly patients' intentions and their perceived effectiveness of using Chinese herbal medicine (CHM), as well as the relations between the herbal medicine use and demographic and clinical factors among Chinese women with breast cancer. We analyzed the data from a population-based sample of 1065 breast cancer women in urban Shanghai. Patients' average age at diagnosis was 48.1 years and the median time from the initial diagnosis to the follow-up survey was 4.3 years. Overall, 98% of patients had used at least one form of CAM therapy after diagnosis of breast cancer. The most popular CAM modality was traditional Chinese medicine (86.7%), followed by the use of supplements (84.8%), physical exercises (65.5%), and support group attendance (16.6%). CHM was used by 86.4% of patients, while acupuncture was used only by 4.9% of patients. Treating cancer (81.5%) was the most common intentions of using CHM. Other cited intentions included enhancing the immune system (12%), preventing metastasis of cancer or managing other discomforts (7.9%), and lessening menopausal symptoms (4.7%). The majority of patients reported that they had benefited from the use of CHM. Patients who were younger, married, had higher education or income, received chemotherapy or radiotherapy, or had recurrence/metastasis of cancer tended to use CHM more frequently than other patients. The relations between patient characteristics and use of CHMs varied with users' intentions. Given the high prevalence of CAM use among breast cancer patients, research is urgently needed to systematically evaluate the efficacy and safety of CAM use, particularly use of herbal medicines.
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- 2004
47. Genetic polymorphisms in uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) and risk of breast cancer
- Author
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Jeffrey R. Smith, Yu-Tang Gao, Olufemi J. Adegoke, Wei Zheng, Xiao-Ou Shu, Joan P. Breyer, and Qiuyin Cai
- Subjects
Adult ,Oncology ,China ,Cancer Research ,medicine.medical_specialty ,Population ,Estrogen receptor ,Breast Neoplasms ,Biology ,Age Distribution ,Breast cancer ,Gene Frequency ,Internal medicine ,Genotype ,medicine ,Genetic predisposition ,Humans ,Genetic Predisposition to Disease ,Glucuronosyltransferase ,Allele ,Family history ,education ,education.field_of_study ,Polymorphism, Genetic ,Odds ratio ,Middle Aged ,medicine.disease ,Logistic Models ,Endocrinology ,Receptors, Estrogen ,Case-Control Studies ,Female ,Receptors, Progesterone - Abstract
Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) is involved in catalyzing estrogen, the hormone that plays a central role in the etiology of breast cancer. A common polymorphism [A(TA)6TAA (allele *1) to A(TA)7TAA change (allele *28)] in the TATA-box of the promoter region of the UGT1A1 gene has been reported to be associated with a reduced transcription of this gene. We investigated the association of this polymorphism with the risk of breast cancer among 1047 breast cancer cases and 1083 community controls in the Shanghai Breast Cancer Study, a population-based case-control study. Approximately same proportion of cases (12.5%) and controls (13.0%) carried the variant allele *28 in the Chinese population (p = 0.32). When stratified by age, carrying the *28 allele was associated with an increased risk of breast cancer among women aged less than 40 years (odds ratio [OR] = 1.7; 95% CI = 1.0-2.7) but not among women 40 years old and over (OR = 0.8; 0.7-1.1). Only a few women were homozygous for the *28 allele, precluding a detailed gene-dose association analysis. Additional analyses showed that, the elevated risk associated with the UGT1A1 *28 allele among young women was primarily seen in women who had a later menarche, short menstrual years, absence of family history of breast cancer, low waist-to-hip ratio, or low body-mass index. These results suggested that the *28 allele in the UGT1A1 gene may be associated with an increased risk for breast cancer among Chinese women under age 40. No significant associations were observed with *28 allele and breast cancer risk by estrogen receptor/progesterone receptor status.
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- 2004
48. Association of body mass index with risk of lung cancer: Evidence from a middle -aged male cohort in Shanghai, China
- Author
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Yu Tang Gao, Jian-Min Yuan, Xue-Li Wang, and En-ju Liu
- Subjects
medicine.medical_specialty ,Proportional hazards model ,business.industry ,Confounding ,Cancer ,Retrospective cohort study ,medicine.disease ,Surgery ,Cohort ,medicine ,Lung cancer ,Prospective cohort study ,business ,Body mass index ,Earth-Surface Processes ,Demography - Abstract
OBJECTIVE To Jnvest~gate the relationship between body mass ~ndex (BMI) and tung cancer risk among men in urban Shanghai, China. METHODS Between January 1,1986 and September 30,1989, a total of 18,244 male readents of urban Shanghai were recruited in the prospective cohort study. The eligible study subjects were those aged 45 to 64 years and w~thout history of cancer. Through July 10 ''~, 2003 (17 years follow-up), 467 new cases of lung cancer were identified in the cohort. Cox regression models were used to estimate the adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS The risk of lung cancer decreased with increasing in BMI. After adjustment for some potential confounding factors, a relative risk of 0.6 (highest versus lowest quintile of BMI) was observed (P-trend =0.01). Stratified by smoking status, an inverse association of body mass index with lung cancer risk still existed among current smokers. There were too few cases of tung cancer to draw a valid result among men who never smoked. The results also showed that the association of BMI with the risk of lung adenocarcinoma was more apparent than with other histological subtypes. CONCLUSION An inverse association of BMI with lung cancer risk may exist among men in Shanghai.
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- 2004
49. Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women's Health Study
- Author
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Wei Zheng, Lawrence H. Kushi, Fan Jin, Yu-Tang Gao, Gong Yang, Xiao-Ou Shu, D. Liu, and Wanqing Wen
- Subjects
China ,Food intake ,Medicine (miscellaneous) ,Diet Surveys ,Sensitivity and Specificity ,Feeding behavior ,Surveys and Questionnaires ,Environmental health ,Vegetables ,Humans ,Food science ,Reproducibility ,Nutrition and Dietetics ,digestive, oral, and skin physiology ,Reproducibility of Results ,Food frequency questionnaire ,Middle Aged ,Diet ,Fruit ,Calibration ,Mental Recall ,population characteristics ,Female ,Seasons ,Psychology ,human activities ,geographic locations - Abstract
To evaluate the validity and reliability of the food frequency questionnaire (FFQ) used in the Shanghai Women's Health Study (SWHS), 200 SWHS participants were recruited for a dietary calibration study. Study participants completed an FFQ at baseline and 24-h dietary recalls (24-HDR) twice per month consecutively for 12 months. At the end of the study, a second FFQ was administered. Of the 200 study participants, 196 completed 24 or more days of 24-h dietary recalls, 191 completed two FFQs from whom the results of this report were based. The FFQ included the foods that accounted for 86% of the foods recorded in the 24-HDR surveys. Validity of the FFQ was evaluated by comparing intake levels of major nutrients and foods obtained from the second FFQ with those derived from the multiple 24-HDR. The median intake for major nutrients, rice, poultry and meat derived from the second FFQ and the 24-HDR was similar, with the differences ranging from 1.3 to 12.1%. The FFQ tended to overestimate the intake level of total vegetables and total fruits, and the differences were explained mainly by over-reporting seasonal vegetables and fruits consumption in the FFQ. Nutrient and food intake assessed by the FFQ and the multiple 24-HDR correlated very well, with the correlation coefficients being 0.59-0.66 for macronutrients, 0.41-0.59 for micronutrients, and 0.41-0.66 for major food groups. The reliability of the FFQ was assessed by comparing the correlation and median intake of nutrients and food groups obtained from the two FFQs that were administered approximately 2 y apart. The median intake levels for selected nutrients and food groups derived from the two FFQs were similar with differences below 10%. At the individual level, the intake levels of these dietary variables obtained from two FFQs also correlated well. When nutrient and food group intakes were categorized into quartiles, FFQ and 24-HDR produced exact agreement rates between 33 and 50%. Misclassification to adjacent quartile was common, ranging from 34-48%, while misclassification to an extreme quartile was rare (1-6%). These data indicate that the SWHS FFQ can reliably and accurately measure usual intake of major nutrients and food groups among women in Shanghai.
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- 2003
50. IGF-1, IGF-2 and IGFBP-3 in prediagnostic serum: association with colorectal cancer in a cohort of Chinese men in Shanghai
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Mimi C. Yu, Yu-Tang Gao, Nicole Probst-Hensch, Jian-Min Yuan, Frank Z. Stanczyk, and R. K. Ross
- Subjects
Male ,China ,Cancer Research ,medicine.medical_specialty ,Alcohol Drinking ,Colorectal cancer ,Statistics as Topic ,Population ,colorectal cancer ,Body Mass Index ,Cohort Studies ,Insulin-Like Growth Factor II ,Risk Factors ,Internal medicine ,medicine ,Humans ,Insulin-Like Growth Factor I ,Risk factor ,education ,education.field_of_study ,business.industry ,Smoking ,Proteins ,Cancer ,Regular Article ,IGFBP-3 ,Middle Aged ,medicine.disease ,IGF-2 ,Insulin-Like Growth Factor Binding Protein 3 ,Endocrinology ,Oncology ,Cohort ,IGF-1 ,Sample collection ,Colorectal Neoplasms ,business ,Body mass index ,Cohort study - Abstract
This is the first study to investigate the associations of IGF-1, IGF-2 and IGFBP-3 concentrations with the risk of colorectal cancer in prospectively collected blood samples from an Oriental population. Between 1986 and 1989 serum samples were collected at baseline from 18 244 men, aged 45–65 years, without a history of cancer and living in Shanghai, China. IGF-1, IGF-2 and IGFBP-3 were measured in the serum of 135 men who developed colorectal cancer over 12 years of follow-up and 661 control subjects drawn from the cohort, who were matched to the index cases by neighbourhood of residence, age, and year and month of sample collection. Serum IGF-1 was not associated with risk of colorectal cancer. IGF-2 and IGFBP-3, on the other hand, exhibited statistically significant, positive associations with colorectal cancer risk when cases were confined to those diagnosed within a relatively short time period after enrolment (within 8 years). After adjustment for body mass index, cigarette smoking and alcohol intake, men in the highest versus the lowest quintile of IGF-2 and IGFBP-3 showed odds ratios of 2.74 (95% Cl = 1.67–4.50; 2-sided P for trend = 0.0008) and 2.85 (95% Cl = 1.69–4.81; 2-sided P for trend = 0.01), respectively. Our data thus suggest that circulating IGF-2 and IGFBP-3 can serve as early indicators of impending colorectal cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com
- Published
- 2001
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