{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T13:01:02Z","timestamp":1761310862041,"version":"3.37.3"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T00:00:00Z","timestamp":1377129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Foundation of Shanghai Municipal Health Bureau","award":["2008Y118"],"award-info":[{"award-number":["2008Y118"]}]},{"name":"Foundation of Shanghai Cancer Institute","award":["SB11-06"],"award-info":[{"award-number":["SB11-06"]}]},{"name":"Intramural Research Program of the NIH and NCI"},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["5R25 CA047888"],"award-info":[{"award-number":["5R25 CA047888"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Altered motility of the gallbladder is associated with an increased risk of gallstones and can result in biliary tract cancers. Cholecystokinin (<jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content>) is an important modulator of gallbladder motility which functions by activating <jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content> type\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> receptor (<jats:italic><jats:styled-content style=\"fixed-case\">CCKAR<\/jats:styled-content><\/jats:italic>). The aim of this study was to determine whether genetic variants in <jats:italic><jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">CCKAR<\/jats:styled-content><\/jats:italic> are associated with the risk of biliary tract cancers and stones.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We investigated the associations between nine single nucleotide polymorphisms in <jats:italic><jats:styled-content style=\"fixed-case\">CCK<\/jats:styled-content><\/jats:italic> and <jats:italic><jats:styled-content style=\"fixed-case\">CCKAR<\/jats:styled-content><\/jats:italic> in a population\u2010based case\u2013control study, including 439 biliary tract cancer cases (253 gallbladder, 133 extrahepatic bile duct, and 53 ampulla of <jats:styled-content style=\"fixed-case\">V<\/jats:styled-content>ater cancer cases), 429 biliary stone cases, and 447 population controls in <jats:styled-content style=\"fixed-case\">S<\/jats:styled-content>hanghai, <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>hina.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that women with the <jats:italic><jats:styled-content style=\"fixed-case\">CCKAR<\/jats:styled-content><\/jats:italic> rs1800855 <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content> genotype had an increased risk of gallbladder cancer (odds ratio\u2009=\u20092.37, 95% confidence interval (<jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>): 1.36\u20134.14) compared with subjects with the <jats:styled-content style=\"fixed-case\">TT<\/jats:styled-content> genotype, and remained significant after <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>onferroni correction (<jats:italic><jats:styled-content style=\"fixed-case\">P<\/jats:styled-content><\/jats:italic>\u2009=\u20090.0056). Additionally, female carriers of the <jats:italic><jats:styled-content style=\"fixed-case\">CCKAR<\/jats:styled-content><\/jats:italic> haplotype <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content> (rs2071011\u2010rs915889\u2010rs3822222\u2010rs1800855) had a reduced risk of gallbladder cancer (odds ratio\u2009=\u20090.61, 95% confidence interval: 0.43\u20130.86) compared with those with the <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">A<\/jats:styled-content> haplotype; the association also remained significant after <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>onferroni correction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that variants in the <jats:italic><jats:styled-content style=\"fixed-case\">CCKAR<\/jats:styled-content><\/jats:italic> gene may influence the risk of gallbladder cancer in women. Additional studies are needed to confirm our findings.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.12278","type":"journal-article","created":{"date-parts":[[2013,5,22]],"date-time":"2013-05-22T11:56:51Z","timestamp":1369223811000},"page":"1476-1481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Variants in <i><scp>CCK<\/scp><\/i> and <i><scp>CCKAR<\/scp><\/i> genes to susceptibility to biliary tract cancers and stones: A population\u2010based study in <scp>S<\/scp>hanghai, <scp>C<\/scp>hina"],"prefix":"10.1111","volume":"28","author":[{"given":"Hong\u2010Li","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ann W.","family":"Hsing","sequence":"additional","affiliation":[{"name":"Cancer Prevention Institute of California  Fremont"},{"name":"Stanford Cancer Institute  Palo Alto California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emily","family":"Vogtmann","sequence":"additional","affiliation":[{"name":"Department of Epidemiology School of Public Health University of Alabama at Birmingham  Birmingham Alabama"},{"name":"Division of Epidemiology Department of Medicine Vanderbilt Epidemiology Center Vanderbilt\u2010Ingram Cancer Center Vanderbilt University School of Medicine  Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa W.","family":"Chu","sequence":"additional","affiliation":[{"name":"Cancer Prevention Institute of California  Fremont"},{"name":"Stanford Cancer Institute  Palo Alto California"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia\u2010Rong","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Ting","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bing\u2010Sheng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"},{"name":"Department of General Surgery Zhongshan Hospital"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Chang","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"},{"name":"Department of Pathology Cancer Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu\u2010Tang","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Epidemiology Shanghai Cancer Institute Renji Hospital Shanghai Jiaotong University School of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2013,8,22]]},"reference":[{"volume-title":"2008 V1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]","year":"2010","author":"Ferlay J","key":"e_1_2_7_2_1"},{"key":"e_1_2_7_3_1","first-page":"112","article-title":"Cancer incidence trends in urban Shanghai, 1972\u20131999","volume":"24","author":"Liu EJ","year":"2004","journal-title":"Tumor"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604047"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgq194"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.34.4.440"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.beem.2004.07.002"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22375"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-0444"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1885"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bth457"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.20098"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2003.11.012"},{"key":"e_1_2_7_14_1","first-page":"G628","article-title":"Cholecystokinin receptors","volume":"269","author":"Wank SA","year":"1995","journal-title":"Am. 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