{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:36:25Z","timestamp":1787027785730,"version":"build-2736575974"},"reference-count":58,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T00:00:00Z","timestamp":1664236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22790518"],"award-info":[{"award-number":["22790518"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23390377"],"award-info":[{"award-number":["23390377"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24790544"],"award-info":[{"award-number":["24790544"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26293347"],"award-info":[{"award-number":["26293347"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17H04324"],"award-info":[{"award-number":["17H04324"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08970"],"award-info":[{"award-number":["17K08970"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["18K08829"],"award-info":[{"award-number":["18K08829"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K09259"],"award-info":[{"award-number":["20K09259"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["H26-Kakushintekigan-ippan-060"],"award-info":[{"award-number":["H26-Kakushintekigan-ippan-060"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19ek0610011"],"award-info":[{"award-number":["JP19ek0610011"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19dk0307071"],"award-info":[{"award-number":["JP19dk0307071"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["22790518"],"award-info":[{"award-number":["22790518"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["23390377"],"award-info":[{"award-number":["23390377"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["24790544"],"award-info":[{"award-number":["24790544"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["26293347"],"award-info":[{"award-number":["26293347"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["17H04324"],"award-info":[{"award-number":["17H04324"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["17K08970"],"award-info":[{"award-number":["17K08970"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["18K08829"],"award-info":[{"award-number":["18K08829"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["20K09259"],"award-info":[{"award-number":["20K09259"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["H26-Kakushintekigan-ippan-060"],"award-info":[{"award-number":["H26-Kakushintekigan-ippan-060"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["JP19ek0610011"],"award-info":[{"award-number":["JP19ek0610011"]}]},{"name":"Ministry of Health, Labour, and Welfare (MHLW) of Japan","award":["JP19dk0307071"],"award-info":[{"award-number":["JP19dk0307071"]}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["22790518"],"award-info":[{"award-number":["22790518"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["23390377"],"award-info":[{"award-number":["23390377"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["24790544"],"award-info":[{"award-number":["24790544"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["26293347"],"award-info":[{"award-number":["26293347"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17H04324"],"award-info":[{"award-number":["17H04324"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17K08970"],"award-info":[{"award-number":["17K08970"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["18K08829"],"award-info":[{"award-number":["18K08829"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["20K09259"],"award-info":[{"award-number":["20K09259"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["H26-Kakushintekigan-ippan-060"],"award-info":[{"award-number":["H26-Kakushintekigan-ippan-060"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19ek0610011"],"award-info":[{"award-number":["JP19ek0610011"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP19dk0307071"],"award-info":[{"award-number":["JP19dk0307071"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Smoking Research Foundation","award":["22790518"],"award-info":[{"award-number":["22790518"]}]},{"name":"Smoking Research Foundation","award":["23390377"],"award-info":[{"award-number":["23390377"]}]},{"name":"Smoking Research Foundation","award":["24790544"],"award-info":[{"award-number":["24790544"]}]},{"name":"Smoking Research Foundation","award":["26293347"],"award-info":[{"award-number":["26293347"]}]},{"name":"Smoking Research Foundation","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}]},{"name":"Smoking Research Foundation","award":["17H04324"],"award-info":[{"award-number":["17H04324"]}]},{"name":"Smoking Research Foundation","award":["17K08970"],"award-info":[{"award-number":["17K08970"]}]},{"name":"Smoking Research Foundation","award":["18K08829"],"award-info":[{"award-number":["18K08829"]}]},{"name":"Smoking Research Foundation","award":["20K09259"],"award-info":[{"award-number":["20K09259"]}]},{"name":"Smoking Research Foundation","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}]},{"name":"Smoking Research Foundation","award":["H26-Kakushintekigan-ippan-060"],"award-info":[{"award-number":["H26-Kakushintekigan-ippan-060"]}]},{"name":"Smoking Research Foundation","award":["JP19ek0610011"],"award-info":[{"award-number":["JP19ek0610011"]}]},{"name":"Smoking Research Foundation","award":["JP19dk0307071"],"award-info":[{"award-number":["JP19dk0307071"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["22790518"],"award-info":[{"award-number":["22790518"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["23390377"],"award-info":[{"award-number":["23390377"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["24790544"],"award-info":[{"award-number":["24790544"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["26293347"],"award-info":[{"award-number":["26293347"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["17H04324"],"award-info":[{"award-number":["17H04324"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["17K08970"],"award-info":[{"award-number":["17K08970"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["18K08829"],"award-info":[{"award-number":["18K08829"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["20K09259"],"award-info":[{"award-number":["20K09259"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["H26-Kakushintekigan-ippan-060"],"award-info":[{"award-number":["H26-Kakushintekigan-ippan-060"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["JP19ek0610011"],"award-info":[{"award-number":["JP19ek0610011"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["JP19dk0307071"],"award-info":[{"award-number":["JP19dk0307071"]}]},{"name":"Japan Society for the Promotion of Science","award":["22790518"],"award-info":[{"award-number":["22790518"]}]},{"name":"Japan Society for the Promotion of Science","award":["23390377"],"award-info":[{"award-number":["23390377"]}]},{"name":"Japan Society for the Promotion of Science","award":["24790544"],"award-info":[{"award-number":["24790544"]}]},{"name":"Japan Society for the Promotion of Science","award":["26293347"],"award-info":[{"award-number":["26293347"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP22H04922"],"award-info":[{"award-number":["JP22H04922"]}]},{"name":"Japan Society for the Promotion of Science","award":["17H04324"],"award-info":[{"award-number":["17H04324"]}]},{"name":"Japan Society for the Promotion of Science","award":["17K08970"],"award-info":[{"award-number":["17K08970"]}]},{"name":"Japan Society for the Promotion of Science","award":["18K08829"],"award-info":[{"award-number":["18K08829"]}]},{"name":"Japan Society for the Promotion of Science","award":["20K09259"],"award-info":[{"award-number":["20K09259"]}]},{"name":"Japan Society for the Promotion of Science","award":["21H03028"],"award-info":[{"award-number":["21H03028"]}]},{"name":"Japan Society for the Promotion of Science","award":["H26-Kakushintekigan-ippan-060"],"award-info":[{"award-number":["H26-Kakushintekigan-ippan-060"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP19ek0610011"],"award-info":[{"award-number":["JP19ek0610011"]}]},{"name":"Japan Society for the Promotion of Science","award":["JP19dk0307071"],"award-info":[{"award-number":["JP19dk0307071"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Considerable individual differences have been widely observed in the sensitivity to opioids. We conducted a genome-wide association study (GWAS) in patients with cancer pain to identify potential candidate single-nucleotide polymorphisms (SNPs) that contribute to individual differences in opioid analgesic requirements in pain treatment by utilizing whole-genome genotyping arrays with more than 650,000 markers. The subjects in the GWAS were 428 patients who provided written informed consent and underwent treatment for pain with opioid analgesics in a palliative care unit at Higashi-Sapporo Hospital. The GWAS showed two intronic SNPs, rs1283671 and rs1283720, in the ANGPT1 gene that encodes a secreted glycoprotein that belongs to the angiopoietin family. These two SNPs were strongly associated with average daily opioid requirements for the treatment of pain in both the additive and recessive models (p &lt; 5.0000 \u00d7 10\u22128). Several other SNPs were also significantly associated with the phenotype. In the gene-based analysis, the association was significant for the SLC2A14 gene in the additive model. These results indicate that these SNPs could serve as markers that predict the efficacy of opioid analgesics in cancer pain treatment. Our findings may provide valuable information for achieving satisfactory pain control and open new avenues for personalized pain treatment.<\/jats:p>","DOI":"10.3390\/cancers14194692","type":"journal-article","created":{"date-parts":[[2022,9,27]],"date-time":"2022-09-27T21:23:27Z","timestamp":1664313807000},"page":"4692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Genome-Wide Association Study Identifies Candidate Loci Associated with Opioid Analgesic Requirements in the Treatment of Cancer Pain"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8286-4651","authenticated-orcid":false,"given":"Daisuke","family":"Nishizawa","sequence":"first","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6166-5335","authenticated-orcid":false,"given":"Takeshi","family":"Terui","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Department of Medicine, Higashi-Sapporo Hospital, Sapporo 003-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-1608","authenticated-orcid":false,"given":"Kunihiko","family":"Ishitani","sequence":"additional","affiliation":[{"name":"Division of Internal Medicine, Department of Medicine, Higashi-Sapporo Hospital, Sapporo 003-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shinya","family":"Kasai","sequence":"additional","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junko","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoko","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Ebata","sequence":"additional","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8342-0278","authenticated-orcid":false,"given":"Kazutaka","family":"Ikeda","sequence":"additional","affiliation":[{"name":"Addictive Substance Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1976","DOI":"10.1097\/j.pain.0000000000001939","article-title":"The revised International Association for the Study of Pain definition of pain: Concepts, challenges, and compromises","volume":"161","author":"Raja","year":"2020","journal-title":"Pain"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1016\/j.jpainsymman.2015.12.340","article-title":"Update on prevalence of pain in patients with cancer: Systematic review and meta-analysis","volume":"51","author":"Hochstenbach","year":"2016","journal-title":"J. Pain Symptom Manag."},{"key":"ref_3","unstructured":"(2022, August 09). WHO Guidelines for the Pharmacological and Radiotherapeutic Management of Cancer Pain in Adults and Adolescents. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789241550390."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.tips.2005.04.001","article-title":"How individual sensitivity to opiates can be predicted by gene analyses","volume":"26","author":"Ikeda","year":"2005","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_5","unstructured":"Preedy, V.R. (2016). Genome-wide association studies and human opioid sensitivity. Neuropathology of Drug Addictions and Substance Misuse Volume 1: Foundations of Understanding, Tobacco, Alcohol, Cannabinoids and Opioids, Academic Press."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1375\/twin.13.5.412","article-title":"Opioid pharmacogenomics using a twin study paradigm: Methods and procedures for determining familial aggregation and heritability","volume":"13","author":"Angst","year":"2010","journal-title":"Twin Res. Hum. Genet."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/j.pain.2012.02.022","article-title":"Pain sensitivity and opioid analgesia: A pharmacogenomic twin study","volume":"153","author":"Angst","year":"2012","journal-title":"Pain"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1399-0004.2012.01923.x","article-title":"Opioid genetics: The key to personalized pain control?","volume":"82","author":"Branford","year":"2012","journal-title":"Clin. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1097\/SPC.0b013e32834f6a07","article-title":"Opioid genetics in the context of opioid switching","volume":"6","author":"Droney","year":"2012","journal-title":"Curr. Opin. Supportive Palliat. Care"},{"key":"ref_10","first-page":"73","article-title":"Pharmacogenomic considerations in opioid analgesia","volume":"5","author":"Vuilleumier","year":"2012","journal-title":"Pharm. Pers. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1097\/AJP.0000000000000636","article-title":"Effects of the OPRM1 A118G polymorphism (rs1799971) on opioid analgesia in cancer pain: A systematic review and meta-analysis","volume":"35","author":"Yu","year":"2019","journal-title":"Clin. J. Pain"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.2217\/pgs-2017-0060","article-title":"Advanced cancer pain: The search for genetic factors correlated with interindividual variability in opioid requirement","volume":"18","author":"Matic","year":"2017","journal-title":"Pharmacogenomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1016\/j.jpainsymman.2021.03.024","article-title":"Genetic factors associated with pain severity, daily opioid dose requirement, and pain response among advanced cancer patients receiving supportive care","volume":"62","author":"Yennurajalingam","year":"2021","journal-title":"J. Pain Symptom Manag."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/j.soncn.2019.04.011","article-title":"Genetic variants associated with cancer pain and response to opioid analgesics: Implications for precision pain management","volume":"35","author":"Yang","year":"2019","journal-title":"Semin. Oncol. Nurs."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1038\/nrg2751","article-title":"Genome-wide association studies in pharmacogenomics","volume":"11","author":"Daly","year":"2010","journal-title":"Nat. Rev. Genet."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/j.pain.2014.05.032","article-title":"TAOK3, a novel genome-wide association study locus associated with morphine requirement and postoperative pain in a retrospective pediatric day surgery population","volume":"155","author":"Li","year":"2014","journal-title":"Pain"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.pain.2009.09.004","article-title":"Association between OPRM1 gene polymorphisms and fentanyl sensitivity in patients undergoing painful cosmetic surgery","volume":"147","author":"Fukuda","year":"2009","journal-title":"Pain"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1038\/mp.2012.164","article-title":"Genome-wide association study identifies a potent locus associated with human opioid sensitivity","volume":"19","author":"Nishizawa","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1200\/JCO.2010.32.6884","article-title":"Prevalence and predictors of cognitive dysfunction in opioid-treated patients with cancer: A multinational study","volume":"29","author":"Kurita","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4581","DOI":"10.1158\/1078-0432.CCR-10-3028","article-title":"Multiple loci modulate opioid therapy response for cancer pain","volume":"17","author":"Galvan","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1177\/1049909113502118","article-title":"Recent advances in palliative cancer care at a regional hospital in Japan","volume":"31","author":"Terui","year":"2014","journal-title":"Am. J. Hosp. Palliat. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1177\/1049909113505137","article-title":"A survey of patients who were referred to our palliative care division from other hospitals and appeared to have obvious indications for cancer chemotherapies","volume":"31","author":"Hirayama","year":"2014","journal-title":"Am. J. Hosp. Palliat. Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1016\/j.jpainsymman.2018.12.001","article-title":"Safe and appropriate use of methadone in hospice and palliative care: Expert consensus white paper","volume":"57","author":"McPherson","year":"2019","journal-title":"J. Pain Symptom Manag."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S0885-3924(02)00643-7","article-title":"A systematic review of hydromorphone in acute and chronic pain","volume":"25","author":"Quigley","year":"2003","journal-title":"J. Pain Symptom Manag."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Cherny, N.I., Fallon, M.T., Kaasa, S., Portenoy, R.K., and Currow, D.C. (2021). Oxford Textbook of Palliative Medicine, Oxford University Press. [6th ed.].","DOI":"10.1093\/med\/9780198821328.001.0001"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"De Leeuw, C.A., Mooij, J.M., Heskes, T., and Posthuma, D. (2015). MAGMA: Generalized gene-set analysis of GWAS data. PLoS Comput. Biol., 11.","DOI":"10.1371\/journal.pcbi.1004219"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1826","DOI":"10.1038\/s41467-017-01261-5","article-title":"Functional mapping and annotation of genetic associations with FUMA","volume":"8","author":"Watanabe","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1086\/519795","article-title":"PLINK: A tool set for whole-genome association and population-based linkage analyses","volume":"81","author":"Purcell","year":"2007","journal-title":"Am. J. Hum. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/bioinformatics\/bth457","article-title":"Haploview: Analysis and visualization of LD and haplotype maps","volume":"21","author":"Barrett","year":"2005","journal-title":"Bioinformatics"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"R122","DOI":"10.1093\/hmg\/ddn288","article-title":"Practical aspects of imputation-driven meta-analysis of genome-wide association studies","volume":"17","author":"Ferreira","year":"2008","journal-title":"Hum. Mol. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Barsh, G.S., Copenhaver, G.P., Gibson, G., and Williams, S.M. (2012). Guidelines for genome-wide association studies. PLoS Genet., 8.","DOI":"10.1371\/journal.pgen.1002812"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"175","DOI":"10.3758\/BF03193146","article-title":"G*Power 3: A flexible statistical power analysis program for the social, behavioral, and biomedical sciences","volume":"39","author":"Faul","year":"2007","journal-title":"Behav. Res. Methods"},{"key":"ref_34","unstructured":"Cohen, J. (1977). Statistical Power Analysis for the Behavioral Sciences, Academic Press. [revised ed.]."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2225","DOI":"10.1126\/science.1069424","article-title":"The structure of haplotype blocks in the human genome","volume":"296","author":"Gabriel","year":"2002","journal-title":"Science"},{"key":"ref_36","unstructured":"GTEx Consortium (2013). The Genotype-Tissue Expression (GTEx) project. Nat. Genet., 45, 580\u2013585."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"D930","DOI":"10.1093\/nar\/gkr917","article-title":"HaploReg: A resource for exploring chromatin states, conservation, and regulatory motif alterations within sets of genetically linked variants","volume":"40","author":"Ward","year":"2012","journal-title":"Nucleic. Acids Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"W600","DOI":"10.1093\/nar\/gkp290","article-title":"SNPinfo: Integrating GWAS and candidate gene information into functional SNP selection for genetic association studies","volume":"37","author":"Xu","year":"2009","journal-title":"Nucleic. Acids Res."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.pain.2009.10.021","article-title":"A GTP cyclohydrolase 1 genetic variant delays cancer pain","volume":"148","author":"Lotsch","year":"2010","journal-title":"Pain"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.1093\/hmg\/ddq131","article-title":"A functional variant in the 3\u2019-UTR of angiopoietin-1 might reduce stroke risk by interfering with the binding efficiency of microRNA 211","volume":"19","author":"Chen","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nature01320","article-title":"Points of control in inflammation","volume":"420","author":"Nathan","year":"2002","journal-title":"Nature"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1097\/01.nrl.0000215789.70804.b0","article-title":"Inflammation, atherosclerosis, and stroke","volume":"12","author":"Elkind","year":"2006","journal-title":"Neurologist"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1097\/MOH.0000000000000361","article-title":"Angiopoietins and Tie2 in vascular inflammation","volume":"24","author":"Parikh","year":"2017","journal-title":"Curr. Opin. Hematol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1016\/S0092-8674(00)81813-9","article-title":"Requisite role of angiopoietin-1, a ligand for the TIE2 receptor, during embryonic angiogenesis","volume":"87","author":"Suri","year":"1996","journal-title":"Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.1016\/j.jaci.2017.05.020","article-title":"Mutation of the angiopoietin-1 gene (ANGPT1) associates with a new type of hereditary angioedema","volume":"141","author":"Bafunno","year":"2018","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1016\/j.jacc.2019.01.051","article-title":"Effect of angiotensin II inhibitors on gastrointestinal bleeding in patients with left ventricular assist devices","volume":"73","author":"Converse","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"39","DOI":"10.2337\/db10-0326","article-title":"Naloxone, but not valsartan, preserves responses to hypoglycemia after antecedent hypoglycemia: Role of metabolic reprogramming in counterregulatory failure","volume":"60","author":"Poplawski","year":"2011","journal-title":"Diabetes"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3372","DOI":"10.1210\/jc.2009-0882","article-title":"Hypoglycemia-associated autonomic failure is prevented by opioid receptor blockade","volume":"94","author":"Leu","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_49","first-page":"E852","article-title":"Opiate blockade enhances hypoglycemic counterregulation in normal and insulin-dependent diabetic subjects","volume":"260","author":"Caprio","year":"1991","journal-title":"Am. J. Physiol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1007\/s13365-015-0356-9","article-title":"Chronic SIV and morphine treatment increases heat shock protein 5 expression at the synapse","volume":"21","author":"Pendyala","year":"2015","journal-title":"J. Neurovirol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1006\/geno.2002.7010","article-title":"GLUT14, a duplicon of GLUT3, is specifically expressed in testis as alternative splice forms","volume":"80","author":"Wu","year":"2002","journal-title":"Genomics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1007\/s12031-012-9748-y","article-title":"Genetic association of SLC2A14 polymorphism with Alzheimer\u2019s disease in a Han Chinese population","volume":"47","author":"Wang","year":"2012","journal-title":"J. Mol. Neurosci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.3945\/ajcn.116.147603","article-title":"The SLC2A14 gene, encoding the novel glucose\/dehydroascorbate transporter GLUT14, is associated with inflammatory bowel disease","volume":"106","author":"Zhouyao","year":"2017","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1111\/j.1530-0277.2010.01156.x","article-title":"Genome-wide association study of alcohol dependence implicates a region on chromosome 11","volume":"34","author":"Edenberg","year":"2010","journal-title":"Alcohol. Clin. Exp. Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1177\/0269881113504017","article-title":"The role of the opioid system in alcohol dependence","volume":"28","author":"Nutt","year":"2014","journal-title":"J. Psychopharmacol."},{"key":"ref_56","first-page":"3","article-title":"Alcohol dependence: Neurobiology and treatment","volume":"73","author":"Michalak","year":"2016","journal-title":"Acta Pol. Pharm."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Yoshida, K., Nishizawa, D., Ichinomiya, T., Ichinohe, T., Hayashida, M., Fukuda, K., and Ikeda, K. (2015). Prediction formulas for individual opioid analgesic requirements based on genetic polymorphism analyses. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0116885"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/papr.13030","article-title":"Establishment of predicting equation for individual sufentanil dosage postoperatively based on gene polymorphisms","volume":"22","author":"Cheng","year":"2022","journal-title":"Pain Pract."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/19\/4692\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:40:17Z","timestamp":1760143217000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/14\/19\/4692"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,27]]},"references-count":58,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["cancers14194692"],"URL":"https:\/\/doi.org\/10.3390\/cancers14194692","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,27]]}}}