{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:12:24Z","timestamp":1776931944942,"version":"3.51.2"},"reference-count":97,"publisher":"Bioscientifica","issue":"4","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2015,8]]},"abstract":"<jats:p>Type 2 diabetes (T2D) has been suggested to be a risk factor for multiple myeloma (MM), but the relationship between the two traits is still not well understood. The aims of this study were to evaluate whether 58 genome-wide-association-studies (GWAS)-identified common variants for T2D influence the risk of developing MM and to determine whether predictive models built with these variants might help to predict the disease risk. We conducted a case\u2013control study including 1420 MM patients and 1858 controls ascertained through the International Multiple Myeloma (IMMEnSE) consortium. Subjects carrying the <jats:italic>KCNQ1<\/jats:italic><jats:sub>rs2237892T<\/jats:sub> allele or the <jats:italic>CDKN2A-2B<\/jats:italic><jats:sub>rs2383208G\/G<\/jats:sub>, <jats:italic>IGF1<\/jats:italic><jats:sub>rs35767T\/T<\/jats:sub> and <jats:italic>MADD<\/jats:italic><jats:sub>rs7944584T\/T<\/jats:sub> genotypes had a significantly increased risk of MM (odds ratio (OR)=1.32\u20132.13) whereas those carrying the <jats:italic>KCNJ11<\/jats:italic><jats:sub>rs5215C<\/jats:sub>, <jats:italic>KCNJ11<\/jats:italic><jats:sub>rs5219T<\/jats:sub> and <jats:italic>THADA<\/jats:italic><jats:sub>rs7578597C<\/jats:sub> alleles or the <jats:italic>FTO<\/jats:italic><jats:sub>rs8050136A\/A<\/jats:sub> and <jats:italic>LTA<\/jats:italic><jats:sub>rs1041981C\/C<\/jats:sub> genotypes showed a significantly decreased risk of developing the disease (OR=0.76\u20130.85). Interestingly, a prediction model including those T2D-related variants associated with the risk of MM showed a significantly improved discriminatory ability to predict the disease when compared to a model without genetic information (area under the curve (AUC)=0.645 vs AUC=0.629; <jats:italic>P<\/jats:italic>=4.05\u00d710<jats:sup>\u2212<\/jats:sup><jats:sup>06<\/jats:sup>). A gender-stratified analysis also revealed a significant gender effect modification for <jats:italic>ADAM30<\/jats:italic><jats:sub>rs2641348<\/jats:sub> and <jats:italic>NOTCH2<\/jats:italic><jats:sub>rs10923931<\/jats:sub> variants (<jats:italic>P<\/jats:italic><jats:sub>interaction<\/jats:sub>=0.001 and 0.0004, respectively). Men carrying the <jats:italic>ADAM30<\/jats:italic><jats:sub>rs2641348C<\/jats:sub> and <jats:italic>NOTCH2<\/jats:italic><jats:sub>rs10923931T<\/jats:sub> alleles had a significantly decreased risk of MM whereas an opposite but not significant effect was observed in women (OR<jats:sub>M<\/jats:sub>=0.71 and OR<jats:sub>M<\/jats:sub>=0.66 vs OR<jats:sub>W<\/jats:sub>=1.22 and OR<jats:sub>W<\/jats:sub>=1.15, respectively). These results suggest that TD2-related variants may influence the risk of developing MM and their genotyping might help to improve MM risk prediction models.<\/jats:p>","DOI":"10.1530\/erc-15-0029","type":"journal-article","created":{"date-parts":[[2015,6,23]],"date-time":"2015-06-23T01:05:08Z","timestamp":1435021508000},"page":"545-559","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-1","source":"Crossref","is-referenced-by-count":14,"title":["Type 2 diabetes-related variants influence the risk of developing multiple myeloma: results from the IMMEnSE consortium"],"prefix":"10.1530","volume":"22","author":[{"given":"Rafael","family":"R\u00edos","sequence":"first","affiliation":[]},{"given":"Carmen Bel\u00e9n","family":"Lupia\u00f1ez","sequence":"additional","affiliation":[]},{"given":"Daniele","family":"Campa","sequence":"additional","affiliation":[]},{"given":"Alessandro","family":"Martino","sequence":"additional","affiliation":[]},{"given":"Joaquin","family":"Mart\u00ednez-L\u00f3pez","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Mart\u00ednez-Bueno","sequence":"additional","affiliation":[]},{"given":"Judit","family":"Varkonyi","sequence":"additional","affiliation":[]},{"given":"Ram\u00f3n","family":"Garc\u00eda-Sanz","sequence":"additional","affiliation":[]},{"given":"Krzysztof","family":"Jamroziak","sequence":"additional","affiliation":[]},{"given":"Charles","family":"Dumontet","sequence":"additional","affiliation":[]},{"given":"Andr\u00e9s Jerez","family":"Cayuela","sequence":"additional","affiliation":[]},{"given":"Marzena","family":"W\u0119tek","sequence":"additional","affiliation":[]},{"given":"Stephano","family":"Landi","sequence":"additional","affiliation":[]},{"given":"Anna Maria","family":"Rossi","sequence":"additional","affiliation":[]},{"given":"Fabienne","family":"Lesueur","sequence":"additional","affiliation":[]},{"given":"Rui Manuel","family":"Reis","sequence":"additional","affiliation":[]},{"given":"Victor","family":"Moreno","sequence":"additional","affiliation":[]},{"given":"Herlander","family":"Marques","sequence":"additional","affiliation":[]},{"given":"Artur","family":"Jurczyszyn","sequence":"additional","affiliation":[]},{"given":"Vibeke","family":"Andersen","sequence":"additional","affiliation":[]},{"given":"Ulla","family":"Vogel","sequence":"additional","affiliation":[]},{"given":"Gabriele","family":"Buda","sequence":"additional","affiliation":[]},{"given":"Enrico","family":"Orciuolo","sequence":"additional","affiliation":[]},{"given":"Svend E H","family":"Jacobsen","sequence":"additional","affiliation":[]},{"given":"Mario","family":"Petrini","sequence":"additional","affiliation":[]},{"given":"Annette J","family":"Vangsted","sequence":"additional","affiliation":[]},{"given":"Federica","family":"Gemignani","sequence":"additional","affiliation":[]},{"given":"Federico","family":"Canzian","sequence":"additional","affiliation":[]},{"given":"Manuel","family":"Jurado","sequence":"additional","affiliation":[]},{"given":"Juan","family":"Sainz","sequence":"additional","affiliation":[]}],"member":"416","reference":[{"key":"2015071018562140000_22.4.545.1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.22718"},{"key":"2015071018562140000_22.4.545.2","doi-asserted-by":"publisher","DOI":"10.1038\/79216"},{"key":"2015071018562140000_22.4.545.3","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.22921"},{"key":"2015071018562140000_22.4.545.4","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2005.12.026"},{"key":"2015071018562140000_22.4.545.5","doi-asserted-by":"publisher","DOI":"10.1126\/science.1156849"},{"key":"2015071018562140000_22.4.545.6","doi-asserted-by":"publisher","DOI":"10.1038\/ng.277"},{"key":"2015071018562140000_22.4.545.7","doi-asserted-by":"publisher","DOI":"10.1046\/j.1440-1711.1999.00822.x"},{"key":"2015071018562140000_22.4.545.8","doi-asserted-by":"crossref","unstructured":"Cander S Karkucak M Gul OO Sag SO Yakut T Ersoy C Tuncel E Erturk E 2014 Association between p16(CDKN2A) C540G polymorphism and tumor behavior in prolactinoma: a single-center study. 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