Journal of Carcinogenesis | Abstract | Polymorphisms = of the BRAFgene predispose males to malignant melanoma

From: Subject: Journal of Carcinogenesis | Abstract | Polymorphisms of the BRAFgene predispose males to malignant melanoma Date: Thu, 18 Mar 2004 14:49:15 -0500 MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_000_0022_01C40CF8.2F265300"; type="text/html" X-MimeOLE: Produced By Microsoft MimeOLE V6.00.2800.1165 This is a multi-part message in MIME format. ------=_NextPart_000_0022_01C40CF8.2F265300 Content-Type: text/html; charset="utf-8" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.carcinogenesis.com/content/2/1/7/abstract =EF=BB=BF Journal of Carcinogenesis | Abstract | Polymorphisms = of the BRAFgene predispose males to malignant melanoma

18-Mar-2004

Journal of=20 Carcinogenesis
Vol= ume=20 2

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Meyer=20 P
Sergi=20 C
Garbe=20 C

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Short=20 paper

Polymorphisms of the BRAF gene predispose males to = malignant=20 melanoma
Peter=20 Meyer¹^{, 2}^{, 3} , Consolato Sergi⁴ and Claus Garbe¹
¹Department of Dermatology, University = Hospital of=20 Tuebingen, Tuebingen, Germany
²Institute of Human = Genetics,=20 University Hospital of Tuebingen, Tuebingen,=20 Germany
³Genefinder Technologies Ltd., Munich,=20 Germany
⁴Directorate of Laboratory Medicine, Bristol = Royal=20 Infirmary, Bristol, United Kingdom

Journal of = Carcinogenesis=20 2003, 2:7 (published=20 14 November 2003)

Abstract

The incidence of malignant melanoma has rapidly = increased=20 in recent years. Evidence points to the role of inheritance in = melanoma=20 development, but specific genetic risk factors are not well = understood.=20 Recent reports indicate a high prevalence of somatic mutations of = the=20 BRAF gene in melanomas and melanocytic nevi. Here we report = that=20 germ-line single nucleotide polymorphisms (SNPs) in BRAF = are=20 significantly associated with melanoma in German males, but not = females.=20 At-risk haplotypes of BRAF are shown. Based upon their = frequencies,=20 we estimate that BRAF could account for a proportion = attributable=20 risk of developing melanoma of 4% in the German population. The = causal=20 variant has yet to be determined. The burden of disease associated = with=20 this variant is greater than that associated with the major = melanoma=20 susceptibility locus CDKN2A, which has an estimated = attributable=20 risk of less than 1%.

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=C2=A9 1999-2004 BioMed Central Ltd = unless otherwise=20 stated < info@biomedcentral.com=20 > Terms and=20 conditions

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__utmsrc +=3D "utmn=3D"+__utmu; if (__utmfsc && __utmfns) {__utmsrc +=3D __utmGetClientInfo(); } if (__utmctm) {__utmsrc +=3D __utmSetCampaignInfo(); } __utmsrc +=3D "&utmr=3D"+__utmr+"&utmp=3D"+loc.pathname+loc.search; __utmi.src =3D __utmsrc; return 0; } function __utmSetCampaignInfo() { var __utmcc =3D ""; var __utmtmp =3D "-"; var __utmnoover =3D 0; var __utmcsc =3D 0; var __utmcnc =3D 0; var __utmi =3D 0; if (!__utmcto || __utmcto =3D=3D "") { __utmcto =3D "15768000"; } var __utmcx =3D new Date(__utmd.getTime()+(__utmcto*1000)); __utmcx =3D " expires=3D"+__utmcx.toGMTString()+";"; var __utmx =3D document.location.search; var __utmz =3D __utmGetCookie(__utmx,"__utmz=3D","&"); if (__utmz !=3D "-") { document.cookie=3D"__utmz=3D"+__utmz+"; = path=3D/;"+__utmcx+__utmdom; return ""; } __utmz =3D document.cookie.indexOf("__utmz=3D"+__utmdh); if (__utmz > -1) { __utmz =3D __utmGetCookie(document.cookie,"__utmz=3D",";"); } else { __utmz =3D "-"; } /*--- check for campaign source info (required field) ---*/ __utmtmp =3D __utmGetCookie(__utmx,__utmcsr+"=3D","&"); if (__utmtmp !=3D "-" && __utmtmp !=3D "") {=20 __utmcc +=3D "utmcsr=3D"+__utmtmp; __utmtmp =3D __utmGetCookie(__utmx,__utmccn+"=3D","&");=20 if (__utmtmp !=3D "-" && __utmtmp !=3D "") __utmcc +=3D = "|utmccn=3D"+__utmtmp;=20 else __utmcc +=3D = "|utmccn=3D(not set)"; __utmtmp =3D __utmGetCookie(__utmx,__utmcmd+"=3D","&");=20 if (__utmtmp !=3D "-" && __utmtmp !=3D "") __utmcc +=3D = "|utmcmd=3D"+__utmtmp; else __utmcc +=3D = "|utmcmd=3D(not set)"; __utmtmp =3D __utmGetCookie(__utmx,__utmctr+"=3D","&");=20 if (__utmtmp !=3D "-" && __utmtmp !=3D "") __utmcc +=3D = "|utmctr=3D"+__utmtmp; __utmtmp =3D __utmGetCookie(__utmx,__utmcct+"=3D","&");=20 if (__utmtmp !=3D "-" && __utmtmp !=3D "") __utmcc +=3D = "|utmcct=3D"+__utmtmp; __utmtmp =3D __utmGetCookie(__utmx,__utmcno+"=3D","&");=20 if (__utmtmp =3D=3D "1") __utmnoover =3D 1; /*--- if previous campaign is set and no override is set return = ---*/ if (__utmz !=3D "-" && __utmnoover =3D=3D 1) return ""; } /*--- check for organic ---*/ if (__utmcc =3D=3D "-" || __utmcc =3D=3D "") { __utmcc =3D __utmGetOrganic();=20 /*--- if previous campaign is set and organic no override term is = found return ---*/ if (__utmz !=3D "-" && __utmcfno =3D=3D 1) return ""; } /*--- check for referral ---*/ if (__utmcc =3D=3D "-" || __utmcc =3D=3D "") { if (__utmfns =3D=3D 1) __utmcc =3D __utmGetReferral();=20 /*--- if previous campaign is set and referral no override term = is found return ---*/ if (__utmz !=3D "-" && __utmcfno =3D=3D 1) return ""; } /*--- set default if z is not yet set ---*/ if (__utmcc =3D=3D "-" || __utmcc =3D=3D "") { if (__utmz =3D=3D "-" && __utmfns =3D=3D 1) { __utmcc =3D = "utmccn=3D(direct)|utmcsr=3D(direct)|utmcmd=3D(none)"; } if (__utmcc =3D=3D "-" || __utmcc =3D=3D "") return ""; } /*--- check if campaign is already set and if it's the same ---*/ if (__utmz !=3D "-") {=20 __utmi =3D __utmz.indexOf("."); if (__utmi > -1) __utmi =3D __utmz.indexOf(".",__utmi+1); if (__utmi > -1) __utmi =3D __utmz.indexOf(".",__utmi+1); if (__utmi > -1) __utmi =3D __utmz.indexOf(".",__utmi+1); __utmtmp =3D __utmz.substring(__utmi + 1,__utmz.length); if (__utmtmp.toLowerCase() =3D=3D __utmcc.toLowerCase()) __utmcsc = =3D 1;=20 __utmtmp =3D __utmz.substring(0,__utmi); if ((__utmi =3D __utmtmp.lastIndexOf(".")) > -1) { __utmtmp =3D __utmtmp.substring(__utmi+1,__utmtmp.length); __utmcnc =3D (__utmtmp*1); } } /*--- set the cookie ---*/ if (__utmcsc =3D=3D 0 || __utmfns =3D=3D 1) { __utmtmp =3D __utmGetCookie(document.cookie,"__utma=3D",";"); if ((__utmi=3D__utmtmp.lastIndexOf(".")) > 9) { __utmns =3D __utmtmp.substring(__utmi+1,__utmtmp.length); __utmns =3D (__utmns*1); } __utmcnc++; if (__utmns =3D=3D 0) __utmns =3D 1; = document.cookie=3D"__utmz=3D"+__utmdh+"."+__utmst+"."+__utmns+"."+__utmcn= c+"."+__utmcc+"; path=3D/; "+__utmcx+__utmdom; } /*--- set the new campaign flag ---*/ if (__utmcsc =3D=3D 0 || __utmfns =3D=3D 1) return "&utmcn=3D1"; else return "&utmcr=3D1"; } function __utmGetReferral() { if (__utmr =3D=3D "0" || __utmr =3D=3D "" || __utmr =3D=3D "-") = return "";=20 var __utmi=3D0; var __utmhn; var __utmkt; /*-- get the hostname of the referral --*/ if ( (__utmi =3D __utmr.indexOf("://")) < 0) return ""; __utmhn =3D __utmr.substring(__utmi+3,__utmr.length); if (__utmhn.indexOf("/") > -1) { __utmkt =3D = __utmhn.substring(__utmhn.indexOf("/"),__utmhn.length); if (__utmkt.indexOf("?") > -1) { __utmkt =3D __utmkt.substring(0,__utmkt.indexOf("?")); } __utmhn =3D __utmhn.substring(0,__utmhn.indexOf("/")); } __utmhn =3D __utmhn.toLowerCase(); for (var ii=3D0;ii<__utmRno.length;ii++) { if (( __utmi=3D__utmhn.indexOf(__utmRno[ii].toLowerCase())) > -1 = && __utmhn.length =3D=3D (__utmi+__utmRno[ii].length)) { __utmcfno =3D = 1; break; } } if (__utmhn.indexOf("www.") =3D=3D 0) { __utmhn =3D __utmhn.substring(4,__utmhn.length); } return = "utmccn=3D(referral)|utmcsr=3D"+__utmhn+"|"+"utmcct=3D"+__utmkt+"|utmcmd=3D= referral"; } function __utmGetOrganic() { if (__utmr =3D=3D "0" || __utmr =3D=3D "" || __utmr =3D=3D "-") = return "";=20 var __utmi=3D0; var __utmhn; var __utmkt; /*-- get the hostname of the referral --*/ if ( (__utmi =3D __utmr.indexOf("://")) < 0) return ""; __utmhn =3D __utmr.substring(__utmi+3,__utmr.length); if (__utmhn.indexOf("/") > -1) { __utmhn =3D __utmhn.substring(0,__utmhn.indexOf("/")); } for (var ii=3D0;ii<__utmOsr.length;ii++) { if (__utmhn.indexOf(__utmOsr[ii]) > -1) { if ( (__utmi =3D __utmr.indexOf("?"+__utmOkw[ii]+"=3D")) > -1 = ||=20 (__utmi =3D __utmr.indexOf("&"+__utmOkw[ii]+"=3D")) > -1) = { __utmkt =3D = __utmr.substring(__utmi+__utmOkw[ii].length+2,__utmr.length); if ( (__utmi =3D __utmkt.indexOf("&")) > -1) { __utmkt =3D __utmkt.substring(0,__utmi); } for (var yy=3D0;yy<__utmOno.length;yy++) { if (__utmOno[yy].toLowerCase() =3D=3D = __utmkt.toLowerCase()) { __utmcfno =3D 1; break; } } return = "utmccn=3D(organic)|utmcsr=3D"+__utmOsr[ii]+"|"+"utmctr=3D"+__utmkt+"|utm= cmd=3Dorganic"; } } } return ""; } function __utmGetClientInfo() { var = __utmtmp=3D"-",__utmsr=3D"-",__utmsa=3D"-",__utmsc=3D"-",__utmbs=3D"-",__= utmul=3D"-"; var __utmje=3D1,__utmce=3D1,__utmtz=3D0; if (self.screen) {=20 __utmsr =3D screen.width+"x"+screen.height; __utmsa =3D screen.availWidth+"x"+screen.availHeight; __utmsc =3D screen.colorDepth+"-bit"; } else if (self.java) { var __utmjk =3D java.awt.Toolkit.getDefaultToolkit(); var __utmjksize =3D __utmjk.getScreenSize(); =20 __utmsr =3D __utmjksize.width+"x"+__utmjksize.height; }=20 if( typeof( window.innerWidth ) =3D=3D 'number' ) { __utmbs =3D window.innerWidth+"x"+window.innerHeight; } else {=20 if (document.documentElement &&=20 (document.documentElement.offsetHeight || = document.documentElement.offsetWidth ) ) { __utmbs =3D = document.documentElement.offsetWidth+"x"+document.documentElement.offsetH= eight; } else if (document.body && (document.body.offsetWidth || = document.body.offsetHeight) ) { __utmbs =3D = document.body.offsetWidth+"x"+document.body.offsetHeight; }=20 } for (var i=3D5;i>=3D0;i--) { var __utmtmp =3D "";=20 document.write(__utmtmp); if (__utmjv !=3D "-") break; } if (navigator.language) { __utmul =3D = navigator.language.toLowerCase(); } else if (navigator.browserLanguage) { __utmul =3D = navigator.browserLanguage.toLowerCase(); } __utmje =3D navigator.javaEnabled()?1:0; if (document.cookie.indexOf("__utmb=3D") < 0) { __utmce =3D "0"; } if (document.cookie.indexOf("__utmc=3D") < 0) { __utmce =3D "0"; } __utmtz =3D __utmd.getTimezoneOffset(); __utmtz =3D __utmTZConvert(__utmtz); __utmtmp =3D""; __utmtmp +=3D = "&utmsr=3D"+__utmsr+"&utmsa=3D"+__utmsa+"&utmsc=3D"+__utmsc+"&utmbs=3D"+_= _utmbs; __utmtmp +=3D = "&utmul=3D"+__utmul+"&utmje=3D"+__utmje+"&utmce=3D"+__utmce+"&utmtz=3D"+_= _utmtz+"&utmjv=3D"+__utmjv; return __utmtmp; } function __utmLinker(__utmlink) { var = __utmlp,__utmi,__utmi2,__utmta=3D"-",__utmtb=3D"-",__utmtc=3D"-",__utmtz=3D= "-"; if (__utmlink && __utmlink !=3D "") {=20 if (document.cookie) { __utmta =3D = __utmGetCookie(document.cookie,"__utma=3D"+__utmdh,";"); __utmtb =3D = __utmGetCookie(document.cookie,"__utmb=3D"+__utmdh,";"); __utmtc =3D = __utmGetCookie(document.cookie,"__utmc=3D"+__utmdh,";"); __utmtz =3D = __utmGetCookie(document.cookie,"__utmz=3D"+__utmdh,";"); __utmlp =3D = "__utma=3D"+__utmta+"&__utmb=3D"+__utmtb+"&__utmc=3D"+__utmtc+"&__utmz=3D= "+__utmtz; } if (__utmlp) { if (__utmlink.indexOf("?") <=3D -1) { document.location =3D = __utmlink+"?"+__utmlp; } else { document.location =3D __utmlink+"&"+__utmlp; } } else { document.location =3D __utmlink; } } } function __utmGetCookie(__utmclist,__utmcname,__utmcsep) { if (!__utmclist || __utmclist =3D=3D "") return "-"; if (!__utmcname || __utmcname =3D=3D "") return "-"; if (!__utmcsep || __utmcsep =3D=3D "") return "-"; var __utmi, __utmi2, __utmi3, __utmtc=3D"-"; __utmi =3D __utmclist.indexOf(__utmcname); __utmi3 =3D __utmcname.indexOf("=3D")+1; if (__utmi > -1) {=20 __utmi2 =3D __utmclist.indexOf(__utmcsep,__utmi); if (__utmi2 < 0) = { __utmi2 =3D __utmclist.length; } __utmtc =3D __utmclist.substring((__utmi+__utmi3),__utmi2);=20 } return __utmtc; } function __utmSetDomain() { if (!__utmdn || __utmdn =3D=3D "" || __utmdn =3D=3D "none") { __utmdn = =3D ""; return 1; } if (__utmdn =3D=3D "auto") { var __utmdomain =3D document.domain; if (__utmdomain.substring(0,4) =3D=3D "www.") { __utmdomain =3D __utmdomain.substring(4,__utmdomain.length); } __utmdn =3D __utmdomain; } if (__utmhash =3D=3D "off") return 1; return __utmHash(__utmdn); } function __utmHash(__utmd) { if (!__utmd || __utmd =3D=3D "") return 1; var __utmhash=3D0, __utmg=3D0; for (var i=3D__utmd.length-1;i>=3D0;i--) { var __utmc =3D parseInt(__utmd.charCodeAt(i));=20 __utmhash =3D ((__utmhash << 6) & 0xfffffff) + __utmc + (__utmc << = 14); if ((__utmg =3D __utmhash & 0xfe00000) !=3D 0) __utmhash =3D = (__utmhash ^ (__utmg >> 21)); } return __utmhash; } function __utmFixA(__utmcs,__utmsp, __utmst) { if (!__utmcs || __utmcs =3D=3D "") return "-"; if (!__utmsp || __utmsp =3D=3D "") return "-"; if (!__utmst || __utmst =3D=3D "") return "-"; var __utmt =3D __utmGetCookie(__utmcs,"__utma=3D",__utmsp); var __utmlt=3D0; var __utmi=3D0; if ((__utmi=3D__utmt.lastIndexOf(".")) > 9) { __utmns =3D __utmt.substring(__utmi+1,__utmt.length); __utmns =3D (__utmns*1)+1; __utmt =3D __utmt.substring(0,(__utmi)); if ((__utmi =3D __utmt.lastIndexOf(".")) > 7) { __utmlt =3D __utmt.substring(__utmi+1,__utmt.length); __utmt =3D __utmt.substring(0,(__utmi)); } if ((__utmi =3D __utmt.lastIndexOf(".")) > 5) { __utmt =3D __utmt.substring(0,(__utmi)); } __utmt +=3D "."+__utmlt+"."+__utmst+"."+__utmns; } return __utmt; } function __utmCheckUTMI(__utmd) { var __utm1A =3D new Array(); var = __utmlst=3D0,__utmpst=3D0,__utmlvt=3D0,__utmlu=3D0,__utmi=3D0,__utmpi=3D0= ; var __utmap =3D "-"; var __utmld =3D ""; var __utmt2; var __utmt =3D document.cookie; while((__utmi =3D __utmt.indexOf("__utm1=3D")) >=3D 0) { __utm1A[__utm1A.length] =3D = __utmGetCookie(__utmt,"__utm1=3D",";"); __utmt =3D __utmt.substring(__utmi+7,__utmt.length); } if (__utm1A.length) { var __utmcts =3D Math.round(__utmd.getTime()/1000); var __utmlex =3D " expires=3D"+__utmd.toGMTString()+";"; __utmt =3D document.cookie;=20 if ((__utmi =3D __utmt.lastIndexOf("__utm3=3D")) >=3D 0) { __utmlst =3D __utmt.substring(__utmi,__utmt.length); __utmlst =3D __utmGetCookie(__utmlst,"__utm3=3D",";"); } if ((__utmi =3D __utmt.lastIndexOf("__utm2=3D")) >=3D 0) { __utmpst =3D __utmt.substring(__utmi,__utmt.length); __utmpst =3D __utmGetCookie(__utmpst,"__utm2=3D",";"); } for (var i=3D0;i<__utm1A.length;i++) { __utmt =3D __utm1A[i]; if ((__utmi =3D __utmt.lastIndexOf(".")) >=3D 0) { __utmt2 =3D (__utmt.substring(0,__utmi))*1; __utmt =3D (__utmt.substring(__utmi+1,__utmt.length))*1; if (__utmlvt =3D=3D 0 || __utmt < __utmlvt) {=20 __utmlvt =3D __utmt; __utmlu =3D __utmt2; } } } if (__utmlvt && __utmlst) {=20 if (!__utmpst || __utmpst > __utmlst) __utmpst =3D __utmlst; __utmap =3D = __utmlu+"."+__utmlvt+"."+__utmpst+"."+__utmlst+".2";=20 } else if (__utmlvt) {=20 if (!__utmpst || __utmpst > __utmcts) __utmpst =3D __utmcts; __utmap =3D = __utmlu+"."+__utmlvt+"."+__utmpst+"."+__utmcts+".2"; } __utmld =3D __utmt =3D document.domain; __utmi=3D__utmpi=3D0; while((__utmi =3D __utmt.indexOf(".",__utmpi+1)) >=3D 0) { if (__utmpi>0) __utmld =3D = __utmt.substring(__utmpi+1,__utmt.length); __utmld =3D " domain=3D"+__utmld+";";=20 document.cookie=3D"__utm1=3D1; path=3D/;"+__utmlex+__utmld; document.cookie=3D"__utm2=3D1; path=3D/;"+__utmlex+__utmld; document.cookie=3D"__utm3=3D1; path=3D/;"+__utmlex+__utmld; __utmpi=3D__utmi; } document.cookie=3D"__utm1=3D1; path=3D/;"+__utmlex; document.cookie=3D"__utm2=3D1; path=3D/;"+__utmlex; document.cookie=3D"__utm3=3D1; path=3D/;"+__utmlex; } return __utmap; } function __utmTZConvert(__utmmz) { var __utmhr=3D0,__utmmn=3D0,__utmsg=3D'+'; if (__utmmz && __utmmz !=3D "") { if (__utmmz <=3D 0) {__utmsg=3D'+'; __utmmz*=3D-1; } else {__utmsg=3D'-'; __utmmz*=3D1; } __utmhr =3D Math.floor((__utmmz/60));=20 __utmmn =3D Math.floor((__utmmz%60));=20 } if (__utmhr < 10) __utmhr =3D "0"+__utmhr; if (__utmmn < 10) __utmmn =3D "0"+__utmmn; return __utmsg+__utmhr+__utmmn; } ------=_NextPart_000_0022_01C40CF8.2F265300--