Is RNASEL:p.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?
Is RNASEL:p.Glu265* a modifier of early-onset breast cancer risk for carriers of high-risk mutations?
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DOI：
10.1186/s12885-018-4028-z
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发表时间：
2018-02-08
期刊：
影响因子：
3.8
通讯作者：
Southey MC
中科院分区：
文献类型：
--
作者：
Nguyen-Dumont T;Teo ZL;Hammet F;Roberge A;Mahmoodi M;Tsimiklis H;Park DJ;Pope BJ;Lonie A;Kapuscinski MK;Mahmood K;ABCFR;Goldgar DE;Giles GG;Winship I;Hopper JL;Southey MC
BRCA1和BRCA2致病突变携带者的乳腺癌风险受到家族聚集的风险因素的影响，包括风险的遗传修饰因子。我们考虑了其他乳腺癌易感基因中高危突变携带者的遗传修饰因子。在已知携带高危突变PALB2:c的家族中。对4名受影响妇女的种系DNA进行了全外显子组测序，其中3名是突变携带者。RNASEL: p。Glu265*在一名50岁前两次原发浸润性乳腺癌的PALB2携带者中被发现。澳大利亚乳腺癌家族登记处的BRCA1、BRCA2、PALB2和RNASEL基因面板检测确定了5个RNASEL携带者：p。591例早发性乳腺癌患者中存在gl265 *。5名携带RNASEL的女性中有3名（60%）。与586名RNASEL非携带者中的30名致病突变携带者相比，Glu265*还携带了一个乳腺癌易感基因的致病突变：p。gl265 * (5%) （p < 0.002）。Taqman基因分型表明RNASEL的等位基因频率为：p。Glu265*在受影响和未受影响的澳大利亚女性中相似，与其他人群一致。我们的研究表明RNASEL:p。Glu265*可能是高危突变携带者早发性乳腺癌易感性的基因修饰因子。需要更大规模的病例和病例对照研究来检验本报告中观察到的关联。
Breast cancer risk for BRCA1 and BRCA2 pathogenic mutation carriers is modified by risk factors that cluster in families, including genetic modifiers of risk. We considered genetic modifiers of risk for carriers of high-risk mutations in other breast cancer susceptibility genes. In a family known to carry the high-risk mutation PALB2:c.3113G>A (p.Trp1038*), whole-exome sequencing was performed on germline DNA from four affected women, three of whom were mutation carriers. RNASEL:p.Glu265* was identified in one of the PALB2 carriers who had two primary invasive breast cancer diagnoses before 50 years. Gene-panel testing of BRCA1, BRCA2, PALB2 and RNASEL in the Australian Breast Cancer Family Registry identified five carriers of RNASEL:p.Glu265* in 591 early onset breast cancer cases. Three of the five women (60%) carrying RNASEL:p.Glu265* also carried a pathogenic mutation in a breast cancer susceptibility gene compared with 30 carriers of pathogenic mutations in the 586 non-carriers of RNASEL:p.Glu265* (5%) (p < 0.002). Taqman genotyping demonstrated that the allele frequency of RNASEL:p.Glu265* was similar in affected and unaffected Australian women, consistent with other populations. Our study suggests that RNASEL:p.Glu265* may be a genetic modifier of risk for early-onset breast cancer predisposition in carriers of high-risk mutations. Much larger case-case and case-control studies are warranted to test the association observed in this report.
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影响因子：
11.2
作者：
Malathi, K;Paranjape, JM;Silverman, RH
通讯作者：
Silverman, RH
影响因子：
11.4
作者：
Zhou, AM;Paranjape, J;Silverman, RH
通讯作者：
Silverman, RH
影响因子：
4
作者：
Southey MC;Goldgar DE;Winqvist R;Pylkäs K;Couch F;Tischkowitz M;Foulkes WD;Dennis J;Michailidou K;van Rensburg EJ;Heikkinen T;Nevanlinna H;Hopper JL;Dörk T;Claes KB;Reis-Filho J;Teo ZL;Radice P;Catucci I;Peterlongo P;Tsimiklis H;Odefrey FA;Dowty JG;Schmidt MK;Broeks A;Hogervorst FB;Verhoef S;Carpenter J;Clarke C;Scott RJ;Fasching PA;Haeberle L;Ekici AB;Beckmann MW;Peto J;Dos-Santos-Silva I;Fletcher O;Johnson N;Bolla MK;Sawyer EJ;Tomlinson I;Kerin MJ;Miller N;Marme F;Burwinkel B;Yang R;Guénel P;Truong T;Menegaux F;Sanchez M;Bojesen S;Nielsen SF;Flyger H;Benitez J;Zamora MP;Perez JI;Menéndez P;Anton-Culver H;Neuhausen S;Ziogas A;Clarke CA;Brenner H;Arndt V;Stegmaier C;Brauch H;Brüning T;Ko YD;Muranen TA;Aittomäki K;Blomqvist C;Bogdanova NV;Antonenkova NN;Lindblom A;Margolin S;Mannermaa A;Kataja V;Kosma VM;Hartikainen JM;Spurdle AB;Investigators K;Australian Ovarian Cancer Study Group;Wauters E;Smeets D;Beuselinck B;Floris G;Chang-Claude J;Rudolph A;Seibold P;Flesch-Janys D;Olson JE;Vachon C;Pankratz VS;McLean C;Haiman CA;Henderson BE;Schumacher F;Le Marchand L;Kristensen V;Alnæs GG;Zheng W;Hunter DJ;Lindstrom S;Hankinson SE;Kraft P;Andrulis I;Knight JA;Glendon G;Mulligan AM;Jukkola-Vuorinen A;Grip M;Kauppila S;Devilee P;Tollenaar RA;Seynaeve C;Hollestelle A;Garcia-Closas M;Figueroa J;Chanock SJ;Lissowska J;Czene K;Darabi H;Eriksson M;Eccles DM;Rafiq S;Tapper WJ;Gerty SM;Hooning MJ;Martens JW;Collée JM;Tilanus-Linthorst M;Hall P;Li J;Brand JS;Humphreys K;Cox A;Reed MW;Luccarini C;Baynes C;Dunning AM;Hamann U;Torres D;Ulmer HU;Rüdiger T;Jakubowska A;Lubinski J;Jaworska K;Durda K;Slager S;Toland AE;Ambrosone CB;Yannoukakos D;Swerdlow A;Ashworth A;Orr N;Jones M;González-Neira A;Pita G;Alonso MR;Álvarez N;Herrero D;Tessier DC;Vincent D;Bacot F;Simard J;Dumont M;Soucy P;Eeles R;Muir K;Wiklund F;Gronberg H;Schleutker J;Nordestgaard BG;Weischer M;Travis RC;Neal D;Donovan JL;Hamdy FC;Khaw KT;Stanford JL;Blot WJ;Thibodeau S;Schaid DJ;Kelley JL;Maier C;Kibel AS;Cybulski C;Cannon-Albright L;Butterbach K;Park J;Kaneva R;Batra J;Teixeira MR;Kote-Jarai Z;Olama AA;Benlloch S;Renner SP;Hartmann A;Hein A;Ruebner M;Lambrechts D;Van Nieuwenhuysen E;Vergote I;Lambretchs S;Doherty JA;Rossing MA;Nickels S;Eilber U;Wang-Gohrke S;Odunsi K;Sucheston-Campbell LE;Friel G;Lurie G;Killeen JL;Wilkens LR;Goodman MT;Runnebaum I;Hillemanns PA;Pelttari LM;Butzow R;Modugno F;Edwards RP;Ness RB;Moysich KB;du Bois A;Heitz F;Harter P;Kommoss S;Karlan BY;Walsh C;Lester J;Jensen A;Kjaer SK;Høgdall E;Peissel B;Bonanni B;Bernard L;Goode EL;Fridley BL;Vierkant RA;Cunningham JM;Larson MC;Fogarty ZC;Kalli KR;Liang D;Lu KH;Hildebrandt MA;Wu X;Levine DA;Dao F;Bisogna M;Berchuck A;Iversen ES;Marks JR;Akushevich L;Cramer DW;Schildkraut J;Terry KL;Poole EM;Stampfer M;Tworoger SS;Bandera EV;Orlow I;Olson SH;Bjorge L;Salvesen HB;van Altena AM;Aben KK;Kiemeney LA;Massuger LF;Pejovic T;Bean Y;Brooks-Wilson A;Kelemen LE;Cook LS;Le ND;Górski B;Gronwald J;Menkiszak J;Høgdall CK;Lundvall L;Nedergaard L;Engelholm SA;Dicks E;Tyrer J;Campbell I;McNeish I;Paul J;Siddiqui N;Glasspool R;Whittemore AS;Rothstein JH;McGuire V;Sieh W;Cai H;Shu XO;Teten RT;Sutphen R;McLaughlin JR;Narod SA;Phelan CM;Monteiro AN;Fenstermacher D;Lin HY;Permuth JB;Sellers TA;Chen YA;Tsai YY;Chen Z;Gentry-Maharaj A;Gayther SA;Ramus SJ;Menon U;Wu AH;Pearce CL;Van Den Berg D;Pike MC;Dansonka-Mieszkowska A;Plisiecka-Halasa J;Moes-Sosnowska J;Kupryjanczyk J;Pharoah PD;Song H;Winship I;Chenevix-Trench G;Giles GG;Tavtigian SV;Easton DF;Milne RL
通讯作者：
Milne RL
影响因子：
51.1
作者：
Krüger, S;Silber, AS;Schackert, HK
通讯作者：
Schackert, HK
影响因子：
9.8
作者：
Park, D. J.;Lesueur, F.;Southey, M. C.
通讯作者：
Southey, M. C.