Evaluation of a candidate breast cancer associated SNP in ERCC4 as a risk modifier in BRCA1 and BRCA2 mutation carriers. Results from the Consortium of Investigators of Modifiers of BRCA1/BRCA2 (CIMBA)

Background:In this study we aimed to evaluate the role of a SNP in intron 1 of the ERCC4 gene (rs744154), previously reported to be associated with a reduced risk of breast cancer in the general population, as a breast cancer risk modifier in BRCA1 and BRCA2 mutation carriers.Methods:We have genotyped rs744154 in 9408 BRCA1 and 5632 BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA) and assessed its association with breast cancer risk using a retrospective weighted cohort approach.Results:We found no evidence of association with breast cancer risk for BRCA1 (per-allele HR: 0.98, 95% CI: 0.93–1.04, P=0.5) or BRCA2 (per-allele HR: 0.97, 95% CI: 0.89–1.06, P=0.5) mutation carriers.Conclusion:This SNP is not a significant modifier of breast cancer risk for mutation carriers, though weak associations cannot be ruled out.

G Rennert | N Weerasooriya | K Offit | M Piedmonte | F. Couch | J. Benítez | R. Eeles | J. Hopper | E. John | A. Spurdle | D. Easton | G. Rennert | M. Greene | K. Offit | A. Antoniou | O. Johannsson | S. Buys | D. Evans | G. Chenevix-Trench | H. Nevanlinna | A. Ouweland | R. Milne | U. Hamann | J. Beesley | Xiaoqing Chen | T. Kirchhoff | K. Nathanson | A. Meindl | R. Schmutzler | C. Luccarini | T. Heikkinen | G. Pita | I. Andrulis | P. Radice | P. Peterlongo | S. Manoukian | A. Toland | J. Simard | S. Verhoef | S. Neuhausen | A. V. D. van den Ouweland | D. Yannoukakos | L. McGuffog | A. Godwin | R. Gershoni-baruch | E. Dagan | E. Friedman | E. Imyanitov | F. Révillion | J. Peyrat | A. Osorio | N. Ditsch | S. Domchek | D. Stoppa-Lyonnet | N. Lindor | A. Viel | S. Peock | M. Cook | C. Oliver | D. Frost | O. Sinilnikova | F. Hogervorst | C. Engel | C. Singer | D. Gschwantler-Kaulich | C. Szabo | M. Zikan | K. Claes | O. Johannsson | K. Kosarin | H. Ozçelik | T. Ramón Y Cajal | S. Hodgson | J. Fricker | H. Lynch | P. Schwartz | T. Hansen | A. Gerdes | J. Boggess | F. Lalloo | S. Blank | B. Arver | M. Daly | D. Goldgar | H. Lynch | P. Morrison | B. Kaufman | B. Malmer | M. Thomassen | Y. Ding | Shimrit Cohen | A. Miron | M. Terry | L. Tizzoni | F. Lejbkowicz | P. Morrison | B. Fiebig | H. Jernström | E. John | G. Pichert | J. Brunet | S. Healey | M. Piedmonte | M. Montagna | T. Caldés | M. Caligo | J. Wijnen | J. Cook | F. Douglas | N. Arnold | H. Deissler | D. Niederacher | R. Varon‐Mateeva | G. Rodriguez | G. Pfeiler | Y. Laitman | Y. Ding | P. Mai | M. de la Hoya | M. Barile | M. Hoya | K. Wakeley | D. Muller | S. Giraud | V. Moncoutier | J. Peyrat | L. Barjhoux | J L Hopper | A Osorio | F Lalloo | G Chenevix-Trench | O Barnett-Griness | M A Caligo | U Hamann | D F Easton | H T Lynch | D Stoppa-Lyonnet | A Meindl | J T Wijnen | P Peterlongo | P Radice | D G Evans | A K Godwin | C F Singer | D. Crüger | D Gschwantler-Kaulich | M. S. Askmalm | R. Schmutzler | B. Versmold | P. Mai | J. Basil | C. Casella | P J Morrison | R Gershoni-Baruch | F Révillion | E Friedman | R. Milne | L. Olivier-Faivre | A-M Gerdes | M Thomassen | R Eeles | S Peock | A. Allavena | D. Cruger | Y. Yassin | S L Neuhausen | I L Andrulis | U. Froster | S Verhoef | A van den Ouweland | B Kaufman | F Douglas | A C Antoniou | J Benítez | N Ditsch | P E Schwartz | T Caldes | A Miron | J Simard | S M Domchek | K Claes | M H Greene | A Viel | M Montagna | H Nevanlinna | G C Rodriguez | D Muller | M Daly | K L Nathanson | D Yannoukakos | A B Spurdle | C I Szabo | C Engel | F B L Hogervorst | D Niederacher | S Manoukian | N Arnold | H Jernström | M de la Hoya | L Foretova | R L Milne | G Pita | T Heikkinen | J Beesley | X Chen | S Healey | Y C Ding | F J Couch | X Wang | N Lindor | M Barile | L Tizzoni | M Zikan | P Mai | F Lejbkowicz | H Ozcelik | D G Cruger | Y Laitman | S Cohen | T Kontorovich | E Dagan | M S Askmalm | B Arver | B Malmer | J Brunet | T Ramón y Cajal | EB Gómez García | M Cook | C T Oliver | D Frost | C Luccarini | G Pichert | J Cook | S Hodgson | O M Sinilnikova | L Barjhoux | V Moncoutier | S Giraud | C Cassini | L Olivier-Faivre | J-P Peyrat | J-P Fricker | E M John | S Buys | M B Terry | Y Yassin | D Goldgar | G Pfeiler | A-C Spiess | Thomas v O Hansen | O T Johannsson | T Kirchhoff | K Kosarin | K Wakeley | J F Boggess | J Basil | S V Blank | A E Toland | C Casella | E N Imyanitov | A Allavena | R K Schmutzler | B Versmold | H Deißler | B Fiebig | R Varon-Mateeva | D Schaefer | U G Froster | L McGuffog | F. Couch | O. Barnett‐Griness | X. Chen | T. R. Y. Cajal | D. Goldgar | J. Hopper | S. Cohen | D. Schaefer | N. Weerasooriya | E. G. Garcia | M. Terry | C. Cassini | M. Thomassen | X. Wang | T. Kontorovich | L. Foretova | A-C Spiess | Cinzia Casella | Frans B. L. Hogervorst | Yosuf A. Yassin | Anna Allavena | P. E. Schwartz | Mark H. Greene | Nayana Weerasooriya | Xin Wang | Anne-Marie Gerdes | D. Evans | A. Spiess | E. B. G. Garcíla | H. Deiler | E. Friedman | Clare T. Oliver | O. Barnett-Griness | D. Evans | Patrick J. Morrison | A. Gerdes | Margaret R. Cook | Dieter Schaefer

[1]  M. Beckmann,et al.  Five Polymorphisms and Breast Cancer Risk: Results from the Breast Cancer Association Consortium , 2009, Cancer Epidemiology Biomarkers & Prevention.

[2]  Leif E. Peterson,et al.  Characterization of BRCA1 and BRCA2 mutations in a large United States sample. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[3]  M. Urioste,et al.  The Average Cumulative Risks of Breast and Ovarian Cancer for Carriers of Mutations in BRCA1 and BRCA2 Attending Genetic Counseling Units in Spain , 2008, Clinical Cancer Research.

[4]  K. Yoshimasu,et al.  Genetic polymorphisms in the nucleotide excision repair pathway and lung cancer risk: A meta-analysis , 2007, International journal of medical sciences.

[5]  M. Seller,et al.  Unusual case of Smith-Lemli-Opitz syndrome "type II". , 1995, American journal of medical genetics.

[6]  M. Urioste,et al.  A haplotype containing the p53 polymorphisms Ins16bp and Arg72Pro modifies cancer risk in BRCA2 mutation carriers , 2006, Human mutation.

[7]  Dieter Niederacher,et al.  Common breast cancer-predisposition alleles are associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers. , 2008, American journal of human genetics.

[8]  K. Lange,et al.  Programs for pedigree analysis: Mendel, Fisher, and dGene , 1988, Genetic epidemiology.

[9]  J. Chang-Claude,et al.  A weighted cohort approach for analysing factors modifying disease risks in carriers of high‐risk susceptibility genes , 2005, Genetic epidemiology.

[10]  R. Kittles,et al.  NAT2 and NER genetic variants and sporadic prostate cancer susceptibility in African Americans , 2008, Prostate Cancer and Prostatic Diseases.

[11]  Leah E. Mechanic,et al.  Polymorphisms in nucleotide excision repair genes, smoking and breast cancer in African Americans and whites: a population-based case-control study. , 2006, Carcinogenesis.

[12]  N. Malats,et al.  Genetic Variation in the Nucleotide Excision Repair Pathway and Bladder Cancer Risk , 2006, Cancer Epidemiology Biomarkers & Prevention.

[13]  Lester L. Peters,et al.  Genome-wide association study identifies novel breast cancer susceptibility loci , 2007, Nature.

[14]  D. Easton,et al.  Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. , 1995, American journal of human genetics.

[15]  J. Hopper,et al.  Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case Series unselected for family history: a combined analysis of 22 studies. , 2003, American journal of human genetics.

[16]  Joaquín Dopazo,et al.  ERCC4 associated with breast cancer risk: a two-stage case-control study using high-throughput genotyping. , 2006, Cancer research.

[17]  R. Freimanis,et al.  Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. , 2008, Carcinogenesis.

[18]  E. Guinó,et al.  Polymorphisms in Genes of Nucleotide and Base Excision Repair: Risk and Prognosis of Colorectal Cancer , 2006, Clinical Cancer Research.

[19]  Georgia Chenevix-Trench,et al.  An international initiative to identify genetic modifiers of cancer risk in BRCA1 and BRCA2 mutation carriers: the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) , 2007, Breast Cancer Research.

[20]  J Chang-Claude,et al.  Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. , 1998, American journal of human genetics.