The role of genetic breast cancer susceptibility variants as prognostic factors
HUMAN MOLECULAR GENETICS
Authors: Fasching, Peter A.; Pharoah, Paul D. P.; Cox, Angela; Nevanlinna, Heli; Bojesen, Stig E.; Karn, Thomas; Broeks, Annegien; van Leeuwen, Flora E.; van 't Veer, Laura J.; Udo, Renate; Dunning, Alison M.; Greco, Dario; Aittomaki, Kristiina; Blomqvist, Carl; Shah, Mitul; Nordestgaard, Borge G.; Flyger, Henrik; Hopper, John L.; Southey, Melissa C.; Apicella, Carmel; Garcia-Closas, Montserrat; Sherman, Mark; Lissowska, Jolanta; Seynaeve, Caroline; Huijts, Petra E. A.; Tollenaar, Rob A. E. M.; Ziogas, Argyrios; Ekici, Arif B.; Rauh, Claudia; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Andrulis, Irene L.; Ozcelik, Hilmi; Mulligan, Anna-Marie; Glendon, Gord; Hall, Per; Czene, Kamila; Liu, Jianjun; Chang-Claude, Jenny; Wang-Gohrke, Shan; Eilber, Ursula; Nickels, Stefan; Doerk, Thilo; Schiekel, Maria; Bremer, Michael; Park-Simon, Tjoung-Won; Giles, Graham G.; Severi, Gianluca; Baglietto, Laura; Hooning, Maartje J.; Martens, John W. M.; Jager, Agnes; Kriege, Mieke; Lindblom, Annika; Margolin, Sara; Couch, Fergus J.; Stevens, Kristen N.; Olson, Janet E.; Kosei, Matthew; Cross, Simon S.; Balasubramanian, Sabapathy P.; Reed, Malcolm W. R.; Miron, Alexander; John, Esther M.; Winqvist, Robert; Pylkas, Katri; Jukkola-Vuorinen, Arja; Kauppila, Saila; Burwinkel, Barbara; Marme, Frederik; Schneeweiss, Andreas; Sohn, Christof; Chenevix-Trench, Georgia; Lambrechts, Diether; Dieudonne, Anne-Sophie; Hatse, Sigrid; van Limbergen, Erik; Benitez, Javier; Milne, Roger L.; Pilar Zamora, M.; Arias Perez, Jose Ignacio; Bonanni, Bernardo; Peissel, Bernard; Loris, Bernard; Peterlongo, Paolo; Rajaraman, Preetha; Schonfeld, Sara J.; Anton-Culver, Hoda; Devilee, Peter; Beckmann, Matthias W.; Slamon, Dennis J.; Phillips, Kelly-Anne; Figueroa, Jonine D.; Humphreys, Manjeet K.; Easton, Douglas F.; Schmidt, Marjanka K.
Abstract
Recent genome-wide association studies identified 11 single nucleotide polymorphisms (SNPs) associated with breast cancer (BC) risk. We investigated these and 62 other SNPs for their prognostic relevance. Confirmed BC risk SNPs rs17468277 (CASP8), rs1982073 (TGFB1), rs2981582 (FGFR2), rs13281615 (8q24), rs3817198 (LSP1), rs889312 (MAP3K1), rs3803662 (TOX3), rs13387042 (2q35), rs4973768 (SLC4A7), rs6504950 (COX11) and rs10941679 (5p12) were genotyped for 25 853 BC patients with the available follow-up; 62 other SNPs, which have been suggested as BC risk SNPs by a GWAS or as candidate SNPs from individual studies, were genotyped for replication purposes in subsets of these patients. Cox proportional hazard models were used to test the association of these SNPs with overall survival (OS) and BC-specific survival (BCS). For the confirmed loci, we performed an accessory analysis of publicly available gene expression data and the prognosis in a different patient group. One of the 11 SNPs, rs3803662 (TOX3) and none of the 62 candidate/GWAS SNPs were associated with OS and/or BCS at P0.01. The genotypic-specific survival for rs3803662 suggested a recessive mode of action [hazard ratio (HR) of rare homozygous carriers1.21; 95 CI: 1.091.35, P0.0002 and HR1.29; 95 CI: 1.121.47, P0.0003 for OS and BCS, respectively]. This association was seen similarly in all analyzed tumor subgroups defined by nodal status, tumor size, grade and estrogen receptor. Breast tumor expression of these genes was not associated with prognosis. With the exception of rs3803662 (TOX3), there was no evidence that any of the SNPs associated with BC susceptibility were associated with the BC survival. Survival may be influenced by a distinct set of germline variants from those influencing susceptibility.
Association between the TOX3 rs3803662 C>T polymorphism and recurrent miscarriage in a southern Chinese population
JOURNAL OF CLINICAL LABORATORY ANALYSIS
Authors: Huang, Wendong; Zhou, Huazhong; Li, Qisen; Pi, Lei; Xu, Yufen; Fu, LanYan; Yang, Yanfang; Lu, Zhaoliang; Che, Di; Gu, Xiaoqiong
Abstract
Background Studies have shown that some genetic polymorphisms associated with breast cancer susceptibility may also be associated with abortion. The TOX3 gene plays a key role during the onset of breast cancer, and reproductive factors such as abortion are risk factors for breast cancer. However, there is currently no study describing the relationship between the TOX3 rs3803662 C>T polymorphism and the risk of recurrent miscarriage. Therefore, we investigated whether the TOX3 rs3803662 C>T polymorphism is associated with recurrent miscarriage susceptibility in this case-control study. Methods We recruited 248 recurrent miscarriage patients and 392 healthy controls from the southern Chinese population and performed genotyping using the TaqMan method. Results The results showed no evidence that TOX3 rs3803662 C>T is associated with recurrent miscarriage (CT and CC: corrected OR = 1.038, 95% CI = 0.737-1.461, P = .8321; TT and CC: adjusted OR = 0.989, 95% CI = 0.591-1.656, P = .9659; dominant model: adjusted OR = 1.027, 95% CI = 0.742-1.423, P = .8712; recessive model: adjusted OR = 0.969, 95% CI = 0.600-1.566, P = .8975). Conclusion According to this study, the TOX3 rs3803662 C>T polymorphism may not be associated with recurrent miscarriage in the southern Chinese population. A larger multicenter study is needed to confirm the results.
COA
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