PURPOSE: The p53 R72P polymorphism has been suggested to play a role in many cancers, including breast cancer. Our aim was to evaluate association of R72P with breast cancer risk as well as histopathologic features of the breast tumors and survival. EXPERIMENTAL DESIGN: The germ line R72P genotype was defined among 939 Finnish familial and 888 unselected breast cancer patients and 736 healthy population controls. The clinical and biological variables were tested for association by univariate analysis and the effects of several variables on survival by Cox's proportional hazards regression model. RESULTS: The distribution of the genotypes was similar in all groups studied, suggesting no association with breast cancer risk. Unselected breast cancer patients with 72P homozygous genotype presented significantly more often with lobular carcinoma, whereas R72 allele carriers had a significantly higher frequency of ductal carcinomas (P = 0.004). No significant association with other histopathologic variables, like tumor grade, hormone receptor status (estrogen and progesterone receptors), or tumor-node-metastasis stage, was observed. Survival analysis showed that unselected breast cancer patients with 72P homozygous genotype had significantly poorer survival than patients with other genotypes (P = 0.003). This effect on survival was independent of p53 expression in the tumors and multivariate analysis showed that 72P homozygous genotype was overall an independent prognostic factor (risk ratio of death, 2.1; 95% confidence interval, 1.4-3.3; P = 0.001). CONCLUSIONS: These results suggest no effect of either R72P allele on breast cancer risk but a significantly reduced survival for 72P homozygous breast cancer patients. The finding of codon 72 genotype as an independent prognostic marker for breast cancer warrants further studies.
PURPOSE: The p53R72P polymorphism has been suggested to play a role in many cancers, including breast cancer. Our aim was to evaluate association of R72P with breast cancer risk as well as histopathologic features of the breast tumors and survival. EXPERIMENTAL DESIGN: The germ line R72P genotype was defined among 939 Finnish familial and 888 unselected breast cancerpatients and 736 healthy population controls. The clinical and biological variables were tested for association by univariate analysis and the effects of several variables on survival by Cox's proportional hazards regression model. RESULTS: The distribution of the genotypes was similar in all groups studied, suggesting no association with breast cancer risk. Unselected breast cancerpatients with 72P homozygous genotype presented significantly more often with lobular carcinoma, whereas R72 allele carriers had a significantly higher frequency of ductal carcinomas (P = 0.004). No significant association with other histopathologic variables, like tumor grade, hormone receptor status (estrogen and progesterone receptors), or tumor-node-metastasis stage, was observed. Survival analysis showed that unselected breast cancerpatients with 72P homozygous genotype had significantly poorer survival than patients with other genotypes (P = 0.003). This effect on survival was independent of p53 expression in the tumors and multivariate analysis showed that 72P homozygous genotype was overall an independent prognostic factor (risk ratio of death, 2.1; 95% confidence interval, 1.4-3.3; P = 0.001). CONCLUSIONS: These results suggest no effect of either R72P allele on breast cancer risk but a significantly reduced survival for 72P homozygous breast cancerpatients. The finding of codon 72 genotype as an independent prognostic marker for breast cancer warrants further studies.
Authors: L Ricks-Santi; T Mason; V Apprey; C Ahaghotu; A McLauchlin; D Josey; G Bonney; G M Dunston Journal: Prostate Date: 2010-12-01 Impact factor: 4.104
Authors: Maral Jamshidi; Marjanka K Schmidt; Thilo Dörk; Montserrat Garcia-Closas; Tuomas Heikkinen; Sten Cornelissen; Alexandra J van den Broek; Peter Schürmann; Andreas Meyer; Tjoung-Won Park-Simon; Jonine Figueroa; Mark Sherman; Jolanta Lissowska; Garrett Teoh Hor Keong; Astrid Irwanto; Marko Laakso; Sampsa Hautaniemi; Kristiina Aittomäki; Carl Blomqvist; Jianjun Liu; Heli Nevanlinna Journal: Int J Cancer Date: 2012-10-25 Impact factor: 7.396
Authors: Marjanka K Schmidt; Johanna Tommiska; Annegien Broeks; Flora E van Leeuwen; Laura J Van't Veer; Paul D P Pharoah; Douglas F Easton; Mitul Shah; Manjeet Humphreys; Thilo Dörk; Scarlett A Reincke; Rainer Fagerholm; Carl Blomqvist; Heli Nevanlinna Journal: Breast Cancer Res Date: 2009-12-18 Impact factor: 6.466
Authors: Pankaj Taneja; Dejan Maglic; Fumitake Kai; Sinan Zhu; Robert D Kendig; Elizabeth A Fry; Kazushi Inoue Journal: Clin Med Insights Oncol Date: 2010-04-20
Authors: O M Sinilnikova; A C Antoniou; J Simard; S Healey; M Léoné; D Sinnett; A B Spurdle; J Beesley; X Chen; M H Greene; J T Loud; F Lejbkowicz; G Rennert; S Dishon; I L Andrulis; S M Domchek; K L Nathanson; S Manoukian; P Radice; I Konstantopoulou; I Blanco; A L Laborde; M Durán; A Osorio; J Benitez; U Hamann; F B L Hogervorst; T A M van Os; H J P Gille; S Peock; M Cook; C Luccarini; D G Evans; F Lalloo; R Eeles; G Pichert; R Davidson; T Cole; J Cook; J Paterson; C Brewer; D J Hughes; I Coupier; S Giraud; F Coulet; C Colas; F Soubrier; E Rouleau; I Bièche; R Lidereau; L Demange; C Nogues; H T Lynch; R K Schmutzler; B Versmold; C Engel; A Meindl; N Arnold; C Sutter; H Deissler; D Schaefer; U G Froster; K Aittomäki; H Nevanlinna; L McGuffog; D F Easton; G Chenevix-Trench; D Stoppa-Lyonnet Journal: Br J Cancer Date: 2009-08-25 Impact factor: 7.640