Soodabeh ShahidSales1, Mehraneh Mehramiz2, Faezeh Ghasemi2,3, Amir Aledavood1, Mehri Shamsi1, Seyed Mahdi Hassanian4,5, Majid Ghayour-Mobarhan2,5, Amir Avan5. 1. Cancer Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 2. Department of Modern Sciences and Technologies, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 3. Department of Medical Biotechnology, Faculty of Medicine, Arak University of Medical Sciences, Arak, Iran. 4. Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran. 5. Metabolic syndrome Research center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Abstract
BACKGROUND: Breast cancer is among the leading cause of cancer-related-deaths in women, supporting the need for the identification of novel prognostic and predictive biomarkers. Recent studies have identified common genetic variants in a region on chromosome 9p21 associated with an increased risk of developing different cancers. Here, we explored the association of a genetic variant in CDKN2A/B, rs10811661, for the first time in 564 subjects with/without breast cancer. METHOD: Genotyping was performed using TaqMan real time PCR method. The associations of this genetic variant with breast cancer risk and pathological information of patients were assessed. RESULTS: We observed that patients with breast cancer had a higher frequency of TT genotype (P<.001) than control group, which was associated with advanced TNM classification (P=.04) and larger tumor size (P=.014), as detected by the recessive genetic inheritance model. Moreover, the logistic regression under recessive genetic model revealed that breast cancer patients with TT had higher risk of breast cancer, compared to CC/CT genotypes (eg, OR=4.9, 95% CI:1.9-12, P=.001), after adjusted for potential confounders, age, BMI, and family history. CONCLUSION: We demonstrated that patients carrying the TT genotype for CDKN2A/B rs10811661 polymorphism had the increased risk of breast cancer susceptibility. However, further investigations are warranted in a larger and prospective setting to explore the value of this marker as a risk stratification marker in breast cancer.
BACKGROUND:Breast cancer is among the leading cause of cancer-related-deaths in women, supporting the need for the identification of novel prognostic and predictive biomarkers. Recent studies have identified common genetic variants in a region on chromosome 9p21 associated with an increased risk of developing different cancers. Here, we explored the association of a genetic variant in CDKN2A/B, rs10811661, for the first time in 564 subjects with/without breast cancer. METHOD: Genotyping was performed using TaqMan real time PCR method. The associations of this genetic variant with breast cancer risk and pathological information of patients were assessed. RESULTS: We observed that patients with breast cancer had a higher frequency of TT genotype (P<.001) than control group, which was associated with advanced TNM classification (P=.04) and larger tumor size (P=.014), as detected by the recessive genetic inheritance model. Moreover, the logistic regression under recessive genetic model revealed that breast cancerpatients with TT had higher risk of breast cancer, compared to CC/CT genotypes (eg, OR=4.9, 95% CI:1.9-12, P=.001), after adjusted for potential confounders, age, BMI, and family history. CONCLUSION: We demonstrated that patients carrying the TT genotype for CDKN2A/Brs10811661 polymorphism had the increased risk of breast cancer susceptibility. However, further investigations are warranted in a larger and prospective setting to explore the value of this marker as a risk stratification marker in breast cancer.
Authors: Amy L Sherborne; Fay J Hosking; Rashmi B Prasad; Rajiv Kumar; Rolf Koehler; Jayaram Vijayakrishnan; Elli Papaemmanuil; Claus R Bartram; Martin Stanulla; Martin Schrappe; Andreas Gast; Sara E Dobbins; Yussanne Ma; Eamonn Sheridan; Malcolm Taylor; Sally E Kinsey; Tracey Lightfoot; Eve Roman; Julie A E Irving; James M Allan; Anthony V Moorman; Christine J Harrison; Ian P Tomlinson; Sue Richards; Martin Zimmermann; Csaba Szalai; Agnes F Semsei; Daniel J Erdelyi; Maja Krajinovic; Daniel Sinnett; Jasmine Healy; Anna Gonzalez Neira; Norihiko Kawamata; Seishi Ogawa; H Phillip Koeffler; Kari Hemminki; Mel Greaves; Richard S Houlston Journal: Nat Genet Date: 2010-05-09 Impact factor: 38.330
Authors: Tadeusz Debniak; Cezary Cybulski; Bohdan Górski; Tomasz Huzarski; Tomasz Byrski; Jacek Gronwald; Anna Jakubowska; Elzbieta Kowalska; Oleg Oszurek; Steven A Narod; Jan Lubiński Journal: Breast Cancer Res Treat Date: 2006-10-24 Impact factor: 4.872
Authors: Kyoko L Yap; Side Li; Ana M Muñoz-Cabello; Selina Raguz; Lei Zeng; Shiraz Mujtaba; Jesús Gil; Martin J Walsh; Ming-Ming Zhou Journal: Mol Cell Date: 2010-06-11 Impact factor: 17.970
Authors: Kathryn P Burdon; Stuart Macgregor; Alex W Hewitt; Shiwani Sharma; Glyn Chidlow; Richard A Mills; Patrick Danoy; Robert Casson; Ananth C Viswanathan; Jimmy Z Liu; John Landers; Anjali K Henders; John Wood; Emmanuelle Souzeau; April Crawford; Paul Leo; Jie Jin Wang; Elena Rochtchina; Dale R Nyholt; Nicholas G Martin; Grant W Montgomery; Paul Mitchell; Matthew A Brown; David A Mackey; Jamie E Craig Journal: Nat Genet Date: 2011-05-01 Impact factor: 38.330
Authors: T Debniak; B Górski; T Huzarski; T Byrski; C Cybulski; A Mackiewicz; S Gozdecka-Grodecka; J Gronwald; E Kowalska; O Haus; E Grzybowska; M Stawicka; M Swiec; K Urbański; S Niepsuj; B Waśko; S Góźdź; P Wandzel; C Szczylik; D Surdyka; A Rozmiarek; O Zambrano; M Posmyk; S A Narod; J Lubinski Journal: J Med Genet Date: 2005-05-06 Impact factor: 6.318
Authors: Eleftheria Zeggini; Michael N Weedon; Cecilia M Lindgren; Timothy M Frayling; Katherine S Elliott; Hana Lango; Nicholas J Timpson; John R B Perry; Nigel W Rayner; Rachel M Freathy; Jeffrey C Barrett; Beverley Shields; Andrew P Morris; Sian Ellard; Christopher J Groves; Lorna W Harries; Jonathan L Marchini; Katharine R Owen; Beatrice Knight; Lon R Cardon; Mark Walker; Graham A Hitman; Andrew D Morris; Alex S F Doney; Mark I McCarthy; Andrew T Hattersley Journal: Science Date: 2007-04-26 Impact factor: 47.728