Amanda I Phipps1, Karen W Makar, Polly A Newcomb. 1. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., M4-C308, Seattle, WA, 98109, USA, aphipps@fhcrc.org.
Abstract
PURPOSE: Approximately 10-30 % of colorectal cancers exhibit somatic mutations in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene (PIK3CA). We evaluated the relationship between PIK3CA mutation status and demographic factors, lifestyle factors, and other tumor characteristics and the relationship between PIK3CA mutation status and colorectal cancer survival. METHODS: The population-based study included postmenopausal women with invasive colorectal cancer diagnosed between 1998 and 2002 in Western Washington State. Participants were interviewed, and tumor specimens were tested for PIK3CA mutations in exons 9 and 20 hotspots, KRAS exon 2 mutations, BRAF p.V600E mutation, and microsatellite instability. We used Cox regression to evaluate the association between PIK3CA mutation status and disease-specific and overall survival. Stratified analyses were conducted by KRAS mutation status. RESULTS: PIK3CA mutations were evident in approximately 13 % of cases (N = 35). Women with PIK3CA-mutated colorectal cancer were significantly more likely than those with PIK3CA wild-type disease to be non-white, to have proximal colon cancer, and to have KRAS-mutated tumors (p < 0.05). In Cox proportional hazards regression analyses, overall survival was poorer, although not statistically significantly so, for women with PIK3CA-mutated versus wild-type colorectal cancer (hazard ratio = 1.74, 95 % confidence interval 0.86-3.50). This association between PIK3CA mutation status and survival was evident only when analyses were restricted to cases without somatic KRAS mutations (hazard ratio = 2.94, 95 % confidence interval 1.12-7.73). CONCLUSIONS: PIK3CA-mutated colorectal cancer appears to have a distinct epidemiologic profile that is of clinical significance. Women with PIK3CA-mutated colorectal cancer experience a poorer prognosis than those with PIK3CA wild-type disease.
PURPOSE: Approximately 10-30 % of colorectal cancers exhibit somatic mutations in the phosphoinositide-3-kinase, catalytic, alpha polypeptide gene (PIK3CA). We evaluated the relationship between PIK3CA mutation status and demographic factors, lifestyle factors, and other tumor characteristics and the relationship between PIK3CA mutation status and colorectal cancer survival. METHODS: The population-based study included postmenopausal women with invasive colorectal cancer diagnosed between 1998 and 2002 in Western Washington State. Participants were interviewed, and tumor specimens were tested for PIK3CA mutations in exons 9 and 20 hotspots, KRAS exon 2 mutations, BRAF p.V600E mutation, and microsatellite instability. We used Cox regression to evaluate the association between PIK3CA mutation status and disease-specific and overall survival. Stratified analyses were conducted by KRAS mutation status. RESULTS:PIK3CA mutations were evident in approximately 13 % of cases (N = 35). Women with PIK3CA-mutated colorectal cancer were significantly more likely than those with PIK3CA wild-type disease to be non-white, to have proximal colon cancer, and to have KRAS-mutated tumors (p < 0.05). In Cox proportional hazards regression analyses, overall survival was poorer, although not statistically significantly so, for women with PIK3CA-mutated versus wild-type colorectal cancer (hazard ratio = 1.74, 95 % confidence interval 0.86-3.50). This association between PIK3CA mutation status and survival was evident only when analyses were restricted to cases without somatic KRAS mutations (hazard ratio = 2.94, 95 % confidence interval 1.12-7.73). CONCLUSIONS:PIK3CA-mutated colorectal cancer appears to have a distinct epidemiologic profile that is of clinical significance. Women with PIK3CA-mutated colorectal cancer experience a poorer prognosis than those with PIK3CA wild-type disease.
Authors: Vicki L J Whitehall; Celestine Rickman; Catherine E Bond; Ingunn Ramsnes; Sonia A Greco; Aarti Umapathy; Diane McKeone; Rebecca J Faleiro; Ron L Buttenshaw; Daniel L Worthley; Sam Nayler; Zhen Zhen Zhao; Grant W Montgomery; Kylie-Ann Mallitt; Jeremy R Jass; Nagahide Matsubara; Kenji Notohara; Tatsuhiro Ishii; Barbara A Leggett Journal: Int J Cancer Date: 2011-11-19 Impact factor: 7.396
Authors: Polly A Newcomb; Yingye Zheng; Victoria M Chia; Libby M Morimoto; V Paul Doria-Rose; Allyson Templeton; Stephen N Thibodeau; John D Potter Journal: Cancer Res Date: 2007-08-01 Impact factor: 12.701
Authors: Sérgia Velho; Carla Oliveira; Ana Ferreira; António Carlos Ferreira; Gianpaolo Suriano; Simó Schwartz; Alex Duval; Fátima Carneiro; José Carlos Machado; Richard Hamelin; Raquel Seruca Journal: Eur J Cancer Date: 2005-07 Impact factor: 9.162
Authors: Daniel J Weisenberger; Kimberly D Siegmund; Mihaela Campan; Joanne Young; Tiffany I Long; Mark A Faasse; Gyeong Hoon Kang; Martin Widschwendter; Deborah Weener; Daniel Buchanan; Hoey Koh; Lisa Simms; Melissa Barker; Barbara Leggett; Joan Levine; Myungjin Kim; Amy J French; Stephen N Thibodeau; Jeremy Jass; Robert Haile; Peter W Laird Journal: Nat Genet Date: 2006-06-25 Impact factor: 38.330
Authors: Kathryn Alsop; Leeanne Mead; Letitia D Smith; Simon G Royce; Andrea A Tesoriero; Joanne P Young; Andrew Haydon; Garry Grubb; Graham G Giles; Mark A Jenkins; John L Hopper; Melissa C Southey Journal: Eur J Cancer Date: 2006-06-09 Impact factor: 9.162
Authors: C R Boland; S N Thibodeau; S R Hamilton; D Sidransky; J R Eshleman; R W Burt; S J Meltzer; M A Rodriguez-Bigas; R Fodde; G N Ranzani; S Srivastava Journal: Cancer Res Date: 1998-11-15 Impact factor: 12.701
Authors: Shuji Ogino; Xiaoyun Liao; Yu Imamura; Mai Yamauchi; Nadine J McCleary; Kimmie Ng; Donna Niedzwiecki; Leonard B Saltz; Robert J Mayer; Renaud Whittom; Alexander Hantel; Al B Benson; Rex B Mowat; Donna Spiegelman; Richard M Goldberg; Monica M Bertagnolli; Jeffrey A Meyerhardt; Charles S Fuchs Journal: J Natl Cancer Inst Date: 2013-11-14 Impact factor: 13.506