Molecular genetics analysis of hereditary breast and ovarian cancer patients in India
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Published:2009-08-06
Issue:1
Volume:7
Page:
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ISSN:1897-4287
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Container-title:Hereditary Cancer in Clinical Practice
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language:en
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Short-container-title:Hered Cancer Clin Pract
Author:
Soumittra Nagasamy,Meenakumari Balaiah,Parija Tithi,Sridevi Veluswami,Nancy Karunakaran N,Swaminathan Rajaraman,Rajalekshmy Kamalalayam R,Majhi Urmila,Rajkumar Thangarajan
Abstract
Abstract
Background
Hereditary cancers account for 5–10% of cancers. In this study BRCA1, BRCA2 and CHEK2*(1100delC) were analyzed for mutations in 91 HBOC/HBC/HOC families and early onset breast and early onset ovarian cancer cases.
Methods
PCR-DHPLC was used for mutation screening followed by DNA sequencing for identification and confirmation of mutations. Kaplan-Meier survival probabilities were computed for five-year survival data on Breast and Ovarian cancer cases separately, and differences were tested using the Log-rank test.
Results
Fifteen (16%) pathogenic mutations (12 in BRCA1 and 3 in BRCA2), of which six were novel BRCA1 mutations were identified. None of the cases showed CHEK2*1100delC mutation. Many reported polymorphisms in the exonic and intronic regions of BRCA1 and BRCA2 were also seen. The mutation status and the polymorphisms were analyzed for association with the clinico-pathological features like age, stage, grade, histology, disease status, survival (overall and disease free) and with prognostic molecular markers (ER, PR, c-erbB2 and p53).
Conclusion
The stage of the disease at diagnosis was the only statistically significant (p < 0.0035) prognostic parameter. The mutation frequency and the polymorphisms were similar to reports on other ethnic populations. The lack of association between the clinico-pathological variables, mutation status and the disease status is likely to be due to the small numbers.
Publisher
Springer Science and Business Media LLC
Subject
Genetics (clinical),Oncology
Reference49 articles.
1. Shanta V, Swaminathan R: Cancer incidence and mortality in Chennai, India 2003–2005. National Cancer registry program, Cancer Institute (WIA), Chennai 2008. 2. Sue Moss: Screening for breast cancer in India – is it an appropriate strategy? J Natl Cancer Inst 2008, 100(18):1290–1300. 10.1093/jnci/djn292 3. Miki Y, Swensen J, Donna Shattuck-Eidens, Futreal PA, Harshman K, Tavtigian S, Qingyun Liu, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugen-Strano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helvering L, Morrison P, Rosteck P, Lai M, Barrett JC, Lewis C, Neuhausen S, Cannon-Albright L, Goldgar D, Wiseman R, Kamb A, Skolnick MH: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1 . Science 1994, 266: 66–71. 10.1126/science.7545954 4. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G: Identification of the breast cancer susceptibility gene BRCA2 . Nature 1995, 378: 789–92. 10.1038/378789a0 5. Heijboer HM, Ouweland Ans, Klijn J, Wasielewski M, Snoo A, Oldenburg R, Hollestelle A, Houben M, Crepin E, Veghel-Plandsoen M, Elstrodt F, Duijn C, Bartels C, Meijers C, Schutte M, McGuffog L, Thompson D, Easton DF, Sodha N, Seal S, Barfoot R, Mangion J, Chang-Claude J, Eccles D, Eeles R, Gareth Evans D, Houlston R, Murday V, Narod S, Peretz T, Julian P, Phelan C, Zhang HX, Szebo C, Derilee P, Goldgar D, Futreal PA, Nathanson KL, Weber BL, Rahman N, Stratton MR: Low-penetrance susceptibility to breast cancer due to CHEK2 *1100delC in non-carriers of BRCA1 or BRCA2 mutations: The CHEK2 breast cancer consortium. Nat Genet 2002, 31: 55–59. 10.1038/ng879
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