Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer.

نویسندگان

  • Kelly L Bolton
  • Georgia Chenevix-Trench
  • Cindy Goh
  • Siegal Sadetzki
  • Susan J Ramus
  • Beth Y Karlan
  • Diether Lambrechts
  • Evelyn Despierre
  • Daniel Barrowdale
  • Lesley McGuffog
  • Sue Healey
  • Douglas F Easton
  • Olga Sinilnikova
  • Javier Benítez
  • María J García
  • Susan Neuhausen
  • Mitchell H Gail
  • Patricia Hartge
  • Susan Peock
  • Debra Frost
  • D Gareth Evans
  • Rosalind Eeles
  • Andrew K Godwin
  • Mary B Daly
  • Ava Kwong
  • Edmond S K Ma
  • Conxi Lázaro
  • Ignacio Blanco
  • Marco Montagna
  • Emma D'Andrea
  • Maria Ornella Nicoletto
  • Sharon E Johnatty
  • Susanne Krüger Kjær
  • Allan Jensen
  • Estrid Høgdall
  • Ellen L Goode
  • Brooke L Fridley
  • Jennifer T Loud
  • Mark H Greene
  • Phuong L Mai
  • Angela Chetrit
  • Flora Lubin
  • Galit Hirsh-Yechezkel
  • Gord Glendon
  • Irene L Andrulis
  • Amanda E Toland
  • Leigha Senter
  • Martin E Gore
  • Charlie Gourley
  • Caroline O Michie
  • Honglin Song
  • Jonathan Tyrer
  • Alice S Whittemore
  • Valerie McGuire
  • Weiva Sieh
  • Ulf Kristoffersson
  • Håkan Olsson
  • Åke Borg
  • Douglas A Levine
  • Linda Steele
  • Mary S Beattie
  • Salina Chan
  • Robert L Nussbaum
  • Kirsten B Moysich
  • Jenny Gross
  • Ilana Cass
  • Christine Walsh
  • Andrew J Li
  • Ronald Leuchter
  • Ora Gordon
  • Montserrat Garcia-Closas
  • Simon A Gayther
  • Stephen J Chanock
  • Antonis C Antoniou
  • Paul D P Pharoah
چکیده

CONTEXT Approximately 10% of women with invasive epithelial ovarian cancer (EOC) carry deleterious germline mutations in BRCA1 or BRCA2. A recent article suggested that BRCA2-related EOC was associated with an improved prognosis, but the effect of BRCA1 remains unclear. OBJECTIVE To characterize the survival of BRCA carriers with EOC compared with noncarriers and to determine whether BRCA1 and BRCA2 carriers show similar survival patterns. DESIGN, SETTING, AND PARTICIPANTS A pooled analysis of 26 observational studies on the survival of women with ovarian cancer, which included data from 1213 EOC cases with pathogenic germline mutations in BRCA1 (n = 909) or BRCA2 (n = 304) and from 2666 noncarriers recruited and followed up at variable times between 1987 and 2010 (the median year of diagnosis was 1998). MAIN OUTCOME MEASURE Five-year overall mortality. RESULTS The 5-year overall survival was 36% (95% CI, 34%-38%) for noncarriers, 44% (95% CI, 40%-48%) for BRCA1 carriers, and 52% (95% CI, 46%-58%) for BRCA2 carriers. After adjusting for study and year of diagnosis, BRCA1 and BRCA2 mutation carriers showed a more favorable survival than noncarriers (for BRCA1: hazard ratio [HR], 0.78; 95% CI, 0.68-0.89; P < .001; and for BRCA2: HR, 0.61; 95% CI, 0.50-0.76; P < .001). These survival differences remained after additional adjustment for stage, grade, histology, and age at diagnosis (for BRCA1: HR, 0.73; 95% CI, 0.64-0.84; P < .001; and for BRCA2: HR, 0.49; 95% CI, 0.39-0.61; P < .001). The BRCA1 HR estimate was significantly different from the HR estimated in the adjusted model (P for heterogeneity = .003). CONCLUSION Among patients with invasive EOC, having a germline mutation in BRCA1 or BRCA2 was associated with improved 5-year overall survival. BRCA2 carriers had the best prognosis.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Polymorphisms in BRCA1 and BRCA2 and risk of epithelial ovarian cancer.

PURPOSE Because inherited BRCA1 or BRCA2 mutations strikingly increase ovarian cancer risk, polymorphisms in these genes could represent low penetrance susceptibility alleles. Previous studies of the BRCA2 N372H polymorphism suggested that HH homozygotes have a modestly increased risk of both breast and ovarian cancer. We have examined whether BRCA2 N372H or common amino acid-changing polymorph...

متن کامل

جهش های ژنتیکی جدید در ژن های اصلی سرطان پستان (BRCA1/BRCA2) در زنان ایرانی مبتلا به سرطان پستان زودرس

Background: Breast cancer is the most common female malignancy and the main cause of death in  mid-aged women. Genetic germ line mutations in BRCAI/BRCA2 in Iranian women with breast or  ovarian cancer have not been yet reported. Materials and methods: Clinical data, family history and blood samples were obtained from 83  females aged less than 45 years with primary breast cancer in order to su...

متن کامل

Assessment of the Prognostic Value of Two Common Variants of BRCA1 and BRCA2 Genes in Ovarian Cancer Patients Treated with Cisplatin and Paclitaxel: A Gynecologic Oncology Group Study

PURPOSE BRCA1/BRCA2 germline mutations appear to enhance the platinum-sensitivity, but little is known about the prognostic relevance of polymorphisms in BRCA1/BRCA2 in epithelial ovarian cancer (EOC). This study evaluated whether common variants of BRCA1/BRCA2 are associated with progression-free survival (PFS) and overall survival (OS) in patients with advanced stage sporadic EOC. EXPERIMEN...

متن کامل

Effects of BRCA1- and BRCA2-related mutations on ovarian and breast cancer survival: a meta-analysis.

PURPOSE To estimate the effects of BRCA1 and BRCA2 mutations on ovarian cancer and breast cancer survival. EXPERIMENTAL DESIGN We searched PubMed and EMBASE for studies that evaluated the associations between BRCA mutations and ovarian or breast cancer survival. Meta-analysis was conducted to generate combined HRs with 95% confidence intervals (CI) for overall survival (OS) and progression-fr...

متن کامل

Defining women at high risk of ovarian cancer.

We read with interest the article by Dr. Pejovic et al. (1) on cytogenetic instability in cultured ovarian epithelial cells from a small number of women at high risk of ovarian cancer. In studies of this sort, the definition of high risk is critical, but risk details for each of the five ‘‘high-risk’’ women in this study were not provided, including pedigree and genetic testing information. The...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • JAMA

دوره 307 4  شماره 

صفحات  -

تاریخ انتشار 2012