Join the Global Breast Cancer Movement
Save this page to myKomen
Go to myKomen
Home > Understanding Breast Cancer > Breast Cancer Research > Table 11: BRCA1 and BRCA2 gene mutations and cancer risk

  


Table 11: BRCA1 and BRCA2 gene mutations and cancer risk

Loading...

 

This summary table contains detailed information about research studies. While viewing summary tables offers an informative glimpse at the science behind many breast cancer guidelines and recommendations, they should be viewed with some caution. There are a number of concepts you must understand to be able to successfully read and interpret research tables. To get some background information about understanding research tables, please see How to Read a Research Table

Introduction: Women who carry a BRCA1 or BRCA2 gene mutation have a greatly increased risk of getting breast and ovarian cancer. Studies, though, show a wide range of risks. It appears that women who have a BRCA1 or BRCA2 mutation have a 60 to 80 percent chance of getting breast cancer by age 70 and a 15 to 60 percent chance of getting ovarian cancer by age 70. In comparison, the average woman in the United States has, by age 70, a seven percent chance of getting breast cancer and a 0.7 percent chance of getting ovarian cancer [1]. BRCA1/2 carriers also seem to have an excess risk of colon cancer, prostate cancer (in male carriers) and some second primary cancers (new cancers that develop after a first breast cancer). However, these data are limited.

People with BRCA1 gene mutations seem to have slightly different cancer risks than those with BRCA2 mutations. However, the two groups are sometimes combined in the table below since there are so few data available on either group alone. Much of the research on genetic mutations and breast cancer risk has been done by the International Breast Cancer Linkage Consortium. This group has collected data on over 200 families worldwide. Each family has at least four family members with breast cancer.

The prevalence of a BRCA1 gene mutation in the general population is quite small (only about one in 800 women) [2]. However, women of Ashkenazi Jewish descent are at greater risk of a carrying a BRCA1/2 mutation, (about one in 40 have either a BRCA1 or BRCA2 mutation) [3].

Study selection criteria: For family based studies--those studies with more than 200 families that have four or more members with breast cancer. For population based studies—representative studies, with at least 100 breast cancer cases. For pooled analyses--studies with at least 400 families. 
 

 Study Study Characteristics
 
Study Population
(number of participants)
 
  Cumulative Risk of Different Types of Cancer by age 70 (95% CI)
     Second Cancers in Women with Breast Cancer
  Breast Cancer Ovarian Cancer Other Cancers Breast Cancer (other side) Ovarian Cancer
Family-based studies
BRCA1

Breast Cancer Linkage Consortium [4,5,6]

BRCA1 mutation carrier families

237 families that have 4 or more members with breast cancer

 87%
(72-95%)
63%*

Colon cancer: Highly increased risk

64%*

44%
(28-56%) 

Evans et al. [7]

BRCA1 mutation carrier families

223 families  68%
(65-71%)
60%      
BRCA2
Breast Cancer Linkage Consortium [8,9,10]

BRCA2 mutation carrier families

 237 families that have 4 or more members with breast cancer  84%
(43-95%)
 27%
(0-47%)
Prostate cancer (men): Highly increased risk  52%
(42-61%)
 
 Population-based studies
Struewing et al. [11] Jewish residents of Washington, DC area 5,318

56%
(40-73%) 

 16%
(6-28%)
Prostate cancer (men):

16%
(4-30%)

   
Begg et al. [12]  Women with breast cancer diagnosed before age 55 1,394

36%
(21-58%)
(BRCA1

 47%
(25-100%)
(BRCA2)

   

48%
(30-67%)
(BRCA1

 59%
(30-84%)
(BRCA2)‡ 

 
King et al. [13] Ashkenazi Jewish women with breast cancer 1,008

69%
(BRCA1

 74%
(BRCA2)

 46%
(BRCA1

 12%
(BRCA2)

     
Niell et al. [14] Ashkenazi Jews 1,002 colon cancer cases     Colon cancer: No excess risk    

Tryggvadottir et al. [15]

Icelandic women with breast cancer and their first-degree relatives

847 women with breast cancer and 2,836 first degree relatives

46.3% (BRCA2)

       

Thorlacius et al. [16]

Icelandic women with breast cancer

575 37%
(22-54%)
(BRCA2
       
Warner et al. [17] Jewish women with breast cancer 457

60% (BRCA1)

28% (BRCA2)

       
Rafner et al. [18] Icelandic women with ovarian cancer 235 cases  

Highly increased risk  (BRCA2)

     

Kirchhoff et al. [19]

Ashkenazi Jewish men with prostate cancer

251    

Prostate cancer (men): Increased risk  (BRCA2)

No excess risk (BRCA1)

   
Pooled analyses

Antoniou et al. [20]

22 studies 429 families

46-59% (BRCA1)

39-51% (BRCA2)

33-36%

(BRCA1)

11-12%

(BRCA2)

Prostate cancer (men): Increased risk

Pancreatic cancer: Increased risk

   

 

* Confidence intervals for these risk estimates were not included in the original article.
† By age 80, cumulative risk of breast cancer increases to 58% (30-80%) for BRCA1 and 58% (38-81%) for BRCA2.
‡ By age 80, cumulative risk of a second breast cancer in the opposite breast increases to 47% (25-100%) for BRCA1 and 60% (34-92%) for BRCA2.

References

1. Ries LAG, Melbert D, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2005, National Cancer Institute. Bethesda, MD, http://seer.cancer.gov/csr/1975_2005/, 2008.

2. Ford D, Easton DF, Peto J. Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence. Am J Hum Genet. 57(6):1457-1462, 1995.

3. Hartge P, Struewing JP, Wacholder S, et al. The prevalence of common BRCA1 and BRCA2 mutations among Ashkenazi Jews. Am J Hum Genet. 64(4):963-970, 1999.

4. Easton DF, Bishop DT, Ford D, Crockford GP. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 52(4):678-701, 1993.

5. Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet. 56(1):265-271, 1995.

6. Ford D, Easton DF, Bishop DT, et al. Breast Cancer Linkage Consortium: Risks of cancer in BRCA1-mutation carriers. Lancet. 343(8899):692-695, 1994.

7. Evans DG, Shenton A, Woodward E, Lalloo F, Howell A, Maher ER. Penetrance estimates for BRCA1 and BRCA2 based on genetic testing in a Clinical Cancer Genetics service setting: risks of breast/ovarian cancer quoted should reflect the cancer burden in the family. BMC Cancer. 8:155, 2008.

8. Ford D, Easton DF, Stratton M, et al. Genetic heterogeneity and penetrance analysis of the BRCA 1 and BRCA 2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 62(3):676-89, 1998.

9. Easton DF, Steele L, Fields P, et al. Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13. Am J Hum Genet. 61(1):120-128, 1997.

10. Cancer risks in BRCA2 mutation carriers. The breast cancer linkage consortium. J Natl Cancer Inst. 91(15):1310-1316, 1999.

11. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Jewish Ashkenazi Jews. N Engl J Med. 336(20):1401-1408, 1997.

12. Begg CB, Haile RW, Borg A, et al. Variation of breast cancer risk among BRCA1/2 carriers. JAMA. 299(2):194-201, 2008.

13. King MC, Marks JH, and Mandell JB. Breast and Ovarian Cancer Risks Due to Inherited Mutations in BRCA1 and BRCA2. Science. 302(5645):643-6, 2003.

14. Niell BL, Rennert G, Bonner JD, et al. BRCA1 and BRCA2 Founder Mutations and the Risk of Colorectal Cancer. J Natl Cancer Inst. 96(1):15-21, 2004.

15. Tryggvadottir L, Sigvaldason H, Olafsdottir GH, et al. Population-based study of changing breast cancer risk in Icelandic BRCA2 mutation carriers, 1920-2000. J Natl Cancer Inst. 98(2):116-22, 2006.

16. Thorlacius S, Struewing JP, Hartge P, et al. Population-based study of risk of breast cancer in carriers of BRCA2 mutation. Lancet. 352(9137):1337-9, 1998.

17. Warner E, Foulkes W, Goodwin P, et al. Prevalence and Penetrance of BRCA1 and BRCA2 Gene Mutations in unselected Ashkenazi Jewish Women with Breast Cancer. J Natl Cancer Inst. 91(14):1241-1247, 1999.

18. Rafner T, Benediksdottir KR, Eldon BJ, et al. BRCA2, but not BRCA1, mutations account for familial ovarian cancer in Iceland: a population-based study. Eur J Cancer. 40(18):2788-93, 2004.

19. Kirchhoff T, Kauff ND, Mitra N, et al. BRCA mutation and risk of prostate cancer in Ashkenazi Jews. Clin Cancer Res. 10(9):2918-21, 2004.

20. Antoniou AC, Cunningham AP, Peto J, et al. The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 98(8):1457-66, 2008.

Updated 09/12/09