Abstract

Men who carry germline mutations in the BRCA2 gene have a higher risk of developing breast carcinoma than men in the general population. Men who carry germline mutations in the BRCA1 gene may also be at a higher risk for breast carcinoma, but this association is not as well established. We evaluated the risks of developing breast carcinoma for male BRCA1 and BRCA2 mutation carriers in the US population based on data from 1939 families with 97 male subjects with breast carcinoma that were collected from eight centers across the National Cancer Institute's Cancer Genetics Network. At all ages, the cumulative risks of male breast cancer were higher in both BRCA1 and BRCA2 mutation carriers than in noncarriers. The relative risks of developing breast cancer were highest for men in their 30s and 40s and decreased with increasing age. Both the relative and cumulative risks were higher for BRCA2 mutation carriers than for BRCA1 mutation carriers. The estimated cumulative risk of breast carcinoma for male BRCA1 mutation carriers at age 70 years was 1.2% (95% confidence interval [CI] = 0.22% to 2.8%) and for BRCA2 mutation carriers, 6.8% (95% CI = 3.2% to 12%).

CONTEXT AND CAVEATS
Prior knowledge

Men who carry germline mutations in the BRCA2 gene have a higher risk of developing breast carcinoma than men in the general population. However, the association between germline mutations in the BRCA1 gene and the risk of breast carcinoma in men is not as well established.

Study design

A retrospective study of the risk of developing breast carcinoma for male BRCA1 and BRCA2 mutation carriers in the United States based on data from 1939 families with 97 men with breast carcinoma that were collected from eight centers across the National Cancer Institute's Cancer Genetics Network.

Contribution

At all ages, the cumulative risks of male breast cancer were higher in both BRCA1 and BRCA2 mutation carriers than in noncarriers. The relative risks of developing breast cancer were highest for men in their 30s and 40s and decreased with increasing age. Both the relative and cumulative risks were higher for BRCA2 mutation carriers than for BRCA1 mutation carriers.

Implications

These risk estimates are important for determining appropriate risk management strategies for the male members of families with germline mutations in BRCA1 or BRCA2.

Limitations

No information about family members' ethnicity group other than their Ashkenazi Jewish ancestry was available, precluding estimates of the penetrance of mutations in BRCA1 and BRCA2 for African Americans.

Male breast carcinoma accounts for less than 1% of all breast cancer cases in the United States ( 1 , 2 ). It is more common in men with a family history of breast cancer. Both genetic linkage and DNA sequencing data have demonstrated that male breast carcinoma is associated with deleterious germline mutations in BRCA2 ( 3 , 4 ). Several studies have examined the incidence of BRCA2 mutations in men with breast cancer ( 5–9 ). In one study that included 237 hereditary breast carcinoma families, 26 families had at least one male member who had been diagnosed with breast carcinoma and in 77%, the disease was linked to mutations in BRCA2 ( 5 ). Couch et al. ( 6 ) found that 14% of 50 male breast cancer patients who were not selected based on a family history of breast cancer had a deleterious BRCA2 mutation. Easton et al. ( 7 ) examined two large BRCA2-linked families that contained four male breast carcinoma cases. The estimated cumulative risk for male breast carcinoma by age 70 years was 6.3%. In a separate study of 164 families with BRCA2 mutations, the estimated cumulative risk of breast cancer for men who carried BRCA2 mutations was 2.8% by 70 years of age and 6.9% by 80 years of age ( 8 ). Recently, Risch et al. ( 9 ) estimated that the relative risk of breast cancer for male BRCA2 carriers was 102 (95% confidence interval [CI] = 9.9 to 1050).

The association between male breast carcinoma and deleterious germline mutations in BRCA1 is less clear. Initial data suggested that inherited male breast cancer was not linked to germline mutations in BRCA1 ( 10 ) and BRCA1 mutations have been detected at very low frequency in several series of unselected male breast cancer patients ( 11–14 ). However, a more recent study ( 15 ) in a series of 10000 individuals reported that 21 of 76 men with breast cancer had mutations in either BRCA1 or BRCA2; more than one-third of those mutations were in BRCA1. Brose et al. ( 16 ) estimated a lifetime risk of male breast cancer of 5.8% in BRCA1 mutation carriers, but this estimate was based on families who sought breast cancer risk counseling and was not adjusted for ascertainment. The purpose of our study was to evaluate the risk of breast carcinoma for male BRCA1 and BRCA2 mutation carriers by using a large sample of US family histories.

We used a database that contained detailed family history information for 1948 families with complete pedigrees that were collected from eight centers across the National Cancer Institute's Cancer Genetics Network (CGN). The CGN has been described in detail ( 17 ). Nine families were excluded from the analysis because of invalid entries in the pedigree. Among the remaining 1939 families, 676 were of Ashkenazi Jewish ancestry. Seven of the eight centers were high-risk counseling clinics, and one was a population-based clinic. Therefore, most of the families were ascertained based on a family history of breast and/or ovarian cancer. The institutional review boards at each participating institution approved the study protocol.

Of the 1939 families included in this analysis, 87 families (4.5%) had one or more male members with breast carcinoma; the total number of male subjects with breast carcinoma was 97. Only one person in each family, i.e., the proband, was genotyped. In 45 families (52%), the male breast cancer patient was the proband. Of the 87 probands, 23 (26%) had detectable BRCA2 mutations and six (7%) had detectable BRCA1 mutations. The median age at diagnosis of male breast cancer was 64 years (range = 24–87 years). There were three male subjects with contralateral breast cancer. Table 1 presents information for the 97 male breast cancer subjects.

Table 1

Male breast cancers, grouped by family

Mutated gene Mutation Ethnicity  Age at first diagnosis * , y   No. of female breast cancers in family † 
BRCA1 633delC Other  46 ‡ 
BRCA1 2931CC→G Other  64 ‡ 
BRCA1 2985del5 Other 73 
BRCA1 5149del5 Other 51 
BRCA1 5296del4 Other 68 
BRCA1 Exon 13 dup Other 42 
BRCA2 379delG Other  79 ‡ , 49  
BRCA2 1128insG Other  48 ‡ 
BRCA2 3034del4 Other  52 ‡ , § 
BRCA2 Y1894X Other  64 ‡ , 70  
BRCA2 6174delT Other  46 ‡ 
BRCA2 6174delT Other  61 ‡ 
BRCA2 6174delT Other  75 ‡ 
BRCA2 7989delC Other  53 ‡ , 70  
BRCA2 1538del4 Other 66 
BRCA2 1982delA Ashkenazi Jewish 85, 71 
BRCA2 2041insA Other 51 
BRCA2 3034del4 Other 47 
BRCA2 3945delA Other 66, 42 
BRCA2 4075delGT Ashkenazi Jewish 70 
BRCA2 5482delC Other 70 
BRCA2 5849del4 Other 62, 65 
BRCA2 5950delCT Other 65 
BRCA2 6051delA Other 58 
BRCA2 6174delT Other 49 
BRCA2 6174delT Ashkenazi Jewish 61 
BRCA2 6659delA Other 49 
BRCA2 9538delAA Other 50 
BRCA2 Q3066X Other 26 
None found – 18 Ashkenazi Jewish  60 ‖ (13.7)  1.56 (1.29) 
None found – 44 Other 64 (12.2) 1.45 (1.38) 
Mutated gene Mutation Ethnicity  Age at first diagnosis * , y   No. of female breast cancers in family † 
BRCA1 633delC Other  46 ‡ 
BRCA1 2931CC→G Other  64 ‡ 
BRCA1 2985del5 Other 73 
BRCA1 5149del5 Other 51 
BRCA1 5296del4 Other 68 
BRCA1 Exon 13 dup Other 42 
BRCA2 379delG Other  79 ‡ , 49  
BRCA2 1128insG Other  48 ‡ 
BRCA2 3034del4 Other  52 ‡ , § 
BRCA2 Y1894X Other  64 ‡ , 70  
BRCA2 6174delT Other  46 ‡ 
BRCA2 6174delT Other  61 ‡ 
BRCA2 6174delT Other  75 ‡ 
BRCA2 7989delC Other  53 ‡ , 70  
BRCA2 1538del4 Other 66 
BRCA2 1982delA Ashkenazi Jewish 85, 71 
BRCA2 2041insA Other 51 
BRCA2 3034del4 Other 47 
BRCA2 3945delA Other 66, 42 
BRCA2 4075delGT Ashkenazi Jewish 70 
BRCA2 5482delC Other 70 
BRCA2 5849del4 Other 62, 65 
BRCA2 5950delCT Other 65 
BRCA2 6051delA Other 58 
BRCA2 6174delT Other 49 
BRCA2 6174delT Ashkenazi Jewish 61 
BRCA2 6659delA Other 49 
BRCA2 9538delAA Other 50 
BRCA2 Q3066X Other 26 
None found – 18 Ashkenazi Jewish  60 ‖ (13.7)  1.56 (1.29) 
None found – 44 Other 64 (12.2) 1.45 (1.38) 
*

When more than one breast cancer was diagnosed in a single man, the age at each diagnosis is presented for BRCA1 and BRCA2 mutation carriers, and the mean age at diagnosis (standard deviation) is presented for noncarriers.

The mean number of female breast cancers (standard deviation) is presented for noncarriers.

Carriage of a mutation was confirmed by genotype analysis.

§

This man had contralateral breast cancer. Cancer in the second breast was diagnosed at age 55 years.

This group includes two men with contralateral male breast cancer: one was diagnosed at ages 58 and 59 years, and the other was diagnosed at age 45 years for both breasts. Both patients were genotyped, but no mutation was found.

We estimated the risk of breast cancer for men who carried a BRCA1 or BRCA2 mutation by assuming that the age-conditional probability of developing cancer at age t was that of a noncarrier multiplied by the relative risk at that age [RR( t )], which was defined as exp(α + β × t ), where α quantifies the relative risk at age 0 and β quantifies the change in relative risk with respect to age. We assumed that the age-conditional probabilities of developing cancer for noncarriers were the same as those for the US male population ( 18 ). We also assumed that the relative risks were the same for Ashkenazi Jewish and non-Ashkenazi Jewish individuals but that the relative risks differed between BRCA1 mutation carriers and BRCA2 mutation carriers.

Because our study included subjects who pursued mutation testing for BRCA1 and BRCA2, it included a greater representation of families with a history of breast and ovarian cancer than studies that have examined unselected cases of male breast cancer. To correct for possible selection bias, we used a retrospective likelihood approach ( 19 ), in which each family's contribution to the likelihood of penetrance parameters is the probability of the genetic test results conditioning on the observed family history. This approach produces unbiased estimates of risk provided that the probability of including a family in the study depends only on the family history ( 19 ) and not on other information relevant to the presence of a genetic mutation (e.g., linkage score). Because all subjects included in this study were the first person in their family to be tested for a BRCA1 or BRCA2 mutation, this approach gives unbiased estimates in our study, even though the selection of subjects into the study involves, to some extent, the subjects' own preferences.

Table 2 presents the estimated age-specific cumulative risks and relative risks of developing breast cancer for male BRCA1 and BRCA2 mutation carriers. Prospective cancer risks are provided in the BRCAPRO program ( 20 , 21 ). At all ages, the cumulative risks of male breast cancer were higher in both BRCA1 and BRCA2 mutation carriers than in noncarriers. The estimated cumulative risk of breast carcinoma for male BRCA1 mutation carriers at age 70 years was 1.2% (95% CI = 0.22% to 2.8%), and for BRCA2 mutation carriers, 6.8% (95% CI = 3.2% to 12%). The relative risks of developing male breast cancer were highest for men in their 30s and 40s and decreased with increasing age. This trend was particularly pronounced in BRCA2 mutation carriers: the relative risk at age 30 years was 22.3 times that at age 70 years.

Table 2

Age-specific cumulative risks and relative risks of developing breast cancer for male BRCA1 and BRCA2 mutation carriers and noncarriers *

 Cumulative breast cancer risk, % (95% CI) RR (95% CI) 
Age, y BRCA1 mutation carrier BRCA2 mutation carrier  No BRCA1 or BRCA2 mutation † BRCA1 mutation carrier BRCA2 mutation carrier 
30  1.7 × 10 −2 (6.8 × 10 −4 to 0.12)  0.18 (0.027 to 0.85)  1.2 × 10 −4 89 (6 to 505) 936 (201 to 3277) 
40 0.12 (0.012 to 0.58) 1.2 (0.3 to 3.6)  1.9 × 10 −3 41 (6 to 170) 396 (129 to 986) 
50 0.3 (0.052 to 1.2) 2.7 (0.94 to 6.6)  8.5 × 10 −3 23 (5 to 61) 178 (76 to 344) 
60 0.62 (0.13 to 1.7) 4.7 (1.9 to 9.5)  2.7 × 10 −2 16 (3 to 40) 84 (38 to 158) 
70 1.2 (0.22 to 2.8) 6.8 (3.2 to 12)  6.7 × 10 −2 12 (1 to 34) 42 (15 to 91) 
80 1.8 (0.3 to 4.5) 8.3 (3.9 to 15) 0.12 11 (0.3 to 34) 22 (5 to 57) 
 Cumulative breast cancer risk, % (95% CI) RR (95% CI) 
Age, y BRCA1 mutation carrier BRCA2 mutation carrier  No BRCA1 or BRCA2 mutation † BRCA1 mutation carrier BRCA2 mutation carrier 
30  1.7 × 10 −2 (6.8 × 10 −4 to 0.12)  0.18 (0.027 to 0.85)  1.2 × 10 −4 89 (6 to 505) 936 (201 to 3277) 
40 0.12 (0.012 to 0.58) 1.2 (0.3 to 3.6)  1.9 × 10 −3 41 (6 to 170) 396 (129 to 986) 
50 0.3 (0.052 to 1.2) 2.7 (0.94 to 6.6)  8.5 × 10 −3 23 (5 to 61) 178 (76 to 344) 
60 0.62 (0.13 to 1.7) 4.7 (1.9 to 9.5)  2.7 × 10 −2 16 (3 to 40) 84 (38 to 158) 
70 1.2 (0.22 to 2.8) 6.8 (3.2 to 12)  6.7 × 10 −2 12 (1 to 34) 42 (15 to 91) 
80 1.8 (0.3 to 4.5) 8.3 (3.9 to 15) 0.12 11 (0.3 to 34) 22 (5 to 57) 
*

CI = confidence interval; RR = relative risk.

The cumulative risk estimates for noncarriers were obtained from the Surveillance, Epidemiology, and End Results database, which does not provide 95% CIs.

Our study has several strengths. First, the US cohort that we used to examine male breast cancer risk is the largest to date, contains families of Ashkenazi Jewish and other ancestries, and provided risk estimates for BRCA1 and BRCA2 mutation carriers in the US population. Such risk estimates are important for determining appropriate risk management strategies for the male members of families with germline mutations in BRCA1 or BRCA2. Our cumulative risk estimates for BRCA2 mutation carriers are similar to those reported by Easton et al. ( 7 ) and Risch et al. ( 9 ). Second, to our knowledge, this study is the first to characterize the risks for male BRCA1 mutation carriers in an unbiased fashion with a large cohort. Our demonstration that BRCA1 mutations are associated with an elevated risk of male breast cancer, but that those risks are still substantially lower than those in BRCA2 mutations carriers, confirms previous suggestions ( 2 , 10 ) that the link between BRCA1 mutations and male breast carcinoma is weaker than that between BRCA2 mutations and male breast cancer.

A potential limitation of our approach is that the values we used for the BRCA1 and BRCA2 mutated allele frequencies were fixed at values derived from the literature instead of estimated from the data. For individuals of Ashkenazi Jewish ancestry, we used mutated allele frequencies of 0.0060 and 0.0067 for BRCA1 and BRCA2, respectively, according to a meta-analysis of published estimates ( 22 ). For individuals who were not of Ashkenazi Jewish ancestry, we used mutated allele frequencies of 0.00058 and 0.00067 for BRCA1 and BRCA2, respectively ( 23 , 24 ). Risch et al. ( 9 ) recently published mutated allele frequencies of 0.0016 and 0.0035 for BRCA1 and BRCA2, respectively, for individuals not of Ashkenazi Jewish ancestry living in Ontario, Canada. This BRCA2 mutated allele frequency is fivefold larger than the frequency we used. To test the robustness of our risk estimates with respect to allele frequency, we repeated the analysis with the higher allele frequencies. As a result, the cumulative risks by age 80 years decreased from 1.8% (95% CI = 0.3% to 4.5%) to 1.5% (95% CI = 0.3% to 3.9%) for BRCA1 and from 8.3% (95% CI = 3.9% to 15%) to 5.1% (95% CI = 2.0% to 11.0%) for BRCA2. The relative risks at younger ages were also smaller than the ones we estimated in the original analysis (e.g., the relative risks for BRCA1 and BRCA2 mutation carriers at age 30 years were 24 [95% CI = 2.4 to 102] and 430 [95% CI = 68 to 1759], respectively). The relative risks gradually decreased with increasing age, and the relative risks at age 80 years (e.g., 11 [95% CI = 1.7 to 34) for BRCA1 mutation carriers and 16 [95% CI = 5.1 to 42] for BRCA2 mutation carriers) were similar to the ones estimated in our original analysis ( Table 2 ). These similar risk estimates suggest that our approach was robust across a range of allele frequencies.

Another limitation of our study is that we had no information about family members' ethnicity group other than their Ashkenazi Jewish ancestry. Therefore, we were not able to estimate the penetrance of mutations in BRCA1 and BRCA2 for African Americans, for whom the male-to-female ratio for breast carcinoma is higher than it is for white populations ( 2 , 25 ).

The male penetrance estimates reported here have been incorporated into the current version of the BayesMendel genetic counseling software and which is available to genetic counselors through the CaGene software package ( 26 ).

Funding

Cancer Genetics Network at Duke University (U24 CA78157) and at The Johns Hopkins University (U24 CA78148); The Johns Hopkins Specialized Projects of Oncology Research Excellence in Breast Cancer (P50CA88843 to G. P.); National Cancer Institute (R01CA105090-01A1 to S. C., G. P., and Y. C. T. and P50CA62924-05 to G. P.).

References

(1)
Landis
SH
Murray
T
Bolden
S
Wingo
PA
Cancer statistics, 1999
CA Cancer J Clin
 , 
1999
, vol. 
49
 (pg. 
8
-
31
)
(2)
Lynch
HT
Watson
P
Narod
SA
The genetic epidemiology of male breast carcinoma
Cancer
 , 
1999
, vol. 
86
 (pg. 
744
-
6
)
(3)
Thorlacius
S
Tryggvadottir
L
Olafsdottir
GH
Jonasson
JG
Ogmundsdottir
HM
Tulinius
H
, et al.  . 
Linkage to BRCA2 region in hereditary male breast cancer
Lancet
 , 
1995
, vol. 
346
 (pg. 
544
-
5
)
(4)
Wooster
R
Bignell
G
Lancaster
J
Swift
S
Seal
S
Mangion
J
, et al.  . 
Identification of the breast cancer susceptibility gene BRCA2
Nature
 , 
1995
, vol. 
378
 (pg. 
789
-
92
)
(5)
Ford
D
Easton
DF
Stratton
M
Narod
S
Goldgar
D
Devilee
P
, et al.  . 
Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families
Am J Hum Genet
 , 
1998
, vol. 
62
 (pg. 
676
-
89
)
(6)
Couch
FJ
Farid
LM
DeShano
ML
Tavtigian
SV
Calzone
K
Campeau
L
, et al.  . 
BRCA2 germline mutations in male breast cancer cases and breast cancer families
Nat Genet
 , 
1996
, vol. 
13
 (pg. 
123
-
5
)
(7)
Easton
DF
Steele
L
Fields
P
Ormiston
W
Averill
D
Daly
PA
, et al.  . 
Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13
Am J Hum Genet
 , 
1997
, vol. 
61
 (pg. 
120
-
8
)
(8)
Thompson
D
Easton
D
Variation in cancer risks, by mutation position, in BRCA2 mutation carriers
Am J Hum Genet
 , 
2001
, vol. 
68
 (pg. 
410
-
19
)
(9)
Risch
HA
McLaughlin
JR
Cole
DE
Rosen
B
Bradley
L
Fan
I
, et al.  . 
Population BRCA1 and BRCA2 mutation frequencies and cancer penetrances: a kin-cohort study in Ontario, Canada
J Natl Cancer Inst
 , 
2006
, vol. 
98
 (pg. 
1694
-
706
)
(10)
Stratton
MR
Ford
D
Neuhasen
S
Seal
S
Wooster
R
Friedman
LS
, et al.  . 
Familial male breast cancer is not linked to the BRCA1 locus on chromosome 17q
Nat Genet
 , 
1994
, vol. 
7
 (pg. 
103
-
7
)
(11)
Struewing
JP
Coriaty
ZM
Ron
E
Livoff
A
Konichezky
M
Cohen
P
, et al.  . 
BRCA1/2 mutations among male patients with breast cancer in Israel
Am J Hum Genet
 , 
1999
, vol. 
65
 (pg. 
1800
-
2
)
(12)
Sverdlov
RS
Barshack
I
Bar Sade
RB
Baruch
RG
Hirsh-Yehezkel
G
Dagan
E
, et al.  . 
Genetic analyses of male breast cancer in Israel
Genet Test
 , 
2000
, vol. 
4
 (pg. 
313
-
7
)
(13)
Friedman
LS
Gayther
SA
Kurosaki
T
Gordon
D
Noble
B
Casey
G
Mutation analysis of BRCA1 and BRCA2 in a male breast cancer population
Am J Hum Genet
 , 
1997
, vol. 
60
 (pg. 
313
-
9
)
(14)
Csokay
B
Udvarhelyi
N
Sulyok
Z
Besznyak
I
Ramus
S
Ponder
B
, et al.  . 
High frequency of germline BRCA2 mutations among Hungarian male breast cancer patients without family history
Cancer Res
 , 
1999
, vol. 
59
 (pg. 
995
-
8
)
(15)
Frank
TS
Deffenbaugh
AM
Reid
JE
Hulick
M
Ward
BE
Lingenfelter
B
, et al.  . 
Clinical characteristics of individuals with germline mutations in BRCA1 and BRCA2: analysis of 10,000 individuals
J Clin Oncol
 , 
2002
, vol. 
20
 (pg. 
1480
-
90
)
(16)
Brose
MS
Rebbeck
TR
Calzone
KA
Stopfer
JE
Nathanson
KL
Weber
BL
Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program
J Natl Cancer Inst
 , 
2002
, vol. 
94
 (pg. 
1365
-
72
)
(17)
Chen
S
Iversen
ES
Friebel
T
Finkelstein
D
Weber
BL
Eisen
A
, et al.  . 
Characterization of BRCA1 and BRCA2 mutations in a large United States sample
J Clin Oncol
 , 
2006
, vol. 
24
 (pg. 
863
-
71
)
(18)
Fay
MP
Pfeiffer
R
Cronin
KA
Le
C
Feuer
EJ
Age-conditional probabilities of developing cancer
Stat Med
 , 
2003
, vol. 
22
 (pg. 
1837
-
48
)
(19)
Kraft
P
Thomas
DC
Bias and efficiency in family-based gene-characterization studies: conditional, prospective, retrospective, and joint likelihoods
Am J Hum Genet
 , 
2000
, vol. 
66
 (pg. 
1119
-
31
)
(20)
Parmigiani
G
Berry
DA
Aguilar
O
Determining carrier probabilities for breast cancer susceptibility genes BRCA1 and BRCA2
Am J Hum Genet
 , 
1998
, vol. 
62
 (pg. 
145
-
58
)
(21)
Chen
S
Wang
W
Broman
K
Katki
HA
Parmigiani
G
BayesMendel: an R environment for Mendelian risk prediction
Stat Appl Genet Mol Biol
 , 
2004
, vol. 
3
 
1
 
Article 21
(22)
Chen
S
Parmigiani
G
Meta-analysis of BRCA1 and BRCA2 penetrance
J Clin Oncol
 , 
2007
, vol. 
25
 (pg. 
1329
-
33
)
(23)
Andersen
TI
Genetic heterogeneity in breast cancer susceptibility
Acta Oncol
 , 
1996
, vol. 
35
 (pg. 
407
-
10
)
(24)
Antoniou
AC
Pharoah
PDP
McMullan
G
Day
NE
Stratton
MR
Peto
J
, et al.  . 
A comprehensive model for familial breast cancer incorporating BRCA1, BRCA2 and other genes
Br J Cancer
 , 
2002
, vol. 
86
 (pg. 
76
-
83
)
(25)
Sasco
AJ
Lowenfels
AB
Pasker-De Jong
P
Review article: epidemiology of male breast cancer. A meta-analysis of published case–control studies and discussion of selected aetiological factors
Int J Cancer
 , 
1993
, vol. 
53
 (pg. 
538
-
49
)
(26)
Euhus
DM
Smith
KC
Robinson
L
Stucky
A
Olopade
OI
Cummings
S
, et al.  . 
Pretest prediction of BRCA1 or BRCA2 mutation by risk counselors and the computer model BRCAPRO
J Natl Cancer Inst
 , 
2002
, vol. 
94
 (pg. 
844
-
51
)
The authors wish to thank the following members of the CGN BRCA1/2 Models Validation Study, who contributed to the original collection of the cohort used: Edwin S. Iversen; Tara M. Friebel; Dianne M. Finkelstein; Barbara L. Weber; Andrea Eisen; Leif E. Peterson; Joellen M. Schildkraut; Claudine Isaacs; Camille Corio; Leoni Leondaridis; Gail Tomlinson; Christopher I. Amos; Louise C. Strong; Donald A. Berry; Jeffrey N. Weitzel; Sharon Sand; Debra Dutson; Rich Kerber; Beth N. Peshkin; and David M. Euhus. The CGN steering committee reviewed the design of the study. The CGN funded part of the study and is responsible for good research practices and for data storage. The CGN and the other funding sources, listed in the Funding section, had no other role in the design, conduct, or reporting of the study.