The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 among Ashkenazi Jews
Jeffery P. Struewing, M.D., Patricia Hartge, Sc.D., Sholom Wacholder, Ph.D., Sonya M. Baker, B.S., Martha Berlin, B.A., Mary McAdams, M.S., Michelle M. Timmerman, B.S., Lawrence C. Brody, Ph.D., and Margaret A. Tucker, M.D.
Background Carriers of germ-line mutations in BRCA1 and BRCA2from families at high risk for cancer have been estimated tohave an 85 percent risk of breast cancer. Since the combinedfrequency of BRCA1 and BRCA2 mutations exceeds 2 percent amongAshkenazi Jews, we were able to estimate the risk of cancerin a large group of Jewish men and women from the Washington,D.C., area.
Methods We collected blood samples from 5318 Jewish subjectswho had filled out epidemiologic questionnaires. Carriers ofthe 185delAG and 5382insC mutations in BRCA1 and the 6174delTmutation in BRCA2 were identified with assays based on the polymerasechain reaction. We estimated the risks of breast and other cancersby comparing the cancer histories of relatives of carriers ofthe mutations and noncarriers.
Results One hundred twenty carriers of a BRCA1 or BRCA2 mutationwere identified. By the age of 70, the estimated risk of breastcancer among carriers was 56 percent (95 percent confidenceinterval, 40 to 73 percent); of ovarian cancer, 16 percent (95percent confidence interval, 6 to 28 percent); and of prostatecancer, 16 percent (95 percent confidence interval, 4 to 30percent). There were no significant differences in the riskof breast cancer between carriers of BRCA1 mutations and carriersof BRCA2 mutations, and the incidence of colon cancer amongthe relatives of carriers was not elevated.
Conclusions Over 2 percent of Ashkenazi Jews carry mutationsin BRCA1 or BRCA2 that confer increased risks of breast, ovarian,and prostate cancer. The risks of breast cancer may be overestimated,but they fall well below previous estimates based on subjectsfrom high-risk families.
Current estimates of the risk of breast cancer in a woman whocarries a BRCA1 or BRCA2 mutation and is from a kindred withmultiple cases of breast or ovarian cancer, or both, range from76 to 87 percent.1,2,3,4 Estimates of the risk of ovarian cancerin a woman from such a kindred range from 32 to 84 percent forcarriers of BRCA1 mutations but are much lower for carriersof BRCA2 mutations.2,3,4 These results were derived from studiesof high-risk families and may not apply to all carriers of BRCA1or BRCA2 mutations.
The large size of the BRCA1 and BRCA2 genes, the dispersed locationsof the more than 140 mutations identified thus far,5,6,7 andthe lack of functional assays hamper the direct estimation ofcarrier frequencies and cancer risks in the general population.However, characteristic BRCA1 and BRCA2 mutations have beenidentified in Ashkenazi Jews, a genetically distinct populationof Jews whose ancestors lived in central and eastern Europe.8,9,10,11,12The combined frequency of the mutations in BRCA1 involving thedeletion of an adenine and guanine (185delAG) and the insertionof a cytosine (5382insC) and the mutation in BRCA2 involvingthe deletion of a thymine (6174delT) exceeds 2 percent.13,14,15Thus, within this group, relatively simple assays can identifyenough carriers to estimate the risk of cancer in the generalpopulation.
Methods
Recruitment of Subjects
Jewish men and women over the age of 20 were recruited fromthe Washington, D.C., area through posters, newspapers, andradio announcements in the general and Jewish media. Steeringand advisory committees composed of members of Jewish organizations,breast-cancer advocacy groups, and medical groups reviewed theprotocol, consent form, and recruitment procedures. The participantsdid not receive their individual test results. The study wasapproved by an institutional review board of the National Institutesof Health.
Collection of Data
The subjects were enrolled at 15 sites over a nine-week period.After giving informed consent, the participants completed aself-administered questionnaire and gave a blood sample. Thequestionnaire included questions on the country of origin ofthe subjects' parents and grandparents; the age, vital status,and cancer history of first-degree relatives, grandparents,and half-siblings; and the numbers and selected cancer historyof aunts and uncles. Participants were also asked to list relativeswho had volunteered or might volunteer for the study. We createdfamily sets using family-history data and information aboutother relatives who had volunteered. A total of 4873 sets werecreated: 326 from 771 related subjects and 4547 from subjectswith no participating relatives. After the family sets werecreated, links between the participants' names and assignedstudy numbers were destroyed.
Phlebotomists used finger-stick procedures to collect 100 to150 µl of blood from each subject, which was then transferredonto collection cards (Isocode, Schleicher and Scheull, Keene,N.H.). DNA was isolated from two 3-mm punches of a blood spotin 96-well trays according to the manufacturer's instructionswith a slight modification. Allele-specific oligonucleotideassays were used to detect two mutations in BRCA1: 185delAGand the deletion of 11 bp at position 188 (188del11). Allele-specificpolymerase-chain-reaction (PCR) assays were used to identifythe 5382insC mutation in BRCA1 and the 6174delT mutation inBRCA2.16 For each mutation, genomic DNA from a person knownto be heterozygous for that mutation was included in 96-wellPCR trays for each assay.
A second round of isolation of DNA and assays was performedon all samples initially scored as positive and on at least250 samples initially scored as negative. There were no falsenegative results and three (2.4 percent) false positive results(two involving 185delAG and one involving 6174delT). Only samplesthat were positive on retesting were considered positive inthe statistical analyses.
Statistical Analysis
Carrier frequencies and exact binomial 95 percent confidenceintervals were calculated for the entire group and for subgroupscategorized according to the age at diagnosis and family history.
To estimate the risks of breast, ovarian, and prostate canceramong carriers of BRCA1 and BRCA2 mutations, we compared thehistory of cancer among the set of 306 female and 273 male first-degreerelatives identified by participants who were found to be carrierswith the history among 13,018 female and 13,324 male first-degreerelatives identified by participants who were not carriers.If two or more family members volunteered for the study, weselected one to define the carrier status of the family andthe set of first-degree relatives, so that no relative was includedmore than once and the number of informative person-years wasmaximized. For example, if one of two sibling volunteers carrieda mutation, the mother was counted only once, as a first-degreerelative of a carrier. The participants' self-reports of cancerwere not considered in the risk calculations.
The probability of disease among the first-degree relativesof carriers of a mutation (R+) can be expressed as
R+ = (p/2 + 1/2)S1 + (1/2 - p/2)S0.
The probability of disease among the first-degree relativesof noncarriers (R-) can be expressed as
R- = pS1 + (1 - p)S0.
In these equations p is the frequency of the mutant allele,S1 the risk of disease among carriers (penetrance), and S0 therisk of disease among noncarriers. By solving two equationsin two unknowns, S1 and S0 can be expressed as functions ofwhat we observed:
S1 = 2R+ - R-
and
S0 = ((1 + p)/(1 - p)) (R- - 2 (p/(1 - p)) R+.
R+ and R- were estimated with Kaplan–Meier curves. Althoughtrue cumulative risks cannot decrease with age, our estimatescan do so because they represent the difference between twocumulative risks. We used a bootstrap method to estimate thevariance of the risk estimates. The reported 95 percent confidenceintervals for the risk of cancer are the 25th and 975th orderedvalues from 1000 random samplings of the data (with replacement),with the family as the unit. We also calculated the risk ofbreast cancer with various groups of participants excluded:survivors of breast and ovarian cancer, female subjects, andthose under the age of 50. To explore the risk of cancers otherthan breast, ovarian, and prostate cancer, we compared the proportionsof carrier and noncarrier families in which at least one caseof cancer was reported, using the chi-square test.
Results
Of the 5331 persons who completed the questionnaire and provideda blood sample, 7 were excluded because they were adopted and6 were excluded for other reasons. Of the remaining 5318 participants,all were genotyped for the 5382insC and 185delAG mutations inBRCA1; 5087 gave permission for the future use of their samples,which were analyzed for the 6174delT mutation in BRCA2; and1000 samples were arbitrarily chosen to be assayed for the 188del11mutation in BRCA1. Forty-six percent of the subjects were underthe age of 50, and nearly 30 percent were men (Table 1). Theparticipants were highly educated, with over 57 percent reportinga postgraduate degree.
Table 1. Demographic Characteristics of the Subjects.
Mutations were found in 120 participants (Table 2). Of these,61 had BRCA1 mutations (185delAG in 41 and 5382insC in 20) and59 had the 6174delT mutation in BRCA2. No 188del11 mutationsin BRCA1 were detected in the 1000 arbitrarily chosen samplesthat were tested. No participant carried more than one of thethree mutations, and no subjects were identified who were homozygousfor the 185delAG mutation. The methods of detection we usedcould not rule out homozygosity for the 5382insC and 6174delTmutations. Younger age at diagnosis among survivors of breastor ovarian cancer and a family history of breast cancer in first-degreerelatives were associated with higher carrier frequencies (Table 2).
Table 2. Carrier Frequencies for BRCA1 or BRCA2 Mutations among the Subjects.
Figure 1A shows the Kaplan–Meier estimates of the reportedincidence of breast cancer among first-degree female relativesof the subjects. From these data the risk of cancer and 95 percentconfidence interval were estimated for all carriers combined(Figure 1B) and for carriers according to the mutation identified(Figure 1C). The estimated risk of breast cancer at the ageof 50 among carriers was 33 percent (95 percent confidence interval,23 to 44 percent), as compared with 4.5 percent (95 percentconfidence interval, 4.0 to 5.0 percent) among noncarriers.The estimated risks among carriers and noncarriers at the ageof 70 were 56 percent (95 percent confidence interval, 40 to73 percent) and 13 percent (95 percent confidence interval,12 to 14 percent), respectively. Excluding the family-historyinformation of subjects who were survivors of breast or ovariancancer lowered the risk estimate at the age of 70 to 54 percent;excluding all female subjects reduced it to 43 percent; andexcluding all subjects under the age of 50 lowered it to 42percent.
Figure 1. Kaplan–Meier Estimates of the Incidence or Risk of Breast Cancer.
Panel A shows the reported incidence of breast cancer among first-degree female relatives of subjects who carried a BRCA1 or BRCA2 mutation and those of subjects who did not. Panel B shows the estimated risk of breast cancer and 95 percent confidence intervals among carriers and noncarriers of a BRCA1 or BRCA2 mutation. The difference in risk between the two groups was statistically significant by the age of 35. Panel C shows the estimated risk of breast cancer among carriers of each of the three mutations. The 95 percent confidence intervals are not shown but are about 50 percent wider than the upper curve in Panel B and are widely overlapping.
The risk of ovarian cancer was also significantly elevated amongcarriers of BRCA1 or BRCA2 mutations (Figure 2A). The estimatedrisk was 7 percent (95 percent confidence interval, 2 to 14percent) by the age of 50 and 16 percent (95 percent confidenceinterval, 6 to 28 percent) by the age of 70. Among noncarriersthe risk of ovarian cancer was 0.4 percent (95 percent confidenceinterval, 0.2 to 0.6 percent) by the age of 50 and 1.6 percent(95 percent confidence interval, 1.2 to 2.0 percent) by theage of 70. The estimated risk by the age of 70 was higher amongcarriers of the 5382insC mutation (22 percent) than among thosewith the 6174delT mutation (18 percent) or the 185delAG mutation(12 percent), but the differences between groups were not statisticallysignificant (Figure 2B).
Figure 2. Estimates of the Risk of Ovarian Cancer.
Panel A shows the estimated risk of ovarian cancer and 95 percent confidence intervals among carriers and noncarriers of BRCA1 or BRCA2 mutations. The differences were statistically significant by the age of 45. Panel B shows the estimated risk of ovarian cancer among carriers of each mutation. Although not shown, the 95 percent confidence intervals are widely overlapping.
The estimated risk of prostate cancer among carriers of a BRCA1or BRCA2 mutation was low before the age of 50, but it was 16percent (95 percent confidence interval, 4 to 30 percent) atthe age of 70, as compared with 3.8 percent (95 percent confidenceinterval, 3.3 to 4.4 percent) among noncarriers (Figure 3A).The risk among carriers of BRCA1 mutations (25 percent) washigher than that among carriers of the BRCA2 mutation (5 percent)at the age of 70, but the difference was smaller by the ageof 80 (Figure 3B).
Figure 3. Estimates of the Risk of Prostate Cancer.
Panel A shows the estimated risk of prostate cancer and 95 percent confidence intervals among carriers and noncarriers of BRCA1 or BRCA2 mutations. The differences were statistically significant by the age of 67. Panel B shows the estimated risk of prostate cancer among carriers of each mutation. Although not shown, the 95 percent confidence intervals are widely overlapping.
Colon cancer was reported less frequently among the familiesof subjects who had a BRCA1 or BRCA2 mutation than among thefamilies of noncarriers (Table 3). Of 16 subjects who reportedhaving a male relative with breast cancer, 1 carried the 6174delTmutation. A comparison of the rates of all cancers (except nonmelanomaskin cancer) reported in families with two or more carriersis shown in Table 3.
Table 3. Percentages of Carriers and Noncarriers of BRCA1 or BRCA2 Mutations with a Family History of Selected Cancers.
Of the 120 subjects who carried a BRCA1 or BRCA2 mutation, 31did not report a family history of breast or ovarian canceramong first- or second-degree relatives. Among the subjectsand their first-degree relatives, there were an average of 3.3women in the families without a history of breast or ovariancancer, as compared with 3.7 in the families with such a history.Among carriers with no family history of breast or ovarian cancerin a first-degree relative, 18 percent had three or more first-degreefemale relatives over the age of 40.
Discussion
From these studies of Jewish subjects, we estimate that therisk of breast cancer among carriers of one of three BRCA1 andBRCA2 mutations is 33 percent by the age of 50 and 56 percentby the age of 70 (95 percent confidence interval, 40 to 73 percent).These estimates fall well below most prior estimates of therisk of cancer among carriers of BRCA1 or BRCA2 mutations fromfamilies with breast cancer, but they concern particular BRCA1and BRCA2 mutations and may not apply to carriers of other mutations.The estimated risk among carriers of the 6174delT mutation inBRCA2 was slightly lower than that among carriers of the 185delAGmutation in BRCA1, and this difference was more pronounced upto the age of 50 (26 percent vs. 34 percent). Previous analysesof small series of Jewish women with early-onset breast cancersuggested that the risk of early-onset disease was much loweramong those with the 6174delT mutation than among those withthe 185delAG mutation.11,14,15,17 Our results suggest that thedifference, if real, is small and decreases in later life, underscoringthe uncertainties inherent in the early stages of this research.The apparent risk of cancer was the highest among carriers ofthe 5382insC mutation in BRCA1, but it was based on small numbersand the differences in risk associated with the three mutationswere not statistically significant.
The estimated risk of ovarian cancer, based on small numbers,was 16 percent by the age of 70 among carriers of a mutation.Surprisingly, the estimated risks were highest among carriersof 5382insC, lowest among carriers of 185delAG, and intermediateamong those with the 6174delT mutation in BRCA2. Earlier datasuggested that the risk of ovarian cancer was higher for BRCA1than for BRCA2 mutations3 and higher for mutations in the 5'end of BRCA1.18 The 6174delT mutation is within a portion ofthe BRCA2 gene that may be associated with a high risk of ovariancancer.19 Studies of larger series may clarify the relativerisk of ovarian cancer for different mutations in BRCA1 andBRCA2.
We found a significantly elevated estimated risk of prostatecancer among carriers of BRCA1 or BRCA2 mutations. This suggeststhat prostate cancer is part of the phenotype for these carriersand supports previous observations.2,20,21 The risk was higheramong carriers of BRCA1 mutations, but the estimates for eachmutation rose considerably after the age of 60, reaching 16percent by the age of 70 and 39 percent by the age of 80. Aprevious study2 showed a higher-than-normal incidence of coloncancer among carriers of BRCA1 mutations, but we did not findthat in this study. Very few subjects reported having male relativeswith breast cancer, and the only carrier reporting having suchrelatives had the 6174delT mutation in BRCA2, which has previouslybeen associated with male breast cancer.3,12,21,22
A family history of several rare cancers in first-degree relativeswas reported more frequently among subjects with mutations thanamong those with no identified mutations. Both pancreatic cancerand lymphoma were reported about twice as frequently in theformer group, but the differences between groups were not significant.Multiple myeloma was reported more frequently among the familiesof carriers, and Hodgkin's disease and lung cancer were morecommon among families with carriers of the 6174delT mutation.Although based on small numbers, these associations point tocancers that may warrant further investigation with respectto BRCA1 and BRCA2.
In our study population, 2.3 percent were carriers of a BRCA1or BRCA2 mutation, a rate that is very close to previous resultsin studies of Ashkenazi Jews.13,14,15 We analyzed 1000 samplesand did not detect 188del11, a BRCA1 mutation found to be commonin one study23 but not in other studies4,7,11,24,25 of thisethnic group. Subjects with a family history of breast or ovariancancer were more likely to have a mutation, but 31 carriersdid not report a history of breast or ovarian cancer among first-or second-degree relatives. A few such persons would be expectedbecause, especially in small families, by chance there may beno female carriers.
Small family size does not entirely explain the absence of afamily history of breast and ovarian cancer among carriers ofa BRCA1 or BRCA2 mutation, however, because 18 percent of thecarriers with no family history of breast or ovarian cancerhad three or more first-degree female relatives over the ageof 40. The observations in this and other studies11,24,26 ofcarriers without a family history of breast cancer contrastwith the estimated risk of breast cancer of approximately 85percent among high-risk pedigrees, suggesting that there maybe considerable variability in the risk of cancer among carriers.This variation may be due to chance, to genetic and environmentalmodifying factors, or to both. The study of families with anapparently low risk of cancer may help elucidate such modifiers,allowing more refined estimates of an individual person's riskof cancer.
The most important limitation of our study is the disproportionatenumber of subjects who reported a family history of breast cancerand, to a lesser degree, of other cancers. This bias would tendto inflate the estimates of the risk of cancer for both carriersand noncarriers. Our estimated risks would be unbiased if thestudy subjects had the same frequency of a family history ofcancer as nonparticipants. Because the frequency of a familyhistory of cancer in our subjects is probably higher than thatin nonparticipants, our estimates are likely to be higher thanthose for the total Jewish population. Among women with no priorhistory of breast or ovarian cancer, 19 percent of those whowere under the age of 50 and 23 percent of those who were 50or older reported having a first-degree relative with breastcancer, as did 16 percent of the men in the study. These ratesare almost twice the rates for control Jewish women in two smallcase–control studies27,28 (and Brinton L: personal communication)and are considerably higher than those from a recent study inwhich the reported rate of a family history of breast cancerseemed especially low.29 The subjects' reports of a historyof familial cancer were not verified in our study or in theseother studies.27,28,29 As compared with the rates of canceramong whites from population-based Surveillance, Epidemiology,and End Results registries,30 our risk estimates for noncarrierswere 68 percent higher for breast cancer, 48 percent higherfor ovarian cancer, and 5 percent higher for prostate cancer.
Precisely how much the bias introduced by the use of volunteersinflated our risk estimates as they apply to the entire Jewishpopulation is unknown, but analysis of subgroups of the datain which the bias is less pronounced indicates the potentialmagnitude of the effect. At the age of 70, the risk of breastcancer was 56 percent among all subjects, 54 percent after theexclusion of women who had survived breast or ovarian cancer,43 percent after the exclusion of female subjects, and 42 percentwhen subjects under the age of 50 were excluded. These analysessuggest that the true risk of breast cancer may be 50 percentor lower, an estimate that is both quantitatively and qualitativelylower than most prior estimates.
All the subjects came from a limited geographic region wherethe relative frequency of specific mutations may differ fromthat in other Jewish communities. Also, there may be unknowngenetic or environmental factors among the Ashkenazi populationthat affect the extrapolation of these risk estimates to otherpopulations carrying the same mutations. We screened for onlyfour specific mutations, but there may be other, as yet undetectedBRCA1 or BRCA2 mutations among Ashkenazi Jews. The analysisof a large number of people with the same mutations is advantageouswith regard to allelic homogeneity, but the degree to whichour risk estimates apply to carriers of other BRCA1 and BRCA2mutations is unknown. Knowing the country of origin of the subjects'grandparents did not differentiate carriers from noncarriers.Fewer than 50 subjects reported exclusively Sephardic ancestors;but since for many of these subjects the reported countriesof origin of all ancestors were in central and eastern Europe,no participants were excluded on the basis of Jewish ethnicgroup.
This community-based study is a departure from previous investigationsof genetic predisposition to cancer in high-risk families. Thecommitment of the Jewish population allowed us to recruit manyvolunteers with little or no family history of breast cancer.But the technical ease of identifying large numbers of carriersof a BRCA1 or BRCA2 mutation forces us to confront the ethicalissues raised by testing for genetic predisposition for cancer,such as the insurability and employability of persons identifiedas carriers and their relatives and the psychological and socialconsequences of the test results.31,32,33,34
We are indebted to David Pee for programming assistance; toPat Barr, Laura Friedan, Deborah Goldstein, Ginny Hartmuller,Dr. Michael Kaback, Rabbi Saul Koss, Dr. Caryn Lerman, ArnaMeyer Mickelson, Rabbi Avis Miller, Pat Newman, Dr. DaniellaSeminara, Rabbi Matthew Simon, Linda Slan, Joe Waksberg, andFran Visco for serving on the steering and advisory committeesfor the study; to Lisa Cadwallader, Nelvis Castro, Carin Cooper,Garry Curtis, Joan Felreis, Shirley Friend, Dannie Hansma, GlennHarke, Lynn Kletzkin, Catherine Law, Kathy Measday, Nancy Nelson,Helen Price, Dina Ra'ad, Phyllis Savino, Melissa Taylor, andthe entire staff involved in data collection for their assistance;to the many volunteer staff at the data-collection sites; andto the participants.
* See NAPS document no. 05401 for 5 pages of supplementary material.Order from NAPS c/o Microfiche Publications, P.O. Box 3513,Grand Central Station, New York, NY 10163-3513.
Source Information
From the Division of Cancer Epidemiology and Genetics, National Cancer Institute (J.P.S., P.H., S.W., M.A.T.), and the Laboratory of Gene Transfer, National Human Genome Research Institute (J.P.S., S.M.B., M.M.T., L.C.B.), National Institutes of Health, Bethesda, Md.; Westat, Inc., Rockville, Md. (M.B.); and IMS, Inc., Silver Spring, Md. (M.M.).
Address reprint requests to Dr. Struewing at the Genetic Epidemiology Branch, Bldg. EPN, Rm. 439, 6130 Executive Blvd., MSC 7372, Bethesda, MD 20892-7372.
References
Easton DF, Bishop DT, Ford D, Crockford GP, Breast Cancer Linkage Consortium. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. Am J Hum Genet 1993;52:678-701. [Medline]
Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE, Breast Cancer Linkage Consortium. Risks of cancer in BRCA1-mutation carriers. Lancet 1994;343:692-695. [CrossRef][Medline]
Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 1994;265:2088-2090. [Free Full Text]
Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Am J Hum Genet 1995;56:265-271. [Medline]
Couch FJ, Weber BL, Breast Cancer Information Core. Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Hum Mutat 1996;8:8-18. [CrossRef][Medline]
Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995;378:789-792. [CrossRef][Medline]
Tavtigian SV, Simard J, Rommens J, et al. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 1996;12:333-337. [CrossRef][Medline]
Struewing JP, Brody LC, Erdos MR, et al. Detection of eight BRCA1 mutations in 10 breast/ovarian cancer families, including 1 family with male breast cancer. Am J Hum Genet 1995;57:1-7. [Medline]
Tonin P, Serova O, Lenoir G, et al. BRCA1 mutations in Ashkenazi Jewish women. Am J Hum Genet 1995;57:189-189. [Medline]
Neuhausen S, Gilewski T, Norton L, et al. Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish women affected by breast cancer. Nat Genet 1996;13:126-128. [CrossRef][Medline]
FitzGerald MG, MacDonald DJ, Krainer M, et al. Germ-line BRCA1 mutations in Jewish and non-Jewish women with early-onset breast cancer. N Engl J Med 1996;334:143-149. [Free Full Text]
Couch FJ, Farid LM, DeShano ML, et al. BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nat Genet 1996;13:123-125. [CrossRef][Medline]
Struewing JP, Abeliovich D, Peretz T, et al. The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 1995;11:198-200. [CrossRef][Medline]
Roa BB, Boyd AA, Volcik K, Richards CS. Ashkenazi Jewish population frequencies for common mutations in BRCA1 and BRCA2. Nat Genet 1996;14:185-187. [CrossRef][Medline]
Oddoux C, Struewing JP, Clayton CM, et al. The carrier frequency of the BRCA2 6174delT mutation among Ashkenazi Jewish individuals is approximately 1%. Nat Genet 1996;14:188-190. [CrossRef][Medline]
Sommer SS, Groszbach AR, Bottema CDK. PCR amplification of specific alleles (PASA) is a general method for rapidly detecting known single-base changes. Biotechniques 1992;12:82-87. [Medline]
Offit K, Gilewski T, McGuire P, et al. Germline BRCA1 185delAG mutations in Jewish women with breast cancer. Lancet 1996;347:1643-1645. [CrossRef][Medline]
Gayther SA, Warren W, Mazoyer S, et al. Germline mutations of the BRCA1 gene in breast and ovarian cancer families provide evidence for a genotype-phenotype correlation. Nat Genet 1995;11:428-433. [CrossRef][Medline]
Gayther SA, Mangion J, Russell P, et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet 1997;15:103-105. [CrossRef][Medline]
Tonin P, Ghadirian P, Phelan C, et al. A large multisite cancer family is linked to BRCA2. J Med Genet 1995;32:982-984. [Abstract]
Thorlacius S, Olafsdottir G, Tryggvadottir L, et al. A single BRCA2 mutation in male and female breast cancer families from Iceland with varied cancer phenotypes. Nat Genet 1996;13:117-119. [CrossRef][Medline]
Phelan CM, Lancaster JM, Tonin P, et al. Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet 1996;13:120-122. [CrossRef][Medline]
Berman DB, Wagner-Costalas J, Schultz DC, Lynch HT, Daly M, Godwin AK. Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG-mutation kindreds. Am J Hum Genet 1996;58:1166-1176. [Medline]
Muto MG, Cramer DW, Tangir J, Berkowitz R, Mok S. Frequency of the BRCA1 185delAG mutation among Jewish women with ovarian cancer and matched population controls. Cancer Res 1996;56:1250-1252. [Free Full Text]
Tonin P, Weber B, Offit K, et al. Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 1996;2:1179-1183. [CrossRef][Medline]
Langston AA, Malone KE, Thompson JD, Daling JR, Ostrander EA. BRCA1 mutations in a population-based sample of young women with breast cancer. N Engl J Med 1996;334:137-142. [Free Full Text]
Brinton LA, Daling JR, Liff JM, et al. Oral contraceptives and breast cancer risk among younger women. J Natl Cancer Inst 1995;87:827-835. [Free Full Text]
Hartge P, Schiffman MH, Hoover R, McGowan L, Lesher L, Norris HJ. A case-control study of epithelial ovarian cancer. Am J Obstet Gynecol 1989;161:10-16. [Medline]
Egan KM, Newcomb PA, Longnecker MP, et al. Jewish religion and risk of breast cancer. Lancet 1996;347:1645-1646. [CrossRef][Medline]
Feuer EJ, Wun LM, Boring CC, Flanders WD, Timmel MJ, Tong T. The lifetime risk of developing breast cancer. J Natl Cancer Inst 1993;85:892-897. [Free Full Text]
Lerman C, Croyle R. Psychological issues in genetic testing for breast cancer susceptibility. Arch Intern Med 1994;154:609-616. [CrossRef][Medline]
Rothenberg KH. Genetic information and health insurance: state legislative approaches. J Law Med Ethics 1995;23:312-319. [Medline]
Hubbard R, Lewontin RC. Pitfalls of genetic testing. N Engl J Med 1996;334:1192-1194. [Free Full Text]
Lapham EV, Kozma C, Weiss JO. Genetic discrimination: perspectives of consumers. Science 1996;274:621-624. [Free Full Text]
Allain, D. C.
(2008). Genetic Counseling and Testing for Common Hereditary Breast Cancer Syndromes: A Paper from the 2007 William Beaumont Hospital Symposium on Molecular Pathology. J. Mol. Diagn.
10: 383-395
[Abstract][Full Text]
Palma, M. D., Domchek, S. M., Stopfer, J., Erlichman, J., Siegfried, J. D., Tigges-Cardwell, J., Mason, B. A., Rebbeck, T. R., Nathanson, K. L.
(2008). The Relative Contribution of Point Mutations and Genomic Rearrangements in BRCA1 and BRCA2 in High-Risk Breast Cancer Families. Cancer Res.
68: 7006-7014
[Abstract][Full Text]
Ostrander, E. A., Udler, M. S.
(2008). The Role of the BRCA2 Gene in Susceptibility to Prostate Cancer Revisited. Cancer Epidemiol. Biomarkers Prev.
17: 1843-1848
[Abstract][Full Text]
Suijkerbuijk, K. P. M., Fackler, M. J., Sukumar, S., van Gils, C. H., van Laar, T., van der Wall, E., Vooijs, M., van Diest, P. J.
(2008). Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer. Ann Oncol
0: mdn409v1-mdn409
[Abstract][Full Text]
De Nicolo, A., Tancredi, M., Lombardi, G., Flemma, C. C., Barbuti, S., Di Cristofano, C., Sobhian, B., Bevilacqua, G., Drapkin, R., Caligo, M. A.
(2008). A Novel Breast Cancer-Associated BRIP1 (FANCJ/BACH1) Germ-line Mutation Impairs Protein Stability and Function. Clin. Cancer Res.
14: 4672-4680
[Abstract][Full Text]
Lynch, H. T., Ferrara, K., Barlogie, B., Coleman, E. A., Lynch, J. F., Weisenburger, D., Sanger, W., Watson, P., Nipper, H., Witt, V., Thome, S.
(2008). Familial Myeloma. NEJM
359: 152-157
[Abstract][Full Text]
Mor, P., Oberle, K.
(2008). Ethical Issues Related To BRCA Gene Testing in Orthodox Jewish Women. Nurs Ethics
15: 512-522
[Abstract]
Byrd, L. M., Shenton, A., Maher, E. R., Woodward, E., Belk, R., Lim, C., Lalloo, F., Howell, A., Jayson, G. C., Evans, G. D.
(2008). Better Life Expectancy in Women with BRCA2 Compared with BRCA1 Mutations Is Attributable to Lower Frequency and Later Onset of Ovarian Cancer. Cancer Epidemiol. Biomarkers Prev.
17: 1535-1542
[Abstract][Full Text]
Wang, Y., Clark, L. N., Louis, E. D., Mejia-Santana, H., Harris, J., Cote, L. J., Waters, C., Andrews, H., Ford, B., Frucht, S., Fahn, S., Ottman, R., Rabinowitz, D., Marder, K.
(2008). Risk of Parkinson Disease in Carriers of Parkin Mutations: Estimation Using the Kin-Cohort Method. Arch Neurol
65: 467-474
[Abstract][Full Text]
Niewoehner, C. B, Schorer, A. E
(2008). Gynaecomastia and breast cancer in men. BMJ
336: 709-713
[Full Text]
Kauff, N. D., Domchek, S. M., Friebel, T. M., Robson, M. E., Lee, J., Garber, J. E., Isaacs, C., Evans, D. G., Lynch, H., Eeles, R. A., Neuhausen, S. L., Daly, M. B., Matloff, E., Blum, J. L., Sabbatini, P., Barakat, R. R., Hudis, C., Norton, L., Offit, K., Rebbeck, T. R.
(2008). Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study. JCO
26: 1331-1337
[Abstract][Full Text]
Chan-Smutko, G., Patel, D., Shannon, K. M., Ryan, P. D.
(2008). Professional Challenges in Cancer Genetic Testing: Who Is the Patient?. The Oncologist
13: 232-238
[Abstract][Full Text]
Begg, C. B., Haile, R. W., Borg, A., Malone, K. E., Concannon, P., Thomas, D. C., Langholz, B., Bernstein, L., Olsen, J. H., Lynch, C. F., Anton-Culver, H., Capanu, M., Liang, X., Hummer, A. J., Sima, C., Bernstein, J. L.
(2008). Variation of Breast Cancer Risk Among BRCA1/2 Carriers. JAMA
299: 194-201
[Abstract][Full Text]
Chetrit, A., Hirsh-Yechezkel, G., Ben-David, Y., Lubin, F., Friedman, E., Sadetzki, S.
(2008). Effect of BRCA1/2 Mutations on Long-Term Survival of Patients With Invasive Ovarian Cancer: The National Israeli Study of Ovarian Cancer. JCO
26: 20-25
[Abstract][Full Text]
Heemskerk-Gerritsen, B. A. M., Brekelmans, C. T. M., Menke-Pluymers, M. B. E., van Geel, A. N., Tilanus-Linthorst, M. M. A., Bartels, C. C. M., Tan, M., Meijers-Heijboer, H. E. J., Klijn, J. G. M., Seynaeve, C.
(2007). Prophylactic Mastectomy in BRCA1/2 Mutation Carriers and Women at Risk of Hereditary Breast Cancer: Long-Term Experiences at the Rotterdam Family Cancer Clinic. Ann. Surg. Oncol.
14: 3335-3344
[Abstract][Full Text]
Jordan, V. C.
(2007). Estrogen Receptors in BRCA1-Mutant Breast Cancer: Now You See Them, Now You Don't. JNCI J Natl Cancer Inst
99: 1655-1657
[Full Text]
Parmigiani, G., Chen, S., Iversen, E. S. Jr, Friebel, T. M., Finkelstein, D. M., Anton-Culver, H., Ziogas, A., Weber, B. L., Eisen, A., Malone, K. E., Daling, J. R., Hsu, L., Ostrander, E. A., Peterson, L. E., Schildkraut, J. M., Isaacs, C., Corio, C., Leondaridis, L., Tomlinson, G., Amos, C. I., Strong, L. C., Berry, D. A., Weitzel, J. N., Sand, S., Dutson, D., Kerber, R., Peshkin, B. N., Euhus, D. M.
(2007). Validity of Models for Predicting BRCA1 and BRCA2 Mutations. ANN INTERN MED
147: 441-450
[Abstract][Full Text]
Underkuffler, L. S.
(2007). Human Genetics Studies: The Case for Group Rights. J Law Med Ethics
35: 383-395
Callahan, M. J., Crum, C. P., Medeiros, F., Kindelberger, D. W., Elvin, J. A., Garber, J. E., Feltmate, C. M., Berkowitz, R. S., Muto, M. G.
(2007). Primary Fallopian Tube Malignancies in BRCA-Positive Women Undergoing Surgery for Ovarian Cancer Risk Reduction. JCO
25: 3985-3990
[Abstract][Full Text]
Bradbury, A. R., Dignam, J. J., Ibe, C. N., Auh, S. L., Hlubocky, F. J., Cummings, S. A., White, M., Olopade, O. I., Daugherty, C. K.
(2007). How Often Do BRCA Mutation Carriers Tell Their Young Children of the Family's Risk for Cancer? A Study of Parental Disclosure of BRCA Mutations to Minors and Young Adults. JCO
25: 3705-3711
[Abstract][Full Text]
Smith, K. L., Adank, M., Kauff, N., Lafaro, K., Boyd, J., Lee, J. B., Hudis, C., Offit, K., Robson, M.
(2007). BRCA Mutations in Women with Ductal Carcinoma In situ. Clin. Cancer Res.
13: 4306-4310
[Abstract][Full Text]
Rennert, G., Bisland-Naggan, S., Barnett-Griness, O., Bar-Joseph, N., Zhang, S., Rennert, H. S., Narod, S. A.
(2007). Clinical Outcomes of Breast Cancer in Carriers of BRCA1 and BRCA2 Mutations. NEJM
357: 115-123
[Abstract][Full Text]
Kauff, N. D., Barakat, R. R.
(2007). Risk-Reducing Salpingo-Oophorectomy in Patients With Germline Mutations in BRCA1 or BRCA2. JCO
25: 2921-2927
[Abstract][Full Text]
Karlan, B. Y., Berchuck, A., Mutch, D.
(2007). The Role of Genetic Testing for Cancer Susceptibility in Gynecologic Practice. Obstet Gynecol
110: 155-167
[Abstract][Full Text]
Douglas, J. A., Levin, A. M., Zuhlke, K. A., Ray, A. M., Johnson, G. R., Lange, E. M., Wood, D. P., Cooney, K. A.
(2007). Common Variation in the BRCA1 Gene and Prostate Cancer Risk. Cancer Epidemiol. Biomarkers Prev.
16: 1510-1516
[Abstract][Full Text]
Kadouri, L., Hubert, A., Rotenberg, Y., Hamburger, T., Sagi, M., Nechushtan, C., Abeliovich, D., Peretz, T.
(2007). Cancer risks in carriers of the BRCA1/2 Ashkenazi founder mutations. J. Med. Genet.
44: 467-471
[Abstract][Full Text]
Weitzel, J. N., Lagos, V. I., Cullinane, C. A., Gambol, P. J., Culver, J. O., Blazer, K. R., Palomares, M. R., Lowstuter, K. J., MacDonald, D. J.
(2007). Limited Family Structure and BRCA Gene Mutation Status in Single Cases of Breast Cancer. JAMA
297: 2587-2595
[Abstract][Full Text]
Tryggvadottir, L., Vidarsdottir, L., Thorgeirsson, T., Jonasson, J. G., Olafsdottir, E. J., Olafsdottir, G. H., Rafnar, T., Thorlacius, S., Jonsson, E., Eyfjord, J. E., Tulinius, H.
(2007). Prostate Cancer Progression and Survival in BRCA2 Mutation Carriers. JNCI J Natl Cancer Inst
99: 929-935
[Abstract][Full Text]
Wang, Y., Clark, L. N., Marder, K., Rabinowitz, D.
(2007). Nonparametric estimation of age-at-onset distributions from censored kin-cohort data. Biometrika
94: 403-403
[Abstract][Full Text]
Machado, P. M., Brandao, R. D., Cavaco, B. M., Eugenio, J., Bento, S., Nave, M., Rodrigues, P., Fernandes, A., Vaz, F.
(2007). Screening for a BRCA2 Rearrangement in High-Risk Breast/Ovarian Cancer Families: Evidence for a Founder Effect and Analysis of the Associated Phenotypes. JCO
25: 2027-2034
[Abstract][Full Text]
Greer, J. B, Whitcomb, D. C
(2007). Role of BRCA1 and BRCA2 mutations in pancreatic cancer. Gut
56: 601-605
[Abstract][Full Text]
Chen, S., Parmigiani, G.
(2007). Meta-Analysis of BRCA1 and BRCA2 Penetrance. JCO
25: 1329-1333
[Abstract][Full Text]
Saslow, D., Boetes, C., Burke, W., Harms, S., Leach, M. O., Lehman, C. D., Morris, E., Pisano, E., Schnall, M., Sener, S., Smith, R. A., Warner, E., Yaffe, M., Andrews, K. S., Russell, C. A., for the American Cancer Society Breast Cancer Advi,
(2007). American Cancer Society Guidelines for Breast Screening with MRI as an Adjunct to Mammography. CA Cancer J Clin
57: 75-89
[Abstract][Full Text]
Jakubowska, A., Gronwald, J., Menkiszak, J., Gorski, B., Huzarski, T., Byrski, T., Edler, L., Lubinski, J., Scott, R. J., Hamann, U.
(2007). The RAD51 135 G>C Polymorphism Modifies Breast Cancer and Ovarian Cancer Risk in Polish BRCA1 Mutation Carriers. Cancer Epidemiol. Biomarkers Prev.
16: 270-275
[Abstract][Full Text]
Soran, A., Falk, J., Bonaventura, M., Keenan, D., Ahrendt, G., Johnson, R.
(2007). Is Routine Sentinel Lymph Node Biopsy Indicated in Women Undergoing Contralateral Prophylactic Mastectomy? Magee-Womens Hospital Experience. Ann. Surg. Oncol.
14: 646-651
[Abstract][Full Text]
Smith, A, Moran, A, Boyd, M C, Bulman, M, Shenton, A, Smith, L, Iddenden, R, Woodward, E R, Lalloo, F, Maher, E R, Evans, D G R
(2007). Phenocopies in BRCA1 and BRCA2 families: evidence for modifier genes and implications for screening. J. Med. Genet.
44: 10-15
[Abstract][Full Text]
Offit, K.
(2006). BRCA Mutation Frequency and Penetrance: New Data, Old Debate. JNCI J Natl Cancer Inst
98: 1675-1677
[Full Text]
Risch, H. A., McLaughlin, J. R., Cole, D. E. C., Rosen, B., Bradley, L., Fan, I., Tang, J., Li, S., Zhang, S., Shaw, P. A., Narod, S. A.
(2006). Population BRCA1 and BRCA2 Mutation Frequencies and Cancer Penetrances: A Kin-Cohort Study in Ontario, Canada. JNCI J Natl Cancer Inst
98: 1694-1706
[Abstract][Full Text]
Clark, L. N., Wang, Y., Karlins, E., Saito, L., Mejia-Santana, H., Harris, J., Louis, E. D., Cote, L. J., Andrews, H., Fahn, S., Waters, C., Ford, B., Frucht, S., Ottman, R., Marder, K.
(2006). Frequency of LRRK2 mutations in early- and late-onset Parkinson disease. Neurology
67: 1786-1791
[Abstract][Full Text]
Brandt-Rauf, S. I., Raveis, V. H., Drummond, N. F., Conte, J. A., Rothman, S. M.
(2006). Ashkenazi Jews and Breast Cancer: The Consequences of Linking Ethnic Identity to Genetic Disease. Am. J. Public Health
96: 1979-1988
[Abstract][Full Text]
Guillem, J. G., Wood, W. C., Moley, J. F., Berchuck, A., Karlan, B. Y., Mutch, D. G., Gagel, R. F., Weitzel, J., Morrow, M., Weber, B. L., Giardiello, F., Rodriguez-Bigas, M. A., Church, J., Gruber, S., Offit, K.
(2006). ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes. JCO
24: 4642-4660
[Abstract][Full Text]
Guillem, J. G., Wood, W. C., Moley, J. F., Berchuck, A., Karlan, B. Y., Mutch, D. G., Gagel, R. F., Weitzel, J., Morrow, M., Weber, B. L., Giardiello, F., Rodriguez-Bigas, M. A., Church, J., Gruber, S., Offit, K.
(2006). ASCO/SSO Review of Current Role of Risk-Reducing Surgery in Common Hereditary Cancer Syndromes. Ann. Surg. Oncol.
13: 1296-1321
[Abstract][Full Text]
Schmeler, K. M., Sun, C. C., Bodurka, D. C., White, K. G., Soliman, P. T., Uyei, A. R., Erlichman, J. L., Arun, B. K., Daniels, M. S., Rimes, S. A., Peterson, S. K., Slomovitz, B. M., Milam, M. R., Gershenson, D. M., Lu, K. H.
(2006). Prophylactic Bilateral Salpingo-Oophorectomy Compared With Surveillance in Women With BRCA Mutations.. Obstet Gynecol
108: 515-520
[Abstract][Full Text]
Malone, K. E., Daling, J. R., Doody, D. R., Hsu, L., Bernstein, L., Coates, R. J., Marchbanks, P. A., Simon, M. S., McDonald, J. A., Norman, S. A., Strom, B. L., Burkman, R. T., Ursin, G., Deapen, D., Weiss, L. K., Folger, S., Madeoy, J. J., Friedrichsen, D. M., Suter, N. M., Humphrey, M. C., Spirtas, R., Ostrander, E. A.
(2006). Prevalence and Predictors of BRCA1 and BRCA2 Mutations in a Population-Based Study of Breast Cancer in White and Black American Women Ages 35 to 64 Years. Cancer Res.
66: 8297-8308
[Abstract][Full Text]
Finch, A., Beiner, M., Lubinski, J., Lynch, H. T., Moller, P., Rosen, B., Murphy, J., Ghadirian, P., Friedman, E., Foulkes, W. D., Kim-Sing, C., Wagner, T., Tung, N., Couch, F., Stoppa-Lyonnet, D., Ainsworth, P., Daly, M., Pasini, B., Gershoni-Baruch, R., Eng, C., Olopade, O. I., McLennan, J., Karlan, B., Weitzel, J., Sun, P., Narod, S. A., for the Hereditary Ovarian Cancer Clinical Study G,
(2006). Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation. JAMA
296: 185-192
[Abstract][Full Text]
Chen, S., Iversen, E. S. Jr, Parmigiani, G.
(2006). In Reply. JCO
24: 3313-3314
[Full Text]
Cohen, P. E., Pollack, S. E., Pollard, J. W.
(2006). Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals. Endocr. Rev.
27: 398-426
[Abstract][Full Text]
Pierce, L. J., Levin, A. M., Rebbeck, T. R., Ben-David, M. A., Friedman, E., Solin, L. J., Harris, E. E., Gaffney, D. K., Haffty, B. G., Dawson, L. A., Narod, S. A., Olivotto, I. A., Eisen, A., Whelan, T. J., Olopade, O. I., Isaacs, C., Merajver, S. D., Wong, J. S., Garber, J. E., Weber, B. L.
(2006). Ten-Year Multi-Institutional Results of Breast-Conserving Surgery and Radiotherapy in BRCA1/2-Associated Stage I/II Breast Cancer. JCO
24: 2437-2443
[Abstract][Full Text]
Yarden, R. I., Papa, M. Z.
(2006). BRCA1 at the crossroad of multiple cellular pathways: approaches for therapeutic interventions.. Molecular Cancer Therapeutics
5: 1396-1404
[Abstract][Full Text]
Plevritis, S. K., Kurian, A. W., Sigal, B. M., Daniel, B. L., Ikeda, D. M., Stockdale, F. E., Garber, A. M.
(2006). Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging.. JAMA
295: 2374-2384
[Abstract][Full Text]
Kang, H. J., Kim, H. J., Rih, J.-K., Mattson, T. L., Kim, K. W., Cho, C.-H., Isaacs, J. S., Bae, I.
(2006). BRCA1 Plays a Role in the Hypoxic Response by Regulating HIF-1{alpha} Stability and by Modulating Vascular Endothelial Growth Factor Expression. J. Biol. Chem.
281: 13047-13056
[Abstract][Full Text]
Hinney, A., Bettecken, T., Tarnow, P., Brumm, H., Reichwald, K., Lichtner, P., Scherag, A., Nguyen, T. T., Schlumberger, P., Rief, W., Vollmert, C., Illig, T., Wichmann, H-E., Schafer, H., Platzer, M., Biebermann, H., Meitinger, T., Hebebrand, J.
(2006). Prevalence, Spectrum, and Functional Characterization of Melanocortin-4 Receptor Gene Mutations in a Representative Population-Based Sample and Obese Adults from Germany. J. Clin. Endocrinol. Metab.
91: 1761-1769
[Abstract][Full Text]
Loud, J. T., Weissman, N. E., Peters, J. A., Giusti, R. M., Wilfond, B. S., Burke, W., Greene, M. H.
(2006). Deliberate Deceit of Family Members: A Challenge to Providers of Clinical Genetics Services. JCO
24: 1643-1646
[Full Text]
Deng, C.-X.
(2006). BRCA1: cell cycle checkpoint, genetic instability, DNA damage response and cancer evolution. Nucleic Acids Res
34: 1416-1426
[Abstract][Full Text]
Ryan, P. D., Harisinghani, M., Lerwill, M. F., Kaufman, D. S.
(2006). Case records of the Massachusetts General Hospital. Case 6-2006. A 71-year-old woman with urinary incontinence and a mass in the bladder.. NEJM
354: 850-856
[Full Text]
Chen, S., Iversen, E. S., Friebel, T., Finkelstein, D., Weber, B. L., Eisen, A., Peterson, L. E., Schildkraut, J. M., Isaacs, C., Peshkin, B. N., Corio, C., Leondaridis, L., Tomlinson, G., Dutson, D., Kerber, R., Amos, C. I., Strong, L. C., Berry, D. A., Euhus, D. M., Parmigiani, G.
(2006). Characterization of BRCA1 and BRCA2 Mutations in a Large United States Sample. JCO
24: 863-871
[Abstract][Full Text]
Tryggvadottir, L., Sigvaldason, H., Olafsdottir, G. H., Jonasson, J. G., Jonsson, T., Tulinius, H., Eyfjord, J. E.
(2006). Population-Based Study of Changing Breast Cancer Risk in Icelandic BRCA2 Mutation Carriers, 1920-2000. JNCI J Natl Cancer Inst
98: 116-122
[Abstract][Full Text]
Ma, Y., Katiyar, P., Jones, L. P., Fan, S., Zhang, Y., Furth, P. A., Rosen, E. M.
(2006). The Breast Cancer Susceptibility Gene BRCA1 Regulates Progesterone Receptor Signaling in Mammary Epithelial Cells. Mol. Endocrinol.
20: 14-34
[Abstract][Full Text]
Kramer, J. L., Velazquez, I. A., Chen, B. E., Rosenberg, P. S., Struewing, J. P., Greene, M. H.
(2005). Prophylactic Oophorectomy Reduces Breast Cancer Penetrance During Prospective, Long-Term Follow-Up of BRCA1 Mutation Carriers. JCO
23: 8629-8635
[Abstract][Full Text]
Gogas, H., Markopoulos, C., Blamey, R.
(2005). Should women be advised to take prophylactic endocrine treatment outside of a clinical trial setting?. Ann Oncol
16: 1861-1866
[Abstract][Full Text]
Rebbeck, T. R., Friebel, T., Wagner, T., Lynch, H. T., Garber, J. E., Daly, M. B., Isaacs, C., Olopade, O. I., Neuhausen, S. L., van 't Veer, L., Eeles, R., Evans, D. G., Tomlinson, G., Matloff, E., Narod, S. A., Eisen, A., Domchek, S., Armstrong, K., Weber, B. L.
(2005). Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group. JCO
23: 7804-7810
[Abstract][Full Text]
Begg, C. B., Orlow, I., Hummer, A. J., Armstrong, B. K., Kricker, A., Marrett, L. D., Millikan, R. C., Gruber, S. B., Anton-Culver, H., Zanetti, R., Gallagher, R. P., Dwyer, T., Rebbeck, T. R., Mitra, N., Busam, K., From, L., Berwick, M., for the Genes Environment and Melanoma (GEM) Study,
(2005). Lifetime Risk of Melanoma in CDKN2A Mutation Carriers in a Population-Based Sample. JNCI J Natl Cancer Inst
97: 1507-1515
[Abstract][Full Text]
Miller, S. M., Roussi, P., Daly, M. B., Buzaglo, J. S., Sherman, K., Godwin, A. K., Balshem, A., Atchison, M. E.
(2005). Enhanced Counseling for Women Undergoing BRCA1/2 Testing: Impact on Subsequent Decision Making About Risk Reduction Behaviors. Health Educ Behav
32: 654-667
[Abstract]
Zhang, Y., Fan, S., Meng, Q., Ma, Y., Katiyar, P., Schlegel, R., Rosen, E. M.
(2005). BRCA1 Interaction with Human Papillomavirus Oncoproteins. J. Biol. Chem.
280: 33165-33177
[Abstract][Full Text]
U.S. Preventive Services Task Force*,
(2005). Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Recommendation Statement. ANN INTERN MED
143: 355-361
[Abstract][Full Text]
Nelson, H. D., Huffman, L. H., Fu, R., Harris, E. L.
(2005). Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review for the U.S. Preventive Services Task Force. ANN INTERN MED
143: 362-379
[Abstract][Full Text]
Rosen, E M, Fan, S, Isaacs, C
(2005). BRCA1 in hormonal carcinogenesis: basic and clinical research. Endocr Relat Cancer
12: 533-548
[Abstract][Full Text]
Hamann, H. A., Somers, T. J., Smith, A. W., Inslicht, S. S., Baum, A.
(2005). Posttraumatic Stress Associated With Cancer History and BRCA1/2 Genetic Testing. Psychosom. Med.
67: 766-772
[Abstract][Full Text]
van Asperen, C J, Brohet, R M, Meijers-Heijboer, E J, Hoogerbrugge, N, Verhoef, S, Vasen, H F A, Ausems, M G E M, Menko, F H, Gomez Garcia, E B, Klijn, J G M, Hogervorst, F B L, van Houwelingen, J C, van't Veer, L J, Rookus, M A, van Leeuwen, F E, on behalf of the Netherlands Collaborative Group o,
(2005). Cancer risks in BRCA2 families: estimates for sites other than breast and ovary. J. Med. Genet.
42: 711-719
[Abstract][Full Text]
Freedman, M. L., Penney, K. L., Stram, D. O., Riley, S., McKean-Cowdin, R., Le Marchand, L., Altshuler, D., Haiman, C. A.
(2005). A Haplotype-Based Case-Control Study of BRCA1 and Sporadic Breast Cancer Risk. Cancer Res.
65: 7516-7522
[Abstract][Full Text]
Wang, C., Fan, S., Li, Z., Fu, M., Rao, M., Ma, Y., Lisanti, M. P., Albanese, C., Katzenellenbogen, B. S., Kushner, P. J., Weber, B., Rosen, E. M., Pestell, R. G.
(2005). Cyclin D1 Antagonizes BRCA1 Repression of Estrogen Receptor {alpha} Activity. Cancer Res.
65: 6557-6567
[Abstract][Full Text]
Weitzel, J. N., Lagos, V., Blazer, K. R., Nelson, R., Ricker, C., Herzog, J., McGuire, C., Neuhausen, S.
(2005). Prevalence of BRCA Mutations and Founder Effect in High-Risk Hispanic Families. Cancer Epidemiol. Biomarkers Prev.
14: 1666-1671
[Abstract][Full Text]
Antoniou, A C, Pharoah, P D P, Narod, S, Risch, H A, Eyfjord, J E, Hopper, J L, Olsson, H, Johannsson, O, Borg, A, Pasini, B, Radice, P, Manoukian, S, Eccles, D M, Tang, N, Olah, E, Anton-Culver, H, Warner, E, Lubinski, J, Gronwald, J, Gorski, B, Tulinius, H, Thorlacius, S, Eerola, H, Nevanlinna, H, Syrjakoski, K, Kallioniemi, O-P, Thompson, D, Evans, C, Peto, J, Lalloo, F, Evans, D G, Easton, D F
(2005). Breast and ovarian cancer risks to carriers of the BRCA1 5382insC and 185delAG and BRCA2 6174delT mutations: a combined analysis of 22 population based studies. J. Med. Genet.
42: 602-603
[Abstract][Full Text]
Cook, J. D., Davis, B. J., Cai, S.-L., Barrett, J. C., Conti, C. J., Walker, C. L.
(2005). Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance. Proc. Natl. Acad. Sci. USA
102: 8644-8649
[Abstract][Full Text]
Weitzel, J. N., Robson, M., Pasini, B., Manoukian, S., Stoppa-Lyonnet, D., Lynch, H. T., McLennan, J., Foulkes, W. D., Wagner, T., Tung, N., Ghadirian, P., Olopade, O., Isaacs, C., Kim-Sing, C., Moller, P., Neuhausen, S. L., Metcalfe, K., Sun, P., Narod, S. A.
(2005). A Comparison of Bilateral Breast Cancers in BRCA Carriers. Cancer Epidemiol. Biomarkers Prev.
14: 1534-1538
[Abstract][Full Text]
Eberl, M. M., Sunga, A. Y., Farrell, C. D., Mahoney, M. C.
(2005). Patients with a Family History of Cancer: Identification and Management. J Am Board Fam Med
18: 211-217
[Abstract][Full Text]
Simeone, A.-M., Deng, C.-X., Kelloff, G. J., Steele, V. E., Johnson, M. M., Tari, A. M.
(2005). N-(4-Hydroxyphenyl)retinamide is more potent than other phenylretinamides in inhibiting the growth of BRCA1-mutated breast cancer cells. Carcinogenesis
26: 1000-1007
[Abstract][Full Text]
Schwartz, M. D., Lerman, C., Brogan, B., Peshkin, B. N., Isaacs, C., DeMarco, T., Hughes Halbert, C., Pennanen, M., Finch, C.
(2005). Utilization of BRCA1/BRCA2 Mutation Testing in Newly Diagnosed Breast Cancer Patients. Cancer Epidemiol. Biomarkers Prev.
14: 1003-1007
[Abstract][Full Text]
Patterson, A. R., Robinson, L. D., Naftalis, E. Z., Haley, B. B., Tomlinson, G. E.
(2005). Custodianship of Genetic Information: Clinical Challenges and Professional Responsibility. JCO
23: 2100-2104
[Full Text]
Gurmankin, A. D., Domchek, S., Stopfer, J., Fels, C., Armstrong, K.
(2005). Patients' Resistance to Risk Information in Genetic Counseling for BRCA1/2. Arch Intern Med
165: 523-529
[Abstract][Full Text]
Narod, S. A., Offit, K.
(2005). Prevention and Management of Hereditary Breast Cancer. JCO
23: 1656-1663
[Full Text]
Leegte, B, van der Hout, A H, Deffenbaugh, A M, Bakker, M K, Mulder, I M, ten Berge, A, Leenders, E P, Wesseling, J, de Hullu, J, Hoogerbrugge, N, Ligtenberg, M J L, Ardern-Jones, A, Bancroft, E, Salmon, A, Barwell, J, Eeles, R, Oosterwijk, J C
(2005). Phenotypic expression of double heterozygosity for BRCA1 and BRCA2 germline mutations. J. Med. Genet.
42: e20-e20
[Full Text]
Khanna, C., Hunter, K.
(2005). Modeling metastasis in vivo. Carcinogenesis
26: 513-523
[Abstract][Full Text]
Lynch, H. T., Watson, P., Tarantolo, S., Wiernik, P. H., Quinn-Laquer, B., Isgur Bergsagel, K., Huiart, L., Olopade, O.I., Sobol, H., Sanger, W., Hogg, D., Weisenburger, D.
(2005). Phenotypic Heterogeneity in Multiple Myeloma Families. JCO
23: 685-693
[Abstract][Full Text]
Parthasarathy, S.
(2005). Architectures of Genetic Medicine: Comparing Genetic Testing for Breast Cancer in the USA and the UK. Social Studies of Science
35: 5-40
[Abstract]
Bourret, P.
(2005). BRCA Patients and Clinical Collectives: New Configurations of Action in Cancer Genetics Practices. Social Studies of Science
35: 41-68
[Abstract]
Wu, K., Hinson, S. R., Ohashi, A., Farrugia, D., Wendt, P., Tavtigian, S. V., Deffenbaugh, A., Goldgar, D., Couch, F. J.
(2005). Functional Evaluation and Cancer Risk Assessment of BRCA2 Unclassified Variants. Cancer Res.
65: 417-426
[Abstract][Full Text]
Cannistra, S. A.
(2004). Cancer of the Ovary. NEJM
351: 2519-2529
[Full Text]
Whittemore, A. S., Gong, G., John, E. M., McGuire, V., Li, F. P., Ostrow, K. L., DiCioccio, R., Felberg, A., West, D. W.
(2004). Prevalence of BRCA1 Mutation Carriers among U.S. Non-Hispanic Whites. Cancer Epidemiol. Biomarkers Prev.
13: 2078-2083
[Abstract][Full Text]
Lorenzo Bermejo, J., Hemminki, K.
(2004). Risk of cancer at sites other than the breast in Swedish families eligible for BRCA1 or BRCA2 mutation testing. Ann Oncol
15: 1834-1841
[Abstract][Full Text]
Oloparde, O. I.
(2004). Genetics in Clinical Cancer Care: A Promise Unfulfilled among Minority Populations. Cancer Epidemiol. Biomarkers Prev.
13: 1683-1686
[Full Text]
Arun, B.
(2004). Ductal Lavage and Risk Assessment of Breast Cancer. The Oncologist
9: 599-605
[Abstract][Full Text]
McGuire, V., Felberg, A., Mills, M., Ostrow, K. L., DiCioccio, R., John, E. M., West, D. W., Whittemore, A. S.
(2004). Relation of Contraceptive and Reproductive History to Ovarian Cancer Risk in Carriers and Noncarriers of BRCA1 Gene Mutations. Am J Epidemiol
160: 613-618
[Abstract][Full Text]
Dempfle, A, Hinney, A, Heinzel-Gutenbrunner, M, Raab, M, Geller, F, Gudermann, T, Schafer, H, Hebebrand, J
(2004). Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index. J. Med. Genet.
41: 795-800
[Full Text]
Wacholder, S.
(2004). Bias in Intervention Studies That Enroll Patients From High-Risk Clinics. JNCI J Natl Cancer Inst
96: 1204-1207
[Abstract][Full Text]
van Roosmalen, M.S., Stalmeier, P.F.M., Verhoef, L.C.G., Hoekstra-Weebers, J.E.H.M., Oosterwijk, J.C., Hoogerbrugge, N., Moog, U., van Daal, W.A.J.
(2004). Randomized Trial of a Shared Decision-Making Intervention Consisting of Trade-Offs and Individualized Treatment Information for BRCA1/2 Mutation Carriers. JCO
22: 3293-3301
[Abstract][Full Text]
