Genetic Epidemiology of Breast and Ovarian Cancers

Newman, Beth; Millikan, Robert C.; King, Mary Claire

doi:10.1093/oxfordjournals.epirev.a017948

Cited by 46 publications

(15 citation statements)

References 101 publications

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“…The studies that indirectly estimated the clinical sensitivity were all published within 5 years of the cloning of BRCA1. 28,[31][32][33][34] The estimates derived from these studies may be higher due to the indirect methods used and/or the limited data available on BRCA1 and BRCA2 mutations at that time. The clinical sensitivity estimate that is reported by some of the common information sources 12,13 references an early study that estimated the contribution of BRCA1 and BRCA2 mutations to breast cancer in families with at least four cases of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

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Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: Public health implications

McClain

Palomaki

Nathanson

et al. 2005

Genetics in Medicine

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Purpose: Mutations in BRCA1 or BRCA2 genes increase breast cancer risk. Assuring reliability of information about these mutations is increasingly important to the health care community; mutation testing is becoming more widespread. We describe a methodology for assessing such information. Methods: Our approach integrates four interdependent epidemiologic parameters: (1) the probability of developing breast cancer, (2) the proportion of breast cancer cases with a BRCA1 or BRCA2 mutation, (3) the proportion of women that carries a mutation, and (4) the proportion of women with a mutation that develops cancer. We assess the plausibility of estimates of these parameters from published reports and commonly accessed information sources. Results: Assuming a fixed probability of developing breast cancer, the following estimates for the other three epidemiologic parameters are derived for women by age 70: 1% to 2% of all breast cancer cases are associated with a BRCA1 or BRCA2 mutation; 1 in 300 to 1 in 465 women carry a mutation; and 35 to 65% of mutation carriers develop breast cancer. Within these ranges, however, only selected combinations are plausible. The proportion of mutation-related breast cancer is lower than listed in some common information sources (1 to 2% vs 6%). Also, penetrance is somewhat lower and the carrier rate somewhat higher. Conclusions: The four epidemiologic parameters can be integrated to test their plausibility. BRCA1 and BRCA2 mutations are associated with only one-third as many breast cancer cases in the Guidelines have been developed to aid clinicians in deciding when to offer BRCA1 and BRCA2 mutation testing. 1-6 These guidelines recommend testing in specific circumstances, such as in women whose family history indicates an inherited predisposition to breast cancer. When a mutation is identified in an index case, cascade testing can be offered to other family members, thereby allowing primary prevention options to be considered. Implementation of BRCA1 and BRCA2 mutation testing by primary care providers has been sporadic and driven, in part, by direct-to-consumer advertising. [7][8][9][10][11] At least two information sources about BRCA1 and BRCA2 mutation testing have been developed for use by primary care providers in the United States. 12,13 In addition, two comprehensive reviews on BRCA1 and BRCA2 and hereditary breast cancer are available via internet access to health care providers, as well as the general public. 14,15 The data summarized by these sources are not always complete and/or consistent, either internally or with each other. These data are composed of three epidemiologic parameters: (1) the penetrance of BRCA1 and BRCA2 mutations, (2) the mutation carrier rate in the general population, and (3) the proportion of all breast cancer cases that is associated with a mutation. Almost all estimates quoted for each of these epidemiologic parameters are indirectly derived in the original studies. For example, there have been no published studies where a large population-based samp...

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Section: Discussionmentioning

confidence: 99%

“…28,33,34 The range of these estimates is also shown in Table 1. We include a sensitivity analysis for this estimate, as well, in our integrated approach.…”

Section: Methodsmentioning

confidence: 99%

Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: Public health implications

McClain

Palomaki

Nathanson

et al. 2005

Genetics in Medicine

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“…The development of breast cancer is a multistage process, dependent on genetic, hormonal, and environmental factors (Claus et al 1991;Gould 1993;Newman et al 1997). Genes such as TP53, BRCA1, and BRCA2 have been identified as being involved in breast cancer susceptibility (Malkin et al 1990;Miki et al 1994;Tavtigian et al 1996).…”

Section: Introductionmentioning

confidence: 99%

Analysis of candidate genes included in the mammary cancer susceptibility 1 (Mcs1) region

et al. 2001

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The rat strain COP is resistant to spontaneous and carcinogen-induced mammary cancer, whereas the strain WF is susceptible. Using genetic linkage analysis of (WF x COP) F1 x WF backcrosses, LC Hsu, LA Shepel and co-workers showed that a region at the centromeric end of Chromosome (Chr) 2 (2q1) segregates with the sensitivity to mammary cancer development. The responsible locus was named Mcs1 (for mammary cancer susceptibility 1). We have developed the chromosome map of the 2q1 region by localizing 18 genes, 4 ESTs, and several anonymous markers, using radiation hybrids and fluorescence in situ hybridization. The region containing Mcs1 was delineated to 2q12-q14. Five of the genes (Mef2c, Map1b, Ccnh, Rasa, Rasgrf2) were assigned to this region and were shown to be expressed in the rat mammary glands, while three possible functional candidate genes, Pi3kr1, Rad17, and Naip, were excluded from the critical region. Since cyclin H, encoded by Ccnh, plays an important role in the control of the cell cycle and since the proteins encoded by Rasa and Rasgrf2 control the activity of the RAS oncoprotein, the corresponding genes appeared as both functional and positional Mcs1 candidates. RT-PCR experiments on RNA extracted from mammary glands of the two rat strains (COP, WF) was done. No amino acid sequence difference was found between the two strains. These results argue against the hypothesis that any of these three genes is Mcs1.

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“…Whereas deleterious variants are relatively rare in the general population, they are common among families with multiple occurrences of breast or ovarian cancer (4)(5)(6). When counseling a woman facing decisions about genotyping for BRCA1 and BRCA2, it is important to accurately evaluate the probability that she carries a deleterious mutation (pretest mutation probability) and the probability that a mutation will be found if she is genotyped (which depends on the accuracy of mutation testing).…”

mentioning

confidence: 99%

Validity of Models for Predicting BRCA1 and BRCA2 Mutations

2007

Ann Intern Med

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Genetic Epidemiology of Breast and Ovarian Cancers

Cited by 46 publications

References 101 publications

Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: Public health implications

Adjusting the estimated proportion of breast cancer cases associated with BRCA1 and BRCA2 mutations: Public health implications

Analysis of candidate genes included in the mammary cancer susceptibility 1 (Mcs1) region

Validity of Models for Predicting BRCA1 and BRCA2 Mutations

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