Familial Risks, Early-Onset Breast Cancer, and BRCA1 and BRCA2 Germline Mutations

Dite, Gillian S.; Jenkins, Mark A.; Southey, Melissa C.; Hocking, Jane; Giles, Graham G.; McCredie, Margaret; Venter, Deon J.; Hopper, John L.

doi:10.1093/jnci/95.6.448

Cited by 161 publications

(163 citation statements)

References 20 publications

Supporting

Mentioning

154

Contrasting

Unclassified

Order By: Relevance

“…Mutations in the high-risk breast cancer-susceptibility genes BRCA1 and BRCA2 account for approximately 15% of this excess familial risk (Easton, 1999;Peto et al, 1999;Anglian Breast Cancer Study Group, 2000;Dite et al, 2003). We had previously derived a breast cancer susceptibility model, the Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm (BOADICEA), based on segregation analysis of breast and ovarian cancer occurrence in a combined data set, including a population-based series of 1484 breast cancer cases and 156 multiple case families from the United Kingdom (Antoniou et al, 2002(Antoniou et al, , 2004.…”

mentioning

confidence: 99%

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

et al. 2008

View full text Add to dashboard Cite

Multiple genetic loci confer susceptibility to breast and ovarian cancers. We have previously developed a model (BOADICEA) under which susceptibility to breast cancer is explained by mutations in BRCA1 and BRCA2, as well as by the joint multiplicative effects of many genes (polygenic component). We have now updated BOADICEA using additional family data from two UK population-based studies of breast cancer and family data from BRCA1 and BRCA2 carriers identified by 22 population-based studies of breast or ovarian cancer. The combined data set includes 2785 families (301 BRCA1 positive and 236 BRCA2 positive). Incidences were smoothed using locally weighted regression techniques to avoid large variations between adjacent intervals. A birth cohort effect on the cancer risks was implemented, whereby each individual was assumed to develop cancer according to calendar period-specific incidences. The fitted model predicts that the average breast cancer risks in carriers increase in more recent birth cohorts. For example, the average cumulative breast cancer risk to age 70 years among BRCA1 carriers is 50% for women born in 1920 -1929 and 58% among women born after 1950. The model was further extended to take into account the risks of male breast, prostate and pancreatic cancer, and to allow for the risk of multiple cancers. BOADICEA can be used to predict carrier probabilities and cancer risks to individuals with any family history, and has been implemented in a user-friendly Web-based program

show abstract

mentioning

confidence: 99%

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

et al. 2008

View full text Add to dashboard Cite

show abstract

“…21 Additional methodologic details from 2 of the study sites have also been published elsewhere. [22][23][24][25] The analysis was based on Caucasian women with a first primary invasive breast cancer who were compared to their sisters and Caucasian women from the general population without a personal history of breast cancer. Women who reported other racial/ethnic backgrounds were not included in this analysis as recruitment of non-Caucasians is continuing.…”

Section: Methodsmentioning

confidence: 99%

An inverse association between ovarian cysts and breast cancer in the breast cancer family registry

Knight

John

Milne

et al. 2005

Intl Journal of Cancer

View full text Add to dashboard Cite

Ovarian cysts of several types are common in women of reproductive age. Their etiology is not well understood but is likely related to perturbations in the hypothalamic-pituitary-gonadal axis. The relationship of ovarian cysts to breast cancer risk is not known, although a negative association with polycystic ovarian syndrome has been reported. Incident, invasive female breast cancer cases, population-based controls and unaffected sisters of cases were studied from 3 countries participating in the Breast Cancer Family Registry: Melbourne and Sydney, Australia; the San Francisco Bay Area, USA; and Ontario, Canada. Using the same questionnaire, information was collected on self-reported history of ovarian cysts and other risk factors. Analyses were based on 3,049 cases, 2,344 population controls and 1,934 sister controls from all sites combined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using both unconditional and conditional logistic regression using an offset term to account for sampling fractions at 2 of the sites. A significantly reduced risk of breast cancer was observed for women reporting a history of ovarian cysts (OR 5 0.70, 95% CI 0.59-0.82, among all cases and all controls). This risk estimate was similar regardless of control group used, within all 3 sites and in both premenopausal and postmenopausal women (ORs ranging from 0.68-0.75, all 95% CI excluded 1.00). A self-reported history of ovarian cysts was strongly and consistently associated with a reduced risk of breast cancer. Further study of ovarian cysts may increase our understanding of hormonal and other mechanisms of breast cancer etiology. ' 2005 Wiley-Liss, Inc.

show abstract

“…TP53 and PTEN mutations are also present in the population at low frequency and lead to very high BC risk associated with rare cancer syndrome, however, population-based studies have estimated that alterations in these genes account only the 15% of the familial risk of BC (Sidransky et al, 1992;FitzGerald et al, 1998;Peto et al, 1999;Dite et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Breast cancer genome-wide association studies: there is strength in numbers

et al. 2011

View full text Add to dashboard Cite

Breast cancer (BC) is a heterogeneous disease that exhibits familial aggregation. Family linkage studies have identified high-penetrance genes, BRCA1, BRCA2, PTEN and TP53, that are responsible for inherited BC syndromes. Moreover, a combination of family-based and population-based approaches indicated that genes involved in DNA repair, such as CHEK2, ATM, BRIP and PALB2, are associated with moderate risk. Therefore, all of these known genes account for only 25% of the familial aggregation cases. Recently, genome wide association studies (GWAS) in BC revealed single nucleotide polymorphisms (SNPs) in five novel genes associated to susceptibility: TNRC9, FGFR2, MAP3K1, H19 and lymphocyte-specific protein 1 (LSP1). The most strongly associated SNP was in intron 2 of the FGFR2 gene that is amplified and overexpressed in 5-10% of BC. rs3803662 of TNRC9 gene has been shown to be the SNP with the strongest association with BC, in particular, this polymorphism seems to be correlated with bone metastases and estrogen receptor positivity. Relevant data indicate that SNP rs889312 in MAP3K1 is correlated with BC susceptibility only in BRCA2 mutation carriers, but is not associated with an increased risk in BRCA1 carriers. Finally, different SNPs in LSP1 and H19 and in minor genes probably were associated with BC risk. New susceptibility allelic variants associated with BC risk were recently discovered including potential causative genes involved in regulation of cell cycle, apoptosis, metabolism and mitochondrial functions. In conclusion, the identification of disease susceptibility loci may lead to a better understanding of the biological mechanism for BC to improve prevention, early detection and treatment.

show abstract

Familial Risks, Early-Onset Breast Cancer, and BRCA1 and BRCA2 Germline Mutations

Abstract: Mutations in genes other than BRCA1 and BRCA2 may be associated with a high risk of breast cancer, especially in young women.

Cited by 161 publications

References 20 publications

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions

An inverse association between ovarian cysts and breast cancer in the breast cancer family registry

Breast cancer genome-wide association studies: there is strength in numbers

Contact Info

Product

Resources

About