Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies

Antoniou, Antonis C.; Pharoah, Paul D.P.; Narod, Steven A.; Risch, Harvey A.; Eyfjörd, J.E.; Hopper, John L.; Loman, Niklas; Olsson, Håkan; Jóhannsson, Óskar T.; Borg, Åke; Pasini, Barbara; Radice, Paolo; Manoukian, Siranoush; Eccles, Diana; Tang, Nelson L.S.; Olàh, Edith; Anton‐Culver, Hoda; Warner, Ellen; Lubiński, Jan; Gronwald, Jacek; Górski, Bohdan; Tulinius, Hrafn; Thorlacius, Steinunn; Eerola, Hannaleena; Nevanlinna, Heli; Syrjäkoski, Kirsi; Kallioniemi, Olli; Thompson, Deborah J.; Evans, Christopher; Peto, Julian; Lalloo, Fiona; Evans, D. Gareth; Easton, Doug

doi:10.1086/375033

Cited by 3,184 publications

(2,383 citation statements)

References 36 publications

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“…Figure 1 shows the cumulative incidence of breast cancer to age 50 years in smokers and non-smokers, based on our estimated relative risk associated with smoking, and the pooled estimates of cumulative risk from Antoniou et al [19]. For BRCA1 carriers, we predict that 60% of smokers will develop breast cancer by age 50 years, compared to about 35% of nonsmokers.…”

Section: Smoking and Breast Cancer Riskmentioning

confidence: 92%

Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years

Whittemore

John

Felberg

et al. 2007

Breast Cancer Res Treat

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Background-Cigarette smoke contains compounds that may damage DNA, and the repair of damage may be impaired in women with germline mutations in BRCA1 or BRCA2. However, the effect of cigarette smoking on breast cancer risk in mutation carriers is the subject of conflicting reports. We have examined the relation between smoking and breast cancer risk in non-Hispanic white women under the age of 50 years who carry a deleterious mutation in BRCA1 or BRCA2.Methods-We conducted a case-control study using data from carriers of mutations in BRCA1 (195 cases and 302 controls) and BRCA2 (128 cases and 179 controls). Personal information, including smoking history, was collected using a common structured questionnaire by eight recruitment sites in four countries. Odds-ratios (OR) for breast cancer risk according to smoking were adjusted for age, family history, parity, alcohol use, and recruitment site. NIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author ManuscriptResults-Compared to non-smokers, the OR for risk of breast cancer for women with five or more pack-years of smoking was 2.3 (95% confidence interval 1.6-3.5) for BRCA1 carriers and 2.6 (1.8-3.9) for BRCA2 carriers. Risk increased 7% per pack-year (p < 0.001) in both groups. The epidemiological evidence on the association of smoking with risk of breast cancer is contradictory. Terry and Rohan in 2002 reviewed the published evidence and concluded that smoking probably did not decrease, and may increase, risk of breast cancer [6]. A combined re-analysis of 53 epidemiological studies, however, did not show smoking to be associated with an increased risk of breast cancer after alcohol use was taken into account [7]. In a meta-analysis in 2005, Johnson found that both active and passive smoking were associated with an increased risk of premenopausal breast cancer [8]. Conclusions-TheseThe biological effects of smoking suggest that genetic variations in acetylation, oxidative damage, and DNA repair, may influence risk of disease. For example, high levels of reactive oxygen species may cause single and double strand breaks. BRCA1 and BRCA2 genes are involved in the repair of such breaks [9], and mutations in these genes may impair the ability of carriers to repair any defects caused by smoking.Lifetime risks of breast cancer among carriers of deleterious mutations in BRCA1 and BRCA2 have been estimated at 40-80% [10][11][12]. Because 20-60% of carriers live to an advanced age, and do not develop breast cancer, there are likely to be other genetic or environmental factors that modify risk. The purpose of the present study was to examine the effects of cigarette smoking on breast cancer risk in a large number of affected (cases) and unaffected (controls) members of families segregating mutations in the BRCA1 or BRCA2 genes.et al.

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Section: Smoking and Breast Cancer Riskmentioning

confidence: 92%

Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years

Whittemore

John

Felberg

et al. 2007

Breast Cancer Res Treat

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“…Other methods are used which depend on the reporting of cancers by family members. The lifetime risk of breast cancer in women who carry a deleterious BRCA1 or BRCA2 mutation is estimated to be as high as 80% -or roughly 10 times greater than that of the general population -but several estimates are lower (Ford et al, 1998;Risch et al, 2001;Antoniou et al, 2003;King et al, 2003). In a cohort of 76 BRCA1 mutation carriers from Rotterdam, eight invasive cancers were detected during 318 person-years of follow-up (Meijers-Heijboer et al, 2001) -an annual incidence of 2.5%.…”

Section: Introductionmentioning

confidence: 99%

Modifiers of risk of hereditary breast cancer

Narod

2006

Oncogene

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Mutations in the BRCA1 and BRCA2 genes confer a high lifetime risk of breast and ovarian cancer. The risk varies from individual to individual, and it appears that the risk has increased in recent generations. These observations imply that non-genetic factors may modify the inherited risk. To date, the factors that appear most strongly to modify the risk include reproductive histories and exogenous hormones. Oral contraceptives are associated with a profound reduction in the risk of ovarian cancer, and with little or no increase in the risk of breast cancer. Other modifying factors include age of menarche, parity, breastfeeding and oophorectomy. The effect of parity is different in BRCA1 and BRCA2 carriers. Multiparity appears to be protective in BRCA1 carriers, but is associated with an increase in risk in BRCA2 carriers. Oophorectomy has been associated with reductions in both the risk of breast and ovarian cancer. Knowledge of these risk factors will be useful for managing risk and for developing prevention strategies.

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“…For example, studies indicate that a mutation in a mismatch repair gene is found in approximately 40% to 80% of families that meet the Amsterdam I criteria and only about 5% to 50% of families meeting the Amsterdam II criteria. 15 Similarly, only about 5% to 10%of unselected patients with breast cancer 16 and 20% to 25% of patients with hereditary breast cancer 17 are found to carry a deleterious BRCA1 or BRCA2 mutation. Additionally, a number of other genes associated either with rare high-penetrance syndromes or a more moderate penetrance were identified.…”

Section: Single/limited Gene Testingmentioning

confidence: 99%

How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing

Lynce

Isaacs

2016

American Society of Clinical Oncology Educational Book

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OVERVIEW The traditional model by which an individual was identified as harboring a hereditary susceptibility to cancer was to test for a mutation in a single gene or a finite number of genes associated with a particular syndrome (e.g., BRCA1 and BRCA2 for hereditary breast and ovarian cancer or mismatch repair genes for Lynch syndrome). The decision regarding which gene or genes to test for was based on a review of the patient’s personal medical history and their family history. With advances in next-generation DNA sequencing technology, offering simultaneous testing for multiple genes associated with a hereditary susceptibility to cancer is now possible. These panels typically include high-penetrance genes, but they also often include moderate- and low-penetrance genes. A number of the genes included in these panels have not been fully characterized either in terms of their cancer risks or their management options. Another way some patients are unexpectedly identified as carrying a germline mutation in a cancer susceptibility gene is at the time they undergo molecular profiling of their tumor, which typically has been carried out to guide treatment choices for their cancer. This article first focuses on the issues that need to be considered when deciding between recommending more targeted testing of a single or a small number of genes associated with a particular syndrome (single/limited gene testing) versus performing a multigene panel. This article also reviews the issues regarding germline risk that occur within the setting of ordering molecular profiling of tumors.

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Average Risks of Breast and Ovarian Cancer Associated with BRCA1 or BRCA2 Mutations Detected in Case Series Unselected for Family History: A Combined Analysis of 22 Studies

Cited by 3,184 publications

References 36 publications

Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years

Smoking and risk of breast cancer in carriers of mutations in BRCA1 or BRCA2 aged less than 50 years

Modifiers of risk of hereditary breast cancer

How Far Do We Go With Genetic Evaluation? Gene, Panel, and Tumor Testing

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