Article

Parity and the risk of breast and ovarian cancer in BRCA1 and BRCA2 mutation carriers.

Grupo de Epidemiología Genética y Molecular, Programa de Genética del Cáncer Humano, Centro Nacional de Investigaciones Oncológicas (CNIO), C/Melchor Fernández Almagro, Madrid, Spain.
Breast Cancer Research and Treatment (Impact Factor: 4.47). 04/2009; 119(1):221-32. DOI: 10.1007/s10549-009-0394-1
Source: PubMed

ABSTRACT Environmental or lifestyle factors are likely to explain part of the heterogeneity in breast and ovarian cancer risk among BRCA1 and BRCA2 mutation carriers. We assessed parity as a risk modifier in 515 and 503 Spanish female carriers of mutations in BRCA1 and BRCA2, respectively. Hazard ratios (HR) and their corresponding 95% confidence intervals (CI) were estimated using weighted Cox proportional hazards regression, adjusted for year of birth and study centre. The results for ever being parous and number of live-births were very similar for carriers of mutations in both genes. For all mutation carriers combined, the estimated HR associated with ever having had a live-birth was 0.74 (95% confidence interval [CI] = 0.55-1.01, P = 0.06), and that associated with each live-birth was 0.87 (95%CI = 0.77-0.98, P = 0.02). The latter association was observed only in women aged 40 and above (HR = 0.81, 95%CI = 0.70-0.94, P = 0.004 vs. HR = 0.99, 95%CI = 0.83-1.18, P = 0.9 for women under age 40), and this trend was highly consistently observed for carriers of mutations in each gene. There was no evidence of an association between breast cancer risk and age at first birth for parous BRCA1 or BRCA2 mutation carriers (P-trend >or= 0.3). The power to detect associations with ovarian cancer risk was much lower, especially for BRCA2 mutation carriers. Nevertheless, having a live-birth was associated with protection for BRCA1 mutation carriers (HR = 0.41, 95%CI = 0.18-0.94, P = 0.03), and a strong and consistent protective effect of age at first birth was observed for parous carriers of mutations in both genes (HR = 0.65, 95%CI = 0.52-0.83, P < 0.001). This is the third independent study to find that, as in the general population, parity appears to be associated with protection from breast cancer in women with mutations in BRCA1 and BRCA2. Parity appears to be protective for ovarian cancer in BRCA1 mutation carriers, but its role in BRCA2 mutation carriers remains unclear. Whether later age at first birth is also protective for ovarian cancer in mutation carriers requires further confirmation.

2 Bookmarks
 · 
221 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary breast and ovarian cancer (HBOC) is caused by a mutation in the BRCA1 or BRCA2 genes. Women with a BRCA1/2 mutation are at increased risks for breast and ovarian cancer and often develop cancer at an earlier age than the general population. However, some women with a BRCA1/2 mutation do not develop breast or ovarian cancer under the age of 50 years. There have been no specific studies on BRCA positive women with no cancer prior to age 50, therefore this study sought to investigate factors within these women with no cancer under age 50 with respect to reproductive risk factors, BMI, tumor pathology, screening history, risk-reducing surgeries, and family history. 241 women were diagnosed with cancer prior to age 50, 92 with cancer at age 50 or older, and 20 women were over age 50 with no cancer. Data were stratified based on BRCA1 and BRCA2 mutation status. Within the cohorts we investigated differences between women who developed cancer prior to age 50 and those who developed cancer at age 50 or older. We also investigated the differences between women who developed cancer at age 50 or older and those who were age 50 or older with no cancer. Of the 92 women with a BRCA1/2 mutation who developed cancer at age 50 or older, 46 developed ovarian cancer first, 45 developed breast cancer, and one had breast and ovarian cancer diagnosed synchronously. BRCA2 carriers diagnosed age 50 or older were more likely to have ER/PR negative breast tumors when compared to BRCA2 carriers who were diagnosed before age 50. This is consistent with one other study that has been performed. Ashkenazi Jewish women with a BRCA1 mutation were more likely to be diagnosed age 50 or older than other ethnicities. Hispanic women with a BRCA2 mutation were more likely to be diagnosed prior to age 50 when compared to other ethnicities. No differences in reproductive factors or BMI were observed. Further characterization of BRCA positive women with no cancer prior to age 50 may aid in finding factors important in the development of breast or ovarian cancer.
    UT Graduate School of Biomedical Sciences at Houston: Dissertations and Theses.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One out of four dogs will develop cancer before the age of 10 years. Many of them will succumb to the disease. Risk factor analysis, tumor prevention, and ways to prognosticate already existing tumors in the individual patient, are important. Canine mammary tumors (CMTs) are the most common type of tumor in intact female dogs and constitute about half of all tumors in female dogs. About half of the CMTs are malignant. The origin of CMTs is considered to be complex, with tumor development likely influenced by both genetic and environmental factors. In Sweden 36% of English Springer spaniels (ESS) are diagnosed with CMTs, suggesting a genetic influence in this breed. Several risk factors predisposing to CMT have been identified, but the majority of inherited risk factors remain unknown. The aim of the research described in this thesis was to study biomarkers, epidemiology and genetic risk factors in canine tumors with the main focus in canine mammary tumors, using a population of a breed at high-risk for this disease in Sweden. In the first study, a study of a serum biomarker in canine tumors, serum thymidine kinase 1 (TK1) -activity in canine malignant lymphoma, leukemia and solid tumors using the standard TK REA and non-radiometric assays was performed. Serum TK1 was proven to be highly effective in diagnosing, prognosticating, and monitoring dogs with hematological neoplasias (lymphoma, leukemia), but the assay was ineffective in detecting TK1 activity in solid tumors such as CMTs. Clinical and histological characteristics of CMTs were described in a population of ESS dogs in Sweden. The reproductive status was shown as an important risk factor for MT development and age of onset and histological subtype affected the survival time after diagnosis of MT-affected dogs. Genetic risk factors for CMTs were further investigated in the following studies. A candidate gene association study in CMTs showed two human breast cancer genes, BRCA1 and BRCA2 that were associated with CMT in ESS dogs. The potential involvement of the major histocompatibility complex (MHC) class II in CMT development was studied and the results indicated diversity of MHC class II haplotypes and identified a haplotype that protected against MT development in ESS dogs. In summary, this thesis provides new information about risk factors for CMT development. The identification of genetic risk factors is critical to improvements in prevention, diagnosis and treatment of these tumors.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although reproductive factors are among the most well-established risk factors for breast cancer in the general population, it is still a matter for debate whether these factors act as risk modifiers among BRCA1 or BRCA2 mutation carriers. This meta-analysis is the first to be performed to determine the relationship between reproductive factors and breast cancer risk among BRCA1 and BRCA2 mutation carriers. We searched the PubMed database up to February 2013. A total of ten studies met the inclusion criteria. The results showed that the reproductive factors may be associated with breast cancer risk only among BRCA1 mutation carriers. No association was found between parity and breast cancer risk. Compared with women at the youngest age in the first-birth category, women in the oldest age category were at a 38% lower risk of breast cancer (RR=0.62, 95%CI=0.45-0.85). Breastfeeding for at least 1 or 2 years was associated with a 37% reduction in breast cancer risk (RR=0.63, 95%CI=0.46-0.86). Women at the oldest age in the menarche category were at a 34% lower risk of breast cancer (RR=0.66, 95%CI=0.53-0.81) than women in the youngest age category. However, none of the reproductive factors were associated with breast cancer risk among BRCA2 mutation carriers. In conclusion, late age at first birth, breastfeeding, and late age at menarche protect against breast cancer in BRCA1 mutation carriers only. Further studies are needed to explore the mechanisms.
    Cancer epidemiology. 12/2013;

Full-text

View
42 Downloads
Available from
Jun 4, 2014