Family history of first and second-degree relatives is known to increase the risk for breast cancer. Less data are available on the risks between defined multiple affected close and distant relatives for which the reliability of data may be an issue. Data on affected males are sparse. These questions and the probable genetic models were addressed in this study by means of a nationwide Swedish Family-Cancer Database. We estimated the effect of family history of breast cancer by Poisson regression for women of at least 30 years of age after adjusting for age, period, region, socioeconomic status, number of children, and age at first birth. The results of the study showed that relative risk (RR) for breast cancer was associated with a first degree as well as second-degree family history. Having at least two female affected first-degree relatives increased the RR at least to 2.8, favoring an additive interaction. The risk was increased around ten times in women with both parents affected. When either a father or a mother was affected, the RRs were nearly identical (RR = 1.73 and 1.74, respectively). The RR for a woman increased more when a brother was affected (RR = 2.48) compared to when a sister was affected (RR = 1.87). Having an affected grandmother showed lower familial excess risks than having an affected half sister (RR = 1.27, and 1.26; and RR = 1.39, and 1.50; respectively, for maternal and paternal relatives). We concluded that when both parents were diagnosed with breast cancer, the risk for the daughter was increased tenfold. Having an affected brother showed a somewhat higher risk than having an affected sister. The data suggest that male breast cancer has a higher genetic basis than female breast cancer, which invites further search of the underlying mechanisms.
Breast cancer Family history
International Classification of Disease
Familial excess risk
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This study was supported by Deutsche Krebshilfe, the Swedish Cancer Society, and The Swedish Council for Working Life and Social Research—LSHC-CT-2004-503465. The Family-Cancer Database was created by linking registers maintained at Statistics Sweden and the Swedish Cancer Registry.
Conflict of interest
The authors declare that they have no conflict of interest.
Collaborative Group on Hormonal Factors in Breast Cancer (2001) Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease. Lancet 358(9291):1389–1399CrossRefGoogle Scholar
Eisen A, Irwin E (2002) Review: breast cancer is associated with a family history of the disease in first degree relatives. Evid Based Nurs 5(3):89PubMedCrossRefGoogle Scholar
Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K et al (2005) Benign breast disease and the risk of breast cancer. N Engl J Med 353(3):229–237PubMedCrossRefGoogle Scholar
Colditz GA, Rosner B (2000) Cumulative risk of breast cancer to age 70 years according to risk factor status: data from the Nurses’ Health Study. Am J Epidemiol 152(10):950–964PubMedCrossRefGoogle Scholar
Czene K, Lichtenstein P, Hemminki K (2002) Environmental and heritable causes of cancer among 9.6 million individuals in the Swedish Family-Cancer Database. Int J Cancer 99(2):260–266PubMedCrossRefGoogle Scholar
Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M et al (2000) Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 343(2):78–85PubMedCrossRefGoogle Scholar
Locatelli I, Lichtenstein P, Yashin AI (2004) The heritability of breast cancer: a Bayesian correlated frailty model applied to Swedish twins data. Twin Res 7(2):182–191PubMedCrossRefGoogle Scholar
O’Donovan PJ, Livingston DM (2010) BRCA1 and BRCA2: breast/ovarian cancer susceptibility gene products and participants in DNA double-strand break repair. Carcinogenesis 31(6):961–967PubMedCrossRefGoogle Scholar
Petrucelli N, Daly MB, Feldman GL (2010) Hereditary breast and ovarian cancer due to mutations in BRCA1 and BRCA2. Genet Med 12(5):245–259PubMedCrossRefGoogle Scholar
Cui J, Hopper JL (2000) Why are the majority of hereditary cases of early-onset breast cancer sporadic? A simulation study. Cancer Epidemiol Biomarkers Prev 9(8):805–812PubMedGoogle Scholar
Bermejo JL, Hemminki K (2005) A population-based assessment of the clustering of breast cancer in families eligible for testing of BRCA1 and BRCA2 mutations. Ann Oncol 16(2):322–329CrossRefGoogle Scholar
Hemminki K, Försti A, Bermejo JL (2008) New cancer susceptibility loci: population and familial risks. Int J Cancer 123(7):1726–1729PubMedCrossRefGoogle Scholar
Fletcher O, Johnson N, Orr N, Hosking FJ, Gibson LJ, Walker K et al (2011) Novel breast cancer susceptibility locus at 9q31.2: results of a genome-wide association study. J Natl Cancer Inst 103(5):425–435PubMedCrossRefGoogle Scholar
Turnbull C, Ahmed S, Morrison J, Pernet D, Renwick A, Maranian M et al (2010) Genome-wide association study identifies five new breast cancer susceptibility loci. Nat Genet 42(6):504–507PubMedCrossRefGoogle Scholar
Fletcher O, Houlston RS (2010) Architecture of inherited susceptibility to common cancer. Nat Rev Cancer 10(5):353–361PubMedCrossRefGoogle Scholar
WHO (1957) Manual of the international statistical classification of diseases, injuries and causes of death: seventh revision. World Health Organization, GenevaGoogle Scholar
Hemminki K, Ji J, Brandt A, Mousavi SM, Sundquist J (2010) The Swedish Family-Cancer Database 2009: prospects for histology-specific and immigrant studies. Int J Cancer 126(10):2259–2267PubMedGoogle Scholar
Daly L (1992) Simple SAS macros for the calculation of exact binomial and Poisson confidence limits. Comput Biol Med 22:351–361PubMedCrossRefGoogle Scholar
Breslow NE, Day NE (1987) Statistical methods in cancer research. Volume II—the design and analysis of cohort studies. IARC Scientific Publications No. 82. International Agency for Research on Cancer, LyonGoogle Scholar
Gómez-Raposo C, Tévar FZ, Moyano MS, Gómez ML, Casado E (2010) Male breast cancer. Cancer Treat Rev 36(6):451–457PubMedCrossRefGoogle Scholar
Orr N, Cooke R, Jones M, Fletcher O, Dudbridge F, Chilcott-Burns S et al (2011) Genetic variants at chromosomes 2q35, 5p12, 6q25.1, 10q26.13, and 16q12.1 influence the risk of breast cancer in men. PLoS Genet 7(9):e1002290PubMedCrossRefGoogle Scholar
Syrjäkoski K, Kuukasjärvi T, Waltering K, Haraldsson K, Auvinen A, Borg A et al (2004) BRCA2 mutations in 154 Finnish male breast cancer patients. Neoplasia 6(5):541–545PubMedCrossRefGoogle Scholar
Couto E, Hemminki K (2007) Estimates of heritable and environmental components of familial breast cancer using family history information. Br J Cancer 96(11):1740–1742PubMedCrossRefGoogle Scholar