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      Changes in body weight and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers

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          Abstract

          Background

          Several anthropometric measures have been found to be associated with the risk of breast cancer. Current weight, body mass index, and adult weight gain appear to be predictors of postmenopausal breast cancer. These factors have been associated with a reduced risk of premenopausal breast cancer. We asked whether there is an association between changes in body weight and the risk of breast cancer in women who carry a mutation in either breast cancer susceptibility gene, BRCA1 or BRCA2.

          Methods

          A matched case–control study was conducted in 1,073 pairs of women carrying a deleterious mutation in either BRCA1 ( n = 797 pairs) or BRCA2 ( n = 276 pairs). Women diagnosed with breast cancer were matched to control subjects by year of birth, mutation, country of residence, and history of ovarian cancer. Information about weight was derived from a questionnaire routinely administered to women who were carriers of a mutation in either gene. Conditional logistic regression was used to estimate the association between weight gain or loss and the risk of breast cancer, stratified by age at diagnosis or menopausal status.

          Results

          A loss of at least 10 pounds in the period from age 18 to 30 years was associated with a decreased risk of breast cancer between age 30 and 49 (odds ratio (OR) = 0.47; 95% confidence interval (CI) 0.28–0.79); weight gain during the same interval did not influence the overall risk. Among the subgroup of BRCA1 mutation carriers who had at least two children, weight gain of more than 10 pounds between age 18 and 30 was associated with an increased risk of breast cancer diagnosed between age 30 and 40 (OR = 1.44, 95% CI 1.01–2.04). Change in body weight later in life (at age 30 to 40) did not influence the risk of either premenopausal or postmenopausal breast cancer.

          Conclusion

          The results from this study suggest that weight loss in early adult life (age 18 to 30) protects against early-onset BRCA-associated breast cancers. Weight gain should also be avoided, particularly among BRCA1 mutation carriers who elect to have at least two pregnancies.

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          Most cited references66

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          Physical status the use and interpretation of anthropometry.

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            Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.

            The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in BRCA2 carriers <50 years of age.
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              Role of the insulin-like growth factor family in cancer development and progression.

              H Yu, T. Rohan (2000)
              The insulin-like growth factors (IGFs) are mitogens that play a pivotal role in regulating cell proliferation, differentiation, and apoptosis. The effects of IGFs are mediated through the IGF-I receptor, which is also involved in cell transformation induced by tumor virus proteins and oncogene products. Six IGF-binding proteins (IGFBPs) can inhibit or enhance the actions of IGFs. These opposing effects are determined by the structures of the binding proteins. The effects of IGFBPs on IGFs are regulated in part by IGFBP proteases. Laboratory studies have shown that IGFs exert strong mitogenic and antiapoptotic actions on various cancer cells. IGFs also act synergistically with other mitogenic growth factors and steroids and antagonize the effect of antiproliferative molecules on cancer growth. The role of IGFs in cancer is supported by epidemiologic studies, which have found that high levels of circulating IGF-I and low levels of IGFBP-3 are associated with increased risk of several common cancers, including those of the prostate, breast, colorectum, and lung. Evidence further suggests that certain lifestyles, such as one involving a high-energy diet, may increase IGF-I levels, a finding that is supported by animal experiments indicating that IGFs may abolish the inhibitory effect of energy restriction on cancer growth. Further investigation of the role of IGFs in linking high energy intake, increased cell proliferation, suppression of apoptosis, and increased cancer risk may provide new insights into the etiology of cancer and lead to new strategies for cancer prevention.
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                Author and article information

                Journal
                Breast Cancer Res
                Breast Cancer Research
                BioMed Central (London )
                1465-5411
                1465-542X
                2005
                19 August 2005
                : 7
                : 5
                : R833-R843
                Affiliations
                [1 ]Centre for Research in Women's Health, Women's College Hospital, University of Toronto, Toronto, ON, Canada
                [2 ]Department of Nutritional Sciences, University of Toronto, ON, Canada
                [3 ]Center for Clinical Cancer Genetics, University of Chicago, Chicago, IL, USA
                [4 ]Epidemiology Research Unit, Research Centre, Centre Hospitalier de l'Universitaire Montréal, CHUM Hôtel Dieu and Département de Nutrition, Faculté du Médecine, Quebec, QC, Canada
                [5 ]Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland
                [6 ]Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA
                [7 ]Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC, USA
                [8 ]Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA, USA
                [9 ]British Columbia Cancer Agency, Vancouver, BC, Canada
                [10 ]London Regional Cancer Center, London, ON, Canada
                [11 ]Departments of Medicine, Human Genetics, and Oncology, McGill University, Montréal, QC, Canada
                [12 ]Sunnybrook and Women's College Health Sciences, Toronto, ON, Canada
                Article
                bcr1293
                10.1186/bcr1293
                1242151
                16168130
                56472fb7-1789-4330-aafc-6bf5c6a21fd6
                Copyright © 2005 Kotsopoulos et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 10 February 2005
                : 31 March 2005
                : 23 June 2005
                : 6 July 2005
                Categories
                Research Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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