Melbourne Students & Learning - Research Publications

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End date: 2013 × Start date: 2013 × Author: Milne, Roger ×

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    Diagnostic Chest X-Rays and Breast Cancer Risk before Age 50 Years for BRCA1 and BRCA2 Mutation Carriers
    John, EM ; McGuire, V ; Thomas, D ; Haile, R ; Ozcelik, H ; Milne, RL ; Felberg, A ; West, DW ; Miron, A ; Knight, JA ; Terry, MB ; Daly, M ; Buys, SS ; Andrulis, IL ; Hopper, JL ; Southey, MC ; Giles, GG ; Apicella, C ; Thorne, H ; Whittemore, AS (AMER ASSOC CANCER RESEARCH, 2013-09)
    BACKGROUND: The effects of low-dose medical radiation on breast cancer risk are uncertain, and few studies have included genetically susceptible women, such as those who carry germline BRCA1 and BRCA2 mutations. METHODS: We studied 454 BRCA1 and 273 BRCA2 mutation carriers ages younger than 50 years from three breast cancer family registries in the United States, Canada, and Australia/New Zealand. We estimated breast cancer risk associated with diagnostic chest X-rays by comparing mutation carriers with breast cancer (cases) with those without breast cancer (controls). Exposure to chest X-rays was self-reported. Mammograms were not considered in the analysis. RESULTS: After adjusting for known risk factors for breast cancer, the ORs for a history of diagnostic chest X-rays, excluding those for tuberculosis or pneumonia, were 1.16 [95% confidence interval (CI), 0.64-2.11] for BRCA1 mutations carriers and 1.22 (95% CI, 0.62-2.42) for BRCA2 mutations carriers. The OR was statistically elevated for BRCA2 mutation carriers with three to five diagnostic chest X-rays (P = 0.01) but not for those with six or more chest X-rays. Few women reported chest fluoroscopy for tuberculosis or chest X-rays for pneumonia; the OR estimates were elevated, but not statistically significant, for BRCA1 mutation carriers. CONCLUSIONS: Our findings do not support a positive association between diagnostic chest X-rays and breast cancer risk before the ages of 50 years for BRCA1 or BRCA2 mutation carriers. IMPACT: Given the increasing use of diagnostic imaging involving higher ionizing radiation doses, further studies of genetically predisposed women are warranted.
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    Evidence of Gene-Environment Interactions between Common Breast Cancer Susceptibility Loci and Established Environmental Risk Factors
    Nickels, S ; Truong, T ; Hein, R ; Stevens, K ; Buck, K ; Behrens, S ; Eilber, U ; Schmidt, M ; Haeberle, L ; Vrieling, A ; Gaudet, M ; Figueroa, J ; Schoof, N ; Spurdle, AB ; Rudolph, A ; Fasching, PA ; Hopper, JL ; Makalic, E ; Schmidt, DF ; Southey, MC ; Beckmann, MW ; Ekici, AB ; Fletcher, O ; Gibson, L ; Silva, IDS ; Peto, J ; Humphreys, MK ; Wang, J ; Cordina-Duverger, E ; Menegaux, F ; Nordestgaard, BG ; Bojesen, SE ; Lanng, C ; Anton-Culver, H ; Ziogas, A ; Bernstein, L ; Clarke, CA ; Brenner, H ; Mueller, H ; Arndt, V ; Stegmaier, C ; Brauch, H ; Bruening, T ; Harth, V ; Mannermaa, A ; Kataja, V ; Kosma, V-M ; Hartikainen, JM ; Lambrechts, D ; Smeets, D ; Neven, P ; Paridaens, R ; Flesch-Janys, D ; Obi, N ; Wang-Gohrke, S ; Couch, FJ ; Olson, JE ; Vachon, CM ; Giles, GG ; Severi, G ; Baglietto, L ; Offit, K ; John, EM ; Miron, A ; Andrulis, IL ; Knight, JA ; Glendon, G ; Mulligan, AM ; Chanock, SJ ; Lissowska, J ; Liu, J ; Cox, A ; Cramp, H ; Connley, D ; Balasubramanian, S ; Dunning, AM ; Shah, M ; Trentham-Dietz, A ; Newcomb, P ; Titus, L ; Egan, K ; Cahoon, EK ; Rajaraman, P ; Sigurdson, AJ ; Doody, MM ; Guenel, P ; Pharoah, PDP ; Schmidt, MK ; Hall, P ; Easton, DF ; Garcia-Closas, M ; Milne, RL ; Chang-Claude, J ; Horwitz, MS (PUBLIC LIBRARY SCIENCE, 2013-03)
    Various common genetic susceptibility loci have been identified for breast cancer; however, it is unclear how they combine with lifestyle/environmental risk factors to influence risk. We undertook an international collaborative study to assess gene-environment interaction for risk of breast cancer. Data from 24 studies of the Breast Cancer Association Consortium were pooled. Using up to 34,793 invasive breast cancers and 41,099 controls, we examined whether the relative risks associated with 23 single nucleotide polymorphisms were modified by 10 established environmental risk factors (age at menarche, parity, breastfeeding, body mass index, height, oral contraceptive use, menopausal hormone therapy use, alcohol consumption, cigarette smoking, physical activity) in women of European ancestry. We used logistic regression models stratified by study and adjusted for age and performed likelihood ratio tests to assess gene-environment interactions. All statistical tests were two-sided. We replicated previously reported potential interactions between LSP1-rs3817198 and parity (Pinteraction = 2.4 × 10(-6)) and between CASP8-rs17468277 and alcohol consumption (Pinteraction = 3.1 × 10(-4)). Overall, the per-allele odds ratio (95% confidence interval) for LSP1-rs3817198 was 1.08 (1.01-1.16) in nulliparous women and ranged from 1.03 (0.96-1.10) in parous women with one birth to 1.26 (1.16-1.37) in women with at least four births. For CASP8-rs17468277, the per-allele OR was 0.91 (0.85-0.98) in those with an alcohol intake of <20 g/day and 1.45 (1.14-1.85) in those who drank ≥ 20 g/day. Additionally, interaction was found between 1p11.2-rs11249433 and ever being parous (Pinteraction = 5.3 × 10(-5)), with a per-allele OR of 1.14 (1.11-1.17) in parous women and 0.98 (0.92-1.05) in nulliparous women. These data provide first strong evidence that the risk of breast cancer associated with some common genetic variants may vary with environmental risk factors.