Minerva Elements Records

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Type: Journal Article × Author: Giles, Graham × Subject: breast cancer ×

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    Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: a genome-wide interaction study
    Rudolph, A ; Hein, R ; Lindstroem, S ; Beckmann, L ; Behrens, S ; Liu, J ; Aschard, H ; Bolla, MK ; Wang, J ; Truong, T ; Cordina-Duverger, E ; Menegaux, F ; Bruening, T ; Harth, V ; Severi, G ; Baglietto, L ; Southey, M ; Chanock, SJ ; Lissowska, J ; Figueroa, JD ; Eriksson, M ; Humpreys, K ; Darabi, H ; Olson, JE ; Stevens, KN ; Vachon, CM ; Knight, JA ; Glendon, G ; Mulligan, AM ; Ashworth, A ; Orr, N ; Schoemaker, M ; Webb, PM ; Guenel, P ; Brauch, H ; Giles, G ; Garcia-Closas, M ; Czene, K ; Chenevix-Trench, G ; Couch, FJ ; Andrulis, IL ; Swerdlow, A ; Hunter, DJ ; Flesch-Janys, D ; Easton, DF ; Hall, P ; Nevanlinna, H ; Kraft, P ; Chang-Claude, J (BIOSCIENTIFICA LTD, 2013-12)
    Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case-control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showing P values for interaction (Pint) <3.0 × 10(-3) were selected for replication using pooled case-control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combined Pint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 near POMP (combined Pint≤8.9 × 10(-6)), two SNPs in SLC25A21 (combined Pint≤4.8 × 10(-5)), and three SNPs in PLCG2 (combined Pint≤4.5 × 10(-5)). The association between lobular BC risk was potentially modified by one SNP in TMEFF2 (combined Pint≤2.7 × 10(-5)), one SNP in CD80 (combined Pint≤8.2 × 10(-6)), three SNPs on chr17 near TMEM132E (combined Pint≤2.2×10(-6)), and two SNPs on chr18 near SLC25A52 (combined Pint≤4.6 × 10(-5)). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.
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    Tumour morphology predicts PALB2 germline mutation status
    Teo, ZL ; Provenzano, E ; Dite, GS ; Park, DJ ; Apicella, C ; Sawyer, SD ; James, PA ; Mitchell, G ; Trainer, AH ; Lindeman, GJ ; Shackleton, K ; Cicciarelli, L ; Buys, SS ; Andrulis, IL ; Mulligan, AM ; Glendon, G ; John, EM ; Terry, MB ; Daly, M ; Odefrey, FA ; Nguyen-Dumont, T ; Giles, GG ; Dowty, JG ; Winship, I ; Goldgar, DE ; Hopper, JL ; Southey, MC (NATURE PUBLISHING GROUP, 2013-07-09)
    BACKGROUND: Population-based studies of breast cancer have estimated that at least some PALB2 mutations are associated with high breast cancer risk. For women carrying PALB2 mutations, knowing their carrier status could be useful in directing them towards effective cancer risk management and therapeutic strategies. We sought to determine whether morphological features of breast tumours can predict PALB2 germline mutation status. METHODS: Systematic pathology review was conducted on breast tumours from 28 female carriers of PALB2 mutations (non-carriers of other known high-risk mutations, recruited through various resources with varying ascertainment) and on breast tumours from a population-based sample of 828 Australian women diagnosed before the age of 60 years (which included 40 BRCA1 and 18 BRCA2 mutation carriers). Tumour morphological features of the 28 PALB2 mutation carriers were compared with those of 770 women without high-risk mutations. RESULTS: Tumours arising in PALB2 mutation carriers were associated with minimal sclerosis (odds ratio (OR)=19.7; 95% confidence interval (CI)=6.0-64.6; P=5 × 10(-7)). Minimal sclerosis was also a feature that distinguished PALB2 mutation carriers from BRCA1 (P=0.05) and BRCA2 (P=0.04) mutation carriers. CONCLUSION: This study identified minimal sclerosis to be a predictor of germline PALB2 mutation status. Morphological review can therefore facilitate the identification of women most likely to carry mutations in PALB2.