Person: Tworoger, Shelley
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Publication Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
(American Association for Cancer Research (AACR), 2016) Kar, S. P.; Beesley, J.; Amin Al Olama, A.; Michailidou, K.; Tyrer, J.; Kote-Jarai, Z.; Lawrenson, K.; Lindstrom, S.; Ramus, S. J.; Thompson, D. J.; Kibel, Adam; Dansonka-Mieszkowska, A.; Michael, A.; Dieffenbach, A. K.; Gentry-Maharaj, A.; Whittemore, A. S.; Wolk, A.; Monteiro, A.; Peixoto, A.; Kierzek, A.; Cox, A.; Rudolph, A.; Gonzalez-Neira, A.; Wu, A. H.; Lindblom, A.; Swerdlow, A.; Ziogas, A.; Ekici, A. B.; Burwinkel, B.; Karlan, B. Y.; Nordestgaard, B. G.; Blomqvist, C.; Phelan, C.; McLean, C.; Pearce, C. L.; Vachon, C.; Cybulski, C.; Slavov, C.; Stegmaier, C.; Maier, C.; Ambrosone, C. B.; Hogdall, C. K.; Teerlink, C. C.; Kang, D.; Tessier, D. C.; Schaid, D. J.; Stram, D. O.; Cramer, Daniel; Neal, D. E.; Eccles, D.; Flesch-Janys, D.; Edwards, D. R. V.; Wokozorczyk, D.; Levine, D. A.; Yannoukakos, D.; Sawyer, E. J.; Bandera, E. V.; Poole, Elizabeth M.; Goode, E. L.; Khusnutdinova, E.; Hogdall, E.; Song, F; Bruinsma, F.; Heitz, F.; Modugno, F.; Hamdy, F. C.; Wiklund, F.; Giles, G. G.; Olsson, H.; Wildiers, H.; Ulmer, H.-U.; Pandha, H.; Risch, H. A.; Darabi, H.; Salvesen, H. B.; Nevanlinna, H.; Gronberg, H.; Brenner, H.; Brauch, H.; Anton-Culver, H.; Song, H.; Lim, H.-Y.; McNeish, I.; Campbell, I.; Vergote, I.; Gronwald, J.; Lubinski, J.; Stanford, J. L.; Benitez, J.; Doherty, J. A.; Permuth, J. B.; Chang-Claude, J.; Donovan, J. L.; Dennis, J.; Schildkraut, J. M.; Schleutker, J.; Hopper, J. L.; Kupryjanczyk, J.; Park, J. Y.; Figueroa, J.; Clements, J. A.; Knight, J. A.; Peto, J.; Cunningham, J. M.; Pow-Sang, J.; Batra, J.; Czene, K.; Lu, K. H.; Herkommer, K.; Khaw, K.-T.; Matsuo, K.; Muir, K.; Offitt, K.; Chen, K.; Moysich, K. B.; Aittoma ki, K.; Odunsi, K.; Kiemeney, L. A.; Massuger, L. F. A. G.; Fitzgerald, L. M.; Cook, L. S.; Cannon-Albright, L.; Hooning, M. J.; Pike, M. C.; Bolla, M. K.; Luedeke, M.; Teixeira, M. R.; Goodman, M. T.; Schmidt, M. K.; Riggan, M.; Aly, M.; Rossing, M. A.; Beckmann, M. W.; Moisse, M.; Sanderson, M.; Southey, M. C.; Jones, M.; Lush, M.; Hildebrandt, M. A. T.; Hou, M.-F.; Schoemaker, M. J.; Garcia-Closas, M.; Bogdanova, N.; Rahman, N.; Le, N. D.; Orr, N.; Wentzensen, N.; Pashayan, N.; Peterlongo, P.; Guenel, P.; Brennan, P.; Paulo, P.; Webb, P. M.; Broberg, P.; Fasching, P. A.; Devilee, P.; Wang, Q.; Cai, Q.; Li, Q.; Kaneva, R.; Butzow, R.; Kopperud, R. K.; Schmutzler, R. K.; Stephenson, R. A.; MacInnis, R. J.; Hoover, R. N.; Winqvist, R.; Ness, R.; Milne, R. L.; Travis, R. C.; Benlloch, S.; Olson, S. H.; McDonnell, S. K.; Tworoger, Shelley; Maia, S.; Berndt, S.; Lee, S. C.; Teo, S.-H.; Thibodeau, S. N.; Bojesen, S. E.; Gapstur, S. M.; Kjaer, S. K.; Pejovic, T.; Tammela, T. L. J.; Do rk, T.; Bru ning, T.; Wahlfors, T.; Key, T. J.; Edwards, T. L.; Menon, U.; Hamann, U.; Mitev, V.; Kosma, V.-M.; Setiawan, V. W.; Kristensen, V.; Arndt, V.; Vogel, W.; Zheng, W.; Sieh, W.; Blot, W. J.; Kluzniak, W.; Shu, X.-O.; Gao, Y.-T.; Schumacher, F.; Freedman, M. L.; Berchuck, A.; Dunning, A. M.; Simard, J.; Haiman, C. A.; Spurdle, A.; Sellers, T. A.; Hunter, David; Henderson, B. E.; Kraft, Peter; Chanock, S. J.; Couch, F. J.; Hall, P.; Gayther, S. A.; Easton, D. F.; Chenevix-Trench, G.; Eeles, R.; Pharoah, P. D. P.; Lambrechts, D.; undefined, undefinedBreast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.
Publication Examining the common aetiology of serous ovarian cancers and basal-like breast cancers using double primaries
(Nature Publishing Group, 2017) Begg, Colin B; Rice, Megan; Zabor, Emily C; Tworoger, ShelleyBackground: The somatic molecular profiles of basal-like breast cancers and high-grade serous ovarian cancers share many similarities, leading to the hypothesis that they have similar aetiologies, in which case they should occur together in the same patient more often than expected. Methods: We identified 545 women with double independent primary cancers of the breast and ovary reported to the California Cancer Registry from 1999 to 2013 and examined the coincidence of subtype combinations. Results: For most subtype combinations the observed frequencies were similar to their expected frequencies, but in 103 observed cases vs 43.8 expected (O/E=2.35; 95% CI 1.90–2.81) a triple-negative breast tumour (typically basal-like) was matched with a serous ovarian tumour (typically high-grade). Conclusions: The results provide compelling evidence that basal-like breast cancer and high-grade serous ovarian cancer share a much more similar aetiology than breast and ovarian cancers more broadly. Further research is needed to clarify the influence of germ-line BRCA1 mutations and other risk factors on these results.
Publication Sleep and survival among women with breast cancer: 30 years of follow-up within the Nurses' Health Study
(Nature Publishing Group, 2017) Trudel-Fitzgerald, Claudia; Zhou, Eric; Poole, Elizabeth M; Zhang, Xuehong; Michels, Karin B; Eliassen, A; Chen, Wendy; Holmes, Michelle; Tworoger, Shelley; Schernhammer, EvaBackground: Breast cancer is a leading cause of cancer death in women. Sleep has been linked with mortality among cancer-free population; however, its association with survival among women with breast cancer is understudied. Methods: Breast cancer patients (N=3682) reported their average sleep duration post diagnosis. Subsamples also provided their pre-diagnosis sleep duration (n=1949) and post-diagnosis sleep difficulties (n=1353). Multivariate Cox models estimated hazard ratios (HR) and confidence intervals (CI) of all-cause, breast cancer, and non-breast cancer mortality. Results: At diagnosis, the mean age was 64.9 years and 91.7% were stage I or II. Women sleeping ⩾9 h per night post diagnosis had a strong higher risk of all-cause (multivariate HRs: MV-HR=1.37, CI=1.10–1.71), breast cancer (MV-HR=1.46, CI=1.02–2.07), and non-breast cancer mortality (MV-HR=1.34, CI=1.01–1.79), compared to women sleeping 8 h per night. Increased sleep duration post diagnosis (vs unchanged) and regular sleep difficulties (vs rare/none) were associated with a strong elevated risk of all-cause mortality (MV-HRincreased duration=1.35, CI=1.04–1.74; MV-HRregular difficulties=1.49, CI=1.02–2.19) and a moderate greater risk of breast cancer and non-breast cancer mortality. Conclusions: Various facets of sleep were associated with higher all-cause mortality risk. If replicated, these findings support evaluation of breast cancer patients' sleep duration and difficulties to identify those at risk for poorer outcomes.