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5. Klinische, morphologische und zellbiologische Charakteristika der Adenome des Mittelohres

Author

Vogt, P, Delventhal, S, Karstens, JH, and Welkoborsky, HJ

Subjects
ddc: 610
Abstract

Einleitung: Adenome des Mittelohres sind seltene Tumoren. Histologisch werden benigne Mittelohradenome mit solidem-, zystischem-, und trabekelartigem Wachstum von lokal aggressiv wachsenden papillären Adenomen unterschieden.Methoden: Es wird über 2 Patienten mit Mittelohradenomen berichtet, die im Jahr 2004 behandelt wurden. Eine 61 jährige Patientin wurde mit Hörminderung und einer otoskopisch glatten polypösen Raumforderung im hinteren Quadranten des Trommelfells vorstellig. In der Kernspintomographie kam eine Raumforderung des Mittelohres ohne knöcherne Arrosion zur Darstellung. Die histologische Untersuchung ergab ein benignes Mittelohradenom. Anders bei einer 93 jährigen Patientin, die mit Hörminderung, Paukenhöhlenerguss und einer Nasenatmungsbehinderung aufgenommen wurde. Im CT zeigte sich ein Tumor im Epipharynx und der lateralen Schädelbasis mit knöcherner Arrosion und Ausbreitung nach intrakraniell. Histologisch wurde ein lokal aggressiv wachsendes Mittelohradenom beschrieben. Es werden die klinischen, histologischen und zellbiologischen Charakteristika (u.a. Proliferationsrate; Expression von Zytokinen; quantitative DNA-Zytometrie) der Tumoren vorgestellt. Schlussfolgerungen: Obwohl es sich bei den Mittelohradenomen um seltene Tumoren handelt, sind sie in die differentialdiagnostischen Überlegungen bei unklaren Raumforderungen des Mittelohres und des Nasopharynx einzubeziehen. Die Therapie besteht in der chirurgischen Entfernung, gegebenenfalls mit postoperativer Strahlentherapie. Tumorbiologische Untersuchungen, wie Ermittlung der Proliferationsrate oder DNA-Zytometrie, erleichtern die Dignitätsdiagnose und die Aggressivitäts- bzw. Prognoseabschätzung.

Published
2005

8. Genome-wide association analysis identifies three new breast cancer susceptibility loci

Author

Ghoussaini, M, Fletcher, O, Michailidou, K, Turnbull, C, Schmidt, MK, Dicks, E, Dennis, J, Wang, Q, Humphreys, MK, Luccarini, C, Baynes, C, Conroy, D, Maranian, M, Ahmed, S, Driver, K, Johnson, N, Orr, N, Silva, IDS, Waisfisz, Q, Meijers-Heijboer, H, Uitterlinden, AG, Rivadeneira, F, Hall, P, Czene, K, Irwanto, A, Liu, J, Nevanlinna, H, Aittomaki, K, Blomqvist, C, Meindl, A, Schmutzler, RK, Mueller-Myhsok, B, Lichtner, P, Chang-Claude, J, Hein, R, Nickels, S, Flesch-Janys, D, Tsimiklis, H, Makalic, E, Schmidt, D, Bui, M, Hopper, JL, Apicella, C, Park, DJ, Southey, M, Hunter, DJ, Chanock, SJ, Broeks, A, Verhoef, S, Hogervorst, FBL, Fasching, PA, Lux, MP, Beckmann, MW, Ekici, AB, Sawyer, E, Tomlinson, I, Kerin, M, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Truong, T, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Milne, RL, Rosario Alonso, M, Gonzalez-Neira, A, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Justenhoven, C, Brauch, H, Bruening, T, Wang-Gohrke, S, Eilber, U, Doerk, T, Schuermann, P, Bremer, M, Hillemanns, P, Bogdanova, NV, Antonenkova, NN, Rogov, YI, Karstens, JH, Bermisheva, M, Prokofieva, D, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Manoukian, S, Bonanni, B, Fortuzzi, S, Peterlongo, P, Couch, FJ, Wang, X, Stevens, K, Lee, A, Giles, GG, Baglietto, L, Severi, G, McLean, C, Alnaes, GG, Kristensen, V, Borrensen-Dale, A-L, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, IL, Glendon, G, Mulligan, AM, Devilee, P, van Asperen, CJ, Tollenaar, RAEM, Seynaeve, C, Figueroa, JD, Garcia-Closas, M, Brinton, L, Lissowska, J, Hooning, MJ, Hollestelle, A, Oldenburg, RA, van den Ouweland, AMW, Cox, A, Reed, MWR, Shah, M, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Jones, M, Schoemaker, M, Ashworth, A, Swerdlow, A, Beesley, J, Chen, X, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Chaiwerawattana, A, Kang, D, Yoo, K-Y, Noh, D-Y, Shen, C-Y, Yu, J-C, Wu, P-E, Hsiung, C-N, Perkins, A, Swann, R, Velentzis, L, Eccles, DM, Tapper, WJ, Gerty, SM, Graham, NJ, Ponder, BAJ, Chenevix-Trench, G, Pharoah, PDP, Lathrop, M, Dunning, AM, Rahman, N, Peto, J, Easton, DF, Ghoussaini, M, Fletcher, O, Michailidou, K, Turnbull, C, Schmidt, MK, Dicks, E, Dennis, J, Wang, Q, Humphreys, MK, Luccarini, C, Baynes, C, Conroy, D, Maranian, M, Ahmed, S, Driver, K, Johnson, N, Orr, N, Silva, IDS, Waisfisz, Q, Meijers-Heijboer, H, Uitterlinden, AG, Rivadeneira, F, Hall, P, Czene, K, Irwanto, A, Liu, J, Nevanlinna, H, Aittomaki, K, Blomqvist, C, Meindl, A, Schmutzler, RK, Mueller-Myhsok, B, Lichtner, P, Chang-Claude, J, Hein, R, Nickels, S, Flesch-Janys, D, Tsimiklis, H, Makalic, E, Schmidt, D, Bui, M, Hopper, JL, Apicella, C, Park, DJ, Southey, M, Hunter, DJ, Chanock, SJ, Broeks, A, Verhoef, S, Hogervorst, FBL, Fasching, PA, Lux, MP, Beckmann, MW, Ekici, AB, Sawyer, E, Tomlinson, I, Kerin, M, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Truong, T, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Nielsen, SF, Flyger, H, Milne, RL, Rosario Alonso, M, Gonzalez-Neira, A, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Dur, CC, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Justenhoven, C, Brauch, H, Bruening, T, Wang-Gohrke, S, Eilber, U, Doerk, T, Schuermann, P, Bremer, M, Hillemanns, P, Bogdanova, NV, Antonenkova, NN, Rogov, YI, Karstens, JH, Bermisheva, M, Prokofieva, D, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Lambrechts, D, Yesilyurt, BT, Floris, G, Leunen, K, Manoukian, S, Bonanni, B, Fortuzzi, S, Peterlongo, P, Couch, FJ, Wang, X, Stevens, K, Lee, A, Giles, GG, Baglietto, L, Severi, G, McLean, C, Alnaes, GG, Kristensen, V, Borrensen-Dale, A-L, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Kauppila, S, Andrulis, IL, Glendon, G, Mulligan, AM, Devilee, P, van Asperen, CJ, Tollenaar, RAEM, Seynaeve, C, Figueroa, JD, Garcia-Closas, M, Brinton, L, Lissowska, J, Hooning, MJ, Hollestelle, A, Oldenburg, RA, van den Ouweland, AMW, Cox, A, Reed, MWR, Shah, M, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Jones, M, Schoemaker, M, Ashworth, A, Swerdlow, A, Beesley, J, Chen, X, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Chaiwerawattana, A, Kang, D, Yoo, K-Y, Noh, D-Y, Shen, C-Y, Yu, J-C, Wu, P-E, Hsiung, C-N, Perkins, A, Swann, R, Velentzis, L, Eccles, DM, Tapper, WJ, Gerty, SM, Graham, NJ, Ponder, BAJ, Chenevix-Trench, G, Pharoah, PDP, Lathrop, M, Dunning, AM, Rahman, N, Peto, J, and Easton, DF

Abstract

Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ∼8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ∼70,000 cases and ∼68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth.

Published
2012

9. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Author

Chan, KYK, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, IDS, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Truong, T, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Arias Perez, JI, Pilar Zamora, M, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, Y-D, Wang-Gohrke, S, Doerk, T, Schuermann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J, Chen, X, Beesley, J, Lambrechts, D, Zhao, H, Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, JWM, Seynaeve, C, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, J, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S, Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, K-Y, Noh, D-Y, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Shen, C-Y, Yu, J-C, Hsu, H-M, Hou, M-F, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, Dunning, AM, Chan, KYK, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, MK, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, IDS, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Truong, T, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Arias Perez, JI, Pilar Zamora, M, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, Y-D, Wang-Gohrke, S, Doerk, T, Schuermann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, J, Chen, X, Beesley, J, Lambrechts, D, Zhao, H, Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, JWM, Seynaeve, C, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, J, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S, Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, K-Y, Noh, D-Y, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, McKay, J, Shen, C-Y, Yu, J-C, Hsu, H-M, Hou, M-F, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, and Dunning, AM

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of

Published
2012

10. 11q13 is a susceptibility locus for hormone receptor positive breast cancer

Author

Lambrechts, D, Truong, T, Justenhoven, C, Humphreys, MK, Wang, J, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Schmidt, MK, Broeks, A, Cornelissen, S, van Hien, R, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Milne, RL, Pilar Zamora, M, Arias Perez, JI, Benitez, J, Hamann, U, Ko, Y-D, Bruening, T, Chang-Claude, J, Eilber, U, Hein, R, Nickels, S, Flesch-Janys, D, Wang-Gohrke, S, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Chenevix-Trench, G, Beesley, J, Chen, X, Menegaux, F, Cordina-Duverger, E, Shen, C-Y, Yu, J-C, Wu, P-E, Hou, M-F, Andrulis, IL, Selander, T, Glendon, G, Mulligan, AM, Anton-Culver, H, Ziogas, A, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Jones, M, Orr, N, Ashworth, A, Swerdlow, A, Severi, G, Baglietto, L, Giles, G, Southey, M, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Yesilyurt, BT, Neven, P, Paridaens, R, Wildiers, H, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Cox, A, Brock, IW, Elliott, G, Cross, SS, Fasching, PA, Schulz-Wendtland, R, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, IDS, Peto, J, Nevanlinna, H, Muranen, TA, Aittomaki, K, Blomqvist, C, Doerk, T, Schuermann, P, Bremer, M, Hillemanns, P, Bogdanova, NV, Antonenkova, NN, Rogov, YI, Karstens, JH, Khusnutdinova, E, Bermisheva, M, Prokofieva, D, Gancev, S, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Nordestgaard, BG, Bojesen, SE, Lanng, C, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Radice, P, Peterlongo, P, Manoukian, S, Bernard, L, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, Devilee, P, Tollenaar, RAEM, Seynaeve, CM, Hooning, MJ, Garcia-Closas, M, Chanock, SJ, Lissowska, J, Sherman, ME, Hall, P, Liu, J, Czene, K, Kang, D, Yoo, K-Y, Noh, D-Y, Lindblom, A, Margolin, S, Dunning, AM, Pharoah, PDP, Easton, DF, Guenel, P, Brauch, H, Lambrechts, D, Truong, T, Justenhoven, C, Humphreys, MK, Wang, J, Hopper, JL, Dite, GS, Apicella, C, Southey, MC, Schmidt, MK, Broeks, A, Cornelissen, S, van Hien, R, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Milne, RL, Pilar Zamora, M, Arias Perez, JI, Benitez, J, Hamann, U, Ko, Y-D, Bruening, T, Chang-Claude, J, Eilber, U, Hein, R, Nickels, S, Flesch-Janys, D, Wang-Gohrke, S, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Chenevix-Trench, G, Beesley, J, Chen, X, Menegaux, F, Cordina-Duverger, E, Shen, C-Y, Yu, J-C, Wu, P-E, Hou, M-F, Andrulis, IL, Selander, T, Glendon, G, Mulligan, AM, Anton-Culver, H, Ziogas, A, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Jones, M, Orr, N, Ashworth, A, Swerdlow, A, Severi, G, Baglietto, L, Giles, G, Southey, M, Marme, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Yesilyurt, BT, Neven, P, Paridaens, R, Wildiers, H, Brenner, H, Mueller, H, Arndt, V, Stegmaier, C, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Cox, A, Brock, IW, Elliott, G, Cross, SS, Fasching, PA, Schulz-Wendtland, R, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, IDS, Peto, J, Nevanlinna, H, Muranen, TA, Aittomaki, K, Blomqvist, C, Doerk, T, Schuermann, P, Bremer, M, Hillemanns, P, Bogdanova, NV, Antonenkova, NN, Rogov, YI, Karstens, JH, Khusnutdinova, E, Bermisheva, M, Prokofieva, D, Gancev, S, Jakubowska, A, Lubinski, J, Jaworska, K, Durda, K, Nordestgaard, BG, Bojesen, SE, Lanng, C, Mannermaa, A, Kataja, V, Kosma, V-M, Hartikainen, JM, Radice, P, Peterlongo, P, Manoukian, S, Bernard, L, Couch, FJ, Olson, JE, Wang, X, Fredericksen, Z, Alnaes, GG, Kristensen, V, Borresen-Dale, A-L, Devilee, P, Tollenaar, RAEM, Seynaeve, CM, Hooning, MJ, Garcia-Closas, M, Chanock, SJ, Lissowska, J, Sherman, ME, Hall, P, Liu, J, Czene, K, Kang, D, Yoo, K-Y, Noh, D-Y, Lindblom, A, Margolin, S, Dunning, AM, Pharoah, PDP, Easton, DF, Guenel, P, and Brauch, H

Abstract

A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P ≤ 3 × 10(-9) ) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 × 10(-39) ). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype.

Published
2012

11. Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

Author

Prokunina-Olsson, L, Kirchhoff, T, Gaudet, MM, Antoniou, AC, McGuffog, L, Humphreys, MK, Dunning, AM, Bojesen, SE, Nordestgaard, BG, Flyger, H, Kang, D, Yoo, K-Y, Noh, D-Y, Ahn, S-H, Dork, T, Schuermann, P, Karstens, JH, Hillemanns, P, Couch, FJ, Olson, J, Vachon, C, Wang, X, Cox, A, Brock, I, Elliott, G, Reed, MWR, Burwinkel, B, Meindl, A, Brauch, H, Hamann, U, Ko, Y-D, Broeks, A, Schmidt, MK, Van 't Veer, LJ, Braaf, LM, Johnson, N, Fletcher, O, Gibson, L, Peto, J, Turnbull, C, Seal, S, Renwick, A, Rahman, N, Wu, P-E, Yu, J-C, Hsiung, C-N, Shen, C-Y, Southey, MC, Hopper, JL, Hammet, F, Van Dorpe, T, Dieudonne, A-S, Hatse, S, Lambrechts, D, Andrulis, IL, Bogdanova, N, Antonenkova, N, Rogov, JI, Prokofieva, D, Bermisheva, M, Khusnutdinova, E, van Asperen, CJ, Tollenaar, RAEM, Hooning, MJ, Devilee, P, Margolin, S, Lindblom, A, Milne, RL, Ignacio Arias, J, Pilar Zamora, M, Benitez, J, Severi, G, Baglietto, L, Giles, GG, Spurdle, AB, Beesley, J, Chen, X, Holland, H, Healey, S, Wang-Gohrke, S, Chang-Claude, J, Mannermaa, A, Kosma, V-M, Kauppinen, J, Kataja, V, Agnarsson, BA, Caligo, MA, Godwin, AK, Nevanlinna, H, Heikkinen, T, Fredericksen, Z, Lindor, N, Nathanson, KL, Domchek, SM, Loman, N, Karlsson, P, Askmalm, MS, Melin, B, von Wachenfeldt, A, Hogervorst, FBL, Verheus, M, Rookus, MA, Seynaeve, C, Oldenburg, RA, Ligtenberg, MJ, Ausems, MGEM, Aalfs, CM, Gille, HJP, Wijnen, JT, Garcia, EBG, Peock, S, Cook, M, Oliver, CT, Frost, D, Luccarini, C, Pichert, G, Davidson, R, Chu, C, Eccles, D, Ong, K-R, Cook, J, Douglas, F, Hodgson, S, Evans, DG, Eeles, R, Gold, B, Pharoah, PDP, Offit, K, Chenevix-Trench, G, Easton, DF, Prokunina-Olsson, L, Kirchhoff, T, Gaudet, MM, Antoniou, AC, McGuffog, L, Humphreys, MK, Dunning, AM, Bojesen, SE, Nordestgaard, BG, Flyger, H, Kang, D, Yoo, K-Y, Noh, D-Y, Ahn, S-H, Dork, T, Schuermann, P, Karstens, JH, Hillemanns, P, Couch, FJ, Olson, J, Vachon, C, Wang, X, Cox, A, Brock, I, Elliott, G, Reed, MWR, Burwinkel, B, Meindl, A, Brauch, H, Hamann, U, Ko, Y-D, Broeks, A, Schmidt, MK, Van 't Veer, LJ, Braaf, LM, Johnson, N, Fletcher, O, Gibson, L, Peto, J, Turnbull, C, Seal, S, Renwick, A, Rahman, N, Wu, P-E, Yu, J-C, Hsiung, C-N, Shen, C-Y, Southey, MC, Hopper, JL, Hammet, F, Van Dorpe, T, Dieudonne, A-S, Hatse, S, Lambrechts, D, Andrulis, IL, Bogdanova, N, Antonenkova, N, Rogov, JI, Prokofieva, D, Bermisheva, M, Khusnutdinova, E, van Asperen, CJ, Tollenaar, RAEM, Hooning, MJ, Devilee, P, Margolin, S, Lindblom, A, Milne, RL, Ignacio Arias, J, Pilar Zamora, M, Benitez, J, Severi, G, Baglietto, L, Giles, GG, Spurdle, AB, Beesley, J, Chen, X, Holland, H, Healey, S, Wang-Gohrke, S, Chang-Claude, J, Mannermaa, A, Kosma, V-M, Kauppinen, J, Kataja, V, Agnarsson, BA, Caligo, MA, Godwin, AK, Nevanlinna, H, Heikkinen, T, Fredericksen, Z, Lindor, N, Nathanson, KL, Domchek, SM, Loman, N, Karlsson, P, Askmalm, MS, Melin, B, von Wachenfeldt, A, Hogervorst, FBL, Verheus, M, Rookus, MA, Seynaeve, C, Oldenburg, RA, Ligtenberg, MJ, Ausems, MGEM, Aalfs, CM, Gille, HJP, Wijnen, JT, Garcia, EBG, Peock, S, Cook, M, Oliver, CT, Frost, D, Luccarini, C, Pichert, G, Davidson, R, Chu, C, Eccles, D, Ong, K-R, Cook, J, Douglas, F, Hodgson, S, Evans, DG, Eeles, R, Gold, B, Pharoah, PDP, Offit, K, Chenevix-Trench, G, and Easton, DF

Abstract

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I(2) = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95%CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

Published
2012

12. Breast Cancer Risk and 6q22.33: Combined Results from Breast Cancer Association Consortium and Consortium of Investigators on Modifiers of BRCA1/2

Author

Kirchhoff, T, Gaudet, MM, Antoniou, AC, McGuffog, L, Humphreys, MK, Dunning, AM, Bojesen, SE, Nordestgaard, BG, Flyger, H, Kang, D, Yoo, KY, Noh, DY, Ahn, SH, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Couch, FJ, Olson, J, Vachon, C, Wang, XS, Cox, A, Brock, I, Elliott, G, Reed, MWR, Burwinkel, B, Meindl, A, Brauch, H, Hamann, U, Ko, YD, Broeks, A, Schmidt, Marjanka K, van 't Veer, LJ (Laura), Braaf, LM, Johnson, N, Fletcher, O, Gibson, L, Peto, J, Turnbull, C, Seal, S, Renwick, A, Rahman, N, Wu, PE, Yu, JC, Hsiung, CN, Shen, CY, Southey, MC, Hopper, JL, Hammet, F, Van Dorpe, T, Dieudonne, AS, Hatse, S, Lambrechts, D, Andrulis, IL, Bogdanova, N, Antonenkova, N, Rogov, JI, Prokofieva, D, Bermisheva, M, Khusnutdinova, E, van Asperen, CJ, Tollenaar, RAEM, Hooning, Maartje, Devilee, P, Margolin, S, Lindblom, A, Milne, RL, Arias, JI, Zamora, MP, Benitez, J, Severi, G, Baglietto, L, Giles, GG, Spurdle, AB, Beesley, J, Chen, XQ, Holland, H, Healey, S, Wang-Gohrke, S, Chang-Claude, J, Mannermaa, A, Kosma, VM, Kauppinen, J, Kataja, V, Agnarsson, BA, Caligo, MA, Godwin, AK, Nevanlinna, H, Heikkinen, T, Fredericksen, Z, Lindor, N, Nathanson, KL, Domchek, SM, Loman, N, Karlsson, P, Askmalm, MS, Melin, B, von Wachenfeldt, A, Hogervorst, FBL, Verheus, M, Rookus, MA, Seynaeve, Caroline, Oldenburg, Rogier, Ligtenberg, MJ, Ausems, MGEM, Aalfs, CM, Gille, HJP, Wijnen, JT, Garcia, EBG, Peock, S, Cook, M, Oliver, CT, Frost, D, Luccarini, C, Pichert, G, Davidson, R, Chu, C, Eccles, D, Ong, KR, Cook, J, Douglas, F, Hodgson, S, Evans, DG, Eeles, R, Gold, B, Pharoah, PDP, Offit, K, Chenevix-Trench, G, Easton, DF, Kirchhoff, T, Gaudet, MM, Antoniou, AC, McGuffog, L, Humphreys, MK, Dunning, AM, Bojesen, SE, Nordestgaard, BG, Flyger, H, Kang, D, Yoo, KY, Noh, DY, Ahn, SH, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Couch, FJ, Olson, J, Vachon, C, Wang, XS, Cox, A, Brock, I, Elliott, G, Reed, MWR, Burwinkel, B, Meindl, A, Brauch, H, Hamann, U, Ko, YD, Broeks, A, Schmidt, Marjanka K, van 't Veer, LJ (Laura), Braaf, LM, Johnson, N, Fletcher, O, Gibson, L, Peto, J, Turnbull, C, Seal, S, Renwick, A, Rahman, N, Wu, PE, Yu, JC, Hsiung, CN, Shen, CY, Southey, MC, Hopper, JL, Hammet, F, Van Dorpe, T, Dieudonne, AS, Hatse, S, Lambrechts, D, Andrulis, IL, Bogdanova, N, Antonenkova, N, Rogov, JI, Prokofieva, D, Bermisheva, M, Khusnutdinova, E, van Asperen, CJ, Tollenaar, RAEM, Hooning, Maartje, Devilee, P, Margolin, S, Lindblom, A, Milne, RL, Arias, JI, Zamora, MP, Benitez, J, Severi, G, Baglietto, L, Giles, GG, Spurdle, AB, Beesley, J, Chen, XQ, Holland, H, Healey, S, Wang-Gohrke, S, Chang-Claude, J, Mannermaa, A, Kosma, VM, Kauppinen, J, Kataja, V, Agnarsson, BA, Caligo, MA, Godwin, AK, Nevanlinna, H, Heikkinen, T, Fredericksen, Z, Lindor, N, Nathanson, KL, Domchek, SM, Loman, N, Karlsson, P, Askmalm, MS, Melin, B, von Wachenfeldt, A, Hogervorst, FBL, Verheus, M, Rookus, MA, Seynaeve, Caroline, Oldenburg, Rogier, Ligtenberg, MJ, Ausems, MGEM, Aalfs, CM, Gille, HJP, Wijnen, JT, Garcia, EBG, Peock, S, Cook, M, Oliver, CT, Frost, D, Luccarini, C, Pichert, G, Davidson, R, Chu, C, Eccles, D, Ong, KR, Cook, J, Douglas, F, Hodgson, S, Evans, DG, Eeles, R, Gold, B, Pharoah, PDP, Offit, K, Chenevix-Trench, G, and Easton, DF

Abstract

Recently, a locus on chromosome 6q22.33 (rs2180341) was reported to be associated with increased breast cancer risk in the Ashkenazi Jewish (AJ) population, and this association was also observed in populations of non-AJ European ancestry. In the present study, we performed a large replication analysis of rs2180341 using data from 31,428 invasive breast cancer cases and 34,700 controls collected from 25 studies in the Breast Cancer Association Consortium (BCAC). In addition, we evaluated whether rs2180341 modifies breast cancer risk in 3,361 BRCA1 and 2,020 BRCA2 carriers from 11 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Based on the BCAC data from women of European ancestry, we found evidence for a weak association with breast cancer risk for rs2180341 (per-allele odds ratio (OR) = 1.03, 95% CI 1.00-1.06, p = 0.023). There was evidence for heterogeneity in the ORs among studies (I-2 = 49.3%; p = <0.004). In CIMBA, we observed an inverse association with the minor allele of rs2180341 and breast cancer risk in BRCA1 mutation carriers (per-allele OR = 0.89, 95% CI 0.80-1.00, p = 0.048), indicating a potential protective effect of this allele. These data suggest that that 6q22.33 confers a weak effect on breast cancer risk.

Published
2012

13. Comparison of 6q25 Breast Cancer Hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC)

Author

Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, Marjanka K, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, ID, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Perez, JIA, Zamora, MP, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Muller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, YD, Wang-Gohrke, S, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, J, Chen, XQ, Beesley, J, Lambrechts, D, Zhao, H (Hui), Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, XS, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, John, Seynaeve, Caroline, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, JJ, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S (Shahana), Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, KY, Noh, DY, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Shen, CY, Yu, JC, Hsu, HM, Hou, MF, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, Dunning, AM, Truong, T, Hein, R, Maranian, M, Hopper, JL, Kapuscinski, MK, Southey, MC, Park, DJ, Schmidt, Marjanka K, Broeks, A, Hogervorst, FBL, Bueno-de-Mesquit, HB, Muir, KR, Lophatananon, A, Rattanamongkongul, S, Puttawibul, P, Fasching, PA, Hein, A, Ekici, AB, Beckmann, MW, Fletcher, O, Johnson, N, Silva, ID, Peto, J, Sawyer, E, Tomlinson, I, Kerin, M, Miller, N, Marmee, F, Schneeweiss, A, Sohn, C, Burwinkel, B, Guenel, P, Cordina-Duverger, E, Menegaux, F, Bojesen, SE, Nordestgaard, BG, Flyger, H, Milne, RL, Perez, JIA, Zamora, MP, Benitez, J, Anton-Culver, H, Ziogas, A, Bernstein, L, Clarke, CA, Brenner, H, Muller, H, Arndt, V, Stegmaier, C, Rahman, N, Seal, S, Turnbull, C, Renwick, A, Meindl, A, Schott, S, Bartram, CR, Schmutzler, RK, Brauch, H, Hamann, U, Ko, YD, Wang-Gohrke, S, Dork, T, Schurmann, P, Karstens, JH, Hillemanns, P, Nevanlinna, H, Heikkinen, T, Aittomaki, K, Blomqvist, C, Bogdanova, NV, Zalutsky, IV, Antonenkova, NN, Bermisheva, M, Prokovieva, D, Farahtdinova, A, Khusnutdinova, E, Lindblom, A, Margolin, S, Mannermaa, A, Kataja, V, Kosma, VM, Hartikainen, J, Chen, XQ, Beesley, J, Lambrechts, D, Zhao, H (Hui), Neven, P, Wildiers, H, Nickels, S, Flesch-Janys, D, Radice, P, Peterlongo, P, Manoukian, S, Barile, M, Couch, FJ, Olson, JE, Wang, XS, Fredericksen, Z, Giles, GG, Baglietto, L, McLean, CA, Severi, G, Offit, K, Robson, M, Gaudet, MM, Vijai, J, Alnaes, GG, Kristensen, V, Borresen-Dale, AL, John, EM, Miron, A, Winqvist, R, Pylkas, K, Jukkola-Vuorinen, A, Grip, M, Andrulis, IL, Knight, JA, Glendon, G, Mulligan, AM, Figueroa, JD, Garcia-Closas, M, Lissowska, J, Sherman, ME, Hooning, M, Martens, John, Seynaeve, Caroline, Collee, M, Hall, P, Humpreys, K, Czene, K, Liu, JJ, Cox, A, Brock, IW, Cross, SS, Reed, MWR, Ahmed, S (Shahana), Ghoussaini, M, Pharoah, PDP, Kang, D, Yoo, KY, Noh, DY, Jakubowska, A, Jaworska, K, Durda, K, Zlowocka, E, Sangrajrang, S, Gaborieau, V, Brennan, P, Mckay, J, Shen, CY, Yu, JC, Hsu, HM, Hou, MF, Orr, N, Schoemaker, M, Ashworth, A, Swerdlow, A, Trentham-Dietz, A, Newcomb, PA, Titus, L, Egan, KM, Chenevix-Trench, G, Antoniou, AC, Humphreys, MK, Morrison, J, Chang-Claude, J, Easton, DF, Dunning, AM, and Truong, T

Abstract

The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6x10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8x10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2x10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8x10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8x10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3x10(-7), p(heterogeneity) = 5.1x10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.

Published
2012

14. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

Author

Leal, SM, Garcia-Closas, M, Hall, P, Nevanlinna, H, Pooley, K, Morrison, J, Richesson, DA, Bojesen, SE, Nordestgaard, BG, Axelsson, CK, Arias, JI, Milne, RL, Ribas, G, Gonzalez-Neira, A, Benitez, J, Zamora, P, Brauch, H, Justenhoven, C, Hamann, U, Ko, Y-D, Bruening, T, Haas, S, Doerk, T, Schuermann, P, Hillemanns, P, Bogdanova, N, Bremer, M, Karstens, JH, Fagerholm, R, Aaltonen, K, Aittomaki, K, Von Smitten, K, Blomqvist, C, Mannermaa, A, Uusitupa, M, Eskelinen, M, Tengstrom, M, Kosma, V-M, Kataja, V, Chenevix-Trench, G, Spurdle, AB, Beesley, J, Chen, X, Devilee, P, Van Asperen, CJ, Jacobi, CE, Tollenaar, RAEM, Huijts, PEA, Klijn, JGM, Chang-Claude, J, Kropp, S, Slanger, T, Flesch-Janys, D, Mutschelknauss, E, Salazar, R, Wang-Gohrke, S, Couch, F, Goode, EL, Olson, JE, Vachon, C, Fredericksen, ZS, Giles, GG, Baglietto, L, Severi, G, Hopper, JL, English, DR, Southey, MC, Haiman, CA, Henderson, BE, Kolonel, LN, Le Marchand, L, Stram, DO, Hunter, DJ, Hankinson, SE, Cox, DG, Tamimi, R, Kraft, P, Sherman, ME, Chanock, SJ, Lissowska, J, Brinton, LA, Peplonska, B, Hooning, MJ, Meijers-Heijboer, H, Collee, JM, Van den Ouweland, A, Uitterlinden, AG, Liu, J, Lin, LY, Yuqing, L, Humphreys, K, Czene, K, Cox, A, Balasubramanian, SP, Cross, SS, Reed, MWR, Blows, F, Driver, K, Dunning, A, Tyrer, J, Ponder, BAJ, Sangrajrang, S, Brennan, P, Mckay, J, Odefrey, F, Gabrieau, V, Sigurdson, A, Doody, M, Struewing, JP, Alexander, B, Easton, DF, Pharoah, PD, Leal, SM, Garcia-Closas, M, Hall, P, Nevanlinna, H, Pooley, K, Morrison, J, Richesson, DA, Bojesen, SE, Nordestgaard, BG, Axelsson, CK, Arias, JI, Milne, RL, Ribas, G, Gonzalez-Neira, A, Benitez, J, Zamora, P, Brauch, H, Justenhoven, C, Hamann, U, Ko, Y-D, Bruening, T, Haas, S, Doerk, T, Schuermann, P, Hillemanns, P, Bogdanova, N, Bremer, M, Karstens, JH, Fagerholm, R, Aaltonen, K, Aittomaki, K, Von Smitten, K, Blomqvist, C, Mannermaa, A, Uusitupa, M, Eskelinen, M, Tengstrom, M, Kosma, V-M, Kataja, V, Chenevix-Trench, G, Spurdle, AB, Beesley, J, Chen, X, Devilee, P, Van Asperen, CJ, Jacobi, CE, Tollenaar, RAEM, Huijts, PEA, Klijn, JGM, Chang-Claude, J, Kropp, S, Slanger, T, Flesch-Janys, D, Mutschelknauss, E, Salazar, R, Wang-Gohrke, S, Couch, F, Goode, EL, Olson, JE, Vachon, C, Fredericksen, ZS, Giles, GG, Baglietto, L, Severi, G, Hopper, JL, English, DR, Southey, MC, Haiman, CA, Henderson, BE, Kolonel, LN, Le Marchand, L, Stram, DO, Hunter, DJ, Hankinson, SE, Cox, DG, Tamimi, R, Kraft, P, Sherman, ME, Chanock, SJ, Lissowska, J, Brinton, LA, Peplonska, B, Hooning, MJ, Meijers-Heijboer, H, Collee, JM, Van den Ouweland, A, Uitterlinden, AG, Liu, J, Lin, LY, Yuqing, L, Humphreys, K, Czene, K, Cox, A, Balasubramanian, SP, Cross, SS, Reed, MWR, Blows, F, Driver, K, Dunning, A, Tyrer, J, Ponder, BAJ, Sangrajrang, S, Brennan, P, Mckay, J, Odefrey, F, Gabrieau, V, Sigurdson, A, Doody, M, Struewing, JP, Alexander, B, Easton, DF, and Pharoah, PD

Abstract

A three-stage genome-wide association study recently identified single nucleotide polymorphisms (SNPs) in five loci (fibroblast growth receptor 2 (FGFR2), trinucleotide repeat containing 9 (TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte-specific protein 1 (LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER-positive (per-allele OR (95%CI) = 1.31 (1.27-1.36)) than ER-negative (1.08 (1.03-1.14)) disease (P for heterogeneity = 10(-13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER-positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs (rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER-negative disease, the strongest association being for rs3803662 in TNRC9 (1.14 (1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis (per-allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER-positive and ER-negative disease are biologically distinct. Understanding

Published
2008

15. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics

Author

Garcia-Closas, M, Hall, P, Nevanlinna, H, Pooley, KA, Morrison, J, Richesson, DA, Bojesen, SE, Nordestgaard, BG, Axelsson, CK, Arias, JI, Milne, RL, Ribas, G, Gonzalez-Neira, A, Benitez, J, Zamora, P, Brauch, H, Justenhoven, C, Hamann, U, Ko, YD, Bruening, T, Haas, S, Dork, T, Schurmann, P, Hillemanns, P, Bogdanova, N, Bremer, M, Karstens, JH, Fagerholm, R, Aaltonen, K, Aittomaki, K, von Smitten, K, Blomqvist, C, Mannermaa, A, Uusitupa, M, Eskelinen, M, Tengstrom, M, Kosma, VM, Kataja, V, Chenevix-Trench, G, Spurdle, AB, Beeslev, J, Chen, X, Devilee, P, van Asperen, CJ, Jacobi, CE, Tollenaar, RA, Huijts, PE, Klijn, Jan, Chang-Claude, J, Kropp, S, Slanger, T, Flesch-Janys, D, Mutschelknauss, E, Salazar, R, Wang-Gohrke, S, Couch, F, Goode, EL, Olson, JE, Vachon, C, Fredericksen, ZS, Giles, GG, Baglietto, L, Severi, G, Hopper, JL, English, DR, Southey, M, Haiman, CA, Henderson, BE, Kolonel, LN, Le Marchand, L, Stram, DO, Hunter, DJ, Hankinson, SE, Cox, DG, Tamimi, R, van Kraft, PJA (Peter), Sherman, M, Chanock, S, Lissowska, J, Brinton, L, Peplonska, B, Hooning, Maartje, Meijers-Heijboer, EJ, Collee, Margriet, van den Ouweland, Ans, Uitterlinden, André, Liu, Jun, Lin, L, Yuqing, L, Humphreys, K, Czene, K, Cox, A, Balasubramanian, SP, Cross, SS, Reed, MWR, Blows, F, Driver, K, Dunning, AJ, Tyrer, J, Garcia-Closas, M, Hall, P, Nevanlinna, H, Pooley, KA, Morrison, J, Richesson, DA, Bojesen, SE, Nordestgaard, BG, Axelsson, CK, Arias, JI, Milne, RL, Ribas, G, Gonzalez-Neira, A, Benitez, J, Zamora, P, Brauch, H, Justenhoven, C, Hamann, U, Ko, YD, Bruening, T, Haas, S, Dork, T, Schurmann, P, Hillemanns, P, Bogdanova, N, Bremer, M, Karstens, JH, Fagerholm, R, Aaltonen, K, Aittomaki, K, von Smitten, K, Blomqvist, C, Mannermaa, A, Uusitupa, M, Eskelinen, M, Tengstrom, M, Kosma, VM, Kataja, V, Chenevix-Trench, G, Spurdle, AB, Beeslev, J, Chen, X, Devilee, P, van Asperen, CJ, Jacobi, CE, Tollenaar, RA, Huijts, PE, Klijn, Jan, Chang-Claude, J, Kropp, S, Slanger, T, Flesch-Janys, D, Mutschelknauss, E, Salazar, R, Wang-Gohrke, S, Couch, F, Goode, EL, Olson, JE, Vachon, C, Fredericksen, ZS, Giles, GG, Baglietto, L, Severi, G, Hopper, JL, English, DR, Southey, M, Haiman, CA, Henderson, BE, Kolonel, LN, Le Marchand, L, Stram, DO, Hunter, DJ, Hankinson, SE, Cox, DG, Tamimi, R, van Kraft, PJA (Peter), Sherman, M, Chanock, S, Lissowska, J, Brinton, L, Peplonska, B, Hooning, Maartje, Meijers-Heijboer, EJ, Collee, Margriet, van den Ouweland, Ans, Uitterlinden, André, Liu, Jun, Lin, L, Yuqing, L, Humphreys, K, Czene, K, Cox, A, Balasubramanian, SP, Cross, SS, Reed, MWR, Blows, F, Driver, K, Dunning, AJ, and Tyrer, J

Published
2008

17. Peripheral tolerance in porcine lung transplantation induced by splenocyte infusion and low dose irradiation – modifications of the protocol for improved clinical feasibility

Author

Warnecke, G, primary, Avsar, M, additional, Dreckmann, K, additional, Knöfel, AK, additional, Madrahimov, N, additional, Thissen, S, additional, Kruse, B, additional, Ziehme, P, additional, Sommer, W, additional, Gottlieb, J, additional, Simon, A, additional, Karstens, JH, additional, Haverich, A, additional, and Strüber, M, additional

Published
2010
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25. Impact of zoledronic acid on control of metastatic spinal cord compression.

Author

Rades D, Hakim SG, Bajrovic A, Karstens JH, Veninga T, Rudat V, Schild SE, Rades, D, Hakim, S G, Bajrovic, A, Karstens, J H, Veninga, T, Rudat, V, and Schild, S E

Abstract

Background: Zoledronic acid was demonstrated to reduce the rate of skeletal-related events, a hypernym including various outcomes, in patients with bone metastases. In contrast to other studies, this matched-pair analysis focused solely on the impact of zoledronic acid on metastatic spinal cord compression (MSCC).Patients and Methods: Data from 98 patients with MSCC receiving radiotherapy plus zoledronic acid were matched 1:2 to 196 patients receiving radiotherapy alone for ten potential prognostic factors. Both groups were compared for local control of MSCC within the irradiated region, overall control of MSCC (local and distant MSCC control), and survival.Results: The 1-year local control rates were 90% after radiotherapy plus zoledronic acid and 81%, after radiotherapy alone (p = 0.042). The 1-year overall control rates were 87% and 75%, respectively (p = 0.016), and the 1-year survival rates were 60% and 52%, respectively (p = 0.17). Results were significant in the Cox proportional hazards model regarding local control (p = 0.024) and overall control (p = 0.008).Conclusion: According to the results of this study, zoledronic acid was associated with improved control of MSCC in irradiated patients. [ABSTRACT FROM AUTHOR]

Published
2012

26. Postoperative periclavicular radiotherapy in breast cancer patients with 1-3 positive axillary lymph nodes. Outcome and morbidity.

Author

Biancosino A, Bremer M, Karstens JH, Biancosino C, Meyer A, Biancosino, A, Bremer, M, Karstens, J H, Biancosino, C, and Meyer, A

Abstract

Purpose: The goal of this work was to examine the possible influence of periclavicular irradiation on outcome of breast cancer patients with 1-3 positive lymph nodes with special emphasis on late toxicity rates.Patients and Methods: Between 1997 and 2000, 235 breast cancer patients (T1-2, 1-3 involved lymph nodes) were treated at our department following breast conservative surgery: 139 patients (59.1%) had one, 62 patients (26.4%) two, and 34 patients (14.5%) three positive lymph nodes. Extracapsular spread (ECS) was described in 72 patients (30.6%). There were 67 patients (28.5%) who received additional radiotherapy to the ipsilateral periclavicular lymph nodes (PCLNI), while 168 patients did not (noPCLNI). Patients were re-examined or contacted by phone with regard to treatment-related late effects.Results: After a median follow-up of 78 months (range 7-107 months), 22 patients (9.4%) developed local, 9 (3.8%) axillary, 4 periclavicular (1.7%), and 41 distant failure (17.4%). The actuarial 8-year locoregional recurrence-free (LRRFS), disease-free (DFS), and overall survival rates (OS) were 83%, 67%, and 74%, respectively. Survival data for the PCLNI vs. noPCLNI group were 72% vs. 89% (p = 0.3), 56% vs. 73% (p = 0.4), and 86% vs. 70% (p = 0.3), respectively. No higher toxicity rates were reported in the PCLNI group compared to the noPCLNI group.Conclusion: We could not demonstrate any difference in outcome in breast cancer patients with 1-3 positive axillary lymph node metastases with or without periclavicular lymph node irradiation. In addition, patients with PCLNI did not complain about higher rates of late toxicities. However, patients with ECS, which may predict for locoregional failure, may benefit from adjuvant periclavicular irradiation. [ABSTRACT FROM AUTHOR]

Published
2012
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27. Prostatakarzinom

Author

G. Durben, Karstens Jh, and J. Ammon

Subjects
Oncology, medicine.medical_specialty, business.industry, Radiography, General Medicine, medicine.disease, Tomography x ray computed, X ray computed, Internal medicine, medicine, Carcinoma, Radionuclide imaging, Tomography, Nuclear medicine, business, Pyelogram
Published
1979
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28. Computertomographie renaler maligner Lymphome

Author

Klose Kc, Karstens Jh, and Schwartz R

Subjects
medicine.medical_specialty, Enhanced ct, business.industry, media_common.quotation_subject, medicine.disease, Lymphoma, Text mining, medicine, Contrast (vision), Radiology, Nuclear Medicine and imaging, Radiology, Tomography, Ct findings, Renal Lymphoma, business, media_common
Abstract

The pre- and postcontrast CT findings of 11 patients with lymphoma involving the kidneys are described. In all cases the renal lesions showed low attenuation values after bolusinjection. In contrary to the literature renal lymphoma might present different attenuation values in the non-contrast enhanced CT scan. The density varies from hypo- to iso- and hyperdens. A bolusinjection of contrast media should be performed to depict even greater nodules.

Published
1983
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29. Unterstützung einer am TNM-System orientierten Bestrahlungsplanung urologischer Tumoren durch die Computertomographie*

Author

Karstens Jh, Ammon J, and Rübben H

Subjects
medicine.medical_specialty, Diagnostic methods, business.industry, Treatment results, Radiation planning, Tumour invasion, medicine.anatomical_structure, Treatment plan, medicine, Radiology, Nuclear Medicine and imaging, Medical physics, Radiology, Tomography, business, Radiation treatment planning, Lymph node
Abstract

From the extensive statistics concerning treatment results of urological tumours which are available from central tumour registers, a first draft of a treatment plan has been worked out, which is based on tumour spread. Since the extent of tumour invasion is documented by the TNM system of the UICC, one is justified in speaking of TNM orientated treatment planning. For planning it is necessary to consider not only tumour type and depth of infiltration of local tissues, but also the lymph node anatomy, whether the nodes are involved or not. Computer tomography assist significantly in the performance of such TNM orientated treatment planning, particularly in determining the extent of the volume to be irradiated, It must be stressed that computer tomography does not replace the use of simulators, but that it is a valuable addition. In our view, computer tomography has also an undoubted value in treatment planning of urological tumours where palliation only is the aim. It provides the possibility of checking the effect of the chosen treatment by a non-invasive diagnostic method.

Published
1978
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30. Lymphangiosis carcinomatosa der Lungen beim Prostatakarzinom

Author

Karstens Jh, R. Lindenfelser, G. Durben, J. Ammon, and W. Frik

Subjects
medicine.medical_specialty, Lung, business.industry, Lymphangitis carcinomatosa, Retrospective cohort study, Autopsy, respiratory system, medicine.disease, medicine.anatomical_structure, Prostate, Carcinoma, Medicine, Radiology, Nuclear Medicine and imaging, Clinical significance, Radiology, business, Pathological
Abstract

Lung metastases from carcinoma of the prostate usually manifest themselves as radiologically diffuse lymphangitis carcinomatosa. Unlike the pathological findings, a radiological diagnosis is relatively uncommon. We have investigated this retrospectively in 230 patients; in 192, radiographs were available for study. In over 10% lung metastases were found, mostly in the form of lymphangitis carcinomatosa. In view of the bad prognostic significance and therapeutic implications of lymphangitis carcinomatosa, it is important to bear this in mind and to look for it radiologically.

Published
1979
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31. Kindliches Neuroblastom mit frühzeitiger beidseitiger Erblindung

Author

Reim M, Sieverts H, Müther Hc, and Karstens Jh

Subjects
medicine.medical_specialty, Periosteum, Bilateral blindness, genetic structures, business.industry, Eye disease, medicine.disease, eye diseases, Surgery, Ophthalmology, medicine.anatomical_structure, Cornea, Neuroblastoma, medicine, sense organs, Radiology, Thickening, Lateral wall, business, Infiltration (medical)
Abstract

The authors present the case history of a child with neuroblastoma and early infiltration of the orbit accompanied by bilateral blindness. The typical clinical signs developed later. The thickening of the periosteum infiltrated by the tumor in the lateral wall of the orbit was demonstrated by computerized tomography. This may be regarded as an early sign of infiltration of the orbit by the neuroblastoma. In the case reported here a severe inflammatory reaction developed in the left orbit and anterior segment during massive chemotherapy and melted the cornea.

Published
1988
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32. Carcinoma of renal parenchyma, renal pelvis and ureter--radiological diagnosis and treatment planning

Author

K.H. Barth, G. Durben, J. Ammon, and Karstens Jh

Subjects
medicine.medical_specialty, Palliative care, Time Factors, medicine.medical_treatment, Adenocarcinoma, Nephrectomy, Renal cell carcinoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, Kidney Pelvis, Neoplasm Metastasis, Neoplasm Staging, Carcinoma, Transitional Cell, business.industry, Ureteral Neoplasms, Palliative Care, Urography, General Medicine, Environmental Exposure, medicine.disease, Prognosis, Kidney Neoplasms, Surgery, Tumor Debulking, Radiation therapy, Transitional cell carcinoma, medicine.anatomical_structure, Oncology, Urinary Bladder Neoplasms, Evaluation Studies as Topic, Carcinogens, Radiology, Neoplasm Recurrence, Local, business, Renal pelvis, Pyelogram
Abstract

VI. Summary Tumors of the renal parenchyma, the renal pelvis and the ureter are regarded as only poorly sensitive to radiation and chemotherapy. Therefore operative removal of the tumor remains the primary treatment. Postoperative radiation, commonly applied to other tumors, is of questionable value in renal cell carcinomas (Table 10). Non-operative techniques should be applied to palliate metastases and recurrences. Their effectiveness alone or in combination remains to a great extent unproven, since even patients with advanced primary tumors may survive several years. However, the basis of the present review was the fact that recent advances in diagnosis allow better evaluation of non-surgical treatment results some of which indeed appear promising. Of particular value in the diagnostic work-up of the postoperative patient are CT and ultrasound, two non-invasive techniques which allow repeated assessment of the effects of radiation therapy, chemotherapy, immunotherapy and also embolization therapy. Based on the TNM-classification system (UICC, 1978) an attempt was made to establish the usefulness of the newer diagnostic and therapeutic modalities for which the following considerations are pertinent: (a) CT and Ultrasound provide considerable improvement in pre-operative evaluation of the suspected renal cell carcinoma and allow exact pre-operative staging. The postoperative follow-up has been improved. CT especially allows control of effectiveness of non-operative procedures. (b) Surgery is still the treatment of choice for renal cell carcinomas, carcinomas of the renal pelvis and the ureter. Nephrectomy in the presence of metastases, however, is only indicated if hematuria, local pain, tumor debulking or treatment of paraneoplastic symptoms is necessary. The possibility of spontaneous remission of metastases does not in itself justify an aggressive surgical regimen. (c) Pre-operative embolization is primarily designed to facilitate surgical removal, however, palliative turnor embolization appears to be a worthwhile method particularly for massive or recurrent hematuria. (d) For metastatic tumors endocrine therapy, chemotherapy and immunotherapy are available. Endocrine therapy may become more important with the availability of antiestrogenes. The effectiveness of chemotherapy may be increased by drug combinations and also by combination of chemotherapy and immunotherapy. (e) Carcinomas of the renal pelvis and ureter are rare entities. Surgery, either radical or segmental is still the treatment of choice. The infrequency of these tumors, does not allow sufficient experience with non-operative treatment for a pertinent recommendation at this time. Extrapolation of results with transitional cell carcinoma of the bladder appears justifiable, especially regarding grading.

Published
1980

33. Mutation analysis of the MDM4 gene in German breast cancer patients.

Author

Reincke S, Govbakh L, Wilhelm B, Jin H, Bogdanova N, Bremer M, Karstens JH, Dörk T, Reincke, Scarlett, Govbakh, Lina, Wilhelm, Bettina, Jin, Haiyan, Bogdanova, Natalia, Bremer, Michael, Karstens, Johann H, and Dörk, Thilo

Abstract

Background: MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.Methods: We sequenced the whole MDM4 coding region and flanking untranslated regions in genomic DNA samples obtained from 40 German patients with familial breast cancer. Selected variants were subsequently screened by RFLP-based assays in an extended set of breast cancer cases and controls.Results: Our resequencing study uncovered two MDM4 coding variants in 4/40 patients. Three patients carried a silent substitution at codon 74 that was linked with another rare variant in the 5'UTR. No association of this allele with breast cancer was found in a subsequent screening of 133 patients with bilateral breast cancer and 136 controls. The fourth patient was heterozygous for the missense substitution D153G which is located in a less conserved region of the MDM4 protein but may affect a predicted phosphorylation site. The D153G substitution only partially segregated with breast cancer in the family and was not identified on additional 680 chromosomes screened.Conclusion: This study did not reveal clearly pathogenic mutations although it uncovered two new unclassified variants at a low frequency. We conclude that there is no evidence for a major role of MDM4 coding variants in the inherited susceptibility towards breast cancer in German patients. [ABSTRACT FROM AUTHOR]

Published
2008
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34. Irradiation before and donor splenocyte infusion immediately after transplantation induce tolerance to lung, but not heart allografts in miniature swine.

Author

Sommer W, Buechler G, Jansson K, Avsar M, Knöfel AK, Salman J, Hoeffler K, Siemeni T, Gottlieb J, Karstens JH, Jonigk D, Reising A, Haverich A, Strüber M, and Warnecke G

Subjects
Allografts immunology, Animals, Female, Graft Rejection immunology, Graft Survival, Immune Tolerance, Immunosuppression Therapy, Leukocytes metabolism, Male, Spleen cytology, Spleen metabolism, Swine, Swine, Miniature, Tacrolimus pharmacology, Time Factors, Tissue Donors, Transplantation Chimera, Transplantation, Homologous, Heart Transplantation methods, Lung Transplantation methods, Transplantation Tolerance
Abstract

Solid organs may differ in their potential to induce and maintain a state of donor-specific tolerance. Previously, we induced stable immunological tolerance in a lung transplantation model in miniature swine. Here, we wished to transfer this established protocol into a heart transplantation model in miniature swine. Heterotopic heart transplantation (HTX) was performed in four and left-sided lung transplantation (LTX) in seven minipigs from gender- and SLA-mismatched donors. All recipients received nonmyeloablative irradiation, donor splenocyte infusion and intravenous pharmacologic immunosuppression for 28 postoperative days. All transplanted hearts were rejected within 95 days. In contrast, four animals of the LTX group developed stable tolerance surviving beyond 500 days, and three further animals rejected 119, 239 and 360 days post-transplantation. In both groups, peripheral blood donor leucocyte chimerism peaked 1 h after reperfusion of the allograft. Importantly, the early chimerism level in the LTX group was significantly higher compared to the HTX group and remained detectable throughout the entire observation period. In conclusion, lungs and hearts vary in their potential to induce a state of tolerance after transplantation in a protocol with pre-operative recipient irradiation and donor splenocyte co-transplantation. This could be due to differential early levels of passenger leucocyte chimerism., (© 2017 Steunstichting ESOT.)

Published
2017
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35. Augmentation of Transient Donor Cell Chimerism and Alloantigen-Specific Regulation of Lung Transplants in Miniature Swine.

Author

Avsar M, Jansson K, Sommer W, Kruse B, Thissen S, Dreckmann K, Knoefel AK, Salman J, Hafer C, Hecker J, Buechler G, Karstens JH, Jonigk D, Länger F, Kaever V, Falk CS, Hewicker-Trautwein M, Ungefroren H, Haverich A, Strüber M, and Warnecke G

Subjects
Animals, Female, Immunosuppression Therapy, Male, Models, Animal, Swine, Swine, Miniature, T-Lymphocytes, Regulatory immunology, Tissue Donors, Transplantation Tolerance, Transplantation, Homologous, Whole-Body Irradiation, Chimerism, Graft Survival immunology, Isoantigens immunology, Lung Transplantation, T-Lymphocytes, Regulatory radiation effects
Abstract

Donor alloantigen infusion induces T cell regulation and transplant tolerance in small animals. Here, we study donor splenocyte infusion in a large animal model of pulmonary transplantation. Major histocompatibility complex-mismatched single lung transplantation was performed in 28 minipigs followed by a 28-day course of methylprednisolone and tacrolimus. Some animals received a perioperative donor or third party splenocyte infusion, with or without low-dose irradiation (IRR) before surgery. Graft survival was significantly prolonged in animals receiving both donor splenocytes and IRR compared with controls with either donor splenocytes or IRR only. In animals with donor splenocytes and IRR, increased donor cell chimerism and CD4(+) CD25(high+) T cell frequencies were detected in peripheral blood associated with decreased interferon-γ production of leukocytes. Secondary third-party kidney transplants more than 2 years after pulmonary transplantation were acutely rejected despite maintained tolerance of the lung allografts. As a cellular control, additional animals received third-party splenocytes or donor splenocyte protein extracts. While animals treated with third-party splenocytes showed significant graft survival prolongation, the subcellular antigen infusion showed no such effect. In conclusion, minipigs conditioned with preoperative IRR and donor, or third-party, splenocyte infusions may develop long-term donor-specific pulmonary allograft survival in the presence of high levels of circulating regulatory T cells., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Published
2016
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36. A new instrument for estimating the survival of patients with metastatic epidural spinal cord compression from esophageal cancer.

Author

Rades D, Huttenlocher S, Bajrovic A, Karstens JH, and Bartscht T

Abstract

Background: This study was initiated to create a predictive instrument for estimating the survival of patients with metastatic epidural spinal cord compression (MESCC) from esophageal cancer., Methods: In 27 patients irradiated for MESCC from esophageal cancer, the following nine characteristics were evaluated for potential impact on survival: age, gender, Eastern Cooperative Oncology Group (ECOG) performance score, histology, number of involved vertebrae, ambulatory status before irradiation, further bone metastases, visceral metastases, and dynamic of developing motor deficits before irradiation. In addition, the impact of the radiation regimen was investigated. According to Bonferroni correction, p-values of < 0.006 were significant representing an alpha level of < 0.05., Results: ECOG performance score (p < 0.001), number of involved vertebrae (p = 0.005), and visceral metastases (p = 0.004) had a significant impact on survival and were included in the predictive instrument. Scoring points for each characteristic were calculated by dividing the 6-months survival rates (in %) by 10. The prognostic score for each patient was obtained by adding the scoring points of the three characteristics. The prognostic scores were 4, 9, 10, 14 or 20 points. Three prognostic groups were formed, 4 points (n = 11), 9-14 points (n = 12) and 20 points (n = 4). The corresponding 6-months survival rates were 0%, 33% and 100%, respectively (p < 0.001). Median survival times were 1 month, 5 months and 16.5 months, respectively., Conclusions: This new instrument allows the physician estimate the 6-months survival probability of an individual patient presenting with MESCC from esophageal cancer. This is important to know for optimally personalizing the treatment of these patients.

Published
2015
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37. Predicting survival of patients with metastatic epidural spinal cord compression from cancer of the head-and-neck.

Author

Rades D, Schild SE, Karstens JH, and Hakim SG

Subjects
Female, Head and Neck Neoplasms pathology, Head and Neck Neoplasms radiotherapy, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Proportional Hazards Models, Retrospective Studies, Spinal Cord Compression etiology, Spinal Neoplasms radiotherapy, Spinal Neoplasms secondary, Head and Neck Neoplasms mortality, Spinal Cord Compression mortality, Spinal Neoplasms mortality
Abstract

Aim: To develop an instrument for estimating survival after irradiation for metastatic epidural spinal cord compression (MESCC) from head and neck cancer., Patients and Methods: In 58 patients, eleven factors were evaluated for influence on survival: age, gender, performance status, tumor site, time from cancer diagnosis until MESCC, affected vertebrae, walking ability, further osseous lesions, organ metastases, time developing motor deficits and radiation regimen. Factors with significant association with survival or a trend (multivariate analysis) were used for scoring., Results: Walking ability, visceral metastases and time to developing motor deficits were included in the score. Scoring points were calculated by dividing 6-month survival rates by 10. Patients' scores were obtained from adding the points of the three factors. Four groups were created, 7-10, 12-15, 16-18 and 21 points. Six-month survival rates were 0%, 27%, 71% and 100% (p<0.001)., Conclusion: With this new instrument, one can estimate 6-month survival probabilities of patients with MESCC from head-and-neck cancer., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Published
2015

38. Metastatic spinal cord compression: a validated survival score for elderly patients.

Author

Rades D, Evers JN, Bajrovic A, Veninga T, Karstens JH, and Schild SE

Subjects
Age Distribution, Aged, Aged, 80 and over, Carcinoma radiotherapy, Causality, Female, Geriatric Assessment statistics & numerical data, Germany epidemiology, Humans, Incidence, Male, Prognosis, Proportional Hazards Models, Radiotherapy, Conformal mortality, Reproducibility of Results, Risk Assessment, Sensitivity and Specificity, Treatment Outcome, Carcinoma mortality, Carcinoma secondary, Spinal Cord Compression mortality, Spinal Cord Compression radiotherapy, Spinal Cord Neoplasms mortality, Spinal Cord Neoplasms radiotherapy, Survival Analysis
Abstract

Background and Purpose: This study aimed to develop a validated survival score for elderly patients with metastatic spinal cord compression (MSCC)., Patients and Methods: In all, 1,128 patients were randomly assigned to the test (n = 564) or validation group (n = 564). In the test group, ten pretreatment factors (age, gender, performance status, primary tumor, number of involved vertebrae, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, time to developing motor deficits) plus the radiation regimen were retrospectively evaluated. Factors significantly associated with survival on multivariate analysis were included in the survival score. The score for each factor was determined by dividing the 6-month survival rate (%) by 10. The prognostic score represented the sum of the scores for each factor., Results: In the multivariate analysis of the test group, age, performance status, primary tumor type, ambulatory status, other bone metastases, visceral metastases, interval from cancer diagnosis to radiotherapy of MSCC, and time to developing motor deficits were significantly associated with survival. Total scores ranged from 25 to 57 points. In the test group, 6-month survival rates were 11 % for 25-39 points, 56 % for 40-48 points, and 97 % for 49-57 points (p < 0.001). In the validation group, 6-month survival rates were 10, 53, and 94 %, respectively (p < 0.001)., Conclusion: Based on the survival scores of the test group, three prognostic groups were identified. The survival rates of the validation group were similar to the test group. This score appears reproducible and can help select the appropriate treatment for elderly patients with MSCC.

Published
2014
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39. A validated score estimating ambulatory status following radiotherapy of elderly patients for metastatic spinal cord compression.

Author

Rades D, Evers JN, Rudat V, Bajrovic A, Karstens JH, and Schild SE

Subjects
Aged, Aged, 80 and over, Female, Humans, Male, Multivariate Analysis, Prognosis, Risk Assessment, Spinal Cord Compression radiotherapy, Spinal Neoplasms radiotherapy, Survival Analysis, Spinal Cord Compression physiopathology, Spinal Neoplasms physiopathology, Spinal Neoplasms secondary, Walking
Abstract

Background: This study was performed to develop a validated score predicting ambulatory status after radiotherapy (RT) alone for metastatic spinal cord compression (MSCC) in elderly patients., Methods: 1,129 elderly patients (≥65 years) were assigned to the test (N = 565) or validation group (N = 564). In the test group, nine pre-treatment factors (age, gender, tumor type, number of involved vertebrae, pre-RT ambulatory status, other bone metastases, visceral metastases, interval cancer diagnosis to RT, time developing motor deficits) and fractionation regimen were investigated. Factors significantly associated with post-RT ambulatory status on multivariate analysis were included in the score. The score for each factor was determined by dividing the post-RT ambulatory rate at 1 month (%) by 10. The total score represented the sum of these scores., Results: In the multivariate analysis of the test group, age, primary tumor type, pre-RT ambulatory status, visceral metastases, and time developing motor deficits were significantly associated with post-RT ambulatory status. Total scores were 19 to 41 points. In the test group, post-RT ambulatory rates were 5% for 19-25 points, 35% for 26-30 points, 80% for 31-34 points, and 98% for 35-41 points (p < 0.001). 6-month survival rates were 11%, 21%, 59% and 76%, respectively. In the validation group, post-RT ambulatory rates were 4%, 33%, 77% and 98%, respectively (p < 0.001)., Conclusions: Patients achieving 19-25 points had very poor functional outcomes and survival, and may receive single-fraction RT for pain relief. Selected patients with 26-34 points may benefit from additional surgery. Patients achieving ≥35 points achieved favorable results after RT alone.

Published
2014
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40. A new prognostic factor for the survival of patients with renal cell carcinoma developing metastatic spinal cord compression.

Author

Rades D, Weber A, Bartscht T, Bajrovic A, Karstens JH, and Schild SE

Subjects
Adult, Aged, Aged, 80 and over, Carcinoma, Renal Cell radiotherapy, Causality, Comorbidity, Female, Germany epidemiology, Humans, Kidney Neoplasms radiotherapy, Male, Middle Aged, Prevalence, Prognosis, Retrospective Studies, Risk Factors, Spinal Cord Compression prevention & control, Spinal Neoplasms radiotherapy, Treatment Outcome, Carcinoma, Renal Cell mortality, Carcinoma, Renal Cell secondary, Kidney Neoplasms mortality, Spinal Cord Compression mortality, Spinal Neoplasms mortality, Spinal Neoplasms secondary, Survival Analysis
Abstract

Background and Purpose: This study aimed to identify a potential association of the number of involved extraspinal organs with the survival of patients with metastatic spinal cord compression (MSCC) from renal cell carcinoma., Patients and Methods: Data of 69 patients irradiated for MSCC from renal cell carcinoma were retrospectively evaluated for survival. The prognostic value of the number of involved extraspinal organs and eight additional factors were investigated. These additional factors included age, gender, performance status, number of involved vertebrae, interval from cancer diagnosis to radiotherapy (RT) of MSCC, ambulatory status prior to RT, time developing motor deficits, and the fractionation regimen (30 Gy in 10 fractions vs. higher doses)., Results: The 6-month survival rates for involvement of 0, 1, and ≥ 2 extraspinal organs were 93, 57, and 21%, respectively (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs maintained significance (risk ratio 2.65; 95% confidence interval 1.64-4.52; p < 0.001). The interval from cancer diagnosis to RT of MSCC (p = 0.013) and ambulatory status prior to RT (p = 0.002) were also independent predictors of survival., Conclusion: The number of involved extraspinal organs is a new prognostic factor of survival in patients with MSCC from renal cell carcinoma and should be considered in future clinical trials.

Published
2014
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41. Number of extraspinal organs with metastases: a prognostic factor of survival in patients with metastatic spinal cord compression (MSCC) from non-small cell lung cancer (NSCLC).

Author

Rades D, Weber A, Karstens JH, Schild SE, and Bartscht T

Subjects
Aged, Carcinoma, Non-Small-Cell Lung secondary, Female, Humans, Kaplan-Meier Estimate, Lung Neoplasms mortality, Male, Middle Aged, Prognosis, Proportional Hazards Models, Spinal Cord Compression etiology, Spinal Cord Neoplasms complications, Spinal Cord Neoplasms secondary, Carcinoma, Non-Small-Cell Lung mortality, Lung Neoplasms pathology, Neoplasm Metastasis pathology, Spinal Cord Compression mortality, Spinal Cord Neoplasms mortality
Abstract

Background/aim: In patients irradiated for MSCC from NSCLC, the number of extraspinal organs involved by metastases was investigated for associations with survival., Patients and Methods: The data of 131 patients irradiated with 10×3 Gy in two weeks for MSCC were evaluated. The number of involved extraspinal organs plus eight other factors were retrospectively analyzed., Results: The 6-month survival rates were 72%, 57%, 20%, and 11% for the involvement of 0, 1, 2, and ≥3 extraspinal organs, respectively (p<0.001). On multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 1.60; 95% CI 1.28-2.00; p<0.001). Gender (p=0.028), ECOG performance score (p=0.001), histology (p=0.014), ambulatory status (p=0.002), and time to developing motor deficits (p=0.041) were also independent prognostic factors for survival., Conclusion: The number of extraspinal organs with metastases is an independent prognostic factor for the survival of NSCLC patients presenting with MSCC and should be considered in future studies.

Published
2014

42. Breast cancer patients with metastatic spinal cord compression. Number of extraspinal organs involved by metastases influences survival.

Author

Weber A, Bartscht T, Karstens JH, Schild SE, and Rades D

Subjects
Aged, Breast Neoplasms pathology, Disease Progression, Dose Fractionation, Radiation, Female, Humans, Middle Aged, Prognosis, Retrospective Studies, Spinal Cord Compression pathology, Spinal Neoplasms mortality, Spinal Neoplasms pathology, Survival Analysis, Breast Neoplasms mortality, Breast Neoplasms radiotherapy, Spinal Cord Compression mortality, Spinal Cord Compression radiotherapy, Spinal Neoplasms radiotherapy, Spinal Neoplasms secondary
Abstract

Background and Purpose: The goal of the present work was to investigate the predictive value of the number of extraspinal organs involved by metastases for the survival of patients with metastatic spinal cord compression (MSCC) from breast cancer., Patients and Methods: Data of 145 breast cancer patients who received 10 fractions of 3 Gy of radiotherapy (RT) alone for MSCC were retrospectively analyzed. Seven potential prognostic factors were investigated including age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, interval from breast cancer diagnosis to RT of MSCC, ambulatory status prior to RT, time to developing motor deficits, and the number of involved extraspinal organs., Results: The 1-year survival rates for involvement of 0, 1, 2, and ≥ 3 extraspinal organs were 86, 73, 36, and 16 % (p < 0.001). In the multivariate analysis, the number of involved extraspinal organs remained significant (risk ratio 2.19; 95 % confidence interval 1.61-3.00; p < 0.001). ECOG performance score (p < 0.001), ambulatory status prior to RT (p = 0.003), and the time to developing motor deficits (p < 0.001) were also significantly associated with survival in the multivariate analysis., Conclusion: The number of extraspinal organs involved by metastases is an independent prognostic factor of survival in patients with MSCC from breast cancer.

Published
2014
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43. Prognostic role of the number of involved extraspinal organs in patients with metastatic spinal cord compression.

Author

Rades D, Weber A, Karstens JH, Schild SE, and Bartscht T

Subjects
Adult, Age Factors, Aged, Aged, 80 and over, Cohort Studies, Female, Humans, Kaplan-Meier Estimate, Male, Middle Aged, Multivariate Analysis, Neoplasm Metastasis radiotherapy, Prognosis, Retrospective Studies, Sex Factors, Spinal Neoplasms pathology, Survival Analysis, Neoplasm Metastasis pathology, Spinal Cord Compression etiology
Abstract

Objective: This study was investigated the prognostic role of the number of involved extraspinal organs in the survival of patients with metastatic spinal cord compression (MSCC)., Methods: Data of 552 patients treated with 30Gy in 10 fractions of radiotherapy (RT) alone for MSCC were retrospectively analyzed. In addition to the number of involved extraspinal organs, eight potential prognostic factors were investigated including age, gender, Eastern Cooperative Oncology Group performance score (ECOG-PS), primary tumor type, number of involved vertebrae, interval from cancer diagnosis to RT, pre-RT ambulatory status, and time developing motor deficits., Results: The 6-month survival rates for the involvement of 0, 1, 2, 3, and ≥4 extraspinal organs were 88%, 55%, 30%, 13%, and 12%, respectively (P<0.001). In the multivariate analysis, number of involved extraspinal organs maintained significance (risk ratio 1.61; 95%-confidence interval 1.47-1.77; P<0.001). On multivariate analysis, gender (P=0.017), ECOG-PS (P<0.001), primary tumor type (P<0.001), interval from cancer diagnosis to RT (P<0.001), pre-RT ambulatory status (P<0.001), and time developing motor deficits (P<0.001) were also independent predictors for survival., Conclusions: The number of involved extraspinal organs is a new and independent prognostic factor in patients with MSCC and should be considered in future clinical trials., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Published
2014
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44. Vestibular schwannoma microsurgery for recurrent tumors after radiation therapy or previous surgical resection.

Author

Hong B, Krauss JK, Bremer M, Karstens JH, Heissler HE, and Nakamura M

Subjects
Adolescent, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Neuroma, Acoustic radiotherapy, Retreatment, Retrospective Studies, Treatment Outcome, Young Adult, Microsurgery, Neuroma, Acoustic surgery, Radiosurgery
Abstract

Objective: The purpose of this study is to compare the outcomes in patients who underwent microsurgical resection for recurrent vestibular schwannoma after microsurgical resection and previous radiation therapy., Study Design: Retrospective study., Setting: University hospital., Patients: Fifteen patients, who underwent microsurgical resection for recurrent vestibular schwannoma after previous surgery (group A), and 5 patients, who underwent microsurgical resection after previous radiation therapy (group B) were included., Intervention: Surgical resection after radiation therapy or previous surgical resection., Main Outcome Measures: Intraoperative findings and postoperative facial nerve function were investigated in groups A and B., Results: Mean tumor volumes were 18.4 ± 2.44 cm3 in group A and 19.0 ± 1.53 cm3 in group B. Total resection was achieved in 10 patients (67%) of group A and in 3 patients (60.0%) of group B. The tumor was more difficult to resect because of severe adhesions to the facial nerve. Anatomic facial nerve preservation could be achieved in 19 patients. Mean follow-up time was 80 months for group A and 28 months for group B. At last follow-up, 7 patients (53.8%) of group A had a good facial nerve function. In 3 patients (75.0%) of group B, the preoperative facial nerve function was preserved postoperatively. Preexistent facial paresis, large tumor with extrameatal growth and brainstem compression correlated with poor postoperative facial nerve function., Conclusion: Surgical outcome of recurrent vestibular schwannoma is more unsatisfactory than after primary surgery. It remains to be clarified whether previous surgery may implicate a higher risk for postoperative facial nerve function than previous radiation therapy upon surgery for tumor recurrence.

Published
2014
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45. Survival in patients with metastatic spinal cord compression from prostate cancer is associated with the number of extra-spinal organs involved.

Author

Weber A, Bartscht T, Karstens JH, Schild SE, and Rades D

Subjects
Aged, Humans, Kaplan-Meier Estimate, Male, Multivariate Analysis, Proportional Hazards Models, Prostatic Neoplasms pathology, Prostatic Neoplasms radiotherapy, Retrospective Studies, Severity of Illness Index, Spinal Cord Compression etiology, Spinal Cord Compression radiotherapy, Spinal Neoplasms radiotherapy, Spinal Neoplasms secondary, Prostatic Neoplasms mortality, Spinal Cord Compression mortality, Spinal Neoplasms mortality
Abstract

Background/aim: To investigate the predictive value of the number of extra-spinal organs involved by metastases for survival in metastatic spinal cord compression (MSCC) from prostate cancer., Patients and Methods: In 95 patients irradiated with 10 × 3 Gy for MSCC from prostate cancer, seven factors were investigated: Age, performance score, number of involved vertebrae, interval from prostate cancer diagnosis to MSCC, pre-radiotherapy ambulatory status, time to motor deficits development, number of involved extra-spinal organs., Results: Six-month survival rates for 0, 1 and ≥ 2 involved extra-spinal organs, were 81, 53 and 33%, respectively (p<0.001). On multivariate analysis, the number of involved extra-spinal organs maintained significance (risk ratio 1.88, p=0.023). Better performance score (p<0.001), longer interval from prostate cancer diagnosis to radiotherapy of MSCC (p<0.001), and being ambulatory prior to radiotherapy (p=0.001) were also positively associated with survival., Conclusion: The number of extra-spinal organs involved by metastases predicts survival in patients with MSCC from prostate cancer.

Published
2013

46. A validated scoring system to identify long-term survivors after radiotherapy for metastatic spinal cord compression.

Author

Rades D, Veninga T, Bajrovic A, Karstens JH, and Schild SE

Subjects
Aged, Disease Progression, Female, Germany, Humans, Long-Term Care, Male, Middle Aged, Neurologic Examination, Particle Accelerators, Radiotherapy Planning, Computer-Assisted, Spinal Cord Compression mortality, Spinal Cord Compression radiotherapy, Spinal Neoplasms mortality, Spinal Neoplasms radiotherapy, Spinal Neoplasms secondary, Survivors
Abstract

Purpose: This study aimed to develop and validate a scoring system to identify long-term survivors after conventional radiotherapy (RT) for metastatic spinal cord compression (MSCC)., Patients and Methods: Data from 1,125 patients who had received long-course RT for MSCC were included in this study. Of these patients, 344 survived for over 12 months and 781 died within a year following RT. Based on differences between the distributions of patient characteristics in the two groups, a scoring system was developed. Scores ranged from 0 to 18 points and 15 points was selected as the cutoff for identifying long-term survivors. Data from the 1,125 long-course RT patients (test group) were compared to data from 773 patients receiving short-course RT (validation group)., Results: A score of ≥ 15 points was associated with a 94 % proportion of long-term survivors. The 15-point cutoff resulted in a specificity of 98 % and a positive predictive value of 94 % for identification of long-term surviving patients. The proportions of long-term survivors for each scoring point in the validation group were very similar to those in the test group., Conclusion: This new scoring system enabled identification of long-term survivors after RT for MSCC with very high specificity and positive predictive value. The score proved to be valid and reproducible.

Published
2013
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47. Segmental dosimetry, toxicity and long-term outcome in patients with prostate cancer treated with permanent seed implants.

Author

Meyer A, Wassermann J, Warszawski-Baumann A, Baumann R, Machtens S, Karstens JH, Christiansen H, Merseburger A, Kuczyk MA, and von Klot C

Subjects
Adult, Aged, Aged, 80 and over, Brachytherapy methods, Follow-Up Studies, Humans, Male, Middle Aged, Preoperative Period, Prospective Studies, Prostatic Neoplasms complications, Quality of Life, Time Factors, Treatment Outcome, Brachytherapy adverse effects, Erectile Dysfunction etiology, Iodine Radioisotopes adverse effects, Prostatic Neoplasms radiotherapy, Radiometry methods, Urination Disorders etiology
Abstract

Unlabelled: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: The development of side effects characteristic for the different treatment methods with impact on the patients' quality of life plays a growing role for individual patients with early stage prostate cancer. Using permanent brachytherapy a high dose to the prostate can be applied with a steep dose gradient to the normal tissue. However, small partial volumes of normal tissue may be exposed to high doses inducing special side effects including lower urinary tract symptoms and/or erectile dysfunction. In the literature there are only few publications so far regarding segmental dosimetry and its influence on side effects and the results are conflicting. We could not identify any dosimetric parameter in segmental dosimetry that may have an influence at certain time intervals on the development of side effects such as lower urinary tract symptoms or erectile dysfunction. However, we could state clearly that the preoperative situation is the most important factor for postoperative outcome., Objective: To report on the side effects of patients with low to low-intermediate risk prostate cancer treated with permanent interstitial brachytherapy with special emphasis on segmental dosimetry., Patients and Methods: A series of 186 consecutive patients treated for early stage prostate cancer receiving definitive I-125 brachytherapy (permanent seed implantation) between November 2001 and April 2005 at our institution were examined for the development of side effects. Morbidity was assessed prospectively using the International Prostate Symptom Score (IPSS) and the International Index of Erectile Function (IIEF-5) in a mean follow-up interval of 30 months. The scores were correlated with segmental dosimetry performed 6 weeks after the implantation., Results: The mean postoperative dose to 90% of the prostate volume (D90) was 180.2 Gy, the mean preoperative IPSS 7.2 and the mean IIEF-5 14.35, with all scores showing a maximum deterioration after 6 weeks with normalization after 24 months. After correlating the segmental dosimetry and the scores at different time intervals, only the baseline scores remained statistically significant in multivariate regression analysis at all time intervals (P < 0.00)., Conclusions: We could not demonstrate a correlation of segmental dosimetry with induction of side effects. There is no relationship between dose exposure of partial volumes and the development of radiation-induced toxicities. The preoperative situation regarding lower urinary tract symptoms and erectile function are the most important factors for postoperative outcome., (© 2013 BJU International.)

Published
2013
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48. Apoptosis gene polymorphisms and risk of prostate cancer: a hospital-based study of German patients treated with brachytherapy.

Author

Meyer A, Coinac I, Bogdanova N, Dubrowinskaja N, Turmanov N, Haubold S, Schürmann P, Imkamp F, von Klot C, Merseburger AS, Machtens S, Bremer M, Hillemanns P, Kuczyk MA, Karstens JH, Serth J, and Dörk T

Subjects
Adult, Aged, Aged, 80 and over, Case-Control Studies, Follow-Up Studies, Germany, Hospitals, University, Humans, Male, Middle Aged, Neoplasm Grading, Neoplasm Staging, Prognosis, Prostatic Neoplasms radiotherapy, Apoptosis genetics, Apoptosis Regulatory Proteins genetics, Biomarkers, Tumor genetics, Brachytherapy, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide genetics, Prostatic Neoplasms genetics
Abstract

Background and Objectives: Prostate cancer has a genetic component, and single nucleotide polymorphisms (SNPs) can contribute to the risk. We aimed to investigate the role of polymorphisms in 10 candidate genes with a key function in apoptosis., Methods and Materials: Eight coding SNPs were chosen in ATM (Ser49Cys), BID (Ser56Cys), CASP8 (Asp302His), CASP10 (Val410Ile), LGALS3 (Pro64His), RASSF1 (Ser133Ala), TP53 (Arg72Pro), and TP53AIP1 (Ala7Val), and two non-coding SNPs were selected in BCL2 (-938C/A) and HDM2 (SNP309). A hospital-based case-control series of 510 prostate cancer patients and 490 healthy males from Northern Germany were genotyped for these polymorphisms., Results: SNP rs4644 in LGALS3 showed evidence for a protective effect of the minor allele, encoding the His64 variant (OR 0.82, 95% CI 0.69;0.99, P = 0.04). Carriers were underrepresented among cases under a dominant model (OR 0.71; 95% CI 0.54;0.92; P = 0.01), and the effect appeared more pronounced in patients diagnosed before the age of 60 years (OR 0.52; 95% CI 0.31;0.85, P = 0.01). The other nine polymorphisms did not vary significantly between cases and controls, though subtle trends were noted for BCL2 (P = 0.07) and CASP10 (P = 0.08). The Asp302His variant of CASP8 tended to associate with a protective effect in the group with higher Gleason score under a dominant model (P = 0.03). Carriers of either the CASP8 or the CASP10 variants were underrepresented in the prostate cancer series (P = 0.02)., Conclusions: These results provide first evidence to implicate the functional Pro64His variant of galectin-3 (LGALS3) in the genetic susceptibility towards prostate cancer. The potential role of polymorphisms in BCL2, CASP8, and CASP10 merits further investigation., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Published
2013
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49. HDR brachytherapy: an option for preventing nonmalignant obstruction in patients after lung transplantation.

Author

Meyer A, Warszawski-Baumann A, Baumann R, Karstens JH, Christiansen H, Gottlieb J, and Welte T

Subjects
Adult, Aged, Airway Obstruction radiotherapy, Bronchoscopy, Combined Modality Therapy, Dilatation, Female, Forced Expiratory Volume radiation effects, Humans, Male, Middle Aged, Postoperative Complications radiotherapy, Radiotherapy Dosage, Retreatment, Secondary Prevention, Young Adult, Airway Obstruction prevention & control, Brachytherapy methods, Lung Transplantation, Postoperative Complications prevention & control
Abstract

Purpose: Interventional bronchoscopy is the main treatment modality in managing benign airway obstructions following lung transplantation. We analyzed the effect of intraluminal brachytherapy on preventing recurrence of hyperplastic tissue., Patients and Methods: From September 2002 to September 2004, a total of 24 intraluminal brachytherapy applications were carried out on 12 lung transplant patients in 15 different locations. A single dose of 3 Gy was calculated at a 5-mm distance from the catheter surface; the target volume included a stenosis plus safety interval of 0.5-1.0 cm., Results: All patients had a mean 10.6 local interventions (Argon plasma coagulation, balloon dilatations, stenting) over 4.4 months before the first application of endobronchial brachytherapy, with a mean amount of 2.4 applications per month. The mean forced expiratory volume in 1 s (FEV1) was 2,219 ml in the 3 months before application of brachytherapy. After endobronchial brachytherapy, all patients experienced improvement in clinical status and respiratory function. The mean level of FEV1 in the 3 months after application was 2,435 ml (p = 0.02), and the number of invasive interventions dropped to a mean rate of 5.2 interventions in the 5.1 months after the first intervention, with an amount of 1 application per month. No treatment-related complications were seen. Four patients were treated twice, 1 patient three times, and 1 patient four times at the same localization., Conclusions: Recurrent symptomatic benign airway obstruction from hyperplastic tissue in the bronchus after lung transplantation can be successfully treated with intraluminal high-dose-rate brachytherapy with a dose of 3 Gy at a 5-mm distance from the catheter surface and a longitudinal safety margin of 1 cm.

Published
2012
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50. 11q13 is a susceptibility locus for hormone receptor positive breast cancer.

Author

Lambrechts D, Truong T, Justenhoven C, Humphreys MK, Wang J, Hopper JL, Dite GS, Apicella C, Southey MC, Schmidt MK, Broeks A, Cornelissen S, van Hien R, Sawyer E, Tomlinson I, Kerin M, Miller N, Milne RL, Zamora MP, Pérez JI, Benítez J, Hamann U, Ko YD, Brüning T, Chang-Claude J, Eilber U, Hein R, Nickels S, Flesch-Janys D, Wang-Gohrke S, John EM, Miron A, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Grip M, Chenevix-Trench G, Beesley J, Chen X, Menegaux F, Cordina-Duverger E, Shen CY, Yu JC, Wu PE, Hou MF, Andrulis IL, Selander T, Glendon G, Mulligan AM, Anton-Culver H, Ziogas A, Muir KR, Lophatananon A, Rattanamongkongul S, Puttawibul P, Jones M, Orr N, Ashworth A, Swerdlow A, Severi G, Baglietto L, Giles G, Southey M, Marmé F, Schneeweiss A, Sohn C, Burwinkel B, Yesilyurt BT, Neven P, Paridaens R, Wildiers H, Brenner H, Müller H, Arndt V, Stegmaier C, Meindl A, Schott S, Bartram CR, Schmutzler RK, Cox A, Brock IW, Elliott G, Cross SS, Fasching PA, Schulz-Wendtland R, Ekici AB, Beckmann MW, Fletcher O, Johnson N, Silva Idos S, Peto J, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Dörk T, Schürmann P, Bremer M, Hillemanns P, Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Khusnutdinova E, Bermisheva M, Prokofieva D, Gancev S, Jakubowska A, Lubinski J, Jaworska K, Durda K, Nordestgaard BG, Bojesen SE, Lanng C, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Radice P, Peterlongo P, Manoukian S, Bernard L, Couch FJ, Olson JE, Wang X, Fredericksen Z, Alnaes GG, Kristensen V, Børresen-Dale AL, Devilee P, Tollenaar RA, Seynaeve CM, Hooning MJ, García-Closas M, Chanock SJ, Lissowska J, Sherman ME, Hall P, Liu J, Czene K, Kang D, Yoo KY, Noh DY, Lindblom A, Margolin S, Dunning AM, Pharoah PD, Easton DF, Guénel P, and Brauch H

Subjects
Female, Genetic Predisposition to Disease genetics, Genome-Wide Association Study, Genotype, Humans, Polymorphism, Single Nucleotide genetics, Risk Factors, White People, Breast Neoplasms genetics, Chromosomes, Human, Pair 11 genetics, Receptors, Estrogen genetics, Receptors, Progesterone genetics
Abstract

A recent two-stage genome-wide association study (GWAS) identified five novel breast cancer susceptibility loci on chromosomes 9, 10, and 11. To provide more reliable estimates of the relative risk associated with these loci and investigate possible heterogeneity by subtype of breast cancer, we genotyped the variants rs2380205, rs1011970, rs704010, rs614367, and rs10995190 in 39 studies from the Breast Cancer Association Consortium (BCAC), involving 49,608 cases and 48,772 controls of predominantly European ancestry. Four of the variants showed clear evidence of association (P ≤ 3 × 10(-9) ) and weak evidence was observed for rs2380205 (P = 0.06). The strongest evidence was obtained for rs614367, located on 11q13 (per-allele odds ratio 1.21, P = 4 × 10(-39) ). The association for rs614367 was specific to estrogen receptor (ER)-positive disease and strongest for ER plus progesterone receptor (PR)-positive breast cancer, whereas the associations for the other three loci did not differ by tumor subtype., (© 2012 Wiley Periodicals, Inc.)

Published
2012
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