Noah Kauff

Positions:

Instructor, Temporary in the Obstetrics and Gynecology

Obstetrics and Gynecology, Gynecologic Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 1993

University of Pennsylvania

Grants:

Publications:

No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer.

OBJECTIVE: Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer risk as well as with survival time. However, prior studies, emphasizing particular subgroups, were relatively small. Therefore, we comprehensively evaluated ovarian and breast cancer risks as well as clinical outcome associated with rs61764370. METHODS: Centralized genotyping and analysis were performed for 140,012 women enrolled in the Ovarian Cancer Association Consortium (15,357 ovarian cancer patients; 30,816 controls), the Breast Cancer Association Consortium (33,530 breast cancer patients; 37,640 controls), and the Consortium of Modifiers of BRCA1 and BRCA2 (14,765 BRCA1 and 7904 BRCA2 mutation carriers). RESULTS: We found no association with risk of ovarian cancer (OR=0.99, 95% CI 0.94-1.04, p=0.74) or breast cancer (OR=0.98, 95% CI 0.94-1.01, p=0.19) and results were consistent among mutation carriers (BRCA1, ovarian cancer HR=1.09, 95% CI 0.97-1.23, p=0.14, breast cancer HR=1.04, 95% CI 0.97-1.12, p=0.27; BRCA2, ovarian cancer HR=0.89, 95% CI 0.71-1.13, p=0.34, breast cancer HR=1.06, 95% CI 0.94-1.19, p=0.35). Null results were also obtained for associations with overall survival following ovarian cancer (HR=0.94, 95% CI 0.83-1.07, p=0.38), breast cancer (HR=0.96, 95% CI 0.87-1.06, p=0.38), and all other previously-reported associations. CONCLUSIONS: rs61764370 is not associated with risk of ovarian or breast cancer nor with clinical outcome for patients with these cancers. Therefore, genotyping this variant has no clinical utility related to the prediction or management of these cancers.
Authors
Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2,; Hollestelle, A; van der Baan, FH; Berchuck, A; Johnatty, SE; Aben, KK; Agnarsson, BA; Aittomäki, K; Alducci, E; Andrulis, IL; Anton-Culver, H; Antonenkova, NN; Antoniou, AC; Apicella, C; Arndt, V; Arnold, N; Arun, BK; Arver, B; Ashworth, A; Australian Ovarian Cancer Study Group,; Baglietto, L; Balleine, R; Bandera, EV; Barrowdale, D; Bean, YT; Beckmann, L; Beckmann, MW; Benitez, J; Berger, A; Berger, R; Beuselinck, B; Bisogna, M; Bjorge, L; Blomqvist, C; Bogdanova, NV; Bojesen, A; Bojesen, SE; Bolla, MK; Bonanni, B; Brand, JS; Brauch, H; Breast Cancer Family Register,; Brenner, H; Brinton, L; Brooks-Wilson, A; Bruinsma, F; Brunet, J; Brüning, T; Budzilowska, A; Bunker, CH; Burwinkel, B; Butzow, R; Buys, SS; Caligo, MA; Campbell, I; Carter, J; Chang-Claude, J; Chanock, SJ; Claes, KBM; Collée, JM; Cook, LS; Couch, FJ; Cox, A; Cramer, D; Cross, SS; Cunningham, JM; Cybulski, C; Czene, K; Damiola, F; Dansonka-Mieszkowska, A; Darabi, H; de la Hoya, M; deFazio, A; Dennis, J; Devilee, P; Dicks, EM; Diez, O; Doherty, JA; Domchek, SM; Dorfling, CM; Dörk, T; Silva, IDS; du Bois, A; Dumont, M; Dunning, AM; Duran, M; Easton, DF; Eccles, D; Edwards, RP; Ehrencrona, H; Ejlertsen, B; Ekici, AB; Ellis, SD; EMBRACE,; Engel, C; Eriksson, M; Fasching, PA; Feliubadalo, L; Figueroa, J; Flesch-Janys, D; Fletcher, O; Fontaine, A; Fortuzzi, S; Fostira, F; Fridley, BL; Friebel, T; Friedman, E; Friel, G; Frost, D; Garber, J; García-Closas, M; Gayther, SA; GEMO Study Collaborators,; GENICA Network,; Gentry-Maharaj, A; Gerdes, A-M; Giles, GG; Glasspool, R; Glendon, G; Godwin, AK; Goodman, MT; Gore, M; Greene, MH; Grip, M; Gronwald, J; Gschwantler Kaulich, D; Guénel, P; Guzman, SR; Haeberle, L; Haiman, CA; Hall, P; Halverson, SL; Hamann, U; Hansen, TVO; Harter, P; Hartikainen, JM; Healey, S; HEBON,; Hein, A; Heitz, F; Henderson, BE; Herzog, J; T Hildebrandt, MA; Høgdall, CK; Høgdall, E; Hogervorst, FBL; Hopper, JL; Humphreys, K; Huzarski, T; Imyanitov, EN; Isaacs, C; Jakubowska, A; Janavicius, R; Jaworska, K; Jensen, A; Jensen, UB; Johnson, N; Jukkola-Vuorinen, A; Kabisch, M; Karlan, BY; Kataja, V; Kauff, N; KConFab Investigators,; Kelemen, LE; Kerin, MJ; Kiemeney, LA; Kjaer, SK; Knight, JA; Knol-Bout, JP; Konstantopoulou, I; Kosma, V-M; Krakstad, C; Kristensen, V; Kuchenbaecker, KB; Kupryjanczyk, J; Laitman, Y; Lambrechts, D; Lambrechts, S; Larson, MC; Lasa, A; Laurent-Puig, P; Lazaro, C; Le, ND; Le Marchand, L; Leminen, A; Lester, J; Levine, DA; Li, J; Liang, D; Lindblom, A; Lindor, N; Lissowska, J; Long, J; Lu, KH; Lubinski, J; Lundvall, L; Lurie, G; Mai, PL; Mannermaa, A; Margolin, S; Mariette, F; Marme, F; Martens, JWM; Massuger, LFAG; Maugard, C; Mazoyer, S; McGuffog, L; McGuire, V; McLean, C; McNeish, I; Meindl, A; Menegaux, F; Menéndez, P; Menkiszak, J; Menon, U; Mensenkamp, AR; Miller, N; Milne, RL; Modugno, F; Montagna, M; Moysich, KB; Müller, H; Mulligan, AM; Muranen, TA; Narod, SA; Nathanson, KL; Ness, RB; Neuhausen, SL; Nevanlinna, H; Neven, P; Nielsen, FC; Nielsen, SF; Nordestgaard, BG; Nussbaum, RL; Odunsi, K; Offit, K; Olah, E; Olopade, OI; Olson, JE; Olson, SH; Oosterwijk, JC; Orlow, I; Orr, N; Orsulic, S; Osorio, A; Ottini, L; Paul, J; Pearce, CL; Pedersen, IS; Peissel, B; Pejovic, T; Pelttari, LM; Perkins, J; Permuth-Wey, J; Peterlongo, P; Peto, J; Phelan, CM; Phillips, K-A; Piedmonte, M; Pike, MC; Platte, R; Plisiecka-Halasa, J; Poole, EM; Poppe, B; Pylkäs, K; Radice, P; Ramus, SJ; Rebbeck, TR; Reed, MWR; Rennert, G; Risch, HA; Robson, M; Rodriguez, GC; Romero, A; Rossing, MA; Rothstein, JH; Rudolph, A; Runnebaum, I; Salani, R; Salvesen, HB; Sawyer, EJ; Schildkraut, JM; Schmidt, MK; Schmutzler, RK; Schneeweiss, A; Schoemaker, MJ; Schrauder, MG; Schumacher, F; Schwaab, I; Scuvera, G; Sellers, TA; Severi, G; Seynaeve, CM; Shah, M; Shrubsole, M; Siddiqui, N; Sieh, W; Simard, J; Singer, CF; Sinilnikova, OM; Smeets, D; Sohn, C; Soller, M; Song, H; Soucy, P; Southey, MC; Stegmaier, C; Stoppa-Lyonnet, D; Sucheston, L; SWE-BRCA,; Swerdlow, A; Tangen, IL; Tea, M-K; Teixeira, MR; Terry, KL; Terry, MB; Thomassen, M; Thompson, PJ; Tihomirova, L; Tischkowitz, M; Toland, AE; Tollenaar, RAEM; Tomlinson, I; Torres, D; Truong, T; Tsimiklis, H; Tung, N; Tworoger, SS; Tyrer, JP; Vachon, CM; Van 't Veer, LJ; van Altena, AM; Van Asperen, CJ; van den Berg, D; van den Ouweland, AMW; van Doorn, HC; Van Nieuwenhuysen, E; van Rensburg, EJ; Vergote, I; Verhoef, S; Vierkant, RA; Vijai, J; Vitonis, AF; von Wachenfeldt, A; Walsh, C; Wang, Q; Wang-Gohrke, S; Wappenschmidt, B; Weischer, M; Weitzel, JN; Weltens, C; Wentzensen, N; Whittemore, AS; Wilkens, LR; Winqvist, R; Wu, AH; Wu, X; Yang, HP; Zaffaroni, D; Pilar Zamora, M; Zheng, W; Ziogas, A; Chenevix-Trench, G; Pharoah, PDP; Rookus, MA; Hooning, MJ; Goode, EL
MLA Citation
Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2, Ellen L., et al. “No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer..” Gynecol Oncol, vol. 141, no. 2, May 2016, pp. 386–401. Pubmed, doi:10.1016/j.ygyno.2015.04.034.
URI
https://scholars.duke.edu/individual/pub1072549
PMID
25940428
Source
pubmed
Published In
Gynecol Oncol
Volume
141
Published Date
Start Page
386
End Page
401
DOI
10.1016/j.ygyno.2015.04.034

DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.
Authors
Osorio, A; Milne, RL; Kuchenbaecker, K; Vaclová, T; Pita, G; Alonso, R; Peterlongo, P; Blanco, I; de la Hoya, M; Duran, M; Díez, O; Ramón Y Cajal, T; Konstantopoulou, I; Martínez-Bouzas, C; Andrés Conejero, R; Soucy, P; McGuffog, L; Barrowdale, D; Lee, A; Swe-Brca,; Arver, B; Rantala, J; Loman, N; Ehrencrona, H; Olopade, OI; Beattie, MS; Domchek, SM; Nathanson, K; Rebbeck, TR; Arun, BK; Karlan, BY; Walsh, C; Lester, J; John, EM; Whittemore, AS; Daly, MB; Southey, M; Hopper, J; Terry, MB; Buys, SS; Janavicius, R; Dorfling, CM; van Rensburg, EJ; Steele, L; Neuhausen, SL; Ding, YC; Hansen, TVO; Jønson, L; Ejlertsen, B; Gerdes, A-M; Infante, M; Herráez, B; Moreno, LT; Weitzel, JN; Herzog, J; Weeman, K; Manoukian, S; Peissel, B; Zaffaroni, D; Scuvera, G; Bonanni, B; Mariette, F; Volorio, S; Viel, A; Varesco, L; Papi, L; Ottini, L; Tibiletti, MG; Radice, P; Yannoukakos, D; Garber, J; Ellis, S; Frost, D; Platte, R; Fineberg, E; Evans, G; Lalloo, F; Izatt, L; Eeles, R; Adlard, J; Davidson, R; Cole, T; Eccles, D; Cook, J; Hodgson, S; Brewer, C; Tischkowitz, M; Douglas, F; Porteous, M; Side, L; Walker, L; Morrison, P; Donaldson, A; Kennedy, J; Foo, C; Godwin, AK; Schmutzler, RK; Wappenschmidt, B; Rhiem, K; Engel, C; Meindl, A; Ditsch, N; Arnold, N; Plendl, HJ; Niederacher, D; Sutter, C; Wang-Gohrke, S; Steinemann, D; Preisler-Adams, S; Kast, K; Varon-Mateeva, R; Gehrig, A; Stoppa-Lyonnet, D; Sinilnikova, OM; Mazoyer, S; Damiola, F; Poppe, B; Claes, K; Piedmonte, M; Tucker, K; Backes, F; Rodríguez, G; Brewster, W; Wakeley, K; Rutherford, T; Caldés, T; Nevanlinna, H; Aittomäki, K; Rookus, MA; van Os, TAM; van der Kolk, L; de Lange, JL; Meijers-Heijboer, HEJ; van der Hout, AH; van Asperen, CJ; Gómez Garcia, EB; Hoogerbrugge, N; Collée, JM; van Deurzen, CHM; van der Luijt, RB; Devilee, P; Hebon,; Olah, E; Lázaro, C; Teulé, A; Menéndez, M; Jakubowska, A; Cybulski, C; Gronwald, J; Lubinski, J; Durda, K; Jaworska-Bieniek, K; Johannsson, OT; Maugard, C; Montagna, M; Tognazzo, S; Teixeira, MR; Healey, S; Investigators, K; Olswold, C; Guidugli, L; Lindor, N; Slager, S; Szabo, CI; Vijai, J; Robson, M; Kauff, N; Zhang, L; Rau-Murthy, R; Fink-Retter, A; Singer, CF; Rappaport, C; Geschwantler Kaulich, D; Pfeiler, G; Tea, M-K; Berger, A; Phelan, CM; Greene, MH; Mai, PL; Lejbkowicz, F; Andrulis, I; Mulligan, AM; Glendon, G; Toland, AE; Bojesen, A; Pedersen, IS; Sunde, L; Thomassen, M; Kruse, TA; Jensen, UB; Friedman, E; Laitman, Y; Shimon, SP; Simard, J; Easton, DF; Offit, K; Couch, FJ; Chenevix-Trench, G; Antoniou, AC; Benitez, J
MLA Citation
Osorio, Ana, et al. “DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers..” Plos Genet, vol. 10, no. 4, Apr. 2014. Pubmed, doi:10.1371/journal.pgen.1004256.
URI
https://scholars.duke.edu/individual/pub1327355
PMID
24698998
Source
pubmed
Published In
Plos Genet
Volume
10
Published Date
Start Page
e1004256
DOI
10.1371/journal.pgen.1004256

Hereditary ovarian cancer: recent molecular insights and their impact on screening strategies.

PURPOSE OF REVIEW: This review will focus on the implications of BRCA status in the patient with high-grade serous ovarian cancer, the differences between BRCA1 and BRCA2 mutations, and the most effective risk-reducing strategies. RECENT FINDINGS: Women with BRCA-associated epithelial ovarian cancer represent a unique group who commonly are diagnosed at a younger age, have advanced high-grade serous disease, have improved sensitivity to platinum-based chemotherapy in both the upfront and recurrent setting, and have an overall improved prognosis. Promising novel therapeutic agents such as poly (ADP-ribose) polymerase inhibitors have increased activity in patients with inherited BRCA mutations and may also have a role in patients with noninherited tumors that have decreased BRCA activity. Risk-reducing salpingo-oophorectomy (RRSO) is effective in decreasing risks of both breast and gynecologic cancer in women with BRCA mutations. However, when counseling women at inherited risk, the inherent phenotypical differences between BRCA1 and BRCA2 mutations must be considered. SUMMARY: Patients with BRCA-associated epithelial ovarian cancer have improved response to platinum-based chemotherapy, improved survival, and may be appropriate candidates for treatment with novel targeted therapies. RRSO remains the most effective risk-reduction strategy in women with BRCA mutations.
Authors
Long, KC; Kauff, ND
MLA Citation
Long, Kara C., and Noah D. Kauff. “Hereditary ovarian cancer: recent molecular insights and their impact on screening strategies..” Curr Opin Oncol, vol. 23, no. 5, Sept. 2011, pp. 526–30. Pubmed, doi:10.1097/CCO.0b013e3283499da9.
URI
https://scholars.duke.edu/individual/pub1327421
PMID
21734577
Source
pubmed
Published In
Current Opinion in Oncology
Volume
23
Published Date
Start Page
526
End Page
530
DOI
10.1097/CCO.0b013e3283499da9

ATR mutations in endometrial cancer: a window into the role of mismatch repair defects.

Authors
MLA Citation
Kauff, Noah D. “ATR mutations in endometrial cancer: a window into the role of mismatch repair defects..” J Clin Oncol, vol. 27, no. 19, July 2009, pp. 3077–78. Pubmed, doi:10.1200/JCO.2009.22.2125.
URI
https://scholars.duke.edu/individual/pub1327416
PMID
19470916
Source
pubmed
Published In
Journal of Clinical Oncology
Volume
27
Published Date
Start Page
3077
End Page
3078
DOI
10.1200/JCO.2009.22.2125

Effect of mammography on breast cancer risk in women with mutations in BRCA1 or BRCA2.

Women who carry mutations in either the BRCA1 or BRCA2 genes are at risk for early-onset breast cancer and are recommended to begin screening mammography at age 25 to 30 years. Results of in vitro and animal studies suggest that BRCA1/BRCA2 mutation carriers are hypersensitive to ionizing radiation and possibly to radiation-induced breast cancer. This study was undertaken to investigate the association of low-dose radiation exposure from mammograms with breast cancer status in BRCA mutation carriers. One hundred sixty-two female mutation carriers provided information at time of genetic testing about exposure to mammograms before enrollment. Using unconditional logistic regression, breast cancer status was not associated with number of mammograms received before diagnosis (affected women) or ascertainment [unaffected women; adjusted odds ratio (OR), 0.94; P = not significant]. A larger group of 213 women provided information about lifetime number of mammograms. There was no association between mammogram exposure and risk in the group as a whole (adjusted OR, 1.04; P = not significant), although there was a modest association in BRCA1 carriers (adjusted OR, 1.08; P = 0.03). These findings indicate that screening mammography is unlikely to be associated with a large increase in breast cancer risk in this population.
Authors
Goldfrank, D; Chuai, S; Bernstein, JL; Ramon Y Cajal, T; Lee, JB; Alonso, MC; Diez, O; Baiget, M; Kauff, ND; Offit, K; Robson, M
MLA Citation
Goldfrank, Deborah, et al. “Effect of mammography on breast cancer risk in women with mutations in BRCA1 or BRCA2..” Cancer Epidemiol Biomarkers Prev, vol. 15, no. 11, Nov. 2006, pp. 2311–13. Pubmed, doi:10.1158/1055-9965.EPI-06-0176.
URI
https://scholars.duke.edu/individual/pub1327369
PMID
17119064
Source
pubmed
Published In
Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
Volume
15
Published Date
Start Page
2311
End Page
2313
DOI
10.1158/1055-9965.EPI-06-0176