Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2015 Apr 2;107(5):djv037.
doi: 10.1093/jnci/djv037. Print 2015 May.

A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

Affiliations
Free PMC article

A Rare Truncating BRCA2 Variant and Genetic Susceptibility to Upper Aerodigestive Tract Cancer

Manon Delahaye-Sourdeix et al. J Natl Cancer Inst. .
Free PMC article

Abstract

Deleterious BRCA2 genetic variants markedly increase risk of developing breast cancer. A rare truncating BRCA2 genetic variant, rs11571833 (K3326X), has been associated with a 2.5-fold risk of lung squamous cell carcinoma but only a modest 26% increase in breast cancer risk. We analyzed the association between BRCA2 SNP rs11571833 and upper aerodigestive tract (UADT) cancer risk with multivariable unconditional logistic regression adjusted by sex and combinations of study and country for 5942 UADT squamous cell carcinoma case patients and 8086 control patients from nine different studies. All statistical tests were two-sided. rs11571833 was associated with UADT cancers (odds ratio = 2.53, 95% confidence interval = 1.89 to 3.38, P = 3x10(-10)) and was present in European, Latin American, and Indian populations but extremely rare in Japanese populations. The association appeared more apparent in smokers (current or former) compared with never smokers (P het = .026). A robust association between a truncating BRCA2 variant and UADT cancer risk suggests that treatment strategies orientated towards BRCA2 mutations may warrant further investigation in UADT tumors.

Figures

Figure 1.
Figure 1.
Association between BRCA2 SNP rs11571833 and upper aerodigestive tract cancer risk. Squares represent odds ratios, size of the square represents the inverse of the variance of the log odds ratios; horizontal lines represent 95% confidence intervals. The solid vertical line indicates an odds ratio of 1 and the dashed vertical line the overall odds ratio. The arrow indicates that the confidence interval of this particular estimate exceeds the scale of the plot. Results derived from a two-sided multivariable unconditional logistic regression adjusted by sex and study-specific country. All statistical tests were two-sided. ACTREC = Advanced Centre for Treatment, Research and Education in Cancer oral cancer study; CI = confidence interval; HNI = Rome (Italy) head and neck cancer study; OR = odds ratio; ORC = IARC multicentre oral cancer case control study; SA = South America.

Comment in

  • BRCA2-branching out too?
    Spitz MR, Liu Y, Amos CI. Spitz MR, et al. J Natl Cancer Inst. 2015 Apr 2;107(5):djv066. doi: 10.1093/jnci/djv066. Print 2015 May. J Natl Cancer Inst. 2015. PMID: 25838449 No abstract available.

Similar articles

  • Tag single nucleotide polymorphisms of alcohol-metabolizing enzymes modify the risk of upper aerodigestive tract cancers: HapMap database analysis.
    Chung CS, Lee YC, Liou JM, Wang CP, Ko JY, Lee JM, Wu MS, Wang HP. Chung CS, et al. Dis Esophagus. 2014 Jul;27(5):493-503. doi: 10.1111/j.1442-2050.2012.01437.x. Epub 2012 Oct 22. Dis Esophagus. 2014. PMID: 23088731
  • BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers.
    Meeks HD, Song H, Michailidou K, Bolla MK, Dennis J, Wang Q, Barrowdale D, Frost D; EMBRACE, McGuffog L, Ellis S, Feng B, Buys SS, Hopper JL, Southey MC, Tesoriero A; kConFab Investigators, James PA, Bruinsma F, Campbell IG; Australia Ovarian Cancer Study Group, Broeks A, Schmidt MK, Hogervorst FB; HEBON, Beckman MW, Fasching PA, Fletcher O, Johnson N, Sawyer EJ, Riboli E, Banerjee S, Menon U, Tomlinson I, Burwinkel B, Hamann U, Marme F, Rudolph A, Janavicius R, Tihomirova L, Tung N, Garber J, Cramer D, Terry KL, Poole EM, Tworoger SS, Dorfling CM, van Rensburg EJ, Godwin AK, Guénel P, Truong T; GEMO Study Collaborators, Stoppa-Lyonnet D, Damiola F, Mazoyer S, Sinilnikova OM, Isaacs C, Maugard C, Bojesen SE, Flyger H, Gerdes AM, Hansen TV, Jensen A, Kjaer SK, Hogdall C, Hogdall E, Pedersen IS, Thomassen M, Benitez J, González-Neira A, Osorio A, Hoya Mde L, Segura PP, Diez O, Lazaro C, Brunet J, Anton-Culver H, Eunjung L, John EM, Neuhausen SL, Ding YC, Castillo D, Weitzel JN, Ganz PA, Nussbaum RL, Chan SB, Karlan BY, Lester J, Wu A, Gayther S, Ramus SJ, Sieh W, Whittermore AS, Monteiro AN, Phelan CM, Terry MB, Piedmonte M, Offit K, Robson M, Levine D, Moysich KB, Cannioto R, Olson SH, Daly MB, Nathanson KL, Domchek SM, Lu KH, Liang D, Hildebrant MA, Ness R, Modugno F, Pearce L, Goodman MT, Thompson PJ, Brenner H, Butterbach K, Meindl A, Hahnen E, Wappenschmidt B, Brauch H, Brüning T, Blomqvist C, Khan S, Nevanlinna H, Pelttari LM, Aittomäki K, Butzow R, Bogdanova NV, Dörk T, Lindblom A, Margolin S, Rantala J, Kosma VM, Mannermaa A, Lambrechts D, Neven P, Claes KB, Maerken TV, Chang-Claude J, Flesch-Janys D, Heitz F, Varon-Mateeva R, Peterlongo P, Radice P, Viel A, Barile M, Peissel B, Manoukian S, Montagna M, Oliani C, Peixoto A, Teixeira MR, Collavoli A, Hallberg E, Olson JE, Goode EL, Hart SN, Shimelis H, Cunningham JM, Giles GG, Milne RL, Healey S, Tucker K, Haiman CA, Henderson BE, Goldberg MS, Tischkowitz M, Simard J, Soucy P, Eccles DM, Le N, Borresen-Dale AL, Kristensen V, Salvesen HB, Bjorge L, Bandera EV, Risch H, Zheng W, Beeghly-Fadiel A, Cai H, Pylkäs K, Tollenaar RA, Ouweland AM, Andrulis IL, Knight JA; OCGN, Narod S, Devilee P, Winqvist R, Figueroa J, Greene MH, Mai PL, Loud JT, García-Closas M, Schoemaker MJ, Czene K, Darabi H, McNeish I, Siddiquil N, Glasspool R, Kwong A, Park SK, Teo SH, Yoon SY, Matsuo K, Hosono S, Woo YL, Gao YT, Foretova L, Singer CF, Rappaport-Feurhauser C, Friedman E, Laitman Y, Rennert G, Imyanitov EN, Hulick PJ, Olopade OI, Senter L, Olah E, Doherty JA, Schildkraut J, Koppert LB, Kiemeney LA, Massuger LF, Cook LS, Pejovic T, Li J, Borg A, Öfverholm A, Rossing MA, Wentzensen N, Henriksson K, Cox A, Cross SS, Pasini BJ, Shah M, Kabisch M, Torres D, Jakubowska A, Lubinski J, Gronwald J, Agnarsson BA, Kupryjanczyk J, Moes-Sosnowska J, Fostira F, Konstantopoulou I, Slager S, Jones M; PRostate cancer AssoCiation group To Investigate Cancer Associated aLterations in the genome, Antoniou AC, Berchuck A, Swerdlow A, Chenevix-Trench G, Dunning AM, Pharoah PD, Hall P, Easton DF, Couch FJ, Spurdle AB, Goldgar DE. Meeks HD, et al. J Natl Cancer Inst. 2015 Nov 19;108(2):djv315. doi: 10.1093/jnci/djv315. Print 2016 Feb. J Natl Cancer Inst. 2015. PMID: 26586665 Free PMC article.
  • Smoking addiction and the risk of upper-aerodigestive-tract cancer in a multicenter case-control study.
    Lee YC, Zugna D, Richiardi L, Merletti F, Marron M, Ahrens W, Pohlabeln H, Lagiou P, Trichopoulos D, Agudo A, Castellsague X, Betka J, Holcatova I, Kjaerheim K, Macfarlane GJ, Macfarlane TV, Talamini R, Barzan L, Canova C, Simonato L, Conway DI, McKinney PA, Thomson P, Znaor A, Healy CM, McCartan BE, Boffetta P, Brennan P, Hashibe M. Lee YC, et al. Int J Cancer. 2013 Dec 1;133(11):2688-95. doi: 10.1002/ijc.28288. Epub 2013 Jun 21. Int J Cancer. 2013. PMID: 23719996 Clinical Trial.
  • Alcohol drinking, cigarette smoking, and the development of squamous cell carcinoma of the esophagus: epidemiology, clinical findings, and prevention.
    Morita M, Kumashiro R, Kubo N, Nakashima Y, Yoshida R, Yoshinaga K, Saeki H, Emi Y, Kakeji Y, Sakaguchi Y, Toh Y, Maehara Y. Morita M, et al. Int J Clin Oncol. 2010 Apr;15(2):126-34. doi: 10.1007/s10147-010-0056-7. Epub 2010 Mar 12. Int J Clin Oncol. 2010. PMID: 20224884 Review.
  • Alcohol dehydrogenase-1B Arg47His polymorphism and upper aerodigestive tract cancer risk: a meta-analysis including 24,252 subjects.
    Guo H, Zhang G, Mai R. Guo H, et al. Alcohol Clin Exp Res. 2012 Feb;36(2):272-8. doi: 10.1111/j.1530-0277.2011.01621.x. Epub 2011 Sep 6. Alcohol Clin Exp Res. 2012. PMID: 21895720 Review.
See all similar articles

Cited by 13 articles

  • Treatment of Pediatric Glioblastoma with Combination Olaparib and Temozolomide Demonstrates 2-Year Durable Response.
    Valiakhmetova A, Gorelyshev S, Konovalov A, Trunin Y, Savateev A, Kram DE, Severson E, Hemmerich A, Edgerly C, Duncan D, Britt N, Huang RSP, Elvin J, Miller V, Ross JS, Gay L, McCorkle J, Rankin A, Erlich RL, Chudnovsky Y, Ramkissoon SH. Valiakhmetova A, et al. Oncologist. 2020 Feb;25(2):e198-e202. doi: 10.1634/theoncologist.2019-0603. Epub 2019 Oct 16. Oncologist. 2020. PMID: 32043779 Free PMC article.
  • Rare Variants in Known Susceptibility Loci and Their Contribution to Risk of Lung Cancer.
    Liu Y, Lusk CM, Cho MH, Silverman EK, Qiao D, Zhang R, Scheurer ME, Kheradmand F, Wheeler DA, Tsavachidis S, Armstrong G, Zhu D, Wistuba II, Chow CB, Behrens C, Pikielny CW, Neslund-Dudas C, Pinney SM, Anderson M, Kupert E, Bailey-Wilson J, Gaba C, Mandal D, You M, de Andrade M, Yang P, Field JK, Liloglou T, Davies M, Lissowska J, Swiatkowska B, Zaridze D, Mukeriya A, Janout V, Holcatova I, Mates D, Milosavljevic S, Scelo G, Brennan P, McKay J, Liu G, Hung RJ, Christiani DC, Schwartz AG, Amos CI, Spitz MR. Liu Y, et al. J Thorac Oncol. 2018 Oct;13(10):1483-1495. doi: 10.1016/j.jtho.2018.06.016. Epub 2018 Jul 4. J Thorac Oncol. 2018. PMID: 29981437 Free PMC article.
  • Association of BRCA2 K3326* With Small Cell Lung Cancer and Squamous Cell Cancer of the Skin.
    Rafnar T, Sigurjonsdottir GR, Stacey SN, Halldorsson G, Sulem P, Pardo LM, Helgason H, Sigurdsson ST, Gudjonsson T, Tryggvadottir L, Olafsdottir GH, Jonasson JG, Alexiusdottir K, Sigurdsson A, Gudmundsson J, Saemundsdottir J, Sigurdsson JK, Johannsdottir H, Uitterlinden A, Vermeulen SH, Galesloot TE, Allain DC, Lacko M, Sigurgeirsson B, Thorisdottir K, Johannsson OT, Sigurdsson F, Ragnarsson GB, Isaksson H, Hardardottir H, Gudbjartsson T, Gudbjartsson DF, Masson G, Kiemeney LAML, Ewart Toland A, Nijsten T, Peters WHM, Olafsson JH, Jonsson S, Thorsteinsdottir U, Thorleifsson G, Stefansson K. Rafnar T, et al. J Natl Cancer Inst. 2018 Sep 1;110(9):967-974. doi: 10.1093/jnci/djy002. J Natl Cancer Inst. 2018. PMID: 29767749 Free PMC article.
  • A novel BRCA2 mutation in prostate cancer sensitive to combined radiotherapy and androgen deprivation therapy.
    Liu Q, Tong D, Liu G, Yi Y, Xu J, Yang X, Wang L, Zhang J, Ye J, Zhang Y, Yuan G, Wang P, Chen R, Guan Y, Yi X, Zhang D, Jiang J. Liu Q, et al. Cancer Biol Ther. 2018 Aug 3;19(8):669-675. doi: 10.1080/15384047.2018.1451278. Epub 2018 Apr 19. Cancer Biol Ther. 2018. PMID: 29580149 Free PMC article.
  • Incidental and clinically actionable genetic variants in 1005 whole exomes and genomes from Qatar.
    Jain A, Gandhi S, Koshy R, Scaria V. Jain A, et al. Mol Genet Genomics. 2018 Aug;293(4):919-929. doi: 10.1007/s00438-018-1431-8. Epub 2018 Mar 20. Mol Genet Genomics. 2018. PMID: 29557500
See all "Cited by" articles

References

    1. Ferlay J, Shin HR, Bray F, et al. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–2917. - PubMed
    1. Stewart B, Kleihues P. World Cancer Report: IARC Press; 2003.
    1. McKay JD, Truong T, Gaborieau V, et al. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PLoS Genet. 2011;7(3):e1001333. - PMC - PubMed
    1. Negri E, Boffetta P, Berthiller J, et al. Family history of cancer: pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Int J Cancer. 2009;124(2):394–401. - PMC - PubMed
    1. Hoeijmakers JH. Genome maintenance mechanisms for preventing cancer. Nature. 2001;411(6835):366–374. - PubMed

Publication types

Feedback