Molecular Epidemiology of Head & Neck Cancer

Funding Source: NCI R01 CA078609-07
PI: Karl Kelsey, MD, MOH, Brown University
Co-Investigators: Michael McClean, ScD, BUSPH; Heather Nelson, PhD, University of Minnesota; Carmen Marsit, PhD, Brown University; Brock Christensen, PhD, Brown University

Funding Source: FAMRI Award# 062555-YSCA
PI: Michael McClean, ScD, BUSPH
Co-Investigators: Karl Kelsey, MD, MOH, Brown University; Carmen Marsit, PhD, Brown University

ebrg_5Head and neck squamous cell carcinoma (HNSCC) is the tenth most common cancer in the US and the sixth most common cancer worldwide. While 75% of HNSCC is attributable to smoking and alcohol consumption, a significant proportion of this disease remains unexplained. Polymorphisms of genes, associated with an increased risk for lung, bladder, and breast cancer, may further alter cancer risk by level of tobacco or alcohol exposure. Tobacco and alcohol by-products are clearly associated with HNSCC, and have been found to induce genetic mutations; therefore, investigation into genetic susceptibility to this disease is warranted. In our population-based multicenter case-control study of HNSCC, we focus on exploring the role of risk factors such as tobacco, alcohol, human papillomavirus, secondhand tobacco smoke, diet, marijuana, and the genetic factors that may modify such relationships.

The first phase of this study included the recruitment of 705 cases and 815 controls in the greater Boston metropolitan area (1999-2003); the second phase began in 2005 and is ongoing, targeting a final sample size of 1300 cases and 1300 controls. Incident cases of HNSCC are identified through seven teaching hospitals located in Boston, Massachusetts. We are currently interviewing and obtaining biologic samples from incident cases and comparable population controls from the greater Boston metropolitan area. We have established a centralized tissue bank, to which we deposit biologic specimens from cases and controls for the purpose of conducting epidemiologic studies of head and neck cancer.

We are also funded to specifically investigate the role of secondhand tobacco smoke (STS) as a risk factor for HNSCC. While it is widely accepted that active smoking and alcohol consumption synergistically increase the risk of HNSCC, the role of STS exposure is considerably less clear and the potential synergistic effect of STS and alcohol on HNSCC risk has yet to be investigated. Utilizing complete histories of STS exposure that have been obtained over time, we are examining STS-related risks at different points in life. Analyzing time-specific exposures may yield insight into the mechanism of action of STS exposure, as well as the mechanism by which alcohol may modify the effect of STS exposure. The collection of vital statistics for cases will also allow us to determine whether the effect of treatment is influenced by STS exposure during treatment.

These findings should lead to an improved characterization of high-risk individuals for whom aggressive preventive measures may be targeted. Our DNA bank and comprehensive epidemiologic approach will also provide an invaluable resource for continuing studies of the molecular and genetic epidemiology of oral cancer.

Publications

  • Liang C, Marsit CJ, Houseman EA, Butler R, Nelson HH, McClean MD, Kelsey KT. 2011. Gene-environment interactions of novel variants associated with head and neck cancer. Head Neck. Published on-line November 2, 2011.
  • Liang C, Marsit CJ, Houseman EA, Butler R, Nelson HH,McClean MD, Kelsey KT. 2011. Gene-environment interactions of novel variants associated with head and neck cancer.Head Neck. Published on-line November 2, 2011.
  • Edefonti V, Hashibe M, Ambrogi F, Parpinel M, Bravi F, Talamini R, Levi F, Yu G, Morgenstern H, Kelsey K, McClean M, Schantz S, Zhang Z, Chuang S, Boffetta P, La Vecchia C, Decarli A. 2011. Nutrient-based dietary patterns and the risk of head and neck cancer: a pooled analysis in the International Head and Neck Cancer Epidemiology consortium. Ann Oncol. Published on-line November 28, 2011. PMCID: PMC3387823
  • Li Q, Chuang S, Neto JE, Menezes E, Matos E, Koifman S, Wünsch-Filho V, Fernandez L, Daudt AW, Curado MP, Winn DM, Franceschi S, Herrero R, Castellsague X, Zhang Z, Lazarus P, Muscat J, McClean MD, Kelsey KT, Hayes RB, Purdue MP, Schwartz SM, Chen C, Benhamou S, Olshan AF, Schantz S, Ferro G, Brennan P, Boffetta P, Hashibe M. 2011. Vitamin or mineral supplement intake and the risk of head and neck cancer: pooled analysis in the INHANCE consortium. Int J Cancer. Published on-line December 15, 2011. PMCID: PMC3376697
  • Poage GM, Butler RA, Houseman EA, McClean MD, Nelson H, Christensen B, Marsit CJ, Kelsey KT. 2012. Identification of an epigenetic profile classifier derived from the local DNA sequence context that is associated with head and neck cancer survival. Cancer Res. 72(11): 2728-37.
  • Chuang S, Jenab M, Heck JE, Bosetti C, Talamini R, Matsuo K, Castellsague X, Franceschi S, Herrero R, Winn DM, La Vecchia C, Morgenstern H, Zhang Z, Levi F, Dal Maso L, Kelsey K, McClean MD, Vaughan T, Lazarus P, Muscat J, Ramroth H, Chen C, Schwartz S, Eluf-Neto J, Hayes RB, Purdue M, Boccia S, Nicolotti N, Zaridze D, Koifman S, Curado MP, Ahrens W, Benhamou S, Matos E, Lagiou P, Szeszenia-Dabrowska N, Olshan AF, Fernandez L, Menezes A, Agudo A, Daudt AW, Merletti F, Macfarlane GJ, Kjaerheim K, Mates D, Holcatova I, Schantz S, Yu G, Simonato L, Brenner H, Muller H, Conway D, Thomson P, Fabianova E, Znaor A, Rudnai P, Healy C, Ferro G, Brennan P, Boffetta P, Hashibe M. 2012. Diet and the risk of head and neck cancer: A pooled analysis in the INHANCE consortium. Cancer Cause Control. 23: 69–88.
  • Anderson KS, Wong J, D’Souza G, Riemer A, Lorch J, Haddad R, Pai S, Longtine J, McClean MD, LaBaer J, Kelsey KT, Posner M. 2011. Serum antibodies to the HPV16 proteome as biomarkers for head and neck cancer. British Journal of Cancer. 104(12): 1896-905. PMCID: PMC3111202
  • Chen D, Truong T, Gaborieau V, Byrnes G, Chabrier A, Chuang S, Olshan AF, Weissler MC, Luo J, Romkes M, Buch S, Nukui T, Franceschi S, Herrero R, Talamini R, Kelsey KT, Christensen B, McClean MD, Lacko M, Manni JJ, Peters WHM, Lubiński J, Trubicka J, Lener M, Muscat JE, Lazarus P, Wei Q, Sturgis EM, Zhang Z, Chang S, Wang R, Schwartz SM, Chen C, Benhamou S, Lagiou P, Holcátová I, Richiardi L, Kjaerheim K, Agudo A, Castellsagué X, Macfarlane TV, Barzan L, Canova C, Thakker NS, Conway DI, Znaor A, Healy CM, Ahrens W, Zaridze D, Szeszenia-Dabrowska N, Lissowska J, Fabianova E, Bucur A, Bencko V, Foretova L, Janout V, Curado MP, Koifman S, Menezes A, Wünsch-Filho V, Neto JE, Fernandez L, Boccia S, Hashibe M, Hayes RB, Boffetta P, Brennan P, McKay JD. 2011. A sex-specific association between a 15q25 variant and upper aerodigestive tract cancers. Cancer Epidemiol Biomarkers Prev. 20(4): 658-64. PMCID: PMC3070066
  • Lubin JH, Muscat J, Gaudet MM, Olshan AF, Curado MP, Dal Maso L, Wünsch-Filho V, Sturgis EM, Szeszenia-Dabrowska N, Castellsague X, Zhang ZF, Smith E, Fernandez L, Matos E, Franceschi S, Fabianova E, Rudnai P, Purdue MP, Mates D, Wei Q, Herrero R, Kelsey K, Morgenstern H, Shangina O, Koifman S, Lissowska J, Levi F, Daudt AW, Neto JE, Chen C, Lazarus P, Winn D, Schwartz SM, Boffetta P, Brennan P, Menezes A, La Vecchia C, McClean MD, Talamini R, Hayes RB, Hashibe M. 2011. An examination of male and female odds ratios by BMI, cigarette smoking, and alcohol consumption for cancers of the oral cavity, pharynx, and larynx in pooled data from 15 case-control studies. Cancer Cause Control. 22(9): 1217-31.
  • McKay JD, Truong T, Gaborieau V, ChabrierA, Chuang S, Byrnes G, Zaridze D, Shangina O, Szeszenia Dabrowska N, Lissowska J, Rudnai P, Fabianova E, Bucur A, Bencko V, Holcatova I, Janout V, Foretova L, Lagiou P, Trichopoulos D, Benhamou S, Bouchardy C, Ahrens W, Merletti F, Richiardi L, Talamini R, Barzan L, Kjaerheim K, Macfarlane GJ, Macfarlane TV, Simonato L, Canova C, Agudo A, Castellsagué X, Lowry R, Conway DI, McKinney PA, Healy CM, Toner ME, Znaor A, Curado MP, Koifman S, Menezes A, Wünsch-Filho V, Neto JE, Fernandez L, Boccia S, Cadoni G, Arzani D, Olshen AF, Weissler MC, Funkhouser WK, Luo J, Lubiński J, Trubicka J, Lener M, Oszutowska D, Schwartz SM, Chen C, Fish S, Doody DR, Muscat JE, Lazarus P, Gallagher CJ, Chang S, Greenland S, Zhang Z, Wei Q, Sturgis EM, Wang L, Franceschi S, Herrero R, Kelsey KT, McClean MD, Marsit C, Nelson H, Romkes M, Buch S, Nukui T, Zhong S, Lacko M, Manni JJ, Peters WHM, Hung RJ, McLaughlin J, Vatten L, Njølstad I, Goodman G, Field JK, Liloglou T, Vineis P, Clavel-Chapelon F, Palli D, Tumino R, Krogh V, Panico S, González CA, Quirós JR, Martínez C, Navarro C, Ardanaz E, Larrañaga N, Khaw KT, Key T, Bueno-de-Mesquita HB, Peeters PHM, Trichopoulou A, Linseisen J, Boeing H, Hallmans G, Overvad K, Tjønneland A, Kumle M, Riboli E, Välk K, Voodern T, Metspalu A, Zelenika D, Boland A, Delepine M, Foglio M, Lechner D, Blanche H, Gut I, Galan P, Heath S, Hashibe M, Hayes RB, Boffetta P, Lathrop M, Brennan P. 2011. A genome-wide association study of upper aerodigestive tract cancers conducted within the INHANCE consortium. PloS Genet. 7(3): e1001333. PMCID: PMC3060072
  • Poage GM, Houseman EA, Christensen BC, Butler R, Avissar-Whiting M, McClean MD, Waterboer T, Pawlita M, Marsit CJ, Kelsey KT. 2011. Global hypomethylation identifies loci targeted for hypermethylation in head and neck cancer. Clin Cancer Res. 17(11): 3579-89. PMCID: PMC3107873
  • Liang C, Pawlita M, Marsit CJ, Smith JF, Bryan JT, Nelson HH, Waterboer T, McClean MD, Kelsey KT. 2010. Comparison of Antibodies to HPV16 early genes with antibodies to L1 and PCR detection of HPV16 in tumor DNA in Head and Neck Cancer: exposure and survival. American Society of Clinical Oncology. June 4-8. Chicago, IL.
  • Anderson KS, Wong J, Posner MR, Lorch J, McClean MD, Kelsey KT. 2010. Proteome-wide Detection of Antibodies to the HPV16 in Head and Neck Cancer Patient Sera. American Society of Clinical Oncology. June 4-8. Chicago, IL.
  • Galeone C, Tavani A, Claudio P, Turati F, Winn D, Levi F, Morgenstern H, Kelsey K, Dal Maso L, Purdue MP, McClean MD, Talamini R, Hayes RB, Franceschi S, Schantz S, Zhang Z, Ferro G, Chuang S, Boffetta P, La Vecchia C, Hashibe M. 2010. Coffee and tea intake and risk of head and neck cancer: Pooled analysis in the International Head and Neck Cancer Epidemiology Consortium. Cancer Epidemiol Biomarkers Prev. 19(7): 1723-36. PMCID: PMC3047460.
  • Christensen BC, Avissar-Whiting M, Ouellet LG, Nelson HH, McClean MD, Marsit CJ, Kelsey KT. 2010. Mature miRNA sequence polymorphism in MIR196A2 is associated with risk and prognosis of head and neck cancer. Clin Cancer Res. 16(14): 3713-20. PMCID: PMC2914465.
  • Lubin JH, Gaudet MM, Olshan AF, Kelsey K, Boffetta P, Brennan P, Castellsague X, Chen C, Curado MP, Dal Maso L, Daudt AW, Fabianova E, Fernandez L, Wünsch-Filho V, Franceschi S, Herrero R, Koifman S, La Vecchia C, Lazarus P, Levi F, Lissowska J, Mates IN, Matos E, McClean MD, Menezes A, Morgenstern H, Muscat J, Neto JE, Purdue MP, Rudnai P, Schwartz SM, Shangina O, Sturgis EM, Szeszenia-Dabrowska N, Talamini R, Wei Q, Winn D, Zhang ZF, Hashibe M, Hayes RB. 2010. Body mass index, cigarette smoking and alcohol consumption and cancers of the oral cavity, pharynx and larynx: modeling odds ratios in pooled case-control data. Am J Epidemiol. 171(12): 1250-61. PMCID: PMC2915496.
  • Poage G, Christensen BC, Houseman EA, McClean MD, Wiencke JK, Posner MR, Clark J, Nelson HH, Marsit CJ, Kelsey KT. 2010. Genetic and epigenetic somatic alterations in head and neck squamous cell carcinomas are globally coordinated but not locally targeted. Plos ONE. 5(3): e9651. PMCID: PMC2836370.
  • Marron M, Boffetta P, Zhang Z, Zaridze D, Wünsch-Filho V, Winn DM, Wei Q, Talamini R, Szeszenia-Dabrowska N, Sturgis EM, Smith E, Schwartz SM, Rudnai P, Purdue M, Olshan AF, Eluf-Neto J, Muscat J, Menezes A, McClean M, Matos E, Mates D, Lissowska J, Levi F, Lazarus P, La Vecchia C, Koifman S, Kelsey KT, Herrero R, Hayes RB, Franceschi S, Fernandez L, Fabianova E, Daudt AW, Dal Maso L, Curado MP, Cadoni G, Chen C, Castellsague X, Boccia S, Benhamou S, Ferro G, Berthiller J, Brennan P, Møller H, Hashibe M. 2010. Cessation of alcohol drinking, tobacco smoking and the reversal of head and neck cancer risk. Int J Epidemiol. 39(1): 182-96. PMCID: PMC2817090.