Abstract
There is increasing evidence that predisposition to some cancers has a genetic component. There is a high incidence of loss of heterozygosity on chromosome 9, in the region of tumour suppressor gene CDKN2A (also known as p16), in sporadic squamous cell cancer of the head and neck (SCCHN). To investigate the possibility that CDKN2A may be involved in the inherited susceptibility to SCCHN, the 3 coding exons of CDKN2A were sequenced in 40 patients who had developed a second primary cancer after an index squamous cell cancer of the head and neck. No mutations were found and we conclude that CDKN2A mutations do not play a major role in cancer susceptibility in this group. © 2001 Cancer Research Campaign www.bjcancer.com
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References
Bedi G, Westra W, Gabrielson E, Koch W and Sidransky D (1996) Multiple head and neck tumours: evidence for clonal origin. Cancer Res 56: 2484–2487
Bongers V, Braakhuis B, Tobi H, Lubson H and Snow GB (1996) The relation between cancer incidence among relatives and the occurrence of multiple primary carcinomas following head and neck cancer. Cancer Epidemiol Biomarker Prev 5: 595–598
Copper M, Jovanic A, Nauta JJ, Braakhuis BJM, de Vries N, van der Waal I and Snow GB (1995) Role of genetic factors in the aetiology of squamous cell carcinoma of the head and neck. Arch Otolaryngol Head Neck Surg 121: 157–160
Day GL and Blot WJ (1992) Second primary tumours in patients with oral cancer. Cancer 70: 14–19
Easton DF, Steele L, Fields P, Ormiston W, Averill D, Daly PA, McManus R, Neuhausen SL, Ford D, Wooster R, Cannon-Albright LA, Stratton MR and Goldgar DE (1997) Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12–13. Am J Hum Genet 61: 120–128
Franco EL, Kowalski LP and Kand JL (1991) Risk factors for second cancers of the upper respiratory and digestive systems: a case-control study. J Clin Epidemiol 44: 615–625
Foulkes WD, Brunet J-S, Kowalski LP, Narod SA and Franco EL (1995) Family history is a risk factor for squamous cell carcinoma of the head and neck in Brazil: a case-control study. Int J Cancer 63: 769–773
Foulkes WD, Brunet J-S, Sieh W, Black MJ, Shenouda G and Narod SA (1996) Familial risk of squamous cell carcinoma: a retrospective case-control study. BMJ 313: 716–721
Gallo O, Sardi I, Pepe G, Franchi A, Attanasio M, Giusti B, Bocciolini C and Abbate R (1999) Multiple primary tumours of the upper aerodigestive tract: is there a role for constitutional mutations in the p53 gene?. Int J Cancer 82: 180–186
Hamel N, Manning A, Black MJ, Tonin PN and Foulkes WD (1999) An absence of founder BRCA2 mutations in individuals with squamous cell carcinoma of the head and neck. Int J Cancer 83: 803–804
Hamoudi RA, De Schouwer PJ and Yuille MA (1998) Improved direct flourescent automated sequencing of PCR products. Trends Genet 1: 1–2
Harland M, Meloni R, Nelleke G, Pinney E, Brookes S, Spurr K, Frischauf A-M, Bataille V, Peters G, Cuzick J, Selby P, Bishop DT and Bishop JN (1997) Germline mutations of the CDKN2A gene in UK melanoma families. Human Molecular Genetics 6: 2061–2067
Harland M, Holland EA, Ghorizo P, Mantelli M, Bianchi-Scarra G, Goldstein AM, Tucker MA, Ponder BA, Mann GJ, Bishop DT and Bishop JN (2000) Mutation screening of the CDKN2A promoter in melanoma families. Genes Chromosomes Cancer 28: 45–57
Hong WK, Lippman SM, Itri LM, Karp DD, Lee JS and Byers RM (1990) Prevention of second primary tumours with isoretinionin squamous-cell carcinoma of the head and neck. New Eng J Med 323: 795–801
Hussussian CJ, Struewing JP, Goldstein AM, Higgins PA, Ally DS, Sheahan MD, Clark WH, Tucker MA and Dracopoli NC (1994) Germline p16 mutations in familial melanoma. Nature Genetics 8: 15–21
Kamb A, Gruis NA, Weaver-Feldhaus J, Liu Q, Harshman K, Tavtigian SV, Stockert E, Day RS 3rd, Johnson BE and Scolnick MH (1994a) A cell cycle regulator potentially involved in the genesis of many tumour types. Science 264: 436–437
Kamb A, Shattuck-Eidens D, Eeles R, Liu Q, Gruis NA, Ding W, Hussey C, Tran T, Miki Y and Weaver FELDHAUSet al (1994b) Analysis of the p16 gene as a candidate for the chromosome 9p melanoma susceptibility locus. Nat Genet 8: 22–26
Liu L, Dilworth D, Gao L, Monzon J, Summers A, Lassam N and Hogg D (1999) Mutation of the CDKN2A 5′ UTR creates an aberrant initiation codon and predisposes to melanoma. Nat Genetics 21: 128–132
Leong P, Banafsheh R, Koch W, Reed A, Eisele D, Lee DJ, Sidransky D, Jen J and Westra W (1998) Distinguishing second primary cancers from lung metastases in patients with head and neck cancer. J Natl Cancer Inst 90: 972–977
Lynch H, Fusaro R, Pester J, Oosterhuis J, Went L and Rumke P (1981) Tumour Spectrum in the FAMM syndrome. Br J Cancer 44: 553–560
Kunkel LM, Smith KD and Boyer SH (1977) Analysis of human Y-chromosome specific reiterated DNA in chromosome variants. Proc Natl Acad Sci 74: 1245–1249
Macfarlane G, Boyle P, Evstifeeva T, Robertson C and Scully C (1994) Rising trends of oral cancer mortality among males worldwide; the return of an old public health problem. Cancer Causes Control 5: 259–265
Maier H, Dietz A, Gewelke U and Heller WD (1991) Occupational exposure to hazardous substances and risk of cancer of the oral cavity, hypopharynx and larynx. Laryngol Rhinol Otol 70: 93–98
Maier H, Dietz A, Gewelke U, Heller WD and Weidauer H (1992) Tobacco, alcohol and the risk of head and neck cancer. Clin Invest 70: 320–327
Miller SA, Dykes DD and Polesky HF (1988) A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16: 1215
Miracca E, Kowalski L and Nagai M (1999) High prevalence of p16 genetic alterations in head and neck tumours. Br J Cancer 81, (4):677–683
Morita M, Kuwano H, Nakashima T, Taketomi A, Baba H, Saito T, Tomoda H, Egashir H, Kawaguchi H, Kitamura K and Sugimachi K (1998) Family aggregation of carcinoma of the hypopharynx and cervical oesophagus: special reference to multiplicity of cancer in the upper aerodigestive tract. Int J Cancer 76: 468–471
Muscat J and Wynder E (1992) Tobacco, alcohol, asbestos and occupational risk factors for laryngeal cancers. Cancer 69: 2244–2251
Parkin DM, Pisani P and Ferlay J (1995) Estimates of the world-wide incidence of eighteen major cancers in 1995. Int J Cancer 54: 594–606
Reed A, Califano J, Cairns P, Westra W, Jones R, Koch W, Ahrendt S, Eby Y, Sewell D, Nawroz H, Bartek J and Sidransky D (1996) High frequency of p16 inactivation in head and neck squamous cell carcinoma. Cancer Res 56: 3630–3633
Scholes A, Woolgar J, Boyle,, Brown JS, Vaughn ED, Hart CA, Jones AS and Field JK (1998) Synchronous oral cancer: independent or common clonal origin. Cancer Res 58: 2003–2006
Serrano M, Hannon G and Beach D (1993) A new regulatory motif in cell cycle control causing specific inhibition of cyclin D/CDK4. Nature 366: 704–707
Sun S, Pollock P, Liu L, Karimi S, Jothy S, Milner B, Renwick A, Lassam N, Hayward N, Hogg D, Narod S and Foulkes W (1997) CDKN2Amutation in a non-FAMM kindred with cancers at multiple sites results in a functionally abnormal protein. Int J Cancer 73: 531–536
Tonin PN, Mes-Masson AM, Futreal PA, Morgan K, Mahon M, Foulkes WD, Cole DE, Provencher D, Ghadirian P and Narod SA (1998) Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families. Am J Hum Genet 63: 1341–1351
Trizna Z and Schantz SP (1992) Hereditary and environmental factors associated with risk and progression of head and neck cancer. Otolaryngol Clin North Am 25: 1089–1103
Vokes EE, Weichselbaum RR, Lippman SM and Hong WK (1993) Head and Neck Cancer. N Eng J Med 328: 184–194
Wang Q, Lasset C, Sobol H and Ozturk M (1996) Evidence of a hereditary p53 syndrome in cancer-prone families. Int J Cancer 65: 554–557
Whelan A, Bartsch D and Goodfellow P (1995) Brief report: a familial syndrome of pancreatic cancer and melanoma of pancreatic cancer and melanoma with a mutation in the CDKN2 tumour-suppressor gene. N Engl J Med 333: 975–977
Worsham M, Wolman S, Carey T, Zarbo RJ, Benninger MS and Van Dyke DL (1995) Common clonal origin of synchronous primary head and neck squamous cell carcinomas: analysis by tumour karyotype and FISH. Hum Pathol 26: 251–261
Yarborough W, Aprelikova O, Pei H, Olshan A and Liu E (1996) Familial Tumour Syndrome Associated With a Germline Nonfunctional p16INK4a Allele. JNCI 88, (20):1489–1491
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Guys and St Thomas’ and Kings Hospital Trusts
Mount Vernon Hospital Trust, Rickmansworth Road, Northwood, Middlesex, HA6 2RN
Mid-Kent Oncology Centre, Hermitage Lane, Maidstone, Kent, ME16 9QQ
Queen Victoria Hospital, East Grinstead
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Jefferies, S., Edwards, S., Hamoudi, R. et al. No germline mutations in CDKN2A (p16) in patients with squamous cell cancer of the head and neck and second primary tumours. Br J Cancer 85, 1383–1386 (2001). https://doi.org/10.1054/bjoc.2001.2068
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DOI: https://doi.org/10.1054/bjoc.2001.2068
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