Summary
We have examined DNA restriction fragment length polymorphisms (RFLP) of the Ha-ras-1 gene in DNA from 118 lung cancer patients and 123 unaffected controls. When DNA samples were digested with MspI/ HpaII restriction endonucleases. Southern blot analysis demonstrated 4 common, 4 intermediate and 7 different rare alleles in the combined population after hybridization to the pGDa1 probe. Six of the rare alleles were unique for the lung cancer group and 1 rare allele for the control group. The frequency of rare alleles in lung cancer patients (10/236) was significantly different (P<0.01) from the control group (1/246). The lung cancer group also had a significantly lower frequency of the common 2.57 kb fragment than the controls (P<0.02). The results thus indicate that Ha-ras genotyping may be of value in lung cancer risk assessment.
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Ayesh R, Idle JR, Ritchie JC, Crothers MJ, Hetzel MR (1984) Metabolic oxidation phenotypes as markers for susceptibility to lung cancer. Nature 312:169–170
Baird M, Balazs I, Giusti A, Miyazaki L, Nicholas L, Wexler K, Kanter E, Glassberg J, Allen F, Rubinstein P, Sussman L (1986) Allele frequency distribution of two highly polymorphic DNA sequences in three ethnic groups and its application to the determination of paternity. Am J Hum Genet 39:489–501
Balazs I, Baird M, Clyne M, Meade E (1989) Human population genetic studies of five hypervariable DNA loci. Am J Hum Genet 44:182–190
Barbacid M (1987) Ras oncogenes. Annu Rev Biochem 56:779–827
Bos JL (1988) The ras gene family and human carcinogenesis. Mutat Res 195:255–271
Capon DJ, Chen EY, Levinson AD, Seeburg PH, Goeddel DV (1983) Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature 302:33–37
Corell B, Zoll B (1988) Comparison between the allelic frequency distribution of the Ha-ras-1 locus in normal individuals and patients with lymphoma, breast, and ovarian cancer. Hum Genet 79:255–259
Durante M, Geri C, Bonatti S, Parenti R (1989) Non-random alkylation of DNA sequences induced in vivo by chemical mutagens. Carcinogenesis 10:1357–1361
Gerhard DS, Dracopoli NC, Bale SJ, Houghton AN, Watkins P, Payne CE, Greene MH, Housman DE (1987) Evidence against Ha-ras1 involvement in sporadic and familial melanoma. Nature 325:73–75
Harris CC (1989) Interindividual variation among humans in carcinogen metabolism. DNA adduct formation and DNA repair. Carcinogenesis 10:1563–1566
Harris CC, Mulvihill JJ, Torgeirsson SS, Minna JD (1980) Individual differences in cancer susceptibility. Ann Intern Med 92:809–825
Hayward NK, Keegan R, Nancarrow DJ, Little MH, Smith PJ, Gardiner RA, Seymour GJ, Kidson C, Lavin MF (1988) c-Ha-ras-1 alleles in bladder cancer. Wilms' tumour and malignant melanoma. Hum Genet 78:115–120
Heighway J, Thatcher N, Cerny T, Hasleton PS (1986) Genetic predisposition to human lung cancer. Br J Cancer 53:453–457
Ishikawa J, Macda S, Takahashi R, Kamidono S, Sugiyama T (1987) Lack of correlation between rare Ha-ras alleles and urothelial cancer in Japan. Int J Cancer 40:474–478
Jeffreys AJ, Royle NJ, Wilson V, Wong Z (1988) Spontaneous mutation rates to new length alleles at tandem-repetitive hypervariable loci in human DNA. Nature 332:278–281
Krontiris TG, Dimartino NA, Colb M, Parkinson DR (1985) Unique allelic restriction fragments of the human Ha-ras locus in leukocyte and tumour DNAs of cancer patients. Nature 313:369–374
Krontiris TG, Dimartino NA, Colb M, Mitcheson D, Parkinson DR (1986) Human restriction fragment length polymorphisms and cancer risk assessment. J Cell Biochem 30:319–329
Krontiris TG, Dimartino NA, Mitcheson HD, Lonergan JA, Begg C, Parkinson DR (1987) Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients. Environ Health Perspect 76:147–153
Law MR, Hetzel MR, Idle JR (1989) Debrisoquine metabolism and genetic predisposition to lung cancer. Br J Cancer 59:686–687
Leder A, Pattengalc PK, Kuo A, Stewart TA, Leder P (1986) Consequences of widespread deregulation of the c-myc gene in transgenic mice: multiple neoplasms and normal development. Cell 45:485–495
Lidereau R, Escot C, Theillet C, Champeme MH, Brunet M, Gest J, Callahan R (1986) High frequency of rare alleles of the human c-Ha-ras-1 proto-oncogene in breast cancer patients. J Natl Cancer Inst 77:697–700
Ryan J, Barker PE, Nesbitt MN, Ruddle FH (1987) KRAS2 as a genetic marker for lung tumor susceptibility in inbred mice. J Natl Cancer Inst 79:1351–1356
Saglio G, Camaschella C, Giai M, Serra A, Guerrasio A, Peirone B, Gasparini P, Mazza U, Ceppellini R, Biglia N, Cortese P, Sismondi P (1988) Distribution of Ha-ras-1 protooncogene alleles in breast cancer patients and in a control population. Breast Cancer Res Treat 11:147–153
Samet J, Humble CG, Pathak DR (1986) Personal and family history of respiratory disease and king cancer risk. Am Rev Respir Dis 134:466–470
Sheng ZM, Guerin M, Gabillot M, Spielmann M, Riou G (1988) c-Ha-ras-1 polymorphism in human breast carcinomas: evidence for a normal distribution of alleles. Oncogene Res 2:245–250
Spandidos DA, Holmes L (1987) Transcriptional enhancer activity in the variable tandem repeat DNA sequence downstream of the human Ha-ras-1 gene. FEBS Lett 218:41–45
Sugimura H, Caporaso NE, Modali RV, Hoover RN, Resau JH, Trump BF, Lonergan JA, Krontiris TG, Mann DL, Weston A, Harris CC (1990) Association of rare alleles of the Harvey ras protooncogene locus with lung cancer. Cancer Res 50:1857–1862
Thein SL, Oscier DC, Flint J, Wainscoat JS (1986) Ha-ras hypervariable alleles in myelodysplasia. Nature 321:84–85
Weston A, Willey JC, Modali R, Sugimura H, McDowell EM, Resau J, Light B, Hangen A, Mann DL, Trump BF, Harris CC (1989) Differential DNA sequence deletions from chromosomes 3, 11, 13 and 17 in squamous-cell carcinoma, large-cell arcinoma, and adenocarcinoma of the human lung. Proc Natl Acad Sci USA 86:5099–5103
Wyllie FS, Wynford-Thomas V, Lemoine NR, Williams GT, Williams ED, Wynford-Thomas D (1988) Ha-ras restriction fragment length polymorphisms in colorectal cancer. Br J Cancer 57:135–138
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Ryberg, D., Tefre, T., Øvrebø, S. et al. Ha-ras-1 alleles in Norwegian lung cancer patients. Hum Genet 86, 40–44 (1990). https://doi.org/10.1007/BF00205169
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DOI: https://doi.org/10.1007/BF00205169