Abstract
Purpose: We investigated the prevalence of single nucleotide polymorphisms in the p16 gene (C540G) and the cyclin D1 gene (G870A), both known to regulate function in G1 arrest and therefore, may play an important role in carcinogenesis. Methods: Using PCR based restriction fragment length polymorphism and single strand conformational polymorphism, we determined single nucleotide exchanges in the p16 and cyclin D1 genes among 56 esophageal adenocarcinomas (ADC) arising in Barrett’s esophagus, 95 cardiac gastric ADC, and in 191 distal gastric ADC. The allelic frequencies were compared to a control group of 253 healthy blood donors. Results: The C/G genotype of p16 was identified in 10.4% of esophageal carcinomas, 13.3% of cardiac carcinomas, and in 14.1% of gastric carcinomas, compared to 17.4% in the healthy control group. All other cases showed the C/C wildtype, as no homozygous G/G nucleotide exchange was detected in the group of cancer patients or in the control group. In esophageal cancer, cyclin D1 G/G genotype was found 28.6%, A/G in 46.4%, and A/A in 25.0%. In cardiac carcinoma, frequency of cyclin D1 genotype was 27.4% for G/G, 57.9% for A/G, and 14.7% for AA. In distal gastric carcinoma, both homozygous genotypes (G/G and A/A) had a frequency of 15.2% each, while the heterozygous A/G genotype occurred in 69.6% of patients. The control group displayed 24.9% G/G, 53.8% A/G, and 21.3% A/A genotype. Conclusions: Our results show that frequencies of p16 or cyclin D1 polymorphisms in gastric and esophageal ADC do not differ significantly from the healthy control group. Therefore, these polymorphisms are unlikely to be associated with risk of ADC of the upper gastrointestinal tract.
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References
Agresti A (1996) An introduction to categorical data analysis. Wiley, New York
Betticher DC, Thatcher N, Altermatt HJ et al (1995) Alternate splicing produces a novel cyclin D1 transcript. Oncogene 11:1005–1011
Falk GW (2002) Barrett’s oesophagus (review). Gastroenterology 122:1569–1591
Haggitt RC (1994) Barrett’s esophagus, dysplasia, and adenocarcinoma. Hum Pathol 25:982–993
Hamilton SR, Aaltonen LA (eds) (2000) World Health Organisation. Classification of tumours. Pathology and genetics of tumours of the digestive system. IARC Press, Lyon
Hemminki K, Forsti A (2002) Proper controls for SNP studies? Carcinogenesis 23:1405
Ito M, Habuchi T, Watanabe J et al (2004) Polymorphism within the cyclin D1 gene is associated with an increased risk of carcinoma in situ in patients with superficial bladder cancer. Urology 64:74–78
Kumar R, Lundh Rozell B, Louhelainen J et al (1998) Mutations in the CDKN2A (p16INK4a) gene in microdissected sporadic primary melanomas. Int J Cancer 75:193–198
Lanzafame S, Torrisi A, Favara C et al (2001) Correlation between intestinal metaplasia of the gastric cardia and gastroesophageal reflux disease. Hepatogastroenterology 48:1007–1010
Le Marchand L, Seifried A, Lum-Jones A et al (2003) Association of the cyclin D1 A870G polymorphism with advanced colorectal cancer. JAMA 290:2843–2848
Lin J, Beerm DG (2004) Molecular biology of upper gastrointestinal malignancies (review). Semin Oncol 31:476–486
Ohata H, Kitauchi S, Yoshimura N et al (2004) Progression of chronic atrophic gastritis associated with Helicobacter pylori infection increases risk of gastric cancer. Int J Cancer 109:138–143
Qiuling S, Yuxin Z, Suhua Z et al (2003) Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population. Carcinogenesis 24:1499–1503
Ruas M, Peters G (1998) The p16INK4a/CDKN2A tumor suppressor and its relatives (review). Biochim Biophys Acta 1378:F115–F177
Sakano S, Berggren P, Kumar R et al (2003) Clinical course of bladder neoplasms and single nucleotide polymorphisms in the CDKN2A gene. Int J Cancer 104:98–103
SAS Institute Inc (2004) SAS/STAT User’s Guide, Version 9.1. SAS Institute Inc., Cary, NC
Sauroja I, Smeds J, Vlaykova T et al (2000) Analysis of G(1)/S checkpoint regulators in metastatic melanoma. Genes Chromosomes Cancer 28:404–414
Siewert JR, Stein H (1998) Classification of adenocarcinoma of the esophago–gastric junction. Br J Cancer 85:1457–1459
Tajima Y, Nakanishi Y, Yoshino T et al (2001) Clinico-pathological study of early adenocarcinoma of the gastric cardia: comparison with early adenocarcinoma of the distal stomach and esophagus. Oncology 61:1–9
Yu C, Lu W, Tan W et al (2003) Lack of association between CCND1 G870A polymorphism and risk of esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 12:176
Zhang J, Li Y, Wang R et al (2003) Association of cyclin D1 (G870A) polymorphism with susceptibility to esophageal and gastric cardiac carcinoma in a northern Chinese population. Int J Cancer 105:281–284
Zheng Y, Shen H, Sturgis EM et al (2001) Cyclin D1 polymorphism and risk for squamous cell carcinoma of the head and neck: a case–control study. Carcinogenesis 22:1195–1199
Zheng Y, Shen H, Sturgis EM et al (2002) Haplotypes of two variants in p16 (CDKN2/MTS-1/INK4a) exon 3 and risk of squamous cell carcinoma of the head and neck: a case–control study. Cancer Epidemiol Biomarkers Prev 11:640–645
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The excellent technical assistance of Mrs. H. Huss, Mrs. C. Pawlik, and Mrs. B. Marhuhn-Debowski is greatly appreciated.
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Geddert, H., Kiel, S., Zotz, R.B. et al. Polymorphism of p16 INK4A and cyclin D1 in adenocarcinomas of the upper gastrointestinal tract. J Cancer Res Clin Oncol 131, 803–808 (2005). https://doi.org/10.1007/s00432-005-0021-4
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DOI: https://doi.org/10.1007/s00432-005-0021-4