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p53 over‐expression and p53 mutations in colon carcinomas: Relation to dietary risk factors
Author(s) -
Voskuil Dorien W.,
Kampman Ellen,
van Kraats Annemieke A.,
Balder Helena F.,
van Muijen Goos N.P.,
Goldbohm R. Alexandra,
van't Veer Pieter
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990531)81:5<675::aid-ijc1>3.0.co;2-6
Subject(s) - medicine , oncology , risk factor , colorectal cancer , mutation , cancer research , expression (computer science) , biology , genetics , cancer , gene , computer science , programming language
Epidemiological studies have suggested that dietary factors may differently affect p53‐dependent and p53‐independent pathways to colon cancer. Results of such studies may depend on the method used to assess p53 status. This case‐control study of 185 colon‐cancer cases and 259 controls examines this relation, using both immunohistochemistry and SSCP(exons 5–8)/sequencing to detect p53 abnormalities. Of 185 carcinomas analyzed using immunohistochemistry, 81 (44%) were categorized as p53 over‐expression. p53 mutations were detected in 59 tumors (32%). A slight increase in risk observed for intake of saturated fat was largely due to an increased risk in cases without p53 over‐expression (OR per 16.1 g/day, 1.46; 95% CI, 1.08–1.97), and no association in cases with p53 over‐expression (OR, 1.07, 95% CI, 0.78–1.47). However, findings were less pronounced when cases were classified by mutation analysis (wild‐type OR, 1.33; 95% CI, 1.01–1.75; mutated OR, 1.16; 95% CI, 0.81–1.65). Similar results were observed for total fat intake. For other nutrients and for vegetable and meat food groups no differences in risk for either p53 pathway were observed, independent of the laboratory technique used. Interestingly, in cases with transversion mutations in the p53 gene, an increased risk was observed for saturated fat (OR, 2.00; 95% CI, 0.97–4.14), in contrast to those with mutations at CpG sites (OR, 0.93; 95% CI, 0.55–1.57). An increase in colon‐cancer risk for the p53‐independent pathway due to fat intake, is more pronounced when using immunohistochemistry. However, mutation analysis is needed to study the possible association with a small group of tumors with transversion mutations. Int. J. Cancer 81:675–681, 1999. © 1999 Wiley‐Liss, Inc.