UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma

Allal Ouhtit, Hisayoshi Nakazawa, Bruce K. Armstrong, Anne Kricker, Ernest Tan, Hiroshi Yamasaki, Dallas R. English

Research output: Contribution to journalArticle

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Abstract

Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG → AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure. Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site. Conclusions: Our results indicate that tandem CC → TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV- radiation exposure.

Original languageEnglish
Pages (from-to)523-531
Number of pages9
JournalJournal of the National Cancer Institute
Volume90
Issue number7
Publication statusPublished - Apr 1 1998

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Basal Cell Carcinoma
Solar System
Mutation Rate
Radiation
Skin
Mutation
p53 Genes
Codon
Odds Ratio
Confidence Intervals
Skin Neoplasms
Tumor Suppressor Genes
Case-Control Studies
Neoplasms
Carcinogenesis
Biopsy
Polymerase Chain Reaction
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ouhtit, A., Nakazawa, H., Armstrong, B. K., Kricker, A., Tan, E., Yamasaki, H., & English, D. R. (1998). UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma. Journal of the National Cancer Institute, 90(7), 523-531.

UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma. / Ouhtit, Allal; Nakazawa, Hisayoshi; Armstrong, Bruce K.; Kricker, Anne; Tan, Ernest; Yamasaki, Hiroshi; English, Dallas R.

In: Journal of the National Cancer Institute, Vol. 90, No. 7, 01.04.1998, p. 523-531.

Research output: Contribution to journalArticle

Ouhtit, A, Nakazawa, H, Armstrong, BK, Kricker, A, Tan, E, Yamasaki, H & English, DR 1998, 'UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma', Journal of the National Cancer Institute, vol. 90, no. 7, pp. 523-531.
Ouhtit A, Nakazawa H, Armstrong BK, Kricker A, Tan E, Yamasaki H et al. UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma. Journal of the National Cancer Institute. 1998 Apr 1;90(7):523-531.
Ouhtit, Allal ; Nakazawa, Hisayoshi ; Armstrong, Bruce K. ; Kricker, Anne ; Tan, Ernest ; Yamasaki, Hiroshi ; English, Dallas R. / UV-radiation-specific p53 mutation frequency in normal skin as a predictor of risk of basal cell carcinoma. In: Journal of the National Cancer Institute. 1998 ; Vol. 90, No. 7. pp. 523-531.
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abstract = "Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG → AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure. Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95{\%} confidence intervals (95{\%} CIs). Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95{\%} CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site. Conclusions: Our results indicate that tandem CC → TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV- radiation exposure.",
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AU - Tan, Ernest

AU - Yamasaki, Hiroshi

AU - English, Dallas R.

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N2 - Background: A strong association has been found between skin cancer and exposure to UV radiation. The p53 tumor suppressor gene (also known as TP53), which is frequently mutated in human cancers, is believed to be an early target in UV radiation-associated skin carcinogenesis. We have previously developed a sensitive, polymerase chain reaction-based method capable of detecting and quantifying a UV radiation-specific mutation in the p53 gene (codons 247 and 248: AAC CGG → AAT TGG) in normal skin. We have used this method to examine whether UV radiation-specific mutation frequency is associated with risk of basal cell carcinoma (BCC) and with sun exposure. Methods: This case-control study in Australia involved 53 case subjects with BCC and 75 control subjects. DNA was isolated from normal skin (mirror-image anatomic site to the cancer site for case subjects and a randomly selected site for control subjects) and assayed for p53 mutation. Relationships between p53 mutation frequency and risk of BCC, sun sensitivity, or sun exposure were estimated by use of odds ratios (ORs) and 95% confidence intervals (95% CIs). Results: Case subjects were more likely to have a p53 mutation than control subjects (OR = 3.1; 95% CI = 1.3-7.1). In addition, the odds of BCC increased monotonically with increasing frequency of p53 mutation. No statistically significant associations could be demonstrated between p53 mutation frequency and age, sex, sensitivity to the sun, pigmentary characteristics, total lifetime sun exposure, or sun exposure to the biopsy site. Conclusions: Our results indicate that tandem CC → TT mutations involving codons 247 and 248 of the p53 gene are associated with an increased risk of BCC but cannot be used as an accurate measure of total UV- radiation exposure.

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