TY - JOUR
T1 - p53 Codon 72 Arg Homozygotes Are Associated with an Increased Risk of Cutaneous Melanoma
AU - Shen, Hongbing
AU - Liu, Zhensheng
AU - Strom, Sara S.
AU - Spitz, Margaret R.
AU - Lee, Jeffrey E.
AU - Gershenwald, Jeffrey E.
AU - Ross, Merrick I.
AU - Mansfield, Paul F.
AU - Duvic, Madeleine
AU - Ananthaswamy, Honnavara N.
AU - Wei, Qingyi
N1 - Funding Information:
We thank David Galloway for his scientific editing, Ms. Margaret Lung for her assistance in recruiting patients, and Ms. Joanne Sider for manuscript preparation. This work was supported by National Cancer Institute grants CA 70334 and National Institute of Environmental Health grant ES 11740 to Q.W., CA 46523 to H.N.A., and CA 16672 to the M. D. Anderson Cancer Center.
PY - 2003/12
Y1 - 2003/12
N2 - The p53 gene plays an important role in cell cycle control, facilitating DNA repair activities in response to DNA damage. Aberrant cell cycle control impairs DNA repair and increases the probability of mutations that can lead to carcinogenesis. The p53 gene is polymorphic at codon 72 (Arg/Pro) of its protein, which is functionally distinct, leading to inquiry into its role in carcinogenesis. In this hospital-based case-control study of 289 newly diagnosed patients with melanoma and 308 cancer-free control subjects, we evaluated whether the p53 codon 72 variant is associated with risk of cutaneous melanoma (CM). The controls were frequency-matched to the cases by age, sex, and ethnicity. The frequency of the p53 Arg allele was 78.2% in cases and 73.2% in controls (p = 0.045), and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 62.6%, 31.1%, and 6.3%, respectively, in the cases, and 53.9%, 38.6%, and 7.5%, respectively, in the controls (p = 0.096). Logistic regression analysis revealed that the p53 Arg/Arg genotype was associated with a significantly increased risk of melanoma (adjusted odds ratio (OR) = 1.43; 95% confidence interval (CI) = 1.02-2.02) compared with other genotypes, and this association was more evident in subgroups of older subjects (OR = 2.32; 95% CI = 1.39-388), and subjects with Fitzpatrick's skin type III or IV (OR = 1.69; 95% CI = 1.11-2.59). In conclusion, this study found some evidence that in subjects over 50, p53 Arg/Arg genotype is associated with increased risk of CM as compared to geno-types Arg/Pro or Pro/Pro. Further larger studies are needed to substantiate our findings.
AB - The p53 gene plays an important role in cell cycle control, facilitating DNA repair activities in response to DNA damage. Aberrant cell cycle control impairs DNA repair and increases the probability of mutations that can lead to carcinogenesis. The p53 gene is polymorphic at codon 72 (Arg/Pro) of its protein, which is functionally distinct, leading to inquiry into its role in carcinogenesis. In this hospital-based case-control study of 289 newly diagnosed patients with melanoma and 308 cancer-free control subjects, we evaluated whether the p53 codon 72 variant is associated with risk of cutaneous melanoma (CM). The controls were frequency-matched to the cases by age, sex, and ethnicity. The frequency of the p53 Arg allele was 78.2% in cases and 73.2% in controls (p = 0.045), and the genotype frequencies of p53 Arg/Arg, Arg/Pro, and Pro/Pro were 62.6%, 31.1%, and 6.3%, respectively, in the cases, and 53.9%, 38.6%, and 7.5%, respectively, in the controls (p = 0.096). Logistic regression analysis revealed that the p53 Arg/Arg genotype was associated with a significantly increased risk of melanoma (adjusted odds ratio (OR) = 1.43; 95% confidence interval (CI) = 1.02-2.02) compared with other genotypes, and this association was more evident in subgroups of older subjects (OR = 2.32; 95% CI = 1.39-388), and subjects with Fitzpatrick's skin type III or IV (OR = 1.69; 95% CI = 1.11-2.59). In conclusion, this study found some evidence that in subjects over 50, p53 Arg/Arg genotype is associated with increased risk of CM as compared to geno-types Arg/Pro or Pro/Pro. Further larger studies are needed to substantiate our findings.
KW - Cell cycle
KW - Genetic susceptibility
KW - Molecular epidemiology
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U2 - 10.1046/j.1523-1747.2003.12648.x
DO - 10.1046/j.1523-1747.2003.12648.x
M3 - Article
C2 - 14675203
AN - SCOPUS:10744225403
SN - 0022-202X
VL - 121
SP - 1510
EP - 1514
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
IS - 6
ER -