Evidence for Selective Expression of the p53 Codon 72 Polymorphs: Implications in Cancer Development

Abstract

Polymorphism at codon 72 of p53 results in either the arginine or proline form of p53, whose functional significance in carcinogenesis is controversial. We have investigated if the expression of these p53 polymorphs is selectively regulated, using mRNA from peripheral blood of healthy Asian (Chinese) and the Caucasian (Polish) arginine/proline (arg/pro) heterozygote subjects. Asians were found to preferentially express the pro allele whereas the Caucasians preferentially express the arg allele. On the contrary, about 75% of the heterozygote Chinese breast cancer patients preferentially expressed the arg allele, which rarely contained any somatic mutations. Moreover, histologically normal tissues from Chinese heterozygote breast cancer patients showed selective expression of the arg allele, in contrast to the preferential expression of the pro allele in heterozygote healthy normal breast tissues. Together, the data suggest that the expression of the different p53 polymorphs is selectively regulated in different ethnic populations, and that the arg allele is activated during cancer development in Asians. Thus, the expression status of the p53 polymorphs, rather than the genotypic status, might be a useful indicator for cancer susceptibility. (Cancer Epidemiol Biomarkers Prev 2005;14(9):2245 -52)

p.R72P, PIN3 Ins16bp Polymorphisms of TP53 and CCR5Δ32 in North Indian Breast Cancer Patients

“…Asians :http://dx.doi.org/10.7314/APJCP.2012.13.7.3305 pR72P, PIN3 Ins16bp Polymorphisms of TP53 and CCR5Δ32 in North Indian Breast Cancer Patients have been reported to express the Pro allele, whereas Caucasians preferentially express the Arg allele; however, ~75% of heterozygote Chinese breast cancer patients expressed the Arg allele (Siddique et al, 2005). In the present case control study, frequency of Pro allele of p.R72P polymorphism was 56.88% in patients and 46.25% in control individuals.…”

CCR5 and p53 codon 72 gene polymorphisms: Implications in breast cancer development

“…Analysis of the data from Siddique et al (5) suggests that the expression of different p53 polymorphisms is selectively regulated in different ethnic populations and that the ARG allele is activated during cancer development in Asians. Thus, the expression status of the p53 polymorphisms, rather than the genotypic status, might be a useful indicator for cancer susceptibility.…”

“…Siddique et al (5) verified that Asians were found to preferentially express the Pro allele, whereas Caucasians preferentially express the Arg allele; however, ~75% of heterozygote Chinese breast cancer patients preferentially expressed the Arg allele.…”

“…Analysis of data from Siddique et al (5) showed that selective pressure occurs against the expression of the codon 72 p53 Arg allele in the healthy Asian germ line arg/pro heterozygotes and provides insights into the uniqueness of population-based expression of the p53 tumor suppressor gene. It also showed a strong correlation between the expression of the p53 arg allele and susceptibility to breast cancer development.…”

TP53 Gene Polymorphisms in Cancer Risk: The Modulating Effect of Ageing, Ethnicity and TP53 Somatic Abnormalities

“…High Low -- (Gemignani et al, 2004;Nikbahkt Dastjerdi, 2011;Ribeiro et al, 1997;Siddique et al, 2005) Identical Capability to transactivation Low High ---- Thomas et al, 1999) cell cycle arrest Low High ---- Pim and Banks, 2004) senescence induction Low High ---- Salvioli et al, 2005) DNA repair Low High High Low High Low (Siddique and Sabapathy, 2006;Wu et al, 2002) genomic stability maintenance Low High --High Low Qiu et al, 2008;Schwartz et al, 2011;Siddique and Sabapathy, 2006) apoptosis activation in extrinsic pathway Low High High Low High Low (Bendesky et al, 2007;Biros et al, 2002;Bonafe et al, 2002;Dumont et al, 2003;Pim and Banks, 2004;Schneider-Stock et al, 2004b;Siddique and Sabapathy, 2006;Wu et al, 2002) in intrinsic pathway High Low suppression of transformed cell growth High Low ---- (Thomas et al, 1999) survival in hypoxia High Low ---- (Sansone et al, 2007;Vannini et al, 2008) (Jeong et al, 2010) reproduction High Low ---- Jeong et al, 2010;Kang et al, 2009;Kay et al, 2006) Moreover, the C allele was found to be increased in women with recurrent implantation failure and individuals undergoing in vitro fertilization (IVF), and is a risk factor for implantation failure after IVF (Kang et al, 2009;Kay et al, 2006). Interestingly, the frequency of the G allele has been positively correlated with low winter temperatures (Shi et al, 2009).…”