P53 codon 72 polymorphism in a taiwanese lung cancer population: Correlation with lung cancer susceptibility and prognosis

Wang, Yi‐Ching; Chen, Shin-Kuang; Lee, Hong-Shen; Chen, Chih-Yi

doi:10.1016/s0378-4274(98)80355-x

Cited by 74 publications

(97 citation statements)

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“…In some studies cancer population comprised patients eligible for surgical treatment (Stages I and II) excluding patients with more advanced tumours (Fan et al, 2000), whereas all of our cases were inoperable lung cancers (Stages IIIb and IV). Additionally, in studies involving advanced tumours, statistical analysis did not reveal any association of p53Pro with lung carcinogenesis (Wang et al, 1999). Moreover, variations in protocols among laboratories, or poor selection of the control group (Makni et al, 2000), could also explain the above mentioned discrepancies.…”

Section: Discussionmentioning

confidence: 93%

“…Several groups confirmed the original finding (Makni et al, 2000;Zehbe et al, 2001), some have shown that the association between p53 Arg/Arg genotype and cancer is unrelated to HPV , while others failed to find an association between p53Arg and cancer (Hamel et al, 2000;Tenti et al, 2000). In lung cancer, several studies found no correlation with p53 codon 72 polymorphism (Birgander et al, 1995;Pierce et al, 2000), while others have found an association with the Pro allele (Kawajiri et al, 1993;Wang et al, 1999;Fan et al, 2000). However, in tumours with loss of heterozygosity (LOH) at the TP53 locus, the Pro allele is preferentially deleted in germline Arg/Pro heterozygotes Kawaguchi et al, 2000;Furihata et al, 2002).…”

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confidence: 99%

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Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes

2002

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The association of p53 codon 72 polymorphism with cancer has been investigated by several scientific groups with controversial results. In the present study, we examined the genotypic frequency of this polymorphism in 54 patients with advanced lung cancer and 99 normal controls from the geographical region of Greece. Sputum and bronchial washing samples from each patient were assayed for the presence of human papillomavirus. Codon 72 heterozygous (Arg/Pro) patients were also analysed for loss of heterozygosity at the TP53 locus, in order to determine the lost p53 allele (Arg or Pro). p53 Arg/Arg genotype was significantly increased in lung cancer patients compared to normal controls (50% vs 24.2%, P50.002). Human papillomavirus was detected only in two patients (3.7%). Loss of heterozygosity at the TP53 locus was found in 14 out of 27 Arg/Pro patients (51.85%). The Pro allele was lost in 11 cases (78.6%), while the Arg allele was lost in three (21.4%). Our results suggest that p53 codon 72 Arg homozygosity is associated with advanced lung cancer, and that the Arg allele is preferentially retained in patients heterozygous for this polymorphism. On the other hand, human papillomavirus infection does not seem to play an important role in lung carcinogenesis.

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Section: Discussionmentioning

confidence: 93%

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confidence: 99%

Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes

2002

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“…The Arg72 variant induces apoptosis more effectively than does the Pro72 variant (3). In smokers, several studies have suggested an increased risk of lung cancer associated with the Pro/Pro genotype (4,5). In contrast, Arg/Arg homozygotes are frequently found in non-smoking patients with lung cancer (5,6).…”

Section: Introductionmentioning

confidence: 99%

p53 codon 72 polymorphism, loss of heterozygosity and high-risk human papillomavirus infection in a low-incidence German esophageal squamous cell carcinoma patient cohort

Pantelis

Pantelis²,

Ruemmele³

et al. 2007

Oncol Rep

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Abstract. Epidemiological studies in endemic geographic regions for esophageal squamous cell carcinoma (ESCC) suggested a number of risk factors, including modifications of the p53 tumor suppressor by codon Arg72Pro polymorphism, loss of heterozygosity (LOH) or human papillomavirus type 16 or 18 (HPV 16/18) infection. The p53 Arg72 variant has been suggested to be a high-risk factor in HPV-associated tumors. The present study analysed these associations in a low incidence geographic region in Germany. Fifty-three paraffinembedded tumors and 53 surrounding normal squamous epithelium were investigated. For detection of p53 codon Arg72Pro polymorphism, direct sequencing for exon 4 was conducted. LOH analysis was performed using three microsatellite markers at the p53 gene locus, and all cases were screened for high-risk HPV infection (HPV 16 and 18) with primer specific PCR and confirmed by sequencing. The p53 codon 72 genotype distribution was identical to published studies of normal Caucasian population, suggesting no general influence of this polymorphism on esophageal cancer risk in Germany. One case showed a p53 mutation in exon 4. p53 LOH was found in 13/44 (30%) informative cases without any correlation to histopathological characteristics. Of 53 (17%) samples, 9 showed HPV 16 or 18 infection. We found no association between p53 codon 72 genotypes and increasing HPV infection rates. Interestingly, 8/9 HPV-positive cases showed at least one p53 Arg72 allele. These results indicate an important role of p53 in ESCC also in low-incidence regions. In combination with the p53 Arg72 variant HPV infection could contribute to the risk of ESCC development in these cases, as has been demonstrated for high-risk regions. IntroductionEsophageal squamous cell carcinoma (ESCC) is one of the six most common malignant diseases in the world with a remarkable geographical distribution (1). Environmental exposures such as tobacco, alcohol, chronic mucosal irritation and ethnic background increase the risk of developing ESCC (2). Moreover, genetic changes affecting the p53 tumor suppressor such as different mutations, loss of heterozygosity (LOH) and high-risk human papillomavirus (HPV) infection are important for carcinogenesis in the esophagus. The p53 gene has a common sequence polymorphism resulting in either proline (CCC) or arginine (CGC) at amino-acid position 72. This polymorphism occurs in the proline-rich domain of the protein, which is necessary to induce apoptosis. The Arg72 variant induces apoptosis more effectively than does the Pro72 variant (3). In smokers, several studies have suggested an increased risk of lung cancer associated with the Pro/Pro genotype (4,5). In contrast, Arg/Arg homozygotes are frequently found in non-smoking patients with lung cancer (5,6).Allelic deletions detected as LOH have been proved useful for mapping regions of DNA that contain tumor suppressor genes (7). Cancer lesions show a high frequency of LOH in the p53 tumor suppressor gene locus on chromosome 17p13.1 measured by repetitive DN...

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“…Lung cancer patients with the Pro/Pro genotype, especially those who were smokers, were more likely to develop lung cancer than those with other genotypes (13,14). On the contrary, non-smokers with lung cancer have an increased frequency of the homozygous Arg genotype (15).…”

Section: Introductionmentioning

confidence: 99%

“…The two alleles of p53 differ biologically. p53Arg induces 5-10 times more apoptosis than p53Pro, which is explained in part by a higher ability of p53Arg to localize to the mitochondria (12).Lung cancer patients with the Pro/Pro genotype, especially those who were smokers, were more likely to develop lung cancer than those with other genotypes (13,14). On the contrary, non-smokers with lung cancer have an increased frequency of the homozygous Arg genotype (15).…”

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p53 codon 72 polymorphisms and random amplified polymorphic DNA analysis of non-melanoma skin cancer through archival formalin-fixed paraffin-embedded tissue

et al. 2011

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Abstract. Non-melanoma skin cancer (NMSC) is classified among the ten most frequent cancers in Malaysia. A common polymorphism at codon 72 of the p53 tumor suppressor gene and its influence on cancer risk has been studied for different types of cancer with mixed and inconsistent results with limited published data on the Malaysian population so far. In the present study, the frequency of p53 codon 72 polymorphism in 60 patients with NMSC was investigated from archival formalin-fixed paraffin-embedded (FFPE) tissue obtained from Hospital Universiti Kebangsaan Malaysia (HUKM). Additionally, random amplified polymorhic DNA -polymorphic chain reaction (RAPD-PCR) was employed for preliminary biomarker development. NMSC FFPE samples (70%) possess Arg/Arg, 20% with Pro/Pro and 10% with Arg/ Pro. In total, there was no significant difference in the p53 codon 72 genotypes between histological types of NMSC, gender, race, tumor location and age group. However, there was an apparent age-associated increase in the Arg/Arg genotype but did not reach statistical significance (P= 0.235). NMSC types and demographic characteristics did not influence genotype distribution. On the other hand, BCC and SCC distributions are influenced by age group, race and tumor location. IntroductionNon-melanoma skin cancer (NMSC) is the most common type of cancer among different populations worldwide.Consisting of two histological types i.e. basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), the BCC accounts for 80% and SCC for the rest (1). Regardless of its low clinical aggressiveness, due to its frequency and cost of treatment, it is a heavy public health burden (2). In Malaysia, official statistics rank NMSC among the ten most common types of cancer in adults (3). Exposure to sun is considered the main causative agent for NMSC (4). However, it cannot account for all of NMSC etiology since other physical and chemical agents, such as ionizing radiation, arsenic and coal tar products, as well as suppression of immune system in transplant patients, are verified causes of NMSC (5). Furthermore, genetic polymorphism is proposed to modify the risk of the disease (6).The p53 tumor suppressor protein plays an essential part in maintaining cellular integrity and tissue homeostasis through its ability to orchestrate the transcriptional activation of other genes (7). A critical region of p53 for signaling apoptosis lies between codons 64 and 92, encoding a proline-rich region of the gene homologous to an SH3 binding domain (8-10) in which there is a common polymorphism resulting in either an arginine (CGC) or a proline (CCC) at codon 72 of exon 4. This is a non-conservative amino acid change and results in a structural change in the protein as the p53Pro variant migrates more slowly than the p53Arg variant in sodium dodecyl sulfatepolyacrylamide gel electrophoresis (11). The two alleles of p53 differ biologically. p53Arg induces 5-10 times more apoptosis than p53Pro, which is explained in part by a higher ability of p53Arg to localize to the m...

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P53 codon 72 polymorphism in a taiwanese lung cancer population: Correlation with lung cancer susceptibility and prognosis

Cited by 74 publications

References 0 publications

Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes

Association of p53 codon 72 polymorphism with advanced lung cancer: the Arg allele is preferentially retained in tumours arising in Arg/Pro germline heterozygotes

p53 codon 72 polymorphism, loss of heterozygosity and high-risk human papillomavirus infection in a low-incidence German esophageal squamous cell carcinoma patient cohort

p53 codon 72 polymorphisms and random amplified polymorphic DNA analysis of non-melanoma skin cancer through archival formalin-fixed paraffin-embedded tissue

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