Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women

Hirabayashi, Yoko; Sawada, Shunsuke; Nagata, K.; Sougawa, Mitsuharu; Ostapenko, Valentina V.; Ohnishi, T.

doi:10.3892/ijmm.7.3.261

Cited by 19 publications

(19 citation statements)

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“…A number of studies have been performed to examine the involvement of the p21/Waf1 codon 31 polymorphism Arg allele on cancer susceptibility. Approximately half of these studies support the idea that this polymorphism correlates with cancer risk (Facher et al, 1995;Mousses et al, 1995;Sjalander et al, 1996;Hachiya et al, 1999;Harima et al, 2001;Chen et al, 2002;Keshava et al, 2002;Huang et al, 2004) while others refute this claim (Gong et al, 1995;Li et al, 1995;Sun et al, 1995;Wan et al, 1996;Lukas et al, 1997;McKenzie et al, 1997;Konishi et al, 2000;Shih et al, 2000;Tsai et al, 2002a, b;Su et al, 2003a;Wu et al, 2004). Discrepancies among these studies may be explained by inadequate sample sizes or inclusion of different ethnic groups in single studies (Facher et al, 1995;Wu et al, 2004).…”

Section: Codon 31 Of P21/waf1mentioning

confidence: 71%

Polymorphisms in the p53 pathway

2006

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Section: Codon 31 Of P21/waf1mentioning

confidence: 71%

Polymorphisms in the p53 pathway

2006

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“…Tumorassociated mutation of the coding region of the WAF1 gene is rare, although it has been reported in a small number of patients with Burkitt's lymphoma [32], prostate cancer [33], and breast cancer [34]. We also detected the somatic mutation of the WAF1 gene in only 3% (2 of 66) patients with cervical cancer [35]. In addition, Shiohara et al [36] have reported that the absence of WAF1 alterations in a large series of 14 human malignancies, including cervical cancers, suggested that WAF1 mutations might not play an important role in either the onset or the progression of these malignancies.…”

Section: Fig 2 (A)mentioning

confidence: 75%

“…Primers used were pU-1M (5Ј-TGTCAAAAACC-GTTGTGTCC-3Ј) and pU-2R (5Ј-GAGCTGTC-GCTTAATTGCTC-3Ј) [19]. Primers pU-1M and pU-2R, corresponding to nucleotide positions 419-439 and 656-676 of HPV 16, can detect HPV types 16,18,31,33,35,52,56,58, and 59. The conditions for PCR amplification were as de-scribed [20].…”

Section: Detection and Typing Of Hpvmentioning

confidence: 99%

Chromosome 6p21.2, 18q21.2 and human papilloma virus (HPV) DNA can predict prognosis of cervical cancer after radiotherapy

Hirabayashi

Sawada

Nagata

et al. 2001

Intl Journal of Cancer

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SUMMARY Loss of heterozygosity (LOH) is one of the most important mechanisms for inactivation of tumor-suppressor genes. Studies of LOH in patients with cervical carcinoma have reported a high frequency of LOH on 3p21.3, 6p21.2, 17p13.1, and 18q21.2. Our study explored whether p53 status, human papilloma virus (HPV), and LOH on chromosome 3p21.3, 6p21.2, 17p13.1, and 18q21.2 are associated with treatment outcome in 65 patients with cervical cancer after radiotherapy. Tumors and normal DNA were analyzed by polymerase chain reaction (PCR) for genetic losses at 10 polymorphic microsatellite loci. The presence of HPV and its type were analyzed by PCR-based assay using the consensus primers for E6, E7, and L1 region. Mutations of the p53 gene were identified by a single-strand conformation polymorphism analysis. Chromosomes 3p21.3, 6p21.2, 17p13.1, and 18q21.2 were involved in the LOH in 23.1%, 41.5%%, 33.8%, and 23.1% of the tumors in our study, respectively. HPV-positive tumors were found in 73.8% of the patients and p53 mutation in 10.8%. The patients with LOH on chromosome 6p21.2 and 18q21.2 survived significantly shorter compared with those without LOH on chromosome 6p21.2 and 18q21.2 in both the overall survival (P = 0.006 and P = 0.007) and the disease-free survival (P = 0.005 and P = 0.008). The HPV-negative patients survived significantly shorter compared with the HPV-positive patients in both the overall survival (P = 0.01) and the disease-free survival (P = 0.04). According to multivariate analysis, HPV status (P = 0.0004, P = 0.01), LOH on 6p21.2 (P = 0.006, P = 0.02), and LOH on 18q21.2 (in both P = 0.01) is a significant predictor of both overall and disease-free survival time. The results of our study suggest that absence of HPV infection, LOH on 6p21.2, and LOH on 18q21.2 are the most important determinants of outcome of patients with cervical carcinoma after radiotherapy.

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“…[2][3][4][5][6][7]24 Considering polymorphisms, in general they have not been found associated with cancer risk or tumor behavior, except for p21 C93A which remains controversial. 6,[8][9][10][11][12][13][14][15][16]25 Interestingly, in a recent study we found the p21 G251A polymorphism, leading to an arginine to glutamine change of codon 84, to be associated with risk of developing locally advanced breast cancer but not to overall breast cancer risk. 18 An explanation could be that this change is not associated with tumor risk per se but eventually may cause an enhanced growth rate of established cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Case control studies on this variant has provided conflicting evidence, suggesting an association to risk of different cancer forms. [8][9][10][11][12][13][14][15][16] In contrast, the only p21B polymorphism previously identified is p21B T35C , 17 previously reported by us not to be associated with breast cancer risk. 18 We here present the results from screening of 521 breast tumor samples for somatic alterations in the p21 WAF1/CIP1 and p21B transcripts.…”

mentioning

confidence: 91%

Mutations and polymorphisms of the p21B transcript in breast cancer

Knappskog¹,

Chrisanthar²,

Staalesen³

et al. 2007

Intl Journal of Cancer

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p21 WAF1/CIP1 , transcribed from the CDKN1A locus, plays a key role executing p53-induced growth arrest. The recent discovery that an alternative transcript, p21B, induces apoptosis, suggests an additional important function of this gene. Here, we report p21 and p21B mutation status in large cohorts of breast cancers and compare distributions of p21B polymorphisms in cancer patients to healthy controls. In 521 breast tumor samples analyzed, only one point mutation affecting the p21B protein was observed. No mutations were found when screening a panel of 20 established cell lines. A novel polymorphism, p21B G128T was identified. Haplotype analysis revealed no association between this variant and the previously identified p21B polymorphism p21B T35C or any of the known p21 WAF1/CIP1 polymorphisms. As previously reported for p21B T35C , distribution of p21B G128T was similar among breast cancer patients and healthy controls (n 5 691 and 1,015; incidence 6.1 vs. 4.8%; p 5 0.273, respectively). No association between p21B G128T or p21B T35C and response to chemotherapy with an anthracycline-containing regimen or paclitaxel was recorded. Our findings do not suggest mutations or polymorphisms of p21B to play a major role with respect to either breast cancer risk or sensitivity towards chemotherapy. ' 2007 Wiley-Liss, Inc.Key words: p21; p21B; polymorphism; breast cancer p21B is a recently discovered protein translated from an alternative transcript of the CDKN1A gene, commonly known as the locus encoding p21 WAF1/CIP1 . Expression of p21B is driven by an independent promoter, and the processed transcript consists of a short first exon spliced to a longer exon harboring the p21B coding region. The promoter as well as the complete coding region of p21B is located within intron 1 of p21 WAF1/CIP1 , thus, the two proteins do not share any amino acid sequence. 1 Transcription of p21B, similar to transcription of p21 WAF1/CIP1 , is induced by p53. 1 However, while p21 WAF1/CIP1 is a mediator of cell cycle arrest through inhibition of the cyclin E-CDK2 complex, p21B has been linked to induction of apoptosis. 1 As a few studies have examined somatic mutations affecting p21 WAF1/CIP1 in human cancers, 2-7 no study has examined mutations affecting the p21B transcript. Several polymorphisms within the CDKN1A locus have been reported, the most prevalent being p21 C93A . Case control studies on this variant has provided conflicting evidence, suggesting an association to risk of different cancer forms. [8][9][10][11][12][13][14][15][16] In contrast, the only p21B polymorphism previously identified is p21B T35C , 17 previously reported by us not to be associated with breast cancer risk. 18 We here present the results from screening of 521 breast tumor samples for somatic alterations in the p21 WAF1/CIP1 and p21B transcripts. Further, we screened blood samples from an additional 170 breast cancer patients (132 patients with operable stage I and II breast cancers and 38 patients with stage III disease) together with samples from 1,015 ...

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Polymorphism of the WAF1 gene is related to susceptibility to cervical cancer in Japanese women

Cited by 19 publications

References 0 publications

Polymorphisms in the p53 pathway

Polymorphisms in the p53 pathway

Chromosome 6p21.2, 18q21.2 and human papilloma virus (HPV) DNA can predict prognosis of cervical cancer after radiotherapy

Mutations and polymorphisms of the p21B transcript in breast cancer

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