Analysis of a germ line polymorphism of the <i>p</i>53 gene in lung cancer patients; discrete results with smoking history

Murata, Motoi; Tagawa, Masatoshi; Kimura, Masaki; Kimura, Hideki; Watanabe, Satoshi; Saisho, Hiromitsu

doi:10.1093/carcin/17.2.261

Cited by 98 publications

(70 citation statements)

References 12 publications

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“…These changes in conjunction with certain environmental exposures (e.g., smoking, lung cancer) may increase the risk for cancer development in people with susceptible genotypes. However, these studies have been inconsistent, most likely because of a number of factors, including racial frequency differences between cases and controls, varied population bases, and lack of Hardy-Weinberg equilibrium in some examined cases (15)(16)(17)(18)(19)(20). In our opinion, these variables and others account for the discrepant results between independent studies examining the polymorphism of p53 at codon 72 and carcinogenesis.…”

Section: Discussionmentioning

confidence: 85%

Polymorphism at Codon 72 of p53 Is Not Associated with Cervical Cancer Risk

et al. 2000

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P53 allelic polymorphism at codon 72 has been studied as a possible predisposing factor for cervical carcinogenesis with inconsistent results. Storey and colleagues recently published the interesting finding of a 7-fold increased risk for cervical cancer in women homozygous for the arginine allele at codon 72. This stimulated a number of independent investigations, the majority of which found no association of cervical cancer and arginine homozygosity.With the use of a modified Storey method for determining codon 72 allelotypes, DNA was examined from 431 microdissected, formalin-fixed, archival cervical conization specimens ranging from low-grade squamous lesions to invasive cancer. An alternative independent method using restriction fragment length polymorphism analysis was performed on all arginine homozygotes and all indeterminate cases for confirmation and final allelotype assignment.With the use of Storey's method alone, logistic regression suggested an association (odds ratio, 1.42) between arginine homozygosity and invasive disease. However, with the use of the combined method for accurate allelotyping, this trend disappeared (odds ratio, 1.00), the discordance was clearly resolvable as being due to methodologic variables.With the use of two separate methods for codon 72 allelotyping and accounting for a number of the issues raised in previously published reports, there is no increased risk for invasive cervical cancer associated with arginine homozygosity at codon 72 of p53.KEY WORDS: Cervix, Neoplasia, p53, Papillomavirus, Polymorphism.Mod Pathol 2000;13(4):373-378Human papillomaviruses (HPVs) are epitheliotropic double-stranded DNA viruses that have been implicated in cervical carcinogenesis. More than 100 HPV genotypes have been identified. Traditionally, HPV genotypes, which are frequently identified in cervical neoplasms, have been segregated into those with a low risk and those with a high risk for malignant transformation. HPV types 6 and 11 are the prototypes of low-risk viruses that are most frequently found in low-grade squamous intraepithelial lesions (LSIL) and condylomata. HPV 16, 18, 31, and 45 account for approximately 80% of invasive cervical carcinomas, and the HPV 16 -related group is overrepresented in high-grade squamous intraepithelial lesions (HSIL) and squamous cancers compared with the HPV 18 -related viruses. The expression of HPV mRNA and proteins provides a coherent model for cervical carcinogenesis (1-3). Within the HPV genomes, the E6 and E7 genes are the driving forces behind epithelial proliferation and transformation. These transcribed genes are conserved and expressed within all HPV-infected pathologies. In many high-risk cervical dysplasias and invasive carcinomas, the E6 and E7 proteins are restrictively transcribed from the HPV genome integrated into the host DNA (4 -6). The link between oncogenesis and the transforming properties of HPV infection was identified by the interaction between these proteins and host cellular tumor suppressor gene products. Specifically, E7...

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Section: Discussionmentioning

confidence: 85%

Polymorphism at Codon 72 of p53 Is Not Associated with Cervical Cancer Risk

et al. 2000

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“…31 Polymorphisms in the intron 3, exon 4 (codon 72), and intron 6 of the gene have been evaluated in case-control studies for risk of various cancers, and the results have been mixed. [25][26][27][28][29][30][31][32] No functional significance of these polymorphisms is currently known. The hypothesized relationship of the codon 72 p53 polymorphism to cancer susceptibility does not yet have a mechanistic basis.…”

Section: Discussionmentioning

confidence: 99%

“…[25][26][27][28][29] For Japanese, risk increased approximately twofold for smoking-related lung cancer among individuals carrying the Pro/Pro genotype compared with those with other genotypes of the codon 72 p53 polymorphism. 25 Among blacks and Mexicans in the United States, the OR of lung cancer associated with the Pro/Pro genotype was significantly elevated only among younger patients and light smokers.…”

Section: Discussionmentioning

confidence: 99%

“…The functional significance of the variant is unknown, but the Pro variant allele of this p53 polymorphism has been studied as a potential risk factor for cancer of the lung, breast, and large bowel, with inconsistent results. [25][26][27][28][29][30][31][32] This study was performed to examine whether the p53 codon 72 polymorphism was associated with susceptibil-ity to HCC using a case-control study nested in a large cohort study of men with chronic HBV infection. Also evaluated were any interactions of the p53 polymorphism with putative HCC risk factors in hepatocarcinogenesis.…”

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confidence: 99%

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Ap53genetic polymorphism as a modulator of hepatocellular carcinoma risk in relation to chronic liver disease, familial tendency, and cigarette smoking in hepatitis B carriers

et al. 1999

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This study evaluated whether the codon 72 p53 polymorphism was related to hepatocellular carcinoma (HCC). Genotypes of p53 were determined in 80 incident cases of HCC and 328 controls nested in a cohort study of 4,841 male chronic hepatitis B carriers. No overall increase in HCC risk with the Pro variant allele of the p53 polymorphism was apparent. However, there were synergistic effects on HCC development for the Pro allele with chronic liver disease and family history of HCC in first-degree relatives. Compared with subjects without the Pro allele and chronic liver disease, the increase in HCC risk associated with chronic liver disease among those without the Pro allele was only threefold. Subjects with both chronic liver disease and the Pro allele were at an increased risk of 7.60 (95% CI ‫؍‬ 2.28-25.31). When subjects without family history of HCC and the Pro allele were considered as the reference group, there was no apparent increased risk of HCC for those without the Pro allele who had family history of HCC. Among those with both factors, there was a significantly increased risk of 3.29 (95% CI ‫؍‬ 1.10-9.85). Both cigarette smoking and glutathione S-transferase M1 genotype modified the risk of HCC associated with the p53 polymorphism. Significantly increased risk associated with the p53 genotype was observed only among smokers who were glutathione S-transferase-null (Pro/Pro vs. Arg/Arg: odds ratio ‫؍‬ 6.46; 95% CI ‫؍‬ 1.55-26.94). The p53 polymorphism also interacted with the cytochrome P450 1A1 and carotenoid levels in smoking-related hepatocarcinogenesis. (HEPATOLOGY 1999;29:697-702.) Chronic infection with hepatitis B virus (HBV) is the major cause of at least 80% of hepatocellular carcinoma (HCC) throughout the world. 1 However, only about one fifth of chronic HBV carriers develop HCC in their lifetime, 2 suggesting that there is interindividual variation in susceptibility to hepatocarcinogenesis.Both viral and chemical carcinogens are involved in the multistage process of human hepatocarcinogenesis.

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“…4 The Arg/Pro polymorphism occurs in a proline-rich domain and results in alteration of electrophoretic mobility of the protein. 5,6 The codon 72 polymorphism has also been shown to affect the behavior of certain p53 mutants and their potential of transforming cells.…”

Section: 2% P=003) Our Results Suggest Thatmentioning

confidence: 99%