p14ARF genetic polymorphisms and susceptibility to second primary malignancy in patients with index squamous cell carcinoma of the head and neck

BACKGROUND:

p14^ARF, an alternate reading frame (ARF) product of the cyclin‐dependent kinase inhibitor 2A locus, plays a critical role in crosstalk between the tumor protein 53 (p53) and retinoblastoma (Rb) pathways and in cellular anticancer mechanisms. Therefore, the authors of this report investigated the association between single nucleotide polymorphisms (SNPs) of the p14^ARF gene and the risk of developing a second primary malignancy (SPM) after an index squamous cell carcinoma of the head and neck (SCCHN).

METHODS:

The log‐rank test and Cox proportional hazards models were used to assess the association of 2 p14^ARF SNPs (reference SNP [rs]3731217 and rs3088440) with SPM‐free survival and with the risk of developing an SPM among 1287 patients who had SCCHN.

RESULTS:

Patients with either p14^ARF variant genotypes of the 2 polymorphisms had a significantly reduced SPM‐free survival compared with patients with no variant genotypes (log‐rank test; P = .006). Compared with the p14^ARF thymine‐thymine (TT) and guanine‐guanine (GG) genotypes, the variant genotypes of p14^ARF TG/GG and guanine‐adenine (GA)/AA were associated with a significantly moderately increased risk of developing an SPM (p14^ARF rs3731217: adjusted hazard ratio [aHR], 1.48; 95% confidence interval [CI], 1.00‐2.19; p14^ARF rs3088440: aHR, 1.61; 95% CI, 1.07‐2.43). Moreover, after combining the variant genotypes of the 2 SNPs, patients who had variant genotypes were at significantly greater risk of developing an SPM compared with patients who had no variant genotypes (aHR, 3.07; 95% CI, 1.54‐6.12), and the risk was particularly pronounced in several subgroups.

CONCLUSIONS:

The current results suggested that there is a modestly increased risk of developing an SPM after an index SCCHN with each p14^ARF polymorphism, and there is an even greater risk of developing an SPM for patients with combined variant genotypes of the 2 SNPs. Therefore, p14^ARF polymorphisms may be susceptible markers of the risk of developing an SPM in patients with SCCHN. Cancer 2011. © 2010 American Cancer Society.     

p73 G4C14‐to‐A4T14 polymorphism and risk of second primary malignancy after index squamous cell carcinoma of head and neck

P73 plays an important role in modulating cell‐cycle control, inducing apoptosis, and inhibiting cell growth. A novel noncoding p73 G4C14‐to‐A4T14 exon 2 polymorphism was associated with risk of squamous cell carcinoma of the head and neck (SCCHN). We hypothesized that p73 G4C14‐to‐A4T14 polymorphism modulates risk of second primary malignancies (SPM) in patients after index SCCHN. We followed a cohort of 1,384 patients diagnosed with incident SCCHN between May 1995 and January 2007 for SPM development. Log‐rank test and Cox proportional hazard models were used to compare SPM‐free survival and SPM risk between the different genotype groups. Our results showed that patients carrying the p73 variant AT allele were less likely to develop SPM compared with the patients with p73 GC/GC genotype (Log‐rank test, p = 0.013). Compared with the p73 GC/GC genotype, there was a significantly reduced risk of SPM associated with the p73 GC/AT genotype (HR, 0.61, 95% CI, 0.40–0.93) and the combined p73 GC/AT+AT/AT genotypes (HR, 0.59, 95% CI, 0.39–0.89), but a nonsignificantly reduced risk for p73 AT/AT genotype (HR, 0.44, 95% CI, 0.14–1.41). The p73 AT allele was significantly associated with risk of SPM in an allele dose‐response manner (p = 0.011 for trend). The risk of SPM associated with p73 variant genotypes (GC/AT+AT/AT) was more pronounced in several subgroups (e.g., older patients, men, minorities, ever smokers, and ever drinkers). Our results support that this p73 polymorphism may be a marker for risk of SPM among patients with an incident SCCHN. © 2009 UICC     

p73 G4C14-to-A4T14 polymorphism and risk of human papillomavirus-associated squamous cell carcinoma of the oropharynx in never smokers and never drinkers

BACKGROUND.

The p53 tumor suppressor protein homolog p73 can be inactivated by oncoprotein E6 of human papillomavirus (HPV). Variation in p73 may alter the interaction between the E6 protein and p73 and, thus, alter the risk for HPV‐associated carcinogenesis. It is believed that the p73 G4C14‐to‐A4T14 polymorphism affects p73 function by altering gene expression; however, whether that polymorphism also alters the risk of HPV type 16 (HPV‐16)‐associated squamous cell carcinoma of the oropharynx (SCCOP) is unknown.

METHODS.

The current case‐control study included a case group of 188 non‐Hispanic white patients with newly diagnosed SCCOP and a control group of 349 healthy individuals. Logistic regression analyses were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for cases and controls stratified by p73 genotype, age, sex, smoking status, alcohol use, and HPV‐16 status. The effects of p73 genotypes on the risk of HPV‐16‐associated SCCOP were explored with further stratification by smoking and drinking status.

RESULTS.

HPV‐16 seropositivity was associated with an increased risk of SCCOP (adjusted OR, 5.98; 95% CI, 3.89‐9.20), especially among never smokers (adjusted OR, 13.8; 95% CI, 5.91‐32.1), never drinkers (adjusted OR, 14.9; 95% CI, 5.24‐42.4), and individuals with p73 variant genotypes (GC/AT and AT/AT; adjusted OR, 7.96; 95% CI, 3.83‐16.5). Moreover, the risk of HPV‐16‐associated SCCOP for individuals who had p73 variant genotypes was particularly high in never smokers and never drinkers.

CONCLUSIONS.

The p73 G4C14‐to‐A4T14 polymorphism may modulate the risk of HPV‐16‐associated SCCOP, and the p73 variant genotypes may be markers of genetic susceptibility to HPV‐16‐associated SCCOP, particularly in never smokers and never drinkers. Cancer 2008. © 2008 American Cancer Society.     

The p73 G4C14‐to‐A4T14 polymorphism is associated with risk of lung cancer in the Han nationality of North China

p73, a structural and functional homolog of p53, plays an important role in tumor carcinogenesis. Previous studies have suggested that the association between the p73 G4C14‐to‐A4T14 polymorphism and the risk of lung cancer, but the results have not been entirely consistent. We examined whether the p73 G4C14‐to‐A4T14 polymorphism was related to the risk of developing lung cancer in a Chinese population. The p73 G4C14‐to‐A4T14 polymorphism was genotyped in 293 lung cancer patients and 380 cancer‐free controls of Han nationality in North China using PCR‐RFLP. Multivariate logistic regression analysis was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). We observed that compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly increased susceptibility to lung cancer (OR, 1.48; 95% CI, 1.08–2.02; P = 0.014). In addition, compared with the GC/GC genotype, the GC/AT genotype was also significantly associated with increased susceptibility to lung cancer (OR, 1.46; 95% CI, 1.06–2.02; P = 0.046). Our findings suggest that the p73 G4C14‐to‐A4T14 polymorphism contributes to the risk of developing lung cancer in Chinese population. © 2012 Wiley Periodicals, Inc.     

Association of a p73 exon 2 G4C14-to-A4T14 polymorphism with risk of squamous cell carcinoma of the head and neck

p73, a novel p53 homolog, has some p53-like activity and plays an important role in modulating cell-cycle control, apoptosis and cell growth. p73 regulates differentiation of head and neck squamous epithelium, and changes in p73 may lead to the development of squamous cell carcinoma of the head and neck (SCCHN). Two linked non-coding exon 2 polymorphisms (designated as G4C14-to-A4T14) were identified recently but their functional relevance is unknown. We hypothesized that this p73 polymorphism plays a role in the etiology of SCCHN. Therefore, in this hospital-based case-control study of 708 patients newly diagnosed with SCCHN and 1229 cancer-free controls, we evaluated the association between the p73 AT variant allele and risk of SCCHN. The controls were frequency-matched to the cases by age (+/-5 years), sex and smoking status, and all subjects were non-Hispanic whites. Our results showed that the frequencies of variant AT allele and genotypes were more common in the cases than in the controls (P = 0.029 and P = 0.009, respectively). Compared with the GC/GC genotype, the variant genotypes (GC/AT + AT/AT) were associated with a statistically significantly increased risk for SCCHN [odds ratio (OR) = 1.33, 95% confidence interval (CI) = 1.10-1.60]. Further stratification analyses by age, sex, smoking and alcohol status and by cancer sites within the head and neck region indicated that this significantly increased risk was more pronounced in younger (< or =50 years) individuals (adjusted OR = 1.70; 95% CI, 1.19-2.43), women (1.61; 1.09-2.37), current smokers (1.77; 1.25-2.51) and patients with oral cancer (1.54; 1.15-2.07). Our results suggest that this p73 polymorphism may be a risk marker for genetic susceptibility to SCCHN.     

Combined effects of the p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer in never-smokers

Because p53 and p73 are associated with critical cellular processes and can be inactivated or degraded by the human papillomavirus (HPV) E6 oncoprotein, we investigated the combined effects of p53 codon 72 and p73 G4C14-to-A4T14 polymorphisms on the risk of HPV16-associated oral cancer. We analyzed genotype data from 326 patients with squamous cell carcinoma of the oral cavity or oropharynx and 349 cancer-free controls. We found that HPV16 seropositivity was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.42; 95% confidence interval (CI), 2.28-5.13], especially among never-smokers (adjusted OR, 8.20; 95% CI, 3.66-18.4) and subjects with variant genotypes [adjusted OR for p53 Arg/Pro + Pro/Pro (Pro carriers), 5.00; 95% CI, 2.72-9.21; adjusted OR for p73 GC/AT + AT/AT (AT carriers), 3.83; 95% CI, 1.98-7.41]. HPV16 seropositivity was also associated with an significantly increased risk of oral cancer in all three risk groups with combined genotypes [adjusted ORs (95% CIs) were 2.28 (1.15-4.54) for p53 Arg/Arg and p73 GC/GC, the low-risk group; 3.97 (2.14-7.36) for p53 Arg/Arg and p73 AT carriers or p53 Pro carriers and p73 GC/GC, the medium-risk group and 5.11 (2.00-13.0) for p53 Pro carriers and p73 AT carriers, the high-risk group]. Moreover, HPV16-seropositive never-smokers in the high-risk group exhibited an approximately 11-fold greater risk of oral cancer (adjusted OR, 11.3; 95% CI, 1.22-106.0) than did HPV16-seronegative never-smokers in the low-risk group. These findings suggest that the combined variants of p53 and p73 significantly increase the risk of HPV16-associated oral cancer, especially among never-smokers.     

Polymorphisms at p53, p73, and MDM2 loci modulate the risk of tobacco associated leukoplakia and oral cancer

Polymorphisms at loci controlling cellular processes such as cell cycle, DNA repair, and apoptosis may modulate the risk of cancer. We examined the association of two linked polymorphisms (G4C14–A4T14) at p73 and one polymorphism (309G > T) at MDM2 promoter with the risk of leukoplakia and oral cancer. The p73 and MDM2 genotypes were determined in 197 leukoplakia patients, 310 oral cancer patients and in 348 healthy control subjects. The p73 GC/AT genotype increased the risk of leukoplakia (OR = 1.6, 95% CI = 1.1–2.3) and oral cancer (OR = 2.4, 95% CI = 1.7–3.3) but the 309G > T MDM2 polymorphism independently could not modify the risk of any of the diseases. Stratification of the study population into subgroups with different tobacco habits showed that the risk of the oral cancer is not modified further for the individuals carrying p73 risk genotype. However, leukoplakia patients with smokeless tobacco habit showed increased risk with combined GC/AT and AT/AT (OR = 3.0, 95% CI = 1.3–7.0) genotypes. A combined analysis was done with our previous published data on p53 codon 72 pro/arg polymorphism. Analysis of pair wise genotype combinations revealed increase in risk for specific p73‐MDM2 and p73‐p53 genotype combinations. Finally, the combined three loci analyses revealed that the presence of at least one risk allele at all three loci increases the risk of both leukoplakia and oral cancer. © 2009 Wiley‐Liss, Inc.     

A possible primary cause of cancer: deficient cellular interactions in endocrine pancreas

Background

Cell cycle deregulation is common in human cancer, and alterations of p27 and p21, two critical cell cycle regulators, have been implicated in the development of many human malignancies. Therefore, we hypothesize that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms modifies risk of second primary malignancy (SPM) in patients with index squamous cell carcinoma of head and neck (SCCHN).

Methods

A cohort of 1,292 patients with index SCCHN was recruited between May 1995 and January 2007 at the M.D. Anderson Cancer Center and followed for SPM occurrence. Patients were genotyped for the three polymorphisms. A log-rank test and Cox proportional hazards models were used to compare SPM-free survival and SPM risk.

Results

We found that patients with p27 109 TG/GG, p21 98 CA/AA and p21 70 CT/TT variant genotypes had a worse SPM-free survival and an increased SPM risk than those with the corresponding p27109 TT, p21 98 CC, and p21 70 CC common genotypes, respectively. After combining the three polymorphisms, there was a trend for significantly increased SPM risk with increasing number of the variant genotypes (P _trend = 0.0002). Moreover, patients with the variant genotypes had an approximately 2.4-fold significantly increased risk for SPM compared with those with no variant genotypes (HR, 2.4, 95% CI, 1.6-3.6).

Conclusions

These results suggest that p27 T109G polymorphism individually or in combination with p21 (C98A and C70T) polymorphisms increases risk of SPM in patients with index SCCHN.     

Modifying effect of MDM4 variants on risk of HPV16-associated squamous cell carcinoma of oropharynx

BACKGROUND:

The p53 pathway plays a critical role in maintaining genomic stability and preventing tumor formation. Given the roles of both MDM4 and HPV16 E6 oncoproteins in inhibition of p53 activity, we tested the hypothesis that MDM4 polymorphisms are associated with the risk of HPV16‐associated squamous cell carcinoma of head and neck (SCCHN).

METHODS:

Genotyping was conducted on 3 tagging single nucleotide polymorphisms (rs11801299 G>A, rs10900598 G>T, and rs1380576 C>G) in MDM4, and serology was used to determine HPV 16 exposure in 380 cases and 335 cancer‐free controls that were frequency‐matched by age, sex, smoking, and drinking status.

RESULTS:

None of 3 MDM4 polymorphisms alone was significantly associated with risk of overall SCCHN. With further analysis stratified by HPV16 serology and tumor site, we found that each polymorphism individually modified the risk of HPV16‐associated squamous cell carcinoma of the oropharynx (SCCOP), and such effect modification was particularly pronounced in never smokers and never drinkers.

CONCLUSION:

The risk of HPV16‐associated SCCOP could be modified by MDM4 polymorphisms. Large and prospective studies are needed to validate our findings. Cancer 2011;. © 2011 American Cancer Society.     

Loss of MTBP expression is associated with reduced survival in a biomarker-defined subset of patients with squamous cell carcinoma of the head and neck

BACKGROUND:

Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta‐analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous.

METHODS:

The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses.

RESULTS:

Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2‐low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log‐rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12‐2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log‐rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39‐5.54) in p53 + ve/MDM2‐low patients.

CONCLUSIONS:

These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status‐dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression. Cancer 2011. © 2011 American Cancer Society.     

A case-control study on the combined effects of p 53 and p 73 polymorphisms on head and neck cancer risk in an Italian population

Background  

The purpose of this study is to analyze the combined effects of selected p 53 and p 73 polymorphisms and their interaction with lifestyle habits on squamous cell carcinoma of the head and neck (SCCHN) risk and progression in an Italian population.     

Combined p53-related genetic variants together with HPV infection increase oral cancer risk

To explore the role of polymorphisms of p53-related genes in etiology of oral cancer, we investigated joint effects of seven putatively functional polymorphisms of p53 (codon 72 Arg/Pro), p73 (4/14 GC/AT), murine double minute 2 gene (MDM2; A2164G and T2580G) and MDM4 (rs11801299 G > A, rs10900598 G > T and rs1380576 C > G) on risk of human papillomavirus (HPV)16-associated oral cancer in a case-control study with 325 cases and 335 cancer-free controls. We found that HPV16 seropositivity alone was associated with an increased risk of oral cancer [adjusted odds ratio (OR), 3.1; 95% confidence interval (CI), 2.1-4.6]. After combining genotypes of seven polymorphisms and using the low-risk group (0-3 combined risk genotypes) and HPV16 seronegativity as the reference group, the medium-risk (4 combined risk genotypes) and high-risk groups (5-7 combined risk genotypes) and HPV16 seronegativity were associated with only an OR of 1.6 (95% CI, 1.1-2.5) and 1.2 (95% CI, 0.7-1.9) for oral cancer risk, respectively, whereas the low-risk, medium-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.1 (95% CI, 1.2-3.6), 4.0 (95% CI, 1.8-9.1) and 19.1 (95% CI, 5.7-64.2), respectively. Notably, such effect modification by these combined risk genotypes was particularly pronounced in young subjects (aged < 50 years), never smokers and patients with oropharyngeal cancer. Taken together, these findings suggest that the combined risk genotypes of p53-related genes may modify risk of HPV16-associated oral cancer, especially in young patients, never-smokers and patients with oropharyngeal cancer. Larger studies are needed to validate our findings.     

Association between a p73 Gene Polymorphism and Genetic Susceptibility to Non-small Cell Lung Cancer in the South of China

Background: This study aimed to identify any association between the p73 gene G4C14-to-A4T14 polymorphismand risk of non-small cell lung cancer (NSCLC) in the south of China. Materials and Methods: We genotypedthe p73 gene polymorphism of peripheral blood DNA from 168 patients with NSCLC and 195 normal controlsusing HRM (high resolution melting) and PCR-CTPP (polymerase chain reaction with confronting two-pairprimers). Results: The results of genotyping by HRM and PCR-CTPP were consistent with direct sequencing,the p73 genotype distribution in 168 lung cancer patients being as follows: GC/GC 101 cases (60.1%), GC/AT 59 cases (35.1%), AT/AT 8 cases (4.8%). The carriers of AT/AT genotype had a significantly reduced riskof NSCLC (OR=0.370; 95%CI: 0.170-0.806; p=0.010) as compared with non-carriers. However, we found norelations between p73 genotypes and histological type (p=0.798, x2=0.452), tumor stage (p=0.806, x2=0.806), orlymph node metastasis (p=0.578, x2=1.098). Conclusions: Our findings suggest that the p73 G4C14-to-A4T14polymorphism may be a modifier of NSCLC susceptibility in the Chinese population.     

Polymorphisms in the p63 and p73 genes are associated with ovarian cancer risk and clinicopathological variables

Objective

p73 and p63 are two structural and functional homologs of p53, and their biological functions in cancer progression have attracted attention due to the presence of variants generated by genetic polymorphisms. Recently, three single nucleotide polymorphisms (SNPs) in the p63 and p73 genes have been associated with female reproduction. In the present study, we aimed to evaluate the relationship between these SNPs and ovarian cancer susceptibility and clinical pathology.

Methods

We genotyped the p63 (rs873330 [Genbank, refSNP ID] T > C [T: original base, C: mutant base]) and p73 (rs4648551 G > A and rs6695978 G > A) SNPs in ovarian cancers and healthy controls and analyzed the distributions of genotype frequencies to evaluate the association of the genotypes with the risk of ovarian cancer and the clinicopathological characteristics. Logistic regression models were applied in statistical analyses.

Results

Our research revealed that p73 rs6695978 G > A was significantly associated with ovarian cancer patients. Women with the A allele were at increased risk of ovarian cancer compared to carriers of the G allele (OR = 1.55; 95% CI:1.07–2.19; P = 0.003). Meanwhile, the at-risk A allele was positively related with the occurrence of mucinous ovarian cancer (OR = 3.48; 95% CI:1.15-6.83; P = 0.001), low degree of differentiation (OR = 1.87; 95% CI:1.03-3.47; P = 0.003), lymph node metastasis (OR = 1.69; 95% CI: 1.14-2.75; P = 0.010) and estrogen receptor positive (OR = 2.72; 95% CI: 1.38-4.81; P = 0.002). However, we were unable to find any associations of the polymorphisms in another two SNPs (rs4648551 G > A, rs873330 T > C) with ovarian cancer risk and clinicopathological parameters.

Conclusions

The p73 rs6695978 G > A polymorphism will serve as a modifier of ovarian cancer susceptibility and prognosis. Further investigations with large sample sizes and of the mechanistic relevance of p73 polymorphism will be warranted     

p73基因多态性与食管癌、贲门癌遗传易感性的关系

背景与目的:p73作为一种抑癌基因,其第二外显子非编码区存在两个单核苷酸多态性(G4C14-A4T14),可以形成茎环结构而影响基因表达。本研究旨在探讨河北省食管癌高发区人群中这两个连锁多态性与食管癌、贲门癌易感性的关系。方法:采用病例-对照研究,以聚合酶链反应-限制性片段长度多态性方法,分析348例食管癌患者、259例贲门癌患者和630例健康对照者的p73基因多态性。结果:具有上消化道肿瘤家族史可明显增加食管癌和贲门癌的发病风险,经性别、年龄和吸烟状况校正的OR值分别1.68(95%CI=1.28～2.20)和1.68(95%CI=1.24～2.26)。p73G4C14-A4T14基因型及等位基因型在食管癌患者、贲门癌患者和健康对照中总体分布差异无显著性。在根据吸烟状况和上消化道肿瘤家族史进行分层分析,发现在无上消化道肿瘤家族史亚组中,携带GC/AT基因型明显增加贲门癌的发病风险(OR=1.71,95%CI=1.14～2.57),而其他亚组中未见p73G4C14-A4T14多态性增加食管癌、贲门癌的发病风险。结论:p73G4C14-A4T14多态性中,携带GC/AT基因型明显增加河北省食管癌高发区无上消化道肿瘤家族史人群贲门癌的发病风险。     

晚期非小细胞肺癌对铂类药物的化疗敏感性与p53和p73基因多态的关系

目的探讨细胞凋亡相关基因p53和p73的遗传多态,与晚期非小细胞肺癌（NSCLC）对铂类药物化疗敏感性的关系。方法以聚合酶链反应（PCR）-限制性片段长度多态性（RFLP）和突变扩增阻抑系统（ARMS）分析方法,对165例以顺铂（DDP）或卡铂（CBP）为主进行化疗的晚期NSCLC患者,进行p53第72密码子Arg→Pro多态,和p73第2外显子G4C14-A4T14多态的检测,2～3个疗程后进行效果评价。以非条件Logistic回归模型比较不同基因型与化疗疗效的关系。结果携带p53 72Pro等位基因患者的化疗敏感性,是携带p53 72Arg／Arg基因型患者的2、46倍（95％CI,1．11～5．45,P=0．026）;而携带至少1个p73突变等位基因（A4T14）的患者,其化疗敏感性是携带p73 G4C14／G4C14基因型患者的2．22倍（95％讲,1．14～4、30,P=0．019）。2个多态位点合并分析结果显示,同时携带p53和p73野生基因型的患者,化疗有效率为7．7％;而携带1个、2个和≥3个p53和p73变异等位基因的患者,化疗有效率分别为34．8％、42．2％和40、7％。结论p53和p73基因遗传多态与晚期NSCLC患者对以铂类药物为主的化疗敏感性有关。     

p73基因多态性与乳腺癌遗传易感性的关系

  目的  探讨p73基因G4C14-A4T14多态性与中国重庆地区汉族女性乳腺癌遗传易感性的关系。  方法  采用病例对照研究, 利用Sequenom Mass Array?iPLEX GOLD系统对170例乳腺癌患者和178例健康者对照的p73基因G4C14-A4T14单核苷酸多态性进行了检测, 并对检测结果进行t检验、χ2检验和非条件Logistic回归分析。  结果  p73基因G4C14-A4T14多态基因型和等位基因型在乳腺癌组和对照组的分布频率差异无统计学意义(χ2=2.750, P=0.253;χ2=2.195, P=0.138);与携带GC/AT和AT/AT基因型的个体比较, 携带GC/GC基因型的个体患三阴性乳腺癌发病风险显著增加(OR=2.992, 95%CI: 1.300~6.890, P=0.010)。  结论  p73基因G4C14-A4T14多态性与中国重庆地区汉族女性三阴性乳腺癌的发病风险相关, GC/GC基因型是中国重庆地区汉族女性三阴性乳腺癌的易感基因型; 携带GC/GC基因型的乳腺癌可能预后不良。      

Association of the p73 Gene G4C14-to-A4T14 Polymorphism with Increased Gastric Cancer Risk in a Northwestern Chinese Population

OBJECTIVE To evaluate the p73 gene G4C14-to-A4T14 double nucleotide polymorphism with both increased gastric cancer(GC) risk and different histological subtypes of GC in a northwestern Chinese population. METHODS Genotyping of the polymorphism of the p73 gene was conducted with PCR-CTPP. RESULTS All 385 GC patients including 305 diffuse-type and 80 intestinal-type cases and 412 healthy controls were investigated.The frequencies of p73 AT/AT,AT/GC,and GC/GC genotypes were 28.1%,47.1%,and 24.8% in the controls,and were 22.0%,45.0%,and 33.0% in GC cases respectively;the GC/GC homozygote frequency was higher in GC cases,mainly in diffuse type compared to the controls with OR=1.71(1.16～2.51) and 1.87 (95%CI,1.24～2.81) respectively.The results showed that carriers of the p73 G4A GC/GC homozygote had a 1.71-time higher risk of GC,especially of the diffuse-type GC compared to the controls. The carriers of the AT/GC heterozygote also had a slightly increased risk of GC cancer,mainly on intestinal-type GC.This is the first report that the p73 G4A double-nucleotide polymorphism is associated with an increased risk of diffuse-type gastric cancer. CONCLUTION The p73 G4A GC/GC genotype is associated with an increased risk of gastric cancer,especially of the GC diffuse-type.