Vitamin D receptor gene polymorphism and prostate cancer risk

BACKGROUND: 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts antiproliferative effect on prostatic cells, mediated through the vitamin D receptor. In a case-control study, we examined whether the vitamin D receptor (VDR) gene polymorphism in exon 9 could affect prostate cancer susceptibility. METHODS: One hundred ninety newly diagnosed prostate cancer patients and 190 age-matched men with benign prostatic hyperplasia (BPH), in whom the presence of prostate cancer was excluded clinically or histologically, were recruited for this study. The VDR TaqI polymorphism was investigated by polymerase chain reaction (PCR) following restriction fragment length polymorphism using DNA from lymphocytes. Depending on the presence or absence of the TaqI restriction site at the third position of codon 352, patients were classified as TT, Tt, or tt. RESULTS: The frequency of the tt genotype was not significantly different between prostate cancer patients (18%) and controls (12%; P = 0.07). The odds ratio (OR), calculated relative to individuals with the TT genotype was 1.76 (95% confidence limit (CL) = 0.90-3.45). After stratification for Gleason score and prostate specific antigen levels in a case-case comparison (n = 190), no significant associations with the VDR genotypes were detectable either. CONCLUSIONS: In this case-control study of Austrian Caucasians, no statistically significant association of the VDR TaqI polymorphism and prostate cancer risk was found.     

南京地区汉族人群TRAIL基因多态性与前列腺癌的易感性研究

目的:探讨南京地区汉族人群中肿瘤坏死因子相关凋亡诱导配体(TRAIL)基因多态性与前列腺癌(PCa)易感性的关系。方法:采用病例对照研究,提取187例PCa患者和237例非PCa健康人(对照组)外周血基因组DNA,应用聚合酶链反应-连接酶特异检测技术(PCR-LDR)分析186例PCa患者和237例对照组TRAIL基因-716位点的多态性,比较不同基因型与PCa易感性的关系。结果:TRAIL基因启动子区存在一个SNP位点(-716A/G),基因型分别为AA型、AG型和GG型;Logistic回归分析显示,携带AG、GG和AG+GG基因型的个体与PCa发病风险之间无明显相关性(OR=0.89,95%CI=0.54～1.47;OR=0.94,95%CI=0.69～1.27;OR=0.87,95%CI=0.54～1.41)。结论:中国南京地区汉族人群中TRAIL基因-716位点基因多态性对PCa易感性无明显影响。     

1667例汉族前列腺癌人群前列腺癌易感性基因多态性验证分析

目的:前列腺癌在工业化国家发病率居男性恶性肿瘤首位,在我国前列腺癌近年发病率不断上升,成为泌尿系统常见恶性肿瘤。本文通过前列腺癌基因多态性分析研究汉族人群前列腺癌易感性危险位点。方法:取1 667例前列腺癌患者与1 525例对照组外周血样双盲利用Sequenom技术进行40个前列腺癌危险位点的SNP分析。结果:40个公认的前列腺癌位点检测结果有16个位点与前列腺癌明显相关(P<0.05);同时发现在不同人种中位于8q24的1、2、5位点与10q11的MSMB编码区及22q13.2编码TTLL1/BIK区域共同决定前列腺癌易感性。结论:汉族前列腺癌人群前列腺癌基因多态性分析结果显示:rs1465618、rs721048、rs12621278、rs7679673、rs12653946、rs339331、rs1512268、rs10086908、rs16901979、rs1447295、rs10993994、rs10896449、rs902774、rs9600079、rs11649743、rs5759167与前列腺癌易感性明显相关。     

中国汉族人群家族性前列腺癌的初步研究

目的:以中国汉族人群为研究对象,估计家族性前列腺癌的发病率,分析家族史对于前列腺癌发生的作用及家族性前列腺癌的临床和病理学特点。方法:回顾性分析我院2014年7月～2016年7月行穿刺并证实为前列腺癌的598例患者的一级亲属前列腺癌家族史。采取病例对照研究分析前列腺癌家族史对于前列腺癌发生的作用,病例组选择年龄56～79岁的495例前列腺癌患者,对照组选择同期接受穿刺且结果为前列腺增生的患者,匹配条件为年龄、民族(汉)和居住地相同。通过比较两组发病年龄、BMI、确诊时的PSA中位数、肿瘤分期、Gleason评分、D’Amico危险因素分级和首要治疗方式,来探究家族性前列腺癌患者和散发性前列腺癌患者临床病理学特点的差异。结果:年龄56～79岁且具有前列腺肿瘤家族史的患者,其前列腺癌发病率显著高于同年龄无前列腺癌家族史的人群(RR=3.0,P=0.010)。598例在我院穿刺并确诊为前列腺癌的患者中,有25例(4.2%)是家族性前列腺癌患者。和散发性前列腺癌患者相比,家族性前列腺癌患者中分级属低或中度危险分级的比例更高,但差异无统计学意义(P>0.05),并且家族性前列腺癌患者更愿意接受根治手术作为其首要治疗方式(P<0.05)。结论:在中国,家族性前列腺癌发生率远低于西方国家。前列腺癌家族史显著增加中国男性前列腺癌的发病风险。家族性与散发性前列腺癌之间并无显著的临床及病理学差异,但家族性前列腺癌患者更愿意接受根治手术作为首要的治疗方式。     

INSPstI polymorphism and prostate cancer in African-American men

BACKGROUND: Both prostate cancer and diabetes mellitus are common diseases in African-American men. High insulin levels and insulin resistance have been implicated in prostate cancer development, which has prompted a recent investigation of a possible role for germline variation in the insulin gene (INS) and prostate cancer risk. METHODS: Four hundred sixty-six African-American men with and without prostate cancer from the Flint Men's Health Study were typed for the INS Pst1 genotype using restriction digest and direct sequencing. An association between the Pst1 genotype and prostate cancer was examined using crude and age-adjusted logistic regression models. RESULTS: African-American men who were homozygous for the INS PstI CC genotype were 1.59 times more likely to be diagnosed with prostate cancer compared to men with the TT or TC genotypes (95% CI = 0.93-2.72). The association appeared stronger among diabetics compared to non-diabetics; however this observation was not statistically significant. CONCLUSIONS: Our study, taken together with the report of Ho et al., suggests that the INS Pst1 CC genotype is associated with prostate cancer risk in African-American men. Germline variation in the INS gene should be more fully explored in multiethnic studies to elucidate the molecular variant(s) associated with prostate carcinogenesis.     

甲基化转移酶基因多态性与前列腺癌发病的相关性研究

目的:探讨DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)(rs16999593,rs2228611)及DNMT3B(rs2424908)基因多态性与南京地区前列腺癌发病风险及病理特征的相关性。方法:采用病例对照研究,招募前列腺癌患者155例设为病例组及155例正常男性设为对照组。采用Mass ARRAY分子量阵列技术进行基因分型技术检测3个多态性位点的基因型。采用Logistic回归模型分析各基因型与前列腺癌发生的关系及其病理参数的关系。结果:rs16999593位点的各基因型在2组中分布频率有显著性差异(P=0.041),CT基因型(OR=0.61,95%CI 0.38~0.99,P=0.043)及CT/CC(OR=0.59,95%CI 0.39~0.92,P=0.017)基因型在对照组的频率显著高于病例组。rs2424908的各基因型在两组中分布有显著性差异(P=0.025),CT基因型(OR=0.73,95%CI 0.58~0.91,P=0.007)及CT/CC基因型(OR=0.57,95%CI 0.36~0.94,P=0.023)在对照组的频率显著高于病例组。在Gleason分级7的病例组中,rs16999593CT/CC(OR=0.47,95%CI 0.28~0.85,P=0.008)及rs2424908CT/CC(OR=0.46,95%CI 0.26~0.85,P=0.009)基因型的频率均显著低于对照组。而在Gleason分级≥7的分组中上述3个多态性位点的基因型频率与对照组均无显著性差异(P均0.05)。结论:DNMT1基因rs16999593CT/CC及DNMT3B基因rs2424908CT/CC基因型与前列腺癌的低风险相关,且与Gleason低评分相关。     

The Val158Met polymorphism of the catechol-O-methyltransferase gene is not associated with the risk of sporadic or latent prostate cancer in Japanese men

AIM: Since catechol estrogens possess carcinogenetic potential, their detoxification may lead to reduced risk of carcinogenesis. Catechol-O-methyltransferase (COMT) catalyzes the O-methylation of catechol estrogens. The enzymatic activity of COMT has been shown to be governed by a functional single-nucleotide polymorphism represented by a G-to-A transition at codon 158, that results in a valine to methionine substitution; this variant form is associated with an up to 4-fold decrease in enzymatic activity. We attempted to investigate whether the Val158Met polymorphism of COMT was associated with the risk of prostate cancer. METHODS: We analysed genomic DNA samples from 324 sporadic prostate cancer patients; 342 controls who had died from causes unrelated to cancer; and 95 Japanese men who were diagnosed as latent prostate cancer by autopsy. The genotyping method we used was a TaqMan assay. RESULTS: Age adjusted odds ratios for sporadic prostate cancer susceptibility were 1.047 (95% CI: 0.630-1.741) for the G/A genotype and 0.858 (95% CI: 0.407-1.804) for the A/A genotype, as compared with those for the G/G genotype. There was no significant association between this polymorphism and latent prostate cancer susceptibility either. CONCLUSIONS: Our results suggested that the Val158Met polymorphism of COMT was not associated with the risk of sporadic or latent prostate cancer in Japanese men.     

Relationship between XRCC1 polymorphisms and susceptibility to prostate cancer in men from Han, Southern China

Aim： To investigate the association among XRCC1 polymorphisms, smoking, drinking and the risk of prostate cancer （PCa） in men from Han, Southern China. Methods： In a case-control study of 207 patients with PCa and 235 cancerfree controls, frequency-matched by age, we genotyped three XRCC1 polymorphisms （codons 194, 280 and 399） using the polymerase chain reaction-restriction fragment length polymorphism （PCR-RELP） method. Results： Among the three polymorphisms, we found that the XRCC1 Arg399Gln variant allele was associated with increased PCa risk （adjusted odd ratio [OR]： 1.67, 95% confident interval [CI]： 1.11-2.51）, but the XRCC1 Arg 194Trp variant allele had a 38% reduction in risk of PCa （adjusted OR： 0.62, 95% CI： 0.41-0.93）. However, there was no significant risk of PCa associated with Arg280His polymorphism. When we evaluated the three polymorphisms together, we found that the individuals with 194Arg/Arg wild-type genotype, Arg280His and Arg399Gln variant genotypes had a significantly higher risk of PCa （adjusted OR： 4.31; 95% CI： 1.24-14.99） than those with three wild-type genotypes. In addition, we found that Arg399Gln variant genotypes had a significant risk of PCa among heavy smokers （adjusted OR： 2.04; 95% CI： 1.03-4.05）. Conclusion： These results suggest that polymorphisms of XRCC1 appear to influence the risk of PCa and may modify risks attributable to environmental exposure.     

Linkage between polymorphisms in the prostate specific antigen ARE1 gene region,prostate cancer risk,and circulating tumor cells

BACKGROUND: The prostate specific antigen (PSA) gene has a polymorphic androgen response element (ARE) sequence with two alleles, A and G. PSA A-allele carriers have higher serum PSA levels in healthy men (HM). METHODS: We analysed DNA samples from 278 (556 alleles) unrelated individuals, 127 HM and 151 prostate cancer (PC) patients, for PSA ARE1 genotypes. RESULTS: The analysis of the frequencies from the 556 alleles indicates a significant overrepresentation of A-allele in the PC group under the age of 67 compared with the HM group (63.3% vs. 48.8%; P = 0.009). We found that men carrying two A-alleles have increased risk for PC onset under the age of 67 (odds ratio [OR] = 2.92; 95% confidence interval [CI], 1.10-7.86; P = 0.013). Multivariate logistic regression analysis confirmed this association (OR = 1.82; 95% CI, 1.03-3.22; P = 0.037). Furthermore, the homozygosity for the A-allele was associated with higher serum PSA levels (P = 0.027) and with the presence of circulating tumor cells in the blood of PC patients (P = 0.018). CONCLUSION: Our results indicate that polymorphism in the PSA gene promoter may be an important biomarker for prostate cancer risk, especially for an earlier onset of PC.     

Luteinizing hormone beta polymorphism and risk of familial and sporadic prostate cancer

BACKGROUND: Circulating testosterone plays an important role in maintenance and growth of prostate cells. Luteinizing hormone (LH), secreted from the anterior pituitary, signals testicular Leydig cells to secrete testosterone. A genetic variant of the LH-beta protein, LH-betaV, exists in up to 40% of Caucasians and is more bioactive than the wild-type protein. We hypothesized that genetically determined variation in LH function might affect susceptibility to prostate cancer via altered testosterone secretion. METHODS: We determined the frequency of the LH-betaV polymorphism (two linked polymorphisms: Trp(8) --> Arg and Ile(15) --> Thr) in familial prostate cancer patients (n = 446), in sporadic prostate cancer patients (n = 388), and in population-based controls without prostate cancer (n = 510) to assess the role of this polymorphism in susceptibility to prostate cancer. RESULTS: A higher frequency of this variant genotype (LH-betaV: Arg(8)/Thr(15)) was observed in familial prostate cancer patients (18.6%) than in controls (13.7%), and after taking into account the correlation of the familial cases and adjusting for age and body mass index (BMI), there was a weak positive association between the variant LH-beta genotype, and risk of familial prostate cancer (OR = 1.29; 95% CI 0.96-1.75). The sporadic case group was also slightly more likely to have a variant genotype (15.2%) compared to the controls (13.7%), and after adjustment for age and BMI, a similar association with this variant was found (OR = 1.33; 95% CI 0.86-02.07). Surgical cases showed a slightly stronger association for the variant LH-beta genotype compared to non-surgical cases, but among the surgical cases there was little variability in risk across nodal status, stage, and tumor grade. CONCLUSIONS: These data are consistent with the hypothesis that the LH-beta variant is a weak risk factor for prostate cancer.     

Association between leptin receptor gene polymorphisms and early-onset prostate cancer

OBJECTIVE: To report a case-control study examining the relationship between polymorphisms in the leptin receptor (OBR) gene and the development of young-onset prostate cancer, because epidemiological studies report that prostate cancer risk is associated with animal fat intake, and thus we investigated if this association occurs via this genetic mechanism. PATIENTS, SUBJECTS AND METHODS: The Lys109Arg (OBR1) and Gln223Arg (OBR2) polymorphisms in the coding region of OBR were studied in blood DNA from 271 patients with prostate cancer aged < 56 years at diagnosis and 277 geographically matched control subjects. Cases were collected through the Cancer Research UK/British Prostate Group Familial Prostate Cancer Study. Blood DNA was genotyped using the polymerase chain reaction and a restriction enzyme digest. RESULTS: There was no statistically significant association between the OBR genotype and prostate cancer risk; men homozygous for 109Arg genotype had a slightly increased risk for prostate cancer, with a relative risk (95% confidence interval) of 1.36 (0.65-2.85), and those homozygous for the 223Arg allele had some reduction in prostate cancer risk, at 0.82 (0.58-1.26), but neither was statistically significant. CONCLUSION: This case-control study showed no significant association between leptin receptor gene polymorphisms and the risk of young-onset prostate cancer, suggesting that genetic variations in OBR are unlikely to have a major role in the development of early-onset prostate cancer in the UK.