GSTM1和GSTT1基因缺失与湖南省衡阳地区汉族人群白癜风的相关性

目的探讨GSTM1和GSTT1基因缺失与湖南省衡阳地区汉族人群白癜风发病的相关性。方法选择湖南省衡阳地区汉族人群中100名白癜风患者(白癜风病例组)和100名健康志愿者(健康对照组)为研究对象,分别采集肘静脉血4mL,提取DNA,应用多重PCR技术检测GSTM1和GSTT1的基因型。结果白癜风病例组GSTM1基因缺失频率高于健康对照组,差异有统计学意义(P0.05);白癜风病例组GSTT1基因缺失频率与健康对照组比较,差异无统计学意义(P0.05);白癜风病例组GSTM1和GSTT1基因均缺失频率与健康对照组比较,差异也有统计学意义(P0.05)。结论湖南衡阳地区汉族人群白癜风发病与GSTM1基因缺失相关。     

血管内皮细胞生长因子基因-460T>C多态性与银屑病易感性的Meta分析

目的:综合分析血管内皮细胞生长因子(vascular endothelial cell growth factor,VEGF)基因-460 TC(rs833061)多态性与银屑病易感性的关系。方法:计算机检索Pubmed、Embase、Cochrane Library、中国知网(CNKI)、维普(VIP)、万方及中国生物医学文献数据库(CBD),收集关于VEGF-460 TC(rs833061)多态性与银屑病易感性的相关研究,采用Meta分析方法对纳入研究进行合并分析和异质性检验,效应量为比值比(OR)及95%可信区间(CI),并检测发表偏倚。应用RevMan 5.2及Stata 12.0软件进行统计学处理。结果:本研究共纳入5篇文献,包括病例698例,对照866例,总体人群Meta分析结果显示VEGF-460 TC(rs833061)多态性与银屑病易感性无明显相关性。按种族进行亚组分析结果显示,在欧洲人群中,CC+CT及CT基因型个体银屑病发病风险较TT基因型个体明显降低(CC+CT vs.TT:OR=0.73,95%CI=0.55~0.97;CT vs.TT:OR=0.67,95%CI=0.49~0.90),而在亚洲人群中差异无统计学意义。结论:VEGF-460 TC(rs833061)基因多态性与欧洲人群银屑病易感性相关,而可能与亚洲人群银屑病易感性无关。欧洲人群中,CC+CT及CT基因型的个体银屑病发病风险可能降低。     

肿瘤坏死因子-α-308位点多态性与系统性红斑狼疮相关性的Meta分析

目的:研究肿瘤坏死因子(TNF)-α-308位点多态性与系统性红斑狼疮(SLE)易感性的相关性。方法:检索Pub Med、中国学术期刊全文数据库(CNKI)、中国生物医学文献数据库(CBM)、万方数据库,检索时间为1997年1月—2015年4月。按照纳入和排除标准收集TNF-α-308位点多态性与SLE易感性的相关性研究的文献,并对其进行质量评价,用Rev Man5.0软件进行Meta分析。结果:共纳入24篇文献,共有SLE患者4104例,健康对照5580例。对总体人群进行Meta分析,发现等位基因A与SLE相关[OR=1.68,95%CI(1.36,2.07),P0.01];将人群按地域分层,发现TNF-α-308 A等位基因与欧洲人群[OR=2.08,95%CI(1.59,2.71),P0.001],亚洲人群[OR=1.44,95%CI(1.04,2.01),P=0.03]SLE易感性相关。结论:欧洲人群和亚洲人群中TNF-α-308位点多态性可能与SLE易感性有关。     

CLOCK基因多态性与广西地区男性不育的相关性研究

目的探讨生物钟基因CLOCK基因多态性与广西地区男性不育的相关性。方法选取2019年3月至10月广西医科大学第一附属医院生殖中心和男性科门诊就诊的149例不育男性患者纳入不育组,根据精液检查分为少弱精不育组和原发性不育组;另选取91例同期体检有自然生育史、近期精液常规检查均为正常的健康男性作为对照组。采用DNA测序技术对CLOCK基因rs3749474和rs4580704位点进行基因分型。采用Logistic回归分析校正年龄后计算OR和95%CI,对CLOCK基因多态性和男性不育的遗传易感性进行关联分析。应用SHEsis软件进行单倍型分析。结果不育组和对照组rs3749474 CC基因型和C等位基因频率分布差异具有统计学意义(P=0.011,OR=2.78,95%CI:1.26～6.11;P=0.008,OR=1.68,95%CI:1.15～2.45)。而rs4580704位点各基因型和等位基因在对照组和不育组中的频率分布差异无统计学意义(P0.05)。亚组分析结果显示,rs3749474和rs4580704位点的基因型和等位基因在对照组和少弱精不育组中的频率分布差异均无统计学意义(P0.05)。而与对照组比较,rs3749474 CC基因型和C等位基因均显著增加男性原发性不育的风险(OR分别为4.81和2.22);rs4580704 CG、GG基因型和G等位基因携带者男性不育的患病风险增加(OR分别为3.78、4.02和2.13)。单倍型分析发现,CG和TC单倍型的频率在原发性不育组和对照组中的分布差异有统计学意义(P0.05)。结论 CLOCK基因rs3749474和rs4580704多态性与广西地区男性原发性不育有相关性。     

雌激素受体-α基因多态性与白癜风相关性研究

目的探讨雌激素受体-α(ER-α)基因多态性与白癜风的相关性。方法应用PCR-RFLP分析技术,检测690例汉族白癜风患者和700例汉族对照者ER-α基因内含子1PvuⅡT/C和XbaIA/G酶切位点基因多态性。结果白癜风组与对照组之间C/T基因型频率(P=0.000)差别有显著性意义,其C等位基因频率亦明显高于对照组(P=0.000,OR1.33,95%CI1.14~1.51);女性患者C/T基因型频率(P=0.001)、C等位基因频率(P=0.002,OR1.41,95%CI1.13~1.75)亦明显高于女性对照组;男性患者和男性对照组C等位基因频率(P=0.043,OR1.25,95%CI1.01~1.56)差别有显著性意义;ER-α基因内含子1XbaⅠA/G酶切多态性男性患者G等位基因频率(P=0.040,OR1.32,95%CI1.01~1.71)明显高于男性对照组;其余各组间差别无显著性意义(P>0.05)。结论ER-α基因PvuII酶切多态性与白癜风存在相关性,携带C等位基因的女性患者更易患白癜风。XbaI酶切多态性可能与男性白癜风患者之间存在相关性。提示ER-α可能是白癜风患者易感性的备选因素。     

补体C1q基因簇rs631090多态性与女性系统性红斑狼疮的相关性研究

目的:确定补体C1q基因簇单核苷酸多态性(single nucleotide polymorphisms,SNPs)与中国女性人群系统性红斑狼疮(SLE)的易感性。方法:111例女性SLE患者及120名女性正常对照者。提取样本基因组DNA后,经普通PCR扩增目的基因,采用二代测序分析C1q基因簇上三个位点(rs631090、rs292001、rs294223)的基因型及等位基因分布。在不同的遗传模式下分析三个位点基因多态性与SLE的相关性。结果:位点rs631090(C1qB)病例组与对照组基因型频率和等位基因分布比较差异均具有统计学意义(P=0.034和P=0.008)。位点rs292001(C1qA)和rs294223(C1qB)的基因型频率及等位基因分布结果在两组间不具统计学差异(P值均大于0.05)。位点rs631090在显性遗传模型下CT/CC基因型在统计学上具有显著保护性作用(OR=0.470,95%CI=0.268-0.823,P0.05)。rs292001和rs294223在三种遗传模型下分析均未发现相关性(P值均大于0.05)。结论:在中国女性人群中rs631090位点SNPs与SLE相关,基因型CT/CC可能为女性SLE保护基因型。     

NLRP3基因单核苷酸多态性与上海地区寻常痤疮患病率的关系分析

目的:探讨NLRP3基因单核苷酸多态性(SNP)与上海地区寻常痤疮患病率的相关性。方法:收集145例中、重度痤疮患者及158例健康人群的临床资料和血液标本,Taq Man探针法对rs10754558和rs4612666位点进行分型,ABI7900扫描分型结果,荧光定量PCR检测NLRP3基因表达水平。结果:中、重度痤疮患者rs10754558位点CC、CG、GG基因型频率分别为0.168、0.476和0.338,对照组为0.285、0.487和0.228,G等位基因的分布频率差异存在统计学意义(P=0.010,OR=1.522,95%CI=1.075~2.098)。痤疮患者与健康人群rs4612666位点基因型差异无统计学意义(P=0.708,OR=1.065,95%CI=0.767~1.479)。结论:NLRP3基因rs10754558位点与上海地区痤疮患病率存在相关性,而rs4612666位点与其无相关性。     

促卵泡生成激素受体多态性与多囊卵巢综合征易感性的Meta分析

目的:探讨促卵泡生成激素受体(FSHR)Ser680Asn位点多态性与多囊卵巢综合征(PCOS)的相关性。方法:通过Pubmed、Embase、Medline和国内数据库等,收集国内外已经发表的有关FSHR Ser680Asn位点多态性与多囊卵巢综合征易感性的文章,筛选出符合纳入和排除标准的文献,通过对各种模型比较,应用Stata12.0对各项研究进行异质性检验,计算合并OR值及其95%CI,并进行敏感性分析和发表偏移的评估。结果:9篇文献纳入本研究,共计PCOS病例1652例,对照4434例。Meta分析显示,总体人群Ser/Ser纯合子与PCOS有显著相关性(OR=0.20,95%CI=0.17-0.24,P=0.000),但在显性模型中未发现与PCOS有明显相关性(OR=1.1,95%CI=0.96-1.26,P=0.151),与之前报道结果不一致。结论:FSHR Ser/Ser纯合子与妇女PCOS的易感性相关。     

包皮环切缝合器与包皮环切吻合器治疗包皮过长和包茎的meta分析

目的:比较包皮环切缝合器与包皮环切吻合器治疗包茎及包皮过长的疗效及并发症发生情况。方法:计算机检索辅以手工及其他方式,检索中外各大数据库及相关期刊建库(或建刊)至2017年3月有关包皮环切缝合器与包皮环切吻合器治疗包茎及包皮过长的随机对照性文献,两位评价员独立按Cochrane系统评价手册5.3进行质量评价标准后,对纳入的结果采用Rev Man 5.3进行Meta分析。结果:纳入随机对照文献20篇,累计病例4801例;Meta分析显示:与包皮环切吻合器相比,包皮环切缝合器术后疼痛评分(WMD=0.05,95%CI:0.00~0.11,P0.00001)、术后外观满意度(OR=4.23,95%CI:3.01~5.95,P0.00001)、愈合时间(WMD=-9.30,95%CI:-11.01~-7.59,P0.00001)、术后迟发出血(OR=4.28,95%CI:1.66~11.02,P=0.003)、术后感染(OR=0.16,95%CI:0.08~0.34,P0.00001)、术后水肿(OR=0.17,95%CI:0.10~0.29,P0.00001)、术后伤口裂开(OR=0.15,95%CI:0.08~0.26,P0.00001)等指标差异明显,有统计学意义;手术时间(WMD=-0.38,95%CI:-1.05~0.29,P=0.27)、术中出血量(WMD=0.05,95%CI:0.00~0.11,P=0.07)差异无统计学意义。结论:与包皮环切吻合器相比,应用包皮环切缝合器行包皮环切术愈合时间短,术后疼痛评分低,术后外观满意度高,术后水肿、感染、伤口裂开等并发症发生率较低;手术时间、术中出血量2项指标未见明显差异;术后迟发性出血发生率较高。但由于各种原因,纳入的文章存在异质性,本结论可信度有待进一步提高。     

中国男男性行为者肛门HPV感染影响因素的Meta分析

目的 探究我国男男性行为者(MSM)群体肛门人乳头瘤病毒(HPV)感染的影响因素。方法 在各大数据库中检索建库至2022年12月15日关于中国MSM肛门HPV感染影响因素的文献,文献筛选后进行质量评价、资料提取,采用Stata16.0软件进行Meta分析。结果 共纳入文献20篇,样本量累计达9 861例。结果显示人类免疫缺陷病毒(HIV)阳性(OR=2.87,95%CI:2.26~3.65)、性交时被插入为主(OR=1.95,95%CI:1.67~2.29)、多个性伴侣(OR=1.60,95%CI:1.16~2.22)、性病史(OR=2.24,95%CI:1.33~3.77)、毒品使用史(OR=1.86,95%CI:1.53~2.26)、肛交(OR=2.07,95%CI:1.61~2.67)、有时使用避孕套(OR=1.51,95%CI:1.20~1.91)、近1年存在商业性性行为(OR=2.09,95%CI:1.31~3.34)、插入与被插入(OR=1.55,95%CI:1.10~2.17)是我国MSM肛门HPV感染的影响因素。结论 我国MSM HPV感染受诸多因素影响,应早期识别高风险人群,提早干预,有效防止HPV感染发生发展。     

GSTM1 and GSTT1 null genotypes as possible heritable factors of rosacea

PURPOSE: Rosacea might be related to an increased activity of reactive oxygen species (ROS) and deficient function of the antioxidant system. Glutathione S-transferases (GSTs) play a primer role in cellular defense against electrophilic chemical species and radical oxygen species. We hypothesized that increased ROS activity or decreased antioxidant potential, possibly induced by GST gene polymorphism, might have a pathogenic role in rosacea. METHODS: The study group consisted of 45 patients with rosacea and 100 control subjects. DNA samples were isolated from blood samples using high pure polymerase chain reaction (PCR) Template preparation Kit. The GSTM1, GSTT1, and P1 polymorphisms were detected using a real-time PCR and fluorescence resonance energy transfer with a Light-Cycler Instrument. Associations between specific genotypes and the development of rosacea were examined using logistic regression analyses to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: GSTM1 and GSTT1 null genotypes were found to be statistically different from control (P=0.005, P=0.009, respectively), and associated with an increased risk of rosacea (OR [95% CI]: 2.84 [1.37-5.89]; OR [95% CI]: 2.68 [1.27-5.67], respectively). There was a statistically significant relationship between both null combination of the GSTM1 and GSTT1 genotype polymorphisms and rosacea (P=0.003, OR [95% CI]: 4.18 [1.57-11.13]). There were no statistically significant differences between patient and control groups for the GSTP1 Ile/Ile, Ile/Val, and Val/Val genotypes (P>0.05). CONCLUSION: We demonstrated a significant association between the GSTT1 and/or GSTM1 null genotypes and rosacea. However, the potential role of GSTs as markers of susceptibility to rosacea needs further studies in larger patient groups.     

Polymorphisms of GSTM1 and GSTT1, sun exposure and the risk of melanoma: a case-control study

Glutathione S-transferases (GSTs) are a family of enzymes that are known to play an important role in cellular protection against oxidative stress, including the oxidative stress caused by ultraviolet radiation. This study focused on the possible involvement of GSTM1 and GSTT1 polymorphisms in risk modulation of cutaneous melanoma. Within a case-control study, the presence of the null polymorphism at GSTM1 and GSTT1 was investigated in 188 cases of cutaneous melanoma and 152 controls. Information on socio-demographic characteristics, medical history, sun exposure and pigmentary characteristics were collected for all subjects. Logistic regression was used to estimate odds ratio (OR) and 95% confidence intervals (CI). An interaction was suggested between the GSTM1 and GSTT1 "null" genotype and episodes of sunburn in childhood OR of interaction (1.65, 95% CI (95% CI) 0.27-9.94). The risk of melanoma among the subset of participants who reported sunburns in childhood and who had both null variants, was nine (OR 9.16; 95% CI 1.18-70.9). The results suggest that subjects carrying both GSTM1 and GSTT1 null polymorphisms and experiencing sunburns in childhood have an extremely high risk of melanoma.     

Glutathione S‐transferase M1 and T1 genetic polymorphism in Egyptian patients with nonsegmental vitiligo

Oxidative stress and accumulation of free radicals might play a role in the pathogenesis of vitiligo. Glutathione S‐transferase (GST) is a multigene family of enzymes that detoxify oxidative stress products. In this study, genotyping by multiplex PCR of GSTM1 and GSTT1 in 101 women with nonsegmental vitiligo vulgaris and 101 age‐matched healthy female volunteers showed that only the GSTM1 null genotype (P = 0.04) was significantly overexpressed in patients with vitiligo. Analysis of the combined effect of GSTM1 and GSTT1 genotyping identified a significant association of risk for vitiligo with the GSTT1/GSTM1 double‐null type only (P = 0.01; OR = 2.69; 95% CI 1.12–6.46). Age of onset of vitiligo was significantly earlier in patients with the T1 null genotype (P < 0.01) and those with the T1?/M1+ and T1?/M1? combined genotypes (P < 0.01 and P = 0.01, respectively). In conclusion, the GSTM1 gene and the GSTM1/GSTT1 double‐null genotype may be a risk factor for vitiligo in Egyptian patients. Inability to cope with oxidative stresses because of GST deficiency may cause early disease onset.     

Glutathione S-transferase polymorphisms in patients with drug eruption

Glutathione S-transferase (GST) enzymes play an important role in drug metabolism. GST is a multigene family of enzymes involved in the detoxification and in a few instances activation of a wide variety of chemicals. Detoxification features make it plausible to search for GST polymorphism in patients with drug eruption. The GSTM (mu), GSTT (theta) and GSTP (pi) have been shown to be polymorphically distributed. The GSTT1, GSTM1 and GSTP1 gene polymorphism were detected using real-time PCR. GSTM1 and GSTT1 null genotypes were found to be associated with an increased risk of drug eruption (OR 2.27, 95% CI 1.20–5.21; OR 2.48, 95% CI 1.12–6.39, respectively). No relationship was observed between the null combination of the GSTM1 and GSTT1 genotype polymorphisms and drug eruption risk (OR 2.65, 95% CI 0.62–11.25). Our results show that GSTP1 polymorphism is not a significant contributor to drug eruption risk. The GSTM1 and GSTT1 gene polymorphisms seem to be associated with the development of drug eruption. Further studies may shed additional light on the role of GSTM1, GSTT1 and GSTP1 in drug eruption.     

Glutathione S-transferase and CYP1A1 gene polymorphisms and non-melanoma skin cancer risk in Italian transplanted patients

Solid organ transplant recipients are at higher risk of non-melanoma skin cancer (NMSC), especially basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Genetic alterations in the production of detoxifying enzymes such as glutathione S-transferase (GST) and CYP1A1 may enhance this risk. We investigated the frequency of GST genotypes (GSTM1, GSTM3, GSTT1 and GSTP1) and CYP1A1 in 239 transplant recipients: 107 cases with NMSC and 132 controls free from NMSC matched for type of transplanted organ, duration of transplantation, sex and age. Allele GSTP1*A was associated with a higher risk of NMSC [odds ratio (OR) 1.7 (1.1-2.5); P = 0.017]. Homozygosity for allele GSTP1 Val(105) was lower in cases [OR 0.3 (0.1-0.8); P = 0.012], especially in patients with SCC [OR 0.1 (0.0-0.7); P = 0.012]. A higher risk of BCC was found in patients with GSTM1 null/null [null/null versus A + B, OR 3.1 (1.4-6.8); P = 0.003]. Analysis of allelism and interaction between allelic variants showed significant association between combined GSTM1 and CYP1A1 Val(462) genotypes, where individuals homozygous for the risk allele GSTM1 null and carrying also the allele CYP1A1 Val(462), show a higher risk of developing NMSC [OR 4.5 (1.1-21.4); P = 0.03], especially SCC [OR 6.5 (1.4-34.4); P = 0.01]. GSTP1 polymorphisms are associated with both BCC and SCC risk. GSTM1 polymorphisms seem to be involved in BCC risk, while GSTM1 null/null genotype combined with CYP1A1 allele Val(462) are associated with a higher risk for SCC, indicating that allelism and/or interactions between allelic variants at other loci may also influence the risk of NMSC, particularly SCC.     

Influence of functional variants Asp312Asn and Lys751Gln of Xeroderma Pigmentosum Group D (XPD) and Glutathione S‐transferase Mu 1 (GSTM1) and Theta 1 (GSTT1) genes on cutaneous melanoma susceptibility and prognosis

We aimed to evaluate whether variants in repair (XPD Asp312Asn, XPD Lys751Gln) and detoxification (GSTM1, GSTT1) genes alter risk, clinicopathological aspects and survival of cutaneous melanoma (CM). Genotyping was performed in 229 CM patients and 258 controls. Individuals with XPD 312Asp/Asn or Asn/Asn plus GSTT1 null genotype were under 2.00 (95% CI: 1.06‐3.79), and XPD 312Asn/Gln haplotype was under 1.44‐fold (95% CI: 0.99‐2.08) increased risks to CM than others. Individuals with GSTM1 plus GSTT1 null genotype had 9.61‐fold (95% CI: 2.28‐40.38) increased risk of metastatic CM. At 60 months of follow‐up, patients with XPD 751Gln/Gln plus GSTT1 null and GSTM1 null plus GSTT1 null genotype presented 7.36 and 3.05 more chances of evolving to death in multivariate Cox analysis, respectively. In conclusion, our data indicate, for the first time, that specific variant combinations of XPD, GSTM1 and GSTT1 may increase susceptibility to CM and influence patients’ clinicopathological features and survival.     

Polymorphisms in glutathione S-transferases are associated with altered risk of nonmelanoma skin cancer in renal transplant recipients: a preliminary analysis

Non-melanoma skin cancer (NMSC) represents a significant cause of morbidity and mortality among renal transplant recipients, with tumors behaving more aggressively than those in nontransplant patients. Not all immunosuppressed patients develop NMSC, however, and in those that do, the rate of accrual and numbers of lesions vary considerably. Though ultraviolet light is critical, it is unlikely that this alone explains the observed phenotypic diversity, suggesting the possible involvement of genetic factors. Furthermore, although twin studies in nontransplant patients with NMSC suggest a low genetic component, several genes associated with susceptibility and outcome in these patients have been identified. Thus, having previously shown that polymorphism in members of the glutathione S-transferase (GST) supergene family is associated with altered NMSC risk in nontransplant patients, we examined allelism in GSTM1, GSTP1, GSTM3, and GSTT1 in 183 renal transplant recipients. GSTM1 null was associated with increased squamous cell carcinoma (SCC) risk (p = 0.042, OR = 3.1). This remained significant after correction for age, gender, and ultraviolet light exposure (p = 0.012, OR = 8.4) and was particularly strong in patients with higher ultraviolet light exposure (e.g., sunbathing score > 3, p = 0.003, OR = 11.5) and in smokers (p = 0.021, OR = 4.8). Analysis of the interaction between GSTM1 null and sunbathing score showed that the two factors were synergistic and individuals with both risk parameters demonstrated a shorter time from transplantation to development of the first SCC (p = 0.012, hazard ratio = 7.1). GSTP1*Ile homozygotes developed larger numbers of SCC (p = 0.002, rate ratio = 7.6), particularly those with lower ultraviolet light exposure and cigarette consumption. GSTM3 and GSTT1 also demonstrated significant associations, though some genotype frequencies were low. These preliminary data suggest that genetic factors mediating protection against oxidative stress are important in NMSC development in immunosuppressed patients and may be useful in identifying high-risk individuals.     

Role of glutathione S-transferases in melanoma susceptibility: association with GSTP1 rs1695 polymorphism

Background Glutathione S‐transferases (GSTs) GSTM1, GSTT1 and GSTP1 are multifunctional enzymes involved in the detoxification of a wide range of reactive oxygen species produced during melanin synthesis and oxidative stress processes. Objectives Single nucleotide polymorphisms (SNPs) in GSTP1 and copy number variants in GSTM1 and GSTT1 may be candidate low‐penetrance variants with a role in susceptibility to malignant melanoma (MM). Methods In this case–control study, 562 Spanish patients with sporadic MM and 338 cancer‐free control subjects were included, and the role of polymorphisms in these GST genes was investigated. Genotypes were established by quantitative real‐time polymerase chain reaction for GSTM1 and GSTT1 while TaqMan probes were used to genotype GSTP1 SNPs. Results The GSTP1 polymorphism rs1695, which encodes the amino acid change p.Ile105Val, was individually associated with MM [odds ratio (OR): 1·32, 95% confidence interval (CI): 1·06–1·63]. Furthermore, individuals carrying one or two MC1R nonsynonymous changes and GSTP1 rs1695 rare allele had an increased risk of developing MM (OR: 3·34, 95% CI: 1·42–8·09 and OR: 20·42, 95% CI: 2·80–417·42, respectively). Conclusions This is the first time that the GSTP1 rs1695 polymorphism is reported to be associated with MM. In addition, this study is one of the largest GST polymorphism studies undertaken in the Spanish population and the first time that copy number variants have been scrutinized in relation to MM.     

Genetic susceptibility to environmental carcinogenesis in Slovenian melanoma patients

The skin acts as the first defence barrier against external environmental pollutants, including chemicals and UV radiation. Cytochrome P450 CYP1A1 and glutathione S-transferases (GSTs) found in melanocytes and skin basal layers were shown to participate both in the metabolism of xenobiotics and in detoxification of reactive oxygen species (ROS). In our study we analysed the distribution of single and combined CYP1A1, GSTM1, GSTT1 and GSTP1 genotypes contributing to inter-individual differences in metabolism of xenobiotics and ROS in 125 Slovenian healthy individuals and in 140 patients with sporadic malignant melanoma. Our results showed no statistically significant differences between melanoma patients and healthy controls in the frequency of polymorphic CYP1A1 and GST genotypes. The risk of developing melanoma was not significantly increased in individuals homo- or heterozygous for the CYP1A1*2A allele combined with GSTM1*0 genotype (OR: 1.86; 95% CI: 0.36-7.71), but increased slightly in carriers of CYP1A1*2A combined with both GSTM1*0 and GSTT1*0 genotypes (OR: 3.42; 95% CI: 0.36-29.6). Our results indicate that factors other than the polymorphic genes coding xenobiotic metabolising enzymes play a major role in protection against environmental carcinogenesis in human skin.