Usefulness of genetic susceptibility and biomarkers for evaluation of environmental health risk

Recent attention is focused on understanding the genetic basis for individual susceptibility to the development of chronic disease. An emphasis is concentrated on establishing an association between inheritance of polymorphic chemical metabolizing genes and development of environmental cancer (e.g., lung cancer among cigarette smokers). The early reports of such associations have been very encouraging. However, some reported positive associations were not substantiated in subsequent studies using larger sample sizes and different ethnic populations. In this review, some confounding factors that contribute to the discrepancies are presented (e.g., ethnic-dependent distribution of variant gene alleles, differential expression of metabolizing genes, and inadequate study design). It is possible that the precision of the association can be improved if the mentioned investigations are complemented with concurrent studies of biological activities/effects. The usefulness of integrating metabolic susceptibility with biomarker measurement for understanding the development of lung cancers is presented. The importance of using adequate sample size and experimental design is emphasized. Development of a reliable approach for prediction of environmental disease not only will provide fundamental information regarding the genetic basis of human disease but will be useful for reducing disease burden in the population and for advancing patient care. Environ. Mol. Mutagen. 37:215-225, 2001. © 2001 Wiley-Liss, Inc.     

Polymorphic metabolizing genes and susceptibility to atherosclerosis among cigarette smokers

Atherosclerosis (AR) is the leading cause of morbidity and mortality in the US and cigarette smoking is a major contributing factor to the disease. Like cigarette smoking in lung cancer, genetic susceptibility may be an important factor in determining who is more likely to develop AR. However, the current emphasis has been on susceptibility based on altered cardiovascular homeostasis. In this investigation, we studied 120 AR patients and 90 matched controls to elucidate the association between polymorphisms in some metabolizing genes (GSTM1, GSTT1, CYP2E1, mEH, PON1, and MPO) and susceptibility to AR. We found that the GSTT1 null allele and the fast allele of mEH(*) (exon 4) are associated with risk for AR. Furthermore, the combined genotypes GSTM1 null/ CYP2E1(*)5B, GSTM1 null/mEH YY, and GSTT1 null/mEH YY are significantly associated with susceptibility to AR (OR = 15.42, 95% CI = 1.33-77.93, P = 0.021; OR = 3.48, 95% CI = 1.63-8.04, P = 0.0008; OR = 3.4; 95% CI = 0.99-17.38, P = 0.05; respectively). We have also conducted cytogenetic analysis to elucidate if induction of chromosome aberrations (CAs) is a biomarker of AR susceptibility. We found that among cigarette smokers (AR patients and smoker controls), individuals having the GSTM1 null allele had a significantly higher frequency of CAs compared to those with the normal allele (P < 0.05). This association was not found among nonsmokers. In addition, individuals who had inherited the CYP2E1(*)5B allele exhibited a significantly higher CA frequency (8.0 +/- 0.82) compared to those with the CYP2E1 wild-type genotype (4.31 +/- 0.35). Since the analysis of genetic susceptibility factors is still in its infancy, our study may stimulate additional investigations to understand the roles of genetic susceptibility and cigarette smoking in AR.     

DNA修复基因hOGG1多态与食管癌遗传易感性

目的：研究修复８－羟基鸟嘌呤的ｈＯＧＧ１基因Ｓｅｒ３２６Ｃｙｓ多态与中国人食管癌易感性的关系。方法：采用病例－对照分子流行病学方法,以ＰＣＲ－单链构象多态（ｓｉｎｇｌｅ ｓｔｒａｎｄ ｃｏｎｆｏｒｍａｔｉｏｎ ｐｏｌｙｍｏｒｐｈｉｓｍ,ＳＳＣＰ）技术,分析了２０１名正常对照和１９６例食管癌患者ｈＯＧＧ１基因第３２６位Ｓｅｒ／Ｓｅｒ、Ｓｅｒ／Ｃｙｓ和Ｃｙｓ／Ｃｙｓ基因型分布,并比较不同基因型与食管癌风险的关系。结果：正常人群的Ｓｅｒ／Ｓｅｒ、Ｓｅｒ／Ｃｙｓ和Ｃｙｓ／Ｃｙｓ基因型频率分别为３３．８％、５２．８％和１３．４％,而食管癌病例组则分别为３９．８％、３８．８％和２１．４％。虽然两组人群的Ｃｙｓ等位基因频率基本相同（３９．８％４０．８％）,但食管癌病例组的Ｃｙｓ／Ｃｙｓ基因型频率显著高于对照组（Ｐ＜０．０５）     

Polymorphisms for chemical metabolizing genes and risk for cervical neoplasia

Infection with high-risk human papillomavirus (HPV) plays a major role in the etiology of cervical cancer (CC). However, most infected women do not develop cancer. Therefore, exposure to other carcinogenic agents may be a contributing risk factor for CC. We investigated the hypothesis that environmental exposure to cigarette smoke and inheritance of polymorphic chemical metabolizing genes (CYP2E1, GSTM1, and mEH) significantly increase the risk for neoplasia. We selected 76 cases with high-grade cervical neoplasia or with invasive CC and 75 matched healthy controls. The collected data support the well-established observation that infection with high-risk HPV is the major risk factor for CC (OR = 75; 95% CI = 26-220). In addition, our data show that women who smoked more than 15 "pack-year" had a significant 6.9-fold increase in risk (95% CI = 1.2-40.3) after adjustment for HPV infection. The CYP2E1 variant genotype did not significantly increase the risk for neoplasia. A significant increase in risk for neoplasia was observed for the low-activity mEH 113 His allele after adjustment for smoking (OR = 3.0; 95% CI = 1.4-6.3). The GSTM1 null genotype was associated with a significant 3.3-fold increased risk for neoplasia (95% CI = 1.0-11.8) compared to women who were GSTM1-positive after adjustment for smoking and HPV infection. Our study suggests that genetic differences in the metabolism of cigarette smoke, particularly GSTM1, may confer susceptibility to CC. Further studies using larger populations will be needed to confirm our observations and to validate data for disease prevention.     

中国人CYP1A1和GSTM1基因多态性及其对个体肺癌易感性的联合效应

目的 在中国江苏肺癌患者和对照人群中,检测CYP1A1 Ile/Val,GSTM1 /0遗传多态性的各基因型及其联合基因型的分布,探讨这些基因型与肺癌个体易感性的关系。方法 配对的病例－对照组各106例,静脉血制备DNA。分别应用等位基因特异性（allele-specific,AS)-PCR和多重差别（multidifferential,MD)-PCR,检测CYP1A1 Ile/Val和GSTM1＋／0的等位基因型。结果 CYP1A1少见等位基因Val/Val纯合子及其与GSTM1基因缺失纯合子（0／0）的联合基因个体,与对照常见基因型个体相比,增加了对肺癌的易感性,其相对危险度（odds ratio,OR)分别为4．02（P＝0．03）和9．38（P＝0．04）;GSTM10／0纯合子及其与CYP1A1 Ile/Val杂合子的联合基因型个体,显著增加了肺癌易感性,其OR值分别是1．92（P＝0．019）和3．27（P＝0．01）。结论 中国江苏人群中,少见基因型CYP1A1 Val/Val,GSTM10/0增加了个体肺癌易感性,在肺癌发生中,上述两种易感基因型间存在协同或相乘作用。     

Possible risk modification by CYP1A1, GSTM1 and GSTT1 gene polymorphisms in lung cancer susceptibility in a South Indian population

Susceptibility to lung cancer has been shown to be modulated by inheritance of polymorphic genes encoding cytochrome P450 1A1 (CYP1A1) and glutathione S transferases (GSTM1 and GSTT1), which are involved in the bioactivation and detoxification of environmental toxins. As the incidence of lung cancer is known to differ according to ethnicity, we have conducted a case-control study of 146 South Indian lung cancer patients along with 146 healthy controls, to assess any association between CYP1A1, GSTM1 and GSTT1 polymorphisms, either separately or in combination, with the likelihood of development of lung cancer in our population. The current weight of evidence from our study indicated that the frequency of CYP1A1 MspI homozygous variant alleles was significantly higher in cases (OR=3.178). We observed a considerable difference in the GSTT1 null deletion frequency in this population when compared with other populations (OR=2.472, 95% CI: 1.191–5.094, P=0.014). There was no relative risk in GSTM1 null genotype when analysed singly (P=0.453). Considering genotype combinations, risk of lung cancer increased remarkably significantly in individuals having one variant allele of CYP1A1, GSTM1, or GSTT1, suggesting gene–gene interactions. Rare genotypic combinations (such as CYP1A1 wild GSTM1 or GSTT1 either null; CYP1A1 variant both GSTM1 and GSTT1 present; CYP1A1 variant GSTM1 or GSTT1 either null), were at higher risk compared to the reference group. Moreover, patients who had smoked <20 pack years and harboured the CYP1A1 variant allele or the GSTT1 null genotype also had a significant risk of lung cancer. Hence our study—the first to analyse a South Indian population—suggests the importance of combined CYP1A1, GSTM1 and GSTT1 polymorphisms in the development of smoking-induced lung cancer.     

Association between bacterial colonization on the tumor, bacterial translocation to the cervical lymph nodes and subsequent postoperative infection in patients with oral cancer

Objective: To investigate the association between postoperative infection, bacterial translocation to the cervical lymph nodes and bacterial colonization on the tumor in oral cancer patients.
Methods: Twenty-one oral mucosal cancer patients (11 male and 10 females: mean age 68.6 years) were studied. They underwent tumor surgery and neck dissection with free flap reconstruction. Ampicillin 1 g was parenterally administered from the start of the surgery as prophylaxis. Isolates from cervical lymph nodes, tumor and postoperative infected wound were studied microbiologically and pathologically.
Results: Bacterial translocation was found in 52 lymph nodes (52/107: 48.6%). Viable bacteria were isolated from 20 tumors (95.2%). Oral microflora and enteric bacteria were isolated. Postoperative infection was found in four cases. In three cases, enteric bacteria ( Klebsiella, Enterobacter, Enterococcus ) isolated from postoperative infections were also found in the tumor or the lymph nodes.
Conclusions: The operative field in oral cancer surgery was colonized by the indigenous flora and enteric bacteria. These were recovered not only from the tumor surface but also from the cervical lymph nodes. Preoperative surveillance culture or tumor culture have value in predicting the bacteriology of postoperative infection, and in selecting the appropriate antibiotic treatment.     

韩国人CYP450 1A1、CYP450 2E1和GSTM1、GSTT1、GSTP1基因座遗传多态性分析

目的 调查代谢相关的CYP4501A1、CYP4502E1和GSTM1、GSIT1、GSTP1基因座在韩国人群中的遗传多态性分布状况。方法 采用多重聚合酶链式反应、聚合酶链式反应-限制性片段长度多态性技术，分析300名韩国健康大学生的CYP1A1基因3′端限制性内切酶Msp Ⅰ位点、CYP2E1基因5′端转录调节区Pst Ⅰ位点和GSTM1、GSTT1缺失与存在、GSTP1基因第5外显子BsmA Ⅰ位点的基因型，计算基因型和基因频率。结果 CYP1A1基因型频率为ml／ml型39．7％、ml／m2型49．7％、m2／m2型10．7％，基因频率为ml 0．645、m2 0．355。CYP2E1基因型频率为cl／cl型66．7％、cl／c2型30％、c2／c2型3．3％，基因频率为C1 0．818、C2 0．182。GSTM1基因缺失型频率为53．3％。GSTT1基因缺失型频率为54．7％。GSTP1基因型频率为Ile／Ile型62％、Ile／Val型34．3％、VaL／Val型3．7％，基因频率为Ile 0．792、Val 0．208。基因分布符合Hardy-Weirtberg平衡定律。结论 韩国人CYP1A1、CYP2E1、GSTM1、GSTT1基因分布与我国人群较为相近，半数以上人缺乏GSTM1和GSTT1基因，纯合缺失型频率超过印度人的3倍。     

Polymorphisms of CYP1A1 and GSTM1 genes and susceptibility to oral cancer

PURPOSE: Oral cancer is the fifth most common form of cancer in the world and comprises 6.5% of all cancer deaths. Since one of the major risk factors for oral cancer is tobacco use, we hypothesized that polymorphic genes coding for tobacco carcinogen-metabolizing enzymes may play a role in oral cancer susceptibility. MATERIALS AND METHODS: To investigate the association between polymorphisms of the CYP1A1 and GSTM1 genes and risks for oral squamous cell carcinoma (OSCC) in the Korean population, the prevalence of the CYP1A1 Mspl and GSTM1 null polymorphisms were examined in 72 patients with histologically confirmed primary OSCC, as well as in 221 healthy control subjects. RESULTS: A significant risk increase for oral cancer was observed among subjects with the homozygous CYP1A1 (m2/m2) genotype (OR=3.8, 95% CI=1.9-7.7), but not the GSTM1 null genotype (OR=0.7, 95% CI=0.4-1.3). Risk for oral cancer was significantly increased in subjects with the homozygous CYP1A1 (m2/m2)genotype, regardless of smoking history (smokers; OR=4.4; 95% CI=1.2-16.3; non- smokers OR=4.9; 95% CI=1.9-12.5). Using the potentially most protective genotype GSTM1 (+)/CYP1A1 [(m1/m1)+ (m1/m2)] as the reference group, an increased risk for oral cancer was observed among subjects with the GSTM1 (+)/ CYP1A1 (m2/m2) (OR= 2.0, 95% CI=0.8-5.2), and GSTM1 (-)/ CYP1A1 (m2/m2) (OR=4.9, 95% CI=1.5-15.5) genotypes (p < 0.009, (chi2 trend test). CONCLUSION: Our results suggest that individuals with a genotype of CYP1A1 (m2/m2) and GSTM1 (-) are highly susceptible for OSCC and that the CYP1A1 (m2/m2) genotype is closely associated with increased risk of OSCC in Koreans.     

前列腺癌患者自我感受负担及其影响因素研究

目的 探讨在调查前列腺癌患者自我感受负担的现状及其相关因素,为临床采取针对性的护理干预措施提供依据,从而提高患者的生活质量。方法 采用一般资料调查表和自我感受负担量表对2014年1月~2017年1月在川北医学院附属医院肿瘤科和泌尿外科就诊的98例前列腺癌患者进行调查。通过询问的方式归纳统计98例研究对象的SPB得分,并对可能影响前列腺癌患者SPB的年龄、婚姻状况、文化程度、家庭人均月收入、疾病临床分期进行单因素分析,观察各影响因素与前列腺癌患者SPB的相关性结果。结果 除去SPB得分＜20分的患者,剩下90.82%的患者存在不同程度的SPB,98例患者的SPB平均得分为（37.16±11.33）分。本组前列腺癌患者在年龄、婚姻状况、家庭人均月收入、疾病临床分期等4个方面的SPB得分对比,差异具有统计学意义（P＜0.05）。结论 前列腺癌患者普遍存在不同程度的SPB,在临床工作中应充分评估影响患者SPB的相关因素,制订有针对性的干预措施,建立良好的护患关系。     

食管癌发病风险与NAD(P)H:醌氧化还原酶1C609T基因多态性

目的 研究NAD(P)H：醌氧化还原酶l[NAD(P)H：quinone oxidoreductase l，NQO1]C609T基因多态性与食管鳞状上皮癌(esophageal squamous cell carcinoma，ESCC)发病风险的关系。方法 应用聚合酶链反应-限制性片段长度多态性方法检测193例ESCC患者及141名正常对照的NQOl C609T多态性位点的基因型。结果 ESCC患者的突变型(T)等位基因频率明显高于健康对照组(X^2=4．86，P=0．028)。ESCC患者的NQO1C／C和C／T基因型频率与健康对照组相比差异无显著性(X^2值分别为2．27和0．127；P值分别为0．132和0．721)，而ESCC患者的T／T基因型频率明显高于对照组(X^2=4．39，P=0．036)。与NQOlC／C及C／T基因型相比，T／T基因型可明显增加患ESCC的风险性(校正OR=1．8l，95％CI：1．04～3．15)，且在有上消化道肿瘤家族史的患者中尤为明显(校正OR=2．22，95％CI：1．18～4．17)。结论 对NQO1 C609T多态性位点的基因型检测可能对判断ESCC高危个体具有指导意义。     

The influence of genetic counselling in the era of DNA testing on knowledge, reproductive intentions and psychological wellbeing

Subjects of reproductive age at risk of having an affected child with a severe single gene disorder such as Duchenne muscular dystrophy (DMD) or cystic fibrosis (CF) were surveyed to ascertain: their views on genetic counselling and antenatal testing; their knowledge of their risk of having an affected child; and their psychological wellbeing. Questionnaires were posted to 209 individuals at 130 addresses; a 65% response rate was achieved. The majority of those surveyed were under 40 years of age (91%), half of them had received genetic counselling only once and for 47% the first encounter was after the diagnosis of their affected child. Most patients expressed their intention to use prenatal testing. However, less than 50% of those counselled knew their risk of having an affected child. Knowledge of risk was associated with the type of disease in the family (p<0.001) (inheritance of DMD was poorly understood by relevant subjects) and was positively associated with the participant's level of education (p<0.05). We did not detect a significant association between the number of intended children and the risk of having an affected child. In terms of family relations, genetic counselling appears to be beneficial for the nuclear family, the couple and their children, but some counsellees reported a detericration in relations with other relatives. The results indicate that couples at risk of having a child with a severe genetic disorder value the counselling provided, but many of them do not remember important facts in relation to their risk status.     

High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus

Bogdanova NV, Antonenkova NN, Rogov YI, Karstens JH, Hillemanns P, Dörk T. High frequency and allele‐specific differences of BRCA1 founder mutations in breast cancer and ovarian cancer patients from Belarus. Breast cancer and ovarian cancer are common malignancies in Belarus accounting for about 3500 and 800 new cases per year, respectively. For breast cancer, the rates and age of onset appear to vary significantly in regions differentially affected by the Chernobyl accident. We assessed the frequency and distribution of three BRCA1 founder mutations 5382insC, 4153delA and Cys61Gly in two hospital‐based series of 1945 unselected breast cancer patients and of 201 unselected ovarian cancer patients from Belarus as well as in 1019 healthy control females from the same population. Any of these mutations were identified in 4.4% of the breast cancer patients, 26.4% of the ovarian cancer patients and 0.5% of the controls. In the breast cancer patients, BRCA1 mutations were strongly associated with earlier age at diagnosis, with oestrogen receptor (ER) negative tumours and with a first‐degree family history of breast cancer, although only 35% of the identified BRCA1 mutation carriers had such a family history. There were no marked differences in the regional distribution of BRCA1 mutations, so that the significant differences in age at diagnosis and family history of breast cancer patients from areas afflicted by the Chernobyl accident could not be explained by BRCA1. We next observed a higher impact and a shifted mutational spectrum of BRCA1 in the series of Byelorussian ovarian cancer patients where the three founder mutations accounted for 26.4% (53/201). While the Cys61Gly mutation appeared underrepresented in ovarian cancer as compared with breast cancer cases from the same population (p = 0.01), the 4153delA mutation made a higher contribution to ovarian cancer than to breast cancer (p < 0.01). BRCA1 mutations were significantly enriched among ovarian cancer cases with a first‐degree family history of breast or ovarian cancer, whereas the median age at ovarian cancer diagnosis was not different between mutation carriers and non‐carriers. Taken together, these results identify three BRCA1 founder mutations as key components of inherited breast and ovarian cancer susceptibility in Belarus and might have implications for cancer prevention, treatment and genetic counselling in this population.     

性化护理对肝癌患者CT引导下射频消融术后 负性情绪及生活质量的影响

目的 研究人性化护理对肝癌患者CT引导下射频消融术后负性情绪、生活质量的影响。方法 选取我院自2016年8月~2017年8月收治的接受CT引导下射频消融术治疗的68例肝癌患者,按随机数字表法分为对照组35例和干预组33例。对照组采取常规护理干预,干预组则采取人性化护理干预,比较两组护理前后负性情绪及生活质量改善情况。结果 护理后,干预组SAS评分为（45.78±0.71）分、SDS评分为（19.65±0.81）分,均低于对照组的（53.55±0.82）分、（23.67±0.89）分,差异具有统计学意义（P＜0.05）;护理后,两组生活质量评分均上升,且干预组高于对照组[（93.64±3.11）分 vs （89.61±5.07）分],差异有统计学意义（P＜0.05）。结论 对接受CT引导下射频消融术治疗的肝癌患者,采取人性化护理干预可有效缓解其负性情绪,提高生活质量。     

CDX2和CYP24A1在大肠癌中的表达

目的 通过研究CDX2、CYP24A1在大肠癌中的表达研究,探讨CDX2和CYP24A1的相关性。方法 应用免疫组化S-P法检测100例大肠癌组织及20例正常大肠癌组织中CDX2和CYP24A1的表达。结果 大肠癌组织中的CDX2和CYP24A1的蛋白表达低于正常大肠癌组织中的表达（P<0.05）, 以正常大肠组织作为对照,CDX2 的蛋白水平表达量为100.00%, 癌旁组织和大肠癌组织的 CDX2 蛋白的相对表达量分别为77.12%、46.65%。CYP24A1 的蛋白水平表达量为 43.81%, 癌旁组织和大肠癌组织的 CYP24A1 蛋白的相对表达量分别为75.00%、96.82%。通过Pearson相关分析显示CDX2蛋白表达水平与CYP24A1蛋白表达水平之间呈显著负相关关系（P<0.05）。结论 CDX2和CYP24A1是具有较高敏感性的肠上皮特异性标志物,联合检测CDX2和CYP24A1的表达有助于鉴别良恶性大肠肿瘤。     

Genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 are associated with susceptibility to lung cancer

The tumor suppressor TP53 pathway plays a crucial role in preventing carcinogenesis through its ability to impose cell cycle arrest and apoptosis following DNA damage and oncogene activation. MDM2 is a key negative regulator of the TP53 pathway and is overexpressed in many cancers as oncoprotein. We investigated the association between genetic variation in the promoter region of MDM2 (c.-5+309G>T, rs2279744:g.G>T) and the coding region of TP53 (c.215G>C, rs1042522:g.G>C, designated Arg72Pro) and the risk of developing lung cancer. The genotypes of 1,106 patients and 1,420 controls were determined by tetra-primer amplification refractory mutation system (ARMS)-PCR or PCR-based restriction fragment length polymorphism (RFLP). Associations with risk of lung cancer were estimated by logistic regression. We observed an increased lung cancer risk associated with the MDM2 GG (odds ratio [OR] = 1.83, 95% confidence interval [CI] = 1.45-2.32) and TG (OR = 1.33, 95% CI = 1.09-1.63) genotypes. An increased risk was also associated with the TP53 Pro/Pro genotype (OR = 1.47, 95% CI = 1.17-1.85, P = 0.003) compared to the Arg/Arg genotype. The gene-gene interaction of MDM2 and TP53 polymorphisms increased lung cancer risk in a supermultiplicative manner (OR for the presence of both MDM2 GG and TP53 Pro/Pro genotypes = 4.56, 95% CI = 2.76-7.54). Significant interactions were observed between these polymorphisms (respectively and jointly) and smoking (OR = 10.41, 95% CI = 5.26-20.58) for smokers with both the MDM2 GG and TP53 Pro/Pro genotypes. In conclusion, genetic polymorphisms in cell cycle regulatory genes MDM2 and TP53 contribute to the risk of developing lung cancer.     

Genetic testing for breast cancer susceptibility: Awareness and interest among women in the general population

Previous research has suggested that demand for genetic testing for breast cancer susceptibility may be quite high, even among those at relatively low risk of carrying a mutation. This study examined the extent to which a group of female HMO enrollees were aware of the discovery of the BRCA1 gene and, without having received detailed information about the test, whether they would be interested in being tested to find out if they have the gene. Factors associated with awareness of and interest in testing were also examined. Four hundred seventy-three women age 50 and over, almost all of whom did not have an increased risk of breast cancer based on family history, were surveyed by telephone. Fifty-one percent of respondents had heard about the discovery of a breast cancer gene. In logistic regression analysis, women who described themselves as comfortable financially, had at least some college education, and were premenopausal were more likely to have heard of the gene discovery than women who were not comfortable financially, had no more than a high school education, and were postmenopausal. Sixty-nine percent of the respondents said that they would be interested in being tested to find out if they had a breast cancer gene. Women who were younger than 60, white, believed their family would benefit if they had a mammogram, and believed that regular mammograms give them a feeling of control over their health, were more likely to be interested in testing than those who were 60 or older, African-American or other, and did not believe that their family would benefit if they had a mammogram or that mammograms give them a feeling of control over their health. These findings have implications for education and counseling. Women who express an interest in being tested must be made fully aware of the limitations and possible consequences of testing. Special efforts may be needed to make information about testing available to women who have low levels of education. Am. J. Med. Genet. 68:43–49, 1997 © 1997 Wiley-Liss, Inc.     

快速康复对肺癌手术患者并发症发生及生活质量的影响研究

目的 探讨实施快速康复对肺癌手术患者并发症发生及生活质量的影响。方法 选取2016年1月~2018年2月接受治疗的肺癌手术患者100例,按照随机数字表法分为观察组和对照组,对照组接受常规肺癌术后护理,观察组则在此基础上接受快速康复护理（FTS）,对比两组患者术后恢复情况、疼痛情况、免疫功能指标及生活质量。结果 肺癌术后,观察组的术后开始通气时间等指标优于对照组,差异有统计学意义（P＜0.05）;观察组在术后12 h、24 h、48 h及72 h的疼痛情况优于对照组,差异有统计学意义（P＜0.05）;观察组术后出现并发症7例（14.00%）,低于对照组15例（30.00%）,差异有统计学意义（P＜0.05）;观察组术后生活质量评分优于对照组,差异有统计学意义（P＜0.05）。结论 肺癌术后对患者实施快速康复护理能提升患者生活质量,减少并发症发生率,效果良好。     

Association between polymorphisms in the biometabolism genes CYP1A1, GSTM1, GSTT1 and GSTP1 in bladder cancer

Numerous enzymes, including Cytochrome P450s (phase I) and Glutathione-S-transferases (phase II), are involved in the metabolic activation and detoxification of carcinogens. Epidemiological studies have consistently demonstrated that bladder cancer is strongly associated with cigarette smoking, and the risk for the development of this neoplasia may be modified by individual differences in carcinogen-metabolizing genes. We investigated the relationship between polymorphisms in the CYP1A1, GSTM1, GSTT1, and GSTP1 genes in a case–control study with 100 bladder cancer patients and 100 controls matched for age, gender, race, and smoking status. The GSTM1, GSTT1, CYP1A1 (A2455→G), and GSTP1 (A313→G) genotypes were determined using a multiplex PCR, an allele specific PCR, and a restriction fragment length polymorphism-PCR method. The present case–controlled association study did not detect any positive or negative association for the GSTM1 and GSTP1 genes [odds ratios (OR) = 1.35; 95% confidence interval (CI) = 0.76–2.41 and OR = 0.75; 95% CI = 0.41–1.38, respectively]. Notably, the genes GSTT1 and CYP1A1 exhibited a statistically significant association with bladder cancer (OR = 1.77; 95% CI = 1.01–3.12 and OR = 1.99; 95% CI = 1.07–3.73). No differences for GSTM1 and GSTP1 genotype prevalence between the bladder cancer cases and the controls were observed, however, the null genotype for the GSTT1 gene and the A/G and G/G variants of the CYP1A1 gene may contribute to the development of bladder cancer.