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Family history, metabolic gene polymorphism, diet and risk of colorectal cancer. 家族史、代谢基因多态性、饮食与结直肠癌风险
Julian Little, J. Faivre
Colorectal cancer is thought to be largely due to dietary factors. There is evidence of familial aggregation of colorectal cancer suggesting that genetic susceptibility may be important in the aetiology of the disease. Only limited data are available comparing risk factors for colorectal cancer with and without a family history. There are arguments suggesting that individuals with a first-degree relative with colorectal cancer are at a greater risk from a diet high in energy than individuals without such a family history. Failure to take into account both genetic and environmental factors can lead to bias in the estimation of disease risk. Genetic polymorphisms interact with dietary intake. A number of associations have been observed between specific genetic polymorphisms and colorectal cancer. But there are inconsistencies between studies, because of methodological limitations in initial studies. Different effects of dietary factors on colorectal cancer risk among individuals with different genotypes or of different effects of a genotype on colorectal cancer risk among individuals with different exposures need to be addressed in future works.
人们认为结直肠癌很大程度上是由饮食因素引起的。有证据表明,结直肠癌的家族聚集表明,遗传易感性可能是重要的疾病的病因。只有有限的数据可以比较有和没有家族史的结直肠癌的危险因素。有观点认为,与没有这种家族史的人相比,有一级亲属患有结直肠癌的人,高能量饮食的风险更大。如果不同时考虑遗传和环境因素,可能导致对疾病风险的估计存在偏差。遗传多态性与饮食摄入相互作用。一些特定的基因多态性和结直肠癌之间的关联已经被观察到。但由于最初研究的方法限制,研究之间存在不一致性。饮食因素对不同基因型个体结直肠癌风险的不同影响,或同一基因型对不同暴露个体结直肠癌风险的不同影响,需要在未来的工作中进一步研究。
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引用次数: 20
Energy intake, overweight, physical exercise and colorectal cancer risk. 能量摄入、超重、体育锻炼和结直肠癌风险。
A. Giacosa, S. Franceschi, C. L. Vecchia, A. Favero, R. Andreatta
Epidemiological studies on risk factors for CRC have focused mainly on diet. In any case, the results of these studies show several inconsistencies, except for the beneficial role of high intake of vegetables and, to some lesser extent, of fruit. Weight and height have also been studied, partly because they reflect the balance between energy intake and expenditure in different age periods. Energy intake, body size and physical activity will be reviewed in this paper focusing mostly on recent data coming from Italian, English and Scandinavian studies. Overweight has long been recognized as a risk factor for hormone related and other cancers and this is confirmed not simply from case-control studies but from large cohort studies as well. The major findings of recent Italian studies are that excessive weight at various ages predicts colorectal cancer risk in men while in women, abdominal obesity, as indicated by a high WHR, represents a more reliable risk indicator. If all men could reduce their BMI below 25, about 9% of male colorectal cancer might be avoided in Italy. A decrease of WHR below 0.82 might reduce colorectal cancer in women by 19%. In addition, the epidemiological evidence consistently shows that physical activity reduces the risk of colon cancer. On the contrary, evidence on rectal cancer is less impressive. Some uncertainty still exists in relation to the intensity and duration of physical activity. In conclusion, body size control along all life and physical activity represent important factors to prevent colon cancer and a wide range of chronic conditions. Therefore, strategies to favour these goals through counselling from health-care providers, regulatory changes and programs aimed at individuals and communities should be implemented.
结直肠癌危险因素的流行病学研究主要集中在饮食方面。无论如何,这些研究的结果显示出一些不一致之处,除了大量摄入蔬菜和水果(在较小程度上)的有益作用。体重和身高也被研究过,部分原因是它们反映了不同年龄段能量摄入和消耗之间的平衡。能量摄入、体型和身体活动将在本文中进行回顾,主要关注来自意大利、英国和斯堪的纳维亚研究的最新数据。长期以来,超重一直被认为是激素相关癌症和其他癌症的风险因素,这不仅从病例对照研究中得到了证实,而且从大型队列研究中也得到了证实。意大利近期研究的主要发现是,不同年龄段的超重可以预测男性患结肠直肠癌的风险,而在女性中,高腰臀比表明的腹部肥胖是更可靠的风险指标。如果所有男性都能将体重指数降至25以下,那么在意大利,大约9%的男性结直肠癌可能会被避免。WHR低于0.82可能使女性结直肠癌发病率降低19%。此外,流行病学证据一致表明,体育活动可以降低患结肠癌的风险。相反,关于直肠癌的证据就不那么令人印象深刻了。体力活动的强度和持续时间仍然存在一些不确定性。总之,在生活和身体活动中控制体型是预防结肠癌和各种慢性疾病的重要因素。因此,应实施战略,通过卫生保健提供者的咨询、规章制度的改变和针对个人和社区的规划来促进这些目标。
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引用次数: 86
Clinical evidence for the adenoma-carcinoma sequence. 腺瘤-癌序列的临床证据。
O. Kronborg, C. Fenger
A review is given on evidence supporting or rejecting the hypothesis of a colorectal adenoma-carcinoma sequence. The majority of studies discuss adenomas from a clinical point of view, but pathology has also been considered in detail, and molecular biology has been touched on. It is concluded the adenoma stage is, most probably, a phase on the way to carcinoma. But it remains to be shown what effect the removal of adenomas will have in the long run on the incidence of colorectal carcinoma.
综述了支持或反对结直肠腺瘤-癌序列假说的证据。大多数研究从临床角度讨论腺瘤,但病理学也被详细考虑,分子生物学也被触及。结论:腺瘤期很可能是向癌发展的一个阶段。但从长远来看,腺瘤的切除对结直肠癌的发病率有什么影响还有待观察。
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引用次数: 38
Are there several types of colorectal carcinomas? Correlations with genetic data. 结直肠癌有几种类型吗?与遗传数据的相关性。
L. Martín, M. Assem, F. Piard
Molecular studies have shown that different genetic pathways are involved in the history of colorectal carcinomas. This suggests that a correlation exists between the molecular, clinical and pathological features of tumours. Two large groups can be individualized: the first group is characterized by allelic losses and hyperdiploidy. These LOH (for loss of heterozygosity)-positive tumours represent 80% of colorectal carcinomas. Among them more than two-thirds are located in the distal colon. They have the worst prognosis. The second group has a normal diploid pattern and a phenotypic microsatellite instability without allelic losses. These tumours represent 10-15% of all colorectal carcinomas and about 30% of the right-sided tumours. They are associated with a better prognosis. In the future, it would perhaps be better to classify colorectal carcinomas according to their molecular features rather than to their topographical localizations.
分子研究表明,不同的遗传途径参与了结直肠癌的历史。这表明肿瘤的分子、临床和病理特征之间存在相关性。两大组可以个体化:第一组的特征是等位基因丢失和高二倍体。这些LOH(杂合性缺失)阳性肿瘤占结肠直肠癌的80%。其中三分之二以上位于结肠远端。他们的预后最差。第二组具有正常的二倍体模式和表型微卫星不稳定性,无等位基因丢失。这些肿瘤占所有结直肠癌的10-15%,约占右侧肿瘤的30%。它们与较好的预后有关。在未来,根据其分子特征而不是其地理位置对结直肠癌进行分类可能会更好。
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引用次数: 20
Germline mutation and genome instability. 种系突变和基因组不稳定性。
S. Olschwang
Colorectal tumorigenesis has been associated with the progressive acquisition of a variety of genomic alterations in neoplastic cells. In 5-10% of cases, a strong family history of cancer suggests a major predisposition, either familial adenomatous polyposis (FAP) or HNPCC syndrome. In 1987, the gene responsible for FAP was localized on chromosome 5q. In 1991, the International Collaborative Group on HNPCC set stringent criteria for the diagnosis of HNPCC, to homogenize families that should be entered in large linkage analyses. In the past five years, five MMR genes could be identified as the site of germline mutations associated with a HNPCC syndrome (MSH2, MLH1, PMS1, PMS2, and MSH6). The TGFbeta RII gene has been found mutated at the germline level in a small number of HNPCC patients. The DNA mismatch repair pathway is essential for the correct maintenance of genetic information. The slippage occurs usually at microsatellite loci and the defect of one MMR gene leads to the accumulation of replication errors in such deficient cells. The tumours that exhibit the highest frequency of RER at microsatellite loci, thus termed RER+, account for 10-15% of all colorectal cancers, and for 92% of those developed in a context of a HNPCC syndrome.
结直肠肿瘤的发生与肿瘤细胞中各种基因组改变的逐渐获得有关。在5-10%的病例中,强烈的癌症家族史表明有主要的易感性,要么是家族性腺瘤性息肉病(FAP),要么是HNPCC综合征。1987年,负责FAP的基因定位在染色体5q上。1991年,HNPCC国际合作小组为HNPCC的诊断制定了严格的标准,以统一应纳入大型连锁分析的家庭。在过去的五年中,五个MMR基因可以被确定为与HNPCC综合征相关的种系突变位点(MSH2, MLH1, PMS1, PMS2和MSH6)。在少数HNPCC患者中发现tgf β RII基因在种系水平发生突变。DNA错配修复途径对遗传信息的正确维护至关重要。滑移通常发生在微卫星位点,一个MMR基因的缺陷会导致这种缺陷细胞中复制错误的积累。在微卫星位点表现出最高RER频率的肿瘤,即RER+,占所有结直肠癌的10-15%,占HNPCC综合征患者的92%。
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引用次数: 26
Cancer screening: an educational challenge? 癌症筛查:教育上的挑战?
M. Moore, H. Tsuda
Advances in identification of the risk factors for cancer development in different organs imply more effective screening for early malignancies. The associated increase in the predictive value, as well as the introduction of procedures with high sensitivity and specificity, provide promise that early intervention will result in a marked decrease in the mortality and morbidity due to a wide range of major cancers. Furthermore, a variety of methods are now available to detect lesions at a sufficiently early stage for curative surgery to be attempted. However, for the full promise to be realized, it is of paramount importance that both physicians and the public at large are fully aware of the potential benefits.
在不同器官中癌症发展的危险因素识别方面的进展意味着更有效地筛查早期恶性肿瘤。预测值的增加,以及高灵敏度和特异性手术的引入,为早期干预将显著降低各种主要癌症的死亡率和发病率提供了希望。此外,现在有多种方法可以在足够早期的阶段检测病变,以便尝试进行治疗性手术。然而,为了充分实现这一承诺,最重要的是医生和广大公众都充分意识到潜在的好处。
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引用次数: 9
Thyroid disorders and breast cancer. 甲状腺疾病和乳腺癌。
S. Shering, Zbar Ap, M. Moriarty, E. McDermott, N. O’higgins, P. Smyth
We have investigated the controversial association between diseases of the thyroid gland and breast carcinoma using methodology which allows positive exclusion of cases of breast disease from control groups and the detection of subclinical alterations in thyroid volume using high resolution ultrasonography, thus addressing the deficiencies of earlier studies. Whereas the prevalence of hyperthyroidism and hypothyroidism in patients with breast carcinoma and in healthy controls without clinical evidence of breast disease was similar, non-toxic goitre was more than twice as common in the breast carcinoma patients. Thyroid volumes were also significantly higher in breast carcinoma patients than in controls; using World Health Organisation criteria, 45.5% of breast carcinoma patients had thyroid enlargement compared with only 10.5% of controls. Finally, antithyroid peroxidase autoantibodies were twice as common in breast cancer patients than in controls. These findings provide clear evidence of a relationship between thyroid disease and breast carcinoma, although the mechanisms underlying this relationship require further study, future studies of breast cancer risk factors should therefore include assessment of thyroid function, antibody status and volume.
我们研究了甲状腺疾病与乳腺癌之间有争议的联系,使用的方法允许从对照组中阳性排除乳腺疾病病例,并使用高分辨率超声检查甲状腺体积的亚临床改变,从而解决了早期研究的不足。在乳腺癌患者和没有乳腺疾病临床证据的健康对照中,甲状腺功能亢进和甲状腺功能减退的患病率相似,但在乳腺癌患者中,无毒甲状腺肿的患病率是前者的两倍多。乳腺癌患者的甲状腺体积也明显高于对照组;根据世界卫生组织的标准,45.5%的乳腺癌患者有甲状腺肿大,而对照组只有10.5%。最后,抗甲状腺过氧化物酶自身抗体在乳腺癌患者中的发生率是对照组的两倍。这些发现为甲状腺疾病和乳腺癌之间的关系提供了明确的证据,尽管这种关系背后的机制需要进一步研究,因此,对乳腺癌危险因素的未来研究应包括甲状腺功能、抗体状态和体积的评估。
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引用次数: 68
Fruit and vegetables, and human cancer. 水果和蔬菜,和人类癌症。
C. Vecchia, A. Tavani
A large body of evidence indicates that high intakes of fruit and vegetables are associated with a reduced risk of cancer at several sites. The association is generally most marked for epithelial cancers, apparently stronger for those of the digestive and respiratory tracts, and somewhat weaker for hormone-related cancers. The relationship between frequency of consumption of vegetables and fruit and cancer risk was analysed using data from a series of case-control studies conducted in northern Italy since 1983. The relative risks (RRs) for most common neoplasms ranged from 0.2 to 0.5 for the highest compared with the lowest tertile of vegetable intake. Protective effects were highest for epithelial neoplasms, but were also observed for hormone-related neoplasms. Fruit was related to reduced RRs for cancers of the oral cavity and pharynx, oesophagus, stomach, larynx, as well as of the urinary tract. There was a specific and consistent pattern of protection by tomatoes, a typical Mediterranean food, with RRs between 0.4 and 0.7, most notably for gastrointestinal neoplasms. No significant association was observed between fruit and vegetable consumption and non-epithelial lymphoid neoplasms. For digestive tract cancer, population attributable risks for low intake of fresh vegetables and fruit ranged from 15 to 40% of all cases in this Mediterranean population. Combined with tobacco and alcohol, the population attributable risks exceeded 85% for men and 55% for women for upper digestive and respiratory tract neoplasms. Thus, from a public health viewpoint, epidemiological evidence indicates that a substantial reduction in epithelial cancer risk can be obtained by increasing fruit and vegetable consumption.
大量证据表明,大量摄入水果和蔬菜与某些部位的癌症风险降低有关。这种关联通常在上皮性癌症中最为明显,在消化道和呼吸道癌症中明显更强,而在激素相关癌症中则稍弱一些。使用自1983年以来在意大利北部进行的一系列病例对照研究的数据,分析了蔬菜和水果消费频率与癌症风险之间的关系。大多数常见肿瘤的相对危险度(rr)范围在0.2到0.5之间,最高的蔬菜摄入量与最低的蔬菜摄入量相比。保护作用在上皮性肿瘤中最高,但在激素相关肿瘤中也观察到。水果与降低口腔癌、咽喉癌、食道癌、胃癌、喉癌以及尿道癌的发病率有关。西红柿是一种典型的地中海食物,它有一种特殊而一致的保护模式,其相对危险度在0.4到0.7之间,对胃肠道肿瘤的影响最为显著。没有观察到水果和蔬菜的摄入量与非上皮性淋巴样肿瘤之间的显著关联。对于消化道癌,在地中海人群中,新鲜蔬菜和水果摄入量低的人群归因风险占所有病例的15%至40%。结合烟草和酒精,上消化道和呼吸道肿瘤的人群归因风险在男性中超过85%,在女性中超过55%。因此,从公共卫生的角度来看,流行病学证据表明,通过增加水果和蔬菜的消费可以大大降低上皮癌的风险。
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引用次数: 118
Cloning of sheep: a possible technique for reprogramming ageing mechanisms. 克隆绵羊:一种重新编程衰老机制的可能技术。
C. Gilbert
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引用次数: 0
N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids. n -亚硝基化合物与人:接触来源、内源性形成和在体液中的发生。
A. Tricker
Based on recent analytical data, total human exogenous exposure to N-nitrosamines is estimated to be 1.10 mumol/day; the major exposure sources are the diet (0.79 mumol/may, 80-120 micrograms/day; 72%), occupational exposure (0.15-0.30 mumol/day; 25%), cigarette smoking (0.02 mumol/day, 3.4 micrograms/day; 2%), and miscellaneous minor sources, including pharmaceutical products, cosmetics, indoor and outdoor air (0.001 mumol/day, 0.1 micrograms/day; 1%). Excretion of apparent total N-nitroso compounds (ATNC) in healthy adults is estimated to be 1.30 +/- 1.05 mumol/day in urine and between 1.56 +/- 1.56 and 3.17 +/- 2.58 mumol/day in faeces. The excretion of volatile N-nitrosamines (N-nitrosodimethylamine), and N-nitrosamine acids and their derivatives (N-nitrososarcosine, N-nitrosoproline, N-nitrosothiazolidine-4-carboxylic acid and N-nitroso-2-methylthiazoline-4-carboxylic acid) accounts for approximately 0.03% and 16.0% of urinary ATNC, respectively. 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol and its O-glucuronide conjugate, two metabolites of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone present in urine of smokers, account for 0.2% of the urinary ATNC response; < 1.5 of the excretion of currently identified N-nitroso compounds in urine. The remaining N-nitroso compounds excreted in urine and those present in faeces are still unidentified. A crude mass balance between exogenous exposure and excretion in urine and faeces indicates that 45-75% of the total human exposure to N-nitroso compounds results through in vivo formation.
根据最近的分析数据,估计人类对n -亚硝胺的总外源性暴露量为1.10毫摩尔/天;主要暴露源为饮食(0.79 μ mol/ 5, 80-120微克/天;72%),职业暴露(0.15-0.30 μ mol/天;25%),吸烟(0.02毫摩尔/天,3.4微克/天;2%),以及其他次要来源,包括药品、化妆品、室内外空气(0.001 μ mol/天,0.1微克/天;1%)。据估计,健康成人尿液中总n -亚硝基化合物(ATNC)的排泄量为1.30 +/- 1.05 μ mol/天,粪便中总n -亚硝基化合物(ATNC)的排泄量为1.56 +/- 1.56至3.17 +/- 2.58 μ mol/天。挥发性n -亚硝胺(n -亚硝基二甲胺)和n -亚硝胺酸及其衍生物(n -亚硝基肌氨酸、n -亚硝基脯氨酸、n -亚硝基噻唑烷-4-羧酸和n -亚硝基-2-甲基噻唑啉-4-羧酸)的排泄量分别约占尿ATNC的0.03%和16.0%。吸烟者尿液中存在4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁醇及其o -葡糖醛酸缀合物4-(甲基亚硝胺)-1-(3-吡啶基)-1-丁酮的两种代谢物,占尿ATNC反应的0.2%;尿中目前确定的n -亚硝基化合物排泄量< 1.5。其余的n -亚硝基化合物排泄尿液和存在于粪便仍未确定。外源性暴露与尿液和粪便排泄之间的粗质量平衡表明,人类对n -亚硝基化合物的总暴露中有45-75%是通过体内形成的。
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引用次数: 230
期刊
European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation
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