The Causes and Prevention of Cancer: The Role of Environment

The idea that synthetic chemicals such as DDT are major contributors to human cancer has been inspired, in part, by Rachel Carson's passionate book, Silent Spring. This chapter discusses evidence showing why this is not true. We also review research on the causes of cancer, and show why much cancer is preventable.Epidemiological evidence indicates several factors likely to have a major effect on reducing rates of cancer: reduction of smoking, increased consumption of fruits and vegetables, and control of infections. Other factors are avoidance of intense sun exposure, increases in physical activity, and reduction of alcohol consumption and possibly red meat. Already, risks of many forms of cancer can be reduced and the potential for further reductions is great. If lung cancer (which is primarily due to smoking) is excluded, cancer death rates are decreasing in the United States for all other cancers combined.Pollution appears to account for less than 1% of human cancer; yet public concern and resource allocation for chemical pollution are very high, in good part because of the use of animal cancer tests in cancer risk assessment. Animal cancer tests, which are done at the maximum tolerated dose (MTD), are being misinterpreted to mean that low doses of synthetic chemicals and industrial pollutants are relevant to human cancer. About half of the chemicals tested, whether synthetic or natural, are carcinogenic to rodents at these high doses. A plausible explanation for the high frequency of positive results is that testing at the MTD frequently can cause chronic cell killing and consequent cell replacement, a risk factor for cancer that can be limited to high doses. Ignoring this greatly exaggerates risks. Scientists must determine mechanisms of carcinogenesis for each substance and revise acceptable dose levels as understanding advances.The vast bulk of chemicals ingested by humans is natural. For example, 99.99% of the pesticides we eat are naturally present in plants to ward off insects and other predators. Half of these natural pesticides tested at the MTD are rodent carcinogens. Reducing exposure to the 0.01% that are synthetic will not reduce cancer rates. On the contrary, although fruits and vegetables contain a wide variety of naturally-occurring chemicals that are rodent carcinogens, inadequate consumption of fruits and vegetables doubles the human cancer risk for most types of cancer. Making them more expensive by reducing synthetic pesticide use will increase cancer. Humans also ingest large numbers of natural chemicals from cooking food. Over a thousand chemicals have been reported in roasted coffee: more than half of those tested (19/28) are rodent carcinogens. There are more rodent carcinogens in a single cup of coffee than potentially carcinogenic pesticide residues in the average American diet in a year, and there are still a thousand chemicals left to test in roasted coffee. This does not mean that coffee is dangerous but rather that animal cancer tests and worst-case risk assessment, build in enormous safety factors and should not be considered true risks.The reason humans can eat the tremendous variety of natural chemical "rodent carcinogens" is that humans, like other animals, are extremely well protected by many general defense enzymes, most of which are inducible (i.e., whenever a defense enzyme is in use, more of it is made). Since the defense enzymes are equally effective against natural and synthetic chemicals one does not expect, nor does one find, a general difference between synthetic and natural chemicals in ability to cause cancer in high-dose rodent tests.The idea that there is an epidemic of human cancer caused by synthetic industrial chemicals is false. In addition, there is a steady rise in life expectancy in the developed countries. Linear extrapolation from the maximum tolerated dose in rodents to low level exposure in humans has led to grossly exaggerated mortality forecasts.Such extrapolations can not be verified by epidemiology. Furthermore, relying on such extrapolations for synthetic chemicals while ignoring the enormous natural background, leads to an imbalanced perception of hazard and allocation of resources. It is the progress of scientific research and technology that will continue to lengthen human life expectancy.Zero exposure to rodent carcinogens cannot be achieved. Low levels of rodent carcinogens of natural origin are ubiquitous in the environment. It is thus impossible to obtain conditions totally free of exposure to rodent carcinogens or to background radiation. Major advances in analytical techniques enable the detection of extremely low concentrations of all substances, whether natural or synthetic, often thousands of times lower than could be detected 30 years ago.Risks compete with risks: society must distinguish between significant and trivial risks. Regulating trivial risks or exposure to substances erroneously inferred to cause cancer at low-doses, can harm health by diverting resources from programs that could be effective in protecting the health of the public. Moreover, wealth creates health: poor people have shorter life expectancy than wealthy people. When money and resources are wasted on trivial problems, society's wealth and hence health is harmed.     

Genomics of Cancer and a New Era for Cancer Prevention

A primary justification for dedicating substantial amounts of research funding to large-scale cancer genomics projects of both somatic and germline DNA is that the biological insights will lead to new treatment targets and strategies for cancer therapy. While it is too early to judge the success of these projects in terms of clinical breakthroughs, an alternative rationale is that new genomics techniques can be used to reduce the overall burden of cancer by prevention of new cases occurring and also by detecting them earlier. In particular, it is now becoming apparent that studying the genomic profile of tumors can help to identify new carcinogens and may subsequently result in implementing strategies that limit exposure. In parallel, it may be feasible to utilize genomic biomarkers to identify cancers at an earlier and more treatable stage using screening or other early detection approaches based on prediagnostic biospecimens. While the potential for these techniques is large, their successful outcome will depend on international collaboration and planning similar to that of recent sequencing initiatives.Since the publication of the initial human genome sequence in 2002, at a cost of around US$3 thousand million, DNA sequencing has advanced to the extent where whole genomes can be sequenced in days for around one millionth of the cost [1]. This has led to a scientific tour de force in projects that aim to understand the genetics of cancer. Large-scale initiatives such as the International Cancer Genome Consortium (ICGC) and the Cancer Genome Atlas (TCGA) for somatic variation, as well as the OncoArray Network for genome-wide studies of germline variation, have harnessed international expertise in oncology, genomics, and bioinformatics with very high levels of funding and have resulted in the coordinated genotyping, sequencing, and cataloging of many thousands of cancer cases [2]. Comprehensive genomic data from all completed cases are being made available to the research community, along with basic clinical information on some, allowing for extensive additional analyses. This initiative has led to a new understanding of how to define specific cancer subtypes and has vastly increased the pace of progress in elucidating the underlying biology of cancer [3].The most prominent visible outcome of the increased understanding of cancer biology is that targeted treatments have been developed or are being tested that aim to block specific molecules that spur the growth or spread of cancer. Although there are some exciting success stories such as the vastly improved survival with imatinib and chronic myelogenous leukemia (CML) or the increased efficacy of Herceptin treatment for women with Her2-positive breast cancer, most of this new generation of targeted treatments promise, at most, only a partial respite from the disease. The typical scenario is that the underlying cancer is not totally eradicated, remnants of the disease evolve and overcome any treatment, and the relapse is severe [4].New targeted therapies are also expensive to develop and to prescribe, some costing over US$100,000 for each patient per year, while being applicable for a smaller number of patients with the relevant subtype of disease. Disease resistance may be overcome through new strategies that combine therapies for specific pathways, and combination therapy of two or more drugs that target independent pathways is likely to hold even greater promise for improving response [5]. Other approaches such as combined use of immune checkpoint inhibitors are also providing exciting results [6], although there remain concerns that the strategy of developing targeted therapies for late-stage disease may be fundamentally flawed, given the inherent complexity and heterogeneity of such tumors [7,8]. A complementary approach would be to focus also on early detection of localized cancer, including the use of screening, when survival is usually a lot more favorable [3], as well as primary prevention in identifying the causes and minimizing exposure. The role of genomics in primary and secondary prevention of cancer has received less attention than treatment, although it is perhaps here that genomics will have its most important contribution in the long term.     

Prostate Cancer Prevention Through Pomegranate Fruit

Prostate cancer (CaP) is the second leading cause of cancer-related deaths among U.S. males with a similar trend in many Western countries. CaP is an ideal candidate disease for chemoprevention because it is typically diagnosed in men over 50 years of age, and thus even a modest delay in disease progression achieved through pharmacological or nutritional intervention could significantly impact the quality of life of these patients. In this regard we and others have proposed the use of dietary antioxidants as candidate CaP chemopreventive agents. The fruit pomegranate derived from the tree Punica granatum has been shown to possess strong antioxidant and anti-inflammatory properties. In a recent study, we showed that pomegranate fruit extract (PFE), through modulations in the cyclin kinase inhibitor-cyclin-cyclin-dependent kinase machinery, resulted in inhibition of cell growth followed by apoptosis of highly aggressive human prostate carcinoma PC3 cells. These events were associated with alterations in the levels of Bax and Bcl-2 shifting the Bax:Bcl-2 ratio in favor of apoptosis. Further, we showed that oral administration of a human acceptable dose of PFE to athymic nude mice implanted with CWR22R1 cells resulted in significant inhibition of tumor growth with concomitant reduction in secretion of prostate-specific antigen (PSA) in the serum. The outcome of this study could have a direct practical implication and translational relevance to CaP patients, because it suggests that pomegranate consumption may retard CaP progression, which may prolong the survival and quality of life of the patients.     

花青素防治乳腺癌研究进展

花青素是自然界分布最广泛的水溶性植物色素之一,主要存在于植物的花、叶和果实中。近年来,流行病学、动物肿瘤模型和离体细胞研究资料提示花青素对多种肿瘤具有化学防治作用。本文就花青素防治乳腺癌的研究进展及其作用机制作一综述。     

HPV感染与宫颈癌预防的研究进展

宫颈癌在全球范围内依然是严重威胁妇女健康的常见恶性肿瘤之一。流行病学调查显示,高危型HPV持续感染是导致宫颈癌发病的主要原因,并且HPV感染具有显著的特点,因此,预防HPV感染是防治宫颈癌的主要途径。已明确性行为是促进HPV感染最重要的辅助因子,个体免疫力低下及年龄因素亦是促进HPV感染的重要因素。研究显示,在全球逐渐开展的预防措施包括对常见的高风险HPV类型进行预防性疫苗接种及包括HPV检测在内的宫颈癌筛查项目的实施已经在降低宫颈癌的发病率方面起到了很重要的作用。近些年来,人们越来越重视HPV检测在宫颈癌筛查程序中的应用。由于HPV的感染率具有显著的地域性差异,我们需要针对各地区的特点以完善相应的宫颈癌筛查程序,从而为宫颈癌防治工作的开展提供重要依据。     

肿瘤标志物在卵巢恶性肿瘤早期误诊预防中的价值

目的:探讨糖类抗原CA125、CEA与CA199联合检测对卵巢癌有一定的鉴别诊断价值。方法:应用化学发光免疫法对126例经病理查证实的卵巢癌患者(试验组)、104例良性肿瘤患者(对照组)进行血清CA125、CEA与CA199检测。结果:试验组血清检测结果和阳性率均明显高于对照组(P<0.01),联合检测阳性率高于单项检测(P<0.01)。结论:应用检验医学进行CA125、CEA与CA199联合检测对卵巢癌有一定的鉴别诊断价值。可降低误诊率。     

十字花科植物中莱菔硫烷防癌机制研究进展

十字花科蔬菜中的异硫氰酸酯--莱菔硫烷(sulforaphane,SF)可以在癌症的起始、发展和增生3个阶段阻滞癌细胞的生长发育,降低癌症发生的风险,其前体物主要存在于西兰花中.本文主要对国内外近年来有关SF对化学致癌物代谢酶的影响、激活抗氧化基因活性、激活转录因子、阻滞细胞周期、诱导细胞凋亡等方面的研究进展进行综述,以探讨SF的防癌机制,为防癌抗癌食品和药物的研发提供参考.