1、Your Lifestyle, Your Genes and CancerNew research explores the complex interactions that cause our most dreaded disease. A look into some of the steps you can take to reduce your risk.By Robert A. Weinberg, Ph.D., and Anthony L. Komaroff, M.D. | NEWSWEEKJun 23, 2008 Issue Weve known for a long time
2、that a high-fat diet, obesity and lack of exercise can increase the risk of developing heart disease and type 2 diabetes, two conditions that affect millions of Americans. What we are finding out now is that those same lifestyle factors also play an important role in cancer. Thats the bad news. The
3、good news is that you can do something about your lifestyle. If we grew thinner, exercised regularly, avoided diets rich in red meat (substituting poultry, fish or vegetable sources of protein) and ate diets rich in fruits and vegetables, and stopped using tobacco, we would prevent 70 percent of all
4、 cancers.The strongest evidence of the importance of lifestyle in cancer is that most common cancers arise at dramatically different rates in different parts of the globe. Several cancers that are extremely common in the United Statescolon, prostate and breast cancerare relatively rare in other part
5、s of the world, occurring only 1/10th or 1/20th as often. Equally striking, when people migrate from other parts of the world to the United States, within a generation their cancer rates approach those of us whose families have lived in this country for a long time. Even if people in other parts of
6、the world stay put, but adopt a U.S. lifestyle, their risk of cancer rises; as Japanese have embraced Western habits, their rates of colon, breast and prostate cancer have skyrocketed.What is it about our lifestyle that raises the risk of many types of cancer? The main culprits seem to be the Wester
7、n diet, obesity and physical inactivity. While weve known about the importance of tobacco and cancer for more than 50 years, we are just beginning to understand how diet, a healthy body weight and regular exercise can protect us against cancerA striking example of the profound influence of diet was
8、reported last summer in The Journal of the American Medical Association. Doctors determined the eating habits of patients with colon cancer in the years following surgical removal of the cancer. Over the next five years, those who ate a traditional Western diet had a threefold greater likelihood of
9、developing a recurrence of the disease than did those who ate a “prudent“ diet rich in fruits and vegetables and including only small amounts of red meat. How had diet affected these patients? The surgery clearly had not removed all their colon-cancer cells: prior to the surgery, some cells had alre
10、ady spread from the primary tumor. The Western diet had somehow stimulated the growth of these small deposits of residual cancer cells.Obesity is the second most important factor in causing cancer in Western populations after tobacco, and there is evidence that maintaining a healthy weight is protec
11、tive against the disease. A study by the American Cancer Society in 2003 found that the heaviest people, in comparison with the leanest, had a significantly increased risk of death from 10 different kinds of cancer in men, and from 12 different kinds in women. The most extreme examples were liver ca
12、ncer in men (nearly fivefold increased risk) and uterine cancer in women (more than sixfold increased risk).Exercise has also been shown to play an important role in protecting against some cancers. For example, the Nurses Health Study reported that women who had one or more hours per day of moderat
13、e exercise had a 30 percent lower risk of colon cancer than women who exercised less. Exercise protects against breast cancer, as well.Lifestyle influences a persons risk for cancer by generating growth-promoting signals that affect cells primed to become cancerous, or that already are cancerous. Wh
14、at primes those cells to become cancerous in the first place are changes in their genes.All tumors begin with one renegade cell. Initially the cell is just one of about 30 trillion or so in the body. It looks no different from the cells around it, and, like those cells, it divides only if the organ
15、its part of needs it to divide. Then, even though the organ around it has enough cells, the renegade cell begins to multiply uncontrollably: one cell becomes two, two become four, four become eight, until the descendants are beyond counting.Cancer is ultimately a disease of malfunctioning genes. Per
16、haps 10 percent of all cancers occur in people who have inherited genes that make them vulnerable. In some cases, those genes are so influential the risk of cancer is very high. However, most of us are born with good genes that succeed in flawlessly organizing our growth and development. After all,
17、our genes have been optimized by more than 600 million years of evolution; they ought to work well. During the course of our lifetimes, though, genes are damaged in various cells throughout the body. It is these mutated genes that drive most cancers.Every cell contains growth-promoting genes called
18、“proto-oncogenes“ and growth-stopping genes called “tumor suppressor“ genes. Mutations that activate a proto-oncogene can cause the gene to release an unceasing stream of growth-stimulating molecular signals that cause the cell to multiply. Conversely, mutations that inactivate tumor-suppressor gene
19、s cause their growth-stopping messages to be silenced. In most human-cancer cells, there are multiple mutationssome that activate oncogenes and some that silence tumor-suppressor genes. In other words, cancer cells have stuck accelerator pedals and faulty brakes. During our lifetime, the cells in ou
20、r bodies will divide 1016 timesthats 10,000 trillion timescreating 10,000 trillion opportunities for our “start“ and “stop“ signals to malfunction, and for a tumor to start.Another important gene, called telomerase, is turned off in healthy cells, causing the cells to die after they have doubled abo
21、ut 50 times. Telomerase is turned on, however, in many cancer cells, which allows them to multiply indefinitely. There are other genes that cause a cell to “commit suicide“ when the cell senses that it has been damaged; if such a cell suicide gene becomes disabled, a cancer cell will be allowed to m
22、ultiply.Genes also affect a cancerous cells ability to metastasizeto detach itself from the primary tumor, crawl through the walls of nearby small blood or lymph vessels and spread through the circulation to other parts of the body. Research published in the past year has identified sets of genes th
23、at normally are active only when cells in an embryo need to migrate from one part of the embryo to another. In cancer cells that metastasize, these long-silent genes have somehow been activated. The genes make it easy for a cell to detach itself from the tissue around it and they improve the cells a
24、bility to move toward and through the walls of blood and lymph vessels. Recently, a small molecule called microRNA-10b was discovered to powerfully affect the ability of breast-cancer cells to metastasize. This is exciting because, at least theoretically, such small molecules are attractive targets
25、for treatments.But what causes the various genetic changes that lead to cancer? Mutation-inducing chemicalsmutagensin our environment can do so. Exhibit A, of course, is tobacco smoke. However, other environmental chemicals that many people suspect of causing cancerfood preservatives, contaminants i
26、n our drinking water, pollutants pouring out of smokestacksrarely do so. In fact, in the developed nations, only 1 to 2 percent of cancers are attributable to such environmental pollutants.Instead, most cancer-inducing mutations occur when cells damage their own genes accidentally. Each of our cells
27、 continuously produces mutation-inducing chemicals as byproducts of its normal metabolism. When our cells generate energy by converting oxygen into water, modified oxygen molecules called “oxygen radicals“ are produced. These radicals strike wildly at all the molecules in our cells, including the DN
28、A of our genes. Although our cells have the ability to repair this damage, the protection is not perfect, and so mutations and mutant genes accumulate as we grow older.Mutations, while necessary, are not sufficient. Something elsesomething from outside the cancer cellneeds to fan the flames. A cell
29、with several mutations may be primed to become cancerous, or may even be in the sluggish early stages of cancer, but that cell usually needs to be stimulated by additional growth-promoting signals to become a full-blown tumor. In fact, development of the great majority of human cancers is likely to
30、be driven by these non-mutagenic “cancer promoting“ molecular signals.We dont know precisely how the Western diet increases our risk of cancer. The foods we eat contain chemicals that can mutate genes and that therefore could cause cancer. For example, red meat cooked at high temperatures generates
31、potent mutagens called heterocyclic amines. Foods contain many different chemicals, and those chemicals are transformed in our body into many other chemicals, making it very difficult to pinpoint just what it is about the Western diet that raises our risk of cancer. But there is no doubt that it doe
32、s.While we dont really understand yet why obesity fosters cancer, cancer promoters could play a role. Obesity leads to high levels of insulin-like growth factor (IGF-1) in the circulation: theoretically, this could protect early-stage cancer cells scattered throughout the body from dying, since insu
33、lin-like growth factor inhibits the action of cell suicide genes. Inflammation also may explain the link between obesity and cancer. Inflammation is a normal body process designed to rid a tissue of infection and to heal it following injury. Cells of the immune system orchestrate inflammation, and s
34、ome of the weapons they deploy are chemical signals called cytokines. Often, inflammation is brief. If your skin is cut, or develops a bacterial infection, inflammation aids in repairing the wound or eliminating the bacteria. Having done its job, inflammation then subsides.However, if you have a con
35、dition that inflammation cannot rapidly heal, then the inflammation becomes protracted, chronic. The injured tissue is constantly bathed in growth-promoting cytokines that tell stem cells in the tissue to begin multiplying, in order to replace the cells that have been injured and destroyed. If any o
36、f these stem cells already have acquired mutations that make them precancerous, cytokines that encourage those cells to multiply can increase the risk that a tumor will start. For example, stomach tissue that can turn cancerous when it is chronically inflamed in response to the bacteria that cause m
37、any stomach ulcers. The same thing happens to the lining of gallbladders after years of irritation from gallstones, or to the liver after years of infection with hepatitis viruses.What does inflammation have to do with obesity? Fat cells release inflammatory chemicals into the circulation that can s
38、timulate the growth of cancer cells. The more overweight we are, the greater the level of inflammatory signals. It is possible that these cytokines act as cancer promoters, but much more research is needed to determine whether that is true.Regular moderate exercise lowers the levels of both IGF-1 an
39、d cytokines in our blood, and it does so even if the exercise does not lead to a healthy weight. It is possible that the lowered levels of these cancer promoters are one explanation for the protective effect of regular exercise. Blood-estrogen levels are lowered by regular exercise in women, and thi
40、s may be another way that regular exercise protects against getting breast cancer.Our growing understanding of cancer genes, and how they are influenced by cancer-promoting chemical signals, already has led to important new diagnostic tests and powerful new treatments, and will likely lead to even m
41、ore important advances in the future. But epidemiological studies of lifestyle and cancer have given us the power, today, to reduce our risk of cancer. While it isnt easy to make changes in lifestyle, it can happen. There are many fewer people using tobacco in the United States today than two genera
42、tions ago, when the risks of tobacco were first revealed. It may take another two generations to further reduce tobacco use, and to improve our diets, weight and exercise patterns, but it can happen. If it does, our grandchildren are likely to look back at our generation, scratch their heads and won
43、der why it took so long for us to escape the disease that many of us feared the most, by simple changes in the way we led our lives.Weinberg is Daniel K. Ludwig Professor for Cancer Research and American Cancer Society Research Professor at MIT, and a Member of the Whitehead Institute. His laborator
44、y discovered the first human oncogene and the first tumor-suppressor gene. He is the author of “One Renegade Cell: The Quest for the Origin of Cancer,“ published by Basic Books, 1999. Komaroff is professor of medicine at Harvard Medical School and editor in chief of the Harvard Health Letter. For mo
45、re information on lifestyle and cancer, go to health.harvard.edu/newsweek. 你的生活方式，你的基因和癌症罗伯特/邵红译原文来自 NEWSWEEK Jun 23, 2008 Issue长久以来，我们已知道高脂肪饮食、肥胖和缺乏锻炼会增加形成心脏病和二型糖尿病的风险，这两种病影响着数百万的美国人。现在我们发现的是这些同样的生活方式因素在癌症的形成有着重要的作用。这是一个坏消息。好消息是你可以改变生活方式。如果我们变瘦些，有规律的锻炼，避免含有丰富红肉的饮食（以家禽肉、鱼肉或蛋白质的蔬菜来源） ，采用含有丰富水果蔬菜的饮食，停
46、止吸烟，我们将可以预防 70%的癌症。生活方式对于癌症的重要性的最强证据是：最常见的癌症在地球的不同地方戏剧化的呈现出不同的比例。一些癌症在美国是极其普遍的，如结肠癌、前列腺癌和乳癌，然而在世界其它地方却是相当少的，仅有十分之一或二十分之一的比率。同样显著的是，当人们从世界其它地方移民到美国时，在一代以内，他们患癌症的比率接近这些已经在这个国家住了很长时间的人们。尽管世界其它地方的人们仍保持低比率的状态，但是采用美国生活方式后，他们患癌症的比率增加了，像日本接受了西方人的习惯，他们患结肠癌、乳癌和前列腺癌的比率突升。会提高许多类型癌症风险的生活方式是什么样子呢？罪魁之首是西方饮食、肥胖和身体静
47、止。尽管我们了解到烟草和癌症的重要性已经五十多年了，我们刚开始知道饮食、一个健康体重和规律的锻炼能够使我们远离癌症。饮食深远影响的一个显著例子发表在去年夏天的美国医疗协会期刊上。医生规定了那些数年来进行移除癌细胞治疗的结肠癌患者们的饮食习惯。五年后，这些食用传统西方饮食的结肠癌患者复发的可能性是采用高水果蔬菜含量和微量的红肉饮食的结肠癌患者的三倍。饮食是怎样影响这些患者的呢？外科手术无疑没有去除他们所有的结肠癌细胞：在外科手术前，一些细胞已经从最初的瘤扩散开来。西方饮食以某种方式刺激了这些残留癌细胞的小病灶的生长。肥胖在引起西方人口癌症的最重要因素中排名第二，仅次于烟草，这有证据表明保持健康体
48、重可以预防疾病。2003 年美国癌症协会有项研究发现：最重的人们，同最瘦的人们比较，死于十种不同类型癌症的风险显著提高，女性中死于十二种不同类型癌症的风险也显著提高。最极端的例子是其中最重男人们患肝癌的风险增加了五倍，最重女人们患子宫癌的风险增加了六倍多。运动在预防一些癌症中也表现出重要的作用。例如，护士健康研究报道：每天进行一个或一个多小时适度运动的女性们，她们患结肠癌的风险比起运动少的女性要低 30%。运动同样预防乳癌。生活方式通过产生促进生长信号，影响主要变成癌或已经癌变的细胞，来影响一个人患癌症的风险。首先促使这些细胞发生癌变是因为他们的基因发生了改变。.所有的瘤都是由一个变异细胞开始
49、的。最初这个细胞仅是身体上大约 30 兆个中的一个。它看起来和周围的细胞没有区别，并且，很像这些细胞，它仅在某个器官局部需要它分裂时才分裂。于是，尽管在这个细胞周围的器官有足够的细胞，变异的细胞开始失控的扩增：一个变异细胞变成两个，两个变成四个，四个变成八个，直到后代细胞不计其数。基因障碍的疾病最终形成癌症。大概所有癌症中的 10%发生在遗传有敏感基因的人们身上，这些基因对患癌症的风险的影响非常高。然而，我们中的大多数人出生时带有成功组织我们生长和发育的良好基因。毕竟，我们的基因经过 60 亿年的进化获得了最优化；它们应该良好得运作。然而在我们一生中，基因在整个身体的不同细胞内受到了损坏。就是这些变异的基因驱使许多种癌症发生。每个细胞包括促进生长基因原癌基因、抑制生长基因肿瘤抑制基因。激活原癌基因的变异促使基因释放一股持续的刺激生长分子信号，从而使细胞分裂。相反地，沉寂肿瘤抑制基因的变异使它们的抑制生长信息沉默。在大多的人类癌症细胞中，有多种多样的变异某些变异激活癌基因、某些变异沉寂肿瘤抑制基因。换句话说，癌细胞粘在加速的踏板和错的车闸上。在我们一生中，在我们体内的细胞会分裂 1016 次10000 兆次为我们“开始”和“停止”的障碍信号和肿瘤的产生创造了 10000 兆个机会。另一个重要的基因称为端粒酶，在健康的
