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Cancer and the Environment: Gene-Enviroment Interaction 8 Moving Forward This year alone, approximately 560,000 Americans will die of cancer-related causes, and almost 1.4 million new cancer cases are expected to be diagnosed. Despite these dire numbers, the data presented at the workshop reinforced the fact that we are making progress in the war against cancer. Most speakers agreed that it was an exiciting time to be in cancer research as we reach a point where we can treat or cure most cancers far more effectively. This is great news; however, as one speaker pointed out, we would prefer not to get cancer in the first place. The workshop laid out a number of strategies for the future of cancer research. The views of the speakers, panelists, and participants do not necessarily reflect the views of the Institute of Medicine or the Roundtable on Environmental Health Sciences, Research, and Medicine. DISPARITIES The success we have begun to see in the war against cancer isn’t equally accesible to all individuals or groups. As discussed by some speakers, several ethnic and racial populations have disturbingly high cancer incidence and mortality rates relative to the population at large, and these differences are even more pronounced for some cancer sites or organs. Reasons for the disparities might include the presence of specific genetic mutations, but they are more likely to reflect differences in environmental exposures, risk behaviors (e.g., tobacco use, diet), and utilization of prevention, screening, and treatment services. The populations with disparities include Hispanics, American Indians, Alaska Natives, Asian and Pacific Islanders, African Americans, Native Hawaiians, blue-collar workers, rural, elderly, and low-income and low-literacy groups. They not only carry a higher burden of cancer, but also are more prone to other diseases and societal problems. Moreover, the burden of cancer is disproportionately borne by the poor and the undereducated, as well as by populations at higher risk due to lifestyle, environmental exposure, or genetic susceptibility.
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Cancer and the Environment: Gene-Enviroment Interaction Achieving better cancer care and control within these underserved and high-risk populations is an extremely important goal. Even with additional emphasis, cancer will likely continue to be one of the leading causes of death in the early years of this century. Furthermore, the aging population will dramatically change the patterns of cancer in this century because cancer risks increase with age. Thus, the need for research on special populations is greater than ever before because these populations are the most vulnerable to negative consequences from the rapidly changing health care system. As several speakers emphasized, “One size does not fit all.” We must be creative in our approach to addressing cancer in various populations. As Dr. Lovell Jones emphasized, if we do what we have always done, then we will get what we always got. For these reasons, many panelists and speakers urged participants to conduct additional research on special populations to address disparities in incidence rates, mortality rates, and access to care in these populations and to put a greater emphasis on environmental disease surveillance including more complete cancer registries across all populations. CANCER PREVENTION Presentations throughout the two days highlighted the fact that many lifestyle and environmental carcinogens have been identified by investigating cancer in populations and that this knowledge has led to new approaches for reducing cancer risk. Yet there is still much to learn about the causes of cancer, particularly why one person with the same cancer-causing exposure (such as smoking or diet) develops cancer, whereas another does not. Individuals’ genetic makeup can affect their risk for developing cancer in ways more subtle than those seen in familial cancer syndromes. Variations in genetic susceptibilities related to how individuals control and respond to endogenous hormone levels, diet, exposure to carcinogens, sun, and infectious agents are likely to influence a given individual’s chance of developing cancer. According to many speakers, the estimates of cancer incidence support the claim that in an ideal world, more than 50 percent of cancers could be prevented if what is already known about the etiology and early course of cancer were acted on and fully adopted. These speakers also noted that tobacco use accounts for 30 to 40 percent of preventable cancer mortality; diet for another 20 to 40 percent; and alcohol, occupational exposure, and pollution for the remaining 5 to 17 percent. We have seen decreases in some cancer rates in the past 50 years due to positive changes in society. For example, stomach cancer and cervical cancer declined from 1950 to 1993 due to changes in food preparation and storage and improvements in medical screening and early treatment, respectively. In the 1990s, there was a modest (1 to 3 percent) overall age-adjusted decrease in cancer death rates. This decrease can be attributed to changes in behavior and environment, for example, successful reductions in smoking and better early
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Cancer and the Environment: Gene-Enviroment Interaction detection of cancer. According to some speakers and panelists, we need additional research and public health focus on preclinical stages of cancer with an emphasis on early diagnosis and intervention. FUTURE RESEARCH AREAS Mounting evidence indicates that mutation patterns detected in certain tumors may be distinct enough to provide a molecular fingerprint that is traceable to specific environmental agents. In large, population-based studies now under way, investigators described how they are exploring the way in which genetic factors and environmental exposures, including those related to lifestyle and diet, interact to influence cancer risk. By using minute quantities of DNA, it is possible to detect gene mutations whose patterns, functions, or effects may point the way to environmental, nutritional, hormonal, and other factors that contribute to cancer. As more information about human genes becomes available, there will be novel opportunities to test the importance of newly discovered genes for both their relation to cancer susceptibility and clues to environmental carcinogens. Development of multigenic models of cancer susceptibility will be an important future approach to predicting, preventing, and diagnosing some cancers, said participants. For example, prostate cancer is a common disease for which there are few well-established risk factors. Pedigree analyses suggest a genetic component for some individuals; however, the majority of prostate cancer cases cannot be explained by a single-gene model, suggesting multigenic etiology. Moreover, the international and racial–ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, suggest that genetic factors are likely to play a central role in determining prostate cancer risk. Even when there is evidence of genetic predisposition, however, future research efforts must focus on gene–environment interactions to fully develop effective cancer prevention and treatment strategies, concluded participants. Thus, even though genetic polymorphisms that predispose some men to prostate cancer or women to breast cancer have been found, the environmental factors that contribute to the actual development of disease must be explored. Moreover, although cancer cases are often clustered in certain families, pedigree analysis indicates that only 5 to 10 percent of cancer patients have a genetic predisposition to the disease. The basic mechanisms for hereditary cancer have been outlined, and a large number of the genes involved have been identified. CANCER REGISTRIES AND LARGE POPULATIONAL STUDIES During the workshop, we heard about a number of cancer registries including the NCI’s SEER program and the Kentucky Cancer Registry, and also about
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Cancer and the Environment: Gene-Enviroment Interaction large population studies (greater than 100,000 individuals) sponsored by the NCI and the American Cancer Society. Several participants suggested that the cancer registry data be combined with other databases to identify new etiologic leads. For example, cancer registry data could be combined with population survey data or environmental data sources such as pesticide usage or hospitalization data. Large epidemiologic consortia could pool data and publish results from several independent investigations simultaneously to quickly determine whether a given result in one study is supported by other studies. Such consortia would facilitate the pooling of data to assess rare subtypes, or combine data from multiply infected families, and would improve reproducibility and other quality control measures. Participants also noted the need for a linked environmental surveillance system. If cancer clusters were identified within the context of a nationwide childhood cancer registry, one could identify similar areas in the United States and look for similar types of clustering. Finally, there are approximately 80,000 industrial chemicals now registered for use, but very few have been tested for their health effects singly, synergistically, or with different kinds of genetic patterns. Hazard assessment for environmental chemicals is essential and would likely require the collaboration of many federal agencies and the private sector. RESEARCH IMPLICATIONS The workshop highlighted a number of potential research implications. Individuals discussed the needs for additional collaboration in multidiscliplinary research. One speaker discussed the need for more discovery-driven research to define the molecular landscape of cancer. This research has to be combined with epidemiological and animal research to fully understand the potential therapeutic implications. We need to continue the trend of investing in research on the preclinical stages of cancer and on early diagnosis. For example, with recent technological advances in molecular biology, several speakers noted the potential for cancer screening—that is, the identification of markers for inherited disease susceptibility, markers for gene alterations suggesting the development of disease, and markers of existing disease. These have important implications for cancer research because they allow the targeting of interventions based on genetic status. Thus, the more that is understood about the fundamental properties of a tumor cell, the more likely it is that an effective intervention can be identified. We also have to include the community in the problem, according to some speakers. If cancer is in the community, then the solution needs to be in the community. When the community is involved and has “buy-in,” we have access to greater amount of relevant data (e.g., lifestyle, exposure) that are critical to understanding cancer in a given geographic area. We need to take research from
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Cancer and the Environment: Gene-Enviroment Interaction the bench to the bedside, and then back to the bench, if we are to make progress, they suggested. Finally, we have to enhance skills and obtain better technologies in the area of risk communication. A few speakers suggested that the media is looking to the scientific community for guidance, but the message must be clear. Individuals in the community are looking for answers but often are frustrated, according to some speakers. POLICY IMPLICATIONS Since the Cancer Act of 1972, many reports on cancer have discussed the policy implications of current cancer research. The Institute of Medicine has released a number of these, including Ensuring Quality Cancer Care and The Unequal Burden of Cancer. One speaker reminded individuals that these reports contained a number of recommendations that have not yet been implemented. Additionally, we will have to allow broad access to population group data, but we must ensure patient consent and protection of patients’ rights. There will be a number of ethical–legal–social implications of genetic research that have to be defined and debated. Handling issues related to technology transfer will continue to be important in order to advance research results. The science community will have to give guidance in these areas to Congress and the public. Overall, many participants felt that we were making tremendous strides in the war on cancer. People felt that being diagnosed with cancer is no longer a death sentence and that the future holds promise for further progress in both treatment and prevention.
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