STUDENT CASE STUDY—STANFORD

CELL PHONES AND CANCER: EVALUATING THE EVIDENCE TO ASSESS POTENTIAL ASSOCIATION

CASE STUDY FOR AAC&U STIRS PROJECT

Jennifer S. Stanford, Assistant Professor of Biology, Drexel University, Philadelphia, PA

STUDENT CASE

Learning ObjectivesThrough their participation in this case study, students should be able to:

Part One1. Explain how an external factor could affect cells to cause cancer development.2. Describe the type of radiation emitted by cell phones.

Part Two3. Describe an experiment that could be done to assess whether the radiofrequency waves

from cell phones are sufficient to allow cells to become cancerous.4. Explain why sample size is important in data analysis and extrapolation.5. Predict results that would allow you to suggest that cell phone use and cancer are

correlated.6. Explain why causation can be difficult to establish in studies involving humans.

Part Three7. Identify limitations of existing epidemiologic studies of cell phone use and cancer.8. Examine data from epidemiologic and experimental studies and analyze whether there

is an association between cell phone use and cancer.9. Conduct a risk/benefit analysis regarding cell phone use and cancer.10. Design a novel, ethical, properly controlled study to evaluate any link between cell

phone use and brain cancer (optional).

Part Four11. Consider costs and benefits and make an evidence-based recommendation about

whether to fund additional research studying the association of cell phone use with brain cancer.

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Preparatory Materials

Before coming to class, please: Read about the International Agency for Research on Cancer categorization of agents

(http://monographs.iarc.fr/ENG/Preamble/currentb6evalrationale0706.php). Start at: Group 1: The agent is carcinogenic to humans (International Agency for Research on Cancer 2011).

Read Part One of the case. Optional:

o Read “I don’t know what to believe. . .” Making sense of science stories. This can be found on the Sense About Science website, on their resources page: http://www.senseaboutscience.org/resources.php (select the “I don’t know what to believe” reference).

To evaluate claims in an article, it is really important to understand which information is valid. This pamphlet will help you think about how to know what to believe when you are reading about science (Sense About Science 2006).

o Find one article from the popular media (i.e., newspaper, magazine, website, etc.) that supports your current view of whether cell phones cause cancer.

Introduction

Cell phones truly are everywhere. As of 2013, the number of cell phone subscriptions worldwide (6.8 billion) nearly equaled the number of people in the world (7.1 billion) (Sanou 2013). As a result, understanding the health implications of cell phone use is important to ensure global public health and safety. One of the biggest health concerns with regard to cell phone use is whether it contributes to cancer development. In fact, in 2011 the International Agency for Research on Cancer (IARC), part of the World Health Organization (WHO), designated cell phones as “Group 2B possibly carcinogenic to humans” (International Agency for Research on Cancer 2011). With that said, other major US organizations including the Food and Drug Administration (FDA), National Institute of Environmental Health Sciences (NIEHS), and the Centers for Disease Control and Prevention (CDC) have indicated that there is not sufficient evidence supporting an association between cell phone use and cancer (National Cancer Institute 2013). What should we believe about cell phone use and cancer? Do additional studies need to be done to allow us to conclusively determine whether cell phones cause cancer? Would such studies be worth funding? These are questions that you will explore through this case as you learn more about the relationship between cell phones and cancer.

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Part One. Cancer Development and the Possible Link to Cell Phones

What Is Cancer?From a biological perspective, cancer is the abnormal, unregulated growth of cells (Figure 1). Our bodies are made up of cells (National Cancer Institute 2014). Some of these cells can undergo a process that allows them to divide to make two cells. This process is necessary for the growth and development of organisms, and to replace damaged or dead cells. Most of the cells in our body do not normally divide unless they receive signals within the body that indicate that more cells of that type are needed (National Cancer Institute 2014). Cancer cells no longer respond properly to signals that tell them to divide or to stop dividing (National Cancer Institute 2014). As a result, these cells divide rapidly leading to the development of an inappropriate mass of cells, called a tumor (National Cancer Institute 2014). Importantly, cells begin to divide inappropriately due to multiple, specific, alterations in cellular DNA (Almeida and Barry 2011). These alterations, or mutations, can be inherited and/or acquired (Almeida and Barry 2011). The changes to cellular DNA can affect the behavior and appearance of the cell leading to the loss of certain cellular properties and the acquisition of others (Almeida and Barry 2011). In other words, cancer is a disease caused by cells that are more apt to divide quickly and grow in inappropriate locations due to DNA mutations (Almeida and Barry 2011; National Cancer Institute 2014).

What Is DNA and How Is it Relevant to Cancer?Our genetic information is contained within our DNA, or deoxyribonucleic acid (Figure 2). DNA is a double stranded, helical macromolecule that is made up of nucleotides. Genes are made up of DNA, and specific genes provide the information to make specific proteins within our cells (Almeida and Barry 2011). Proteins are the molecules that carry out many of the functional roles in our cells. As a result, a mutation, or change to the sequence, in DNA could lead to the production of proteins that are abnormal in terms of their shape and function (Almeida and Barry 2011). Proteins that have abnormal functions can affect the behavior of our cells.

DNA mutations, or alterations in the DNA sequence, can either be inherited or spontaneous. Inherited mutations

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Figure 1: Loss of Normal Growth Control (Source:

http://www.cancer.gov/PublishedContent/Images/images/research/science/cancer4-new.jpg)

Figure 2: DNA Structure (Source: http://www.cancer.gov/PublishedContent/Image

s/cancertopics/understandingcancer/cancer/cancer40.jpg)

STUDENT CASE STUDY—STANFORD

are acquired from an individual’s parents (Almeida and Barry 2011). Spontaneous mutations can happen throughout the life of a cell (Almeida and Barry 2011). A spontaneous mutation can arise as a result of DNA damage. DNA damage, and thus spontaneous mutations, can occur because of cellular exposure to carcinogens or infectious agents, though there are also other reasons why spontaneous mutations can occur (Almeida and Barry 2011). Interestingly, approximately 90% of all diagnosed cancers are the result of the acquisition of spontaneous mutations (Almeida and Barry 2011). In other words, the vast majority of cancers arise due to DNA mutations that are acquired in response to cellular exposure to environmental factors such as carcinogens, as opposed to being caused by inherited factors.

Does a Mutation in any Gene Cause Cancer? Not every mutation in a DNA molecule within a cell will lead to cancer development. It has been suggested that of all of the human genes, mutations in only about one percent of these genes are relevant to causing cancer development (Futreal et al. 2004). To become cancerous, cells must contain or acquire mutations in genes that are relevant to processes related to cancer development, such as cell division, cell migration, and/or DNA repair (Almeida and Barry 2011). Two classes of genes that are commonly mutated in cancer are proto-oncogenes and tumor suppressor genes (Almeida and Barry 2011).

A common analogy when discussing proto-oncogenes is to think of the cell as a car (CancerQuest 2012). In this analogy, proto-oncogenes encode proteins that function similarly to a gas pedal on a car. In response to the proper signals, such as a green light, the gas pedal can be depressed to tell the car to go. Similarly, proto-oncogenes function to tell a cell to grow and divide in response to proper conditions both within and outside the cell (Almeida and Barry 2011). If proto-oncogenes are mutated to form oncogenes, this can lead to an increase in the rate of cell division, which is abnormal. While proto-oncogenes only promote cell division if the proper signals or conditions are present, oncogenes promote cell division all of the time (Almeida and Barry 2011). This means that oncogenes promote cell division whether or not signals are present that tell the cell to divide. In the analogy, this would be similar to permanently putting a brick on the gas pedal. In that case, the car would be pushed to move forward, regardless of environmental signals.

Tumor suppressor genes are another class of genes mutated in cancer. The products of these genes prevent cells from dividing until the internal and/or external conditions are appropriate for cell division (Almeida and Barry 2011). To continue with the car analogy, these gene products function similarly to a brake pedal. In response to proper signals, such as stop signs or red lights, the brake pedal can be activated to prevent the car from moving. Similarly, tumor suppressor genes can be activated in response to the proper signals to prevent the cell from dividing (Almeida and Barry 2011). Mutations that inactivate these genes are problematic because the products are no longer able to stop cell growth and division in response to environmental factors. Just like if the brake line in a car is cut, a cell without a functional copy

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Figure 3: Cancer Tends to Involve Multiple Mutations (Source:

http://www.cancer.gov/PublishedContent/Images/cancertopics/understandingcancer/cancer/cancer49.jpg)

STUDENT CASE STUDY—STANFORD

of a tumor suppressor gene will have a hard time with inhibiting cell division in response to relevant environmental signals.

Importantly, a mutation in one gene alone is not sufficient to cause cancer (Figure 3). The development of cancer is a multi-step process that requires acquisition of multiple mutations within cells (Hanahan and Weinberg 2000). This is because there are systems of checks and balances within the cell to keep the cell functioning properly. For example, if a cell contains an oncogene, the products of functional tumor suppressor genes could still prevent cell division until conditions are appropriate for cell division to occur.

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Why Is there Concern that Cell Phones Are Dangerous?Cell phones have been brought under scrutiny because they emit radio waves, which are a form of electromagnetic radiation (Linet and Inskip 2010; National Cancer Institute 2013). Not all electromagnetic radiation is problematic for human health. Electromagnetic radiation can be classified into two general categories: ionizing and non-ionizing (Figure 4). While ionizing radiation can directly damage DNA, non-ionizing radiation cannot (Linet and Inskip 2010; National Cancer Institute 2013). For example, X-rays are a form of ionizing radiation that has been shown to be detrimental to human health at certain levels. Visible light is a form of non-ionizing electromagnetic radiation, as are the radio waves emitted by cell phones (Linet and Inskip 2010; National Cancer Institute 2013). Although radio waves do not damage DNA, they can heat biological tissue, though at a level that is insufficient to increase body temperature (Linet and Inskip 2010; National Cancer Institute 2013) or alter biological materials (Moulder et al. 1999).

To assess the health risks of cell phones, experiments have been conducted using radiofrequency radiation at levels equivalent to those emitted by cell phones. These experiments will be described later in this case. To better understand these experiments, it is useful to learn some of the terminology used to describe electromagnetic energy. The frequency of electromagnetic energy is the number of cycles of an electromagnetic wave that occur in a second (World Health Organization 2013). Frequency is measured using Hertz (Hz) as the unit, where 1 Hz is equivalent to one cycle per second (World Health Organization 2013). Cell phones typically have frequencies ranging from 450 MHz to 2.7 GHz (World Health Organization 2011). The power of electromagnetic radiation is typically measured in watts (World Health Organization 2013). A watt (W) is a unit that is used to describe the amount of energy consumed per second, where 1W is equivalent to the consumption of one joule per second. The peak powers of cell phones range from 0.1 to 2 watts (World Health Organization 2011). To measure radiofrequency energy in the human body, Specific Absorption Rate (SAR) can be used as a way to determine exposure strength (Federal Communications Commission 2013). SAR is the power of RF wave absorbed per unit mass of tissue, and is typically measured in units of watts/kg. Currently the limit set by the US Federal Communications Commission is 1.6 W/kg (Federal Communications Commission 2013).

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Figure 4: The Electromagnetic Spectrum (Source: http://www.arpansa.gov.au/radiationprotection/basics/ion_n

onion.cfm)

STUDENT CASE STUDY—STANFORD

Question 1: Does the IARC categorization of cell phones into Group 2B indicate that cell phones cause cancer? Why or why not?

Question 2: Carcinomas are the most common type of cancer. Lung cancer, prostate cancer, breast cancer, and colon cancer are examples of carcinomas. Carcinomas are cancers that are derived from epithelial cells. These are the cells that line the walls and cavities of the body and outside of the body. Based on the information you’ve learned thus far, why do you think that the majority of diagnosed cancers are carcinomas?

Question 3: Considering what you have learned about cancer, what would a cell phone have to do in order to cause cancer?

Question 4: Do you think that radiofrequency waves are likely to cause cancer? Why or why not?

Part Two: Radiofrequency Exposure and Its Effects

How Do We Know What We Know about Cancer?It is very common in the popular media to see or hear statements such as X causes Y. For example, cell phones cause cancer. It is important to note that scientists apply stringent standards before they use the term causation to describe the relationship between two variables. Non-scientists do not always apply these standards before using this term. As a result, sometimes the popular media uses the term causation in a way that misrepresents existing evidence. Causation is the idea that one event causes another. In this case, if X causes Y and it is the only thing that causes Y, then if X doesn’t happen then Y won’t happen either. Correlation (also termed “association”) is the idea that one event happens at the same time as another (Graziano and Raulin 2009). For example, X and Y could be caused by the same event, event Z. In that case, if X doesn’t happen, that doesn’t necessarily mean that Y will not happen. It is important to distinguish between causation and association. If two events always occur together that does not necessarily mean that one is causing the other. Importantly, the only type of research that allows you to determine causation is experimental research (Graziano and Raulin 2009). This is because experimental research is the only kind of research that allows for manipulation of a variable.

In order to assess whether a particular environmental factor causes cancer, one approach is to conduct experiments to assess what effects that factor has on cells and organisms. By exposing cells directly to a potential carcinogen (cancer causing substance), it is possible to ask whether that substance causes mutations in DNA or changes to the rate of cell division, for example. Typically, experiments are set up to ask questions about the relationship between two variables, an independent variable and a dependent variable (Graziano and Raulin 2009). The independent variable is the variable that is changed by the experimenter (Graziano and Raulin 2009). The dependent variable is the variable that may or may not change in response to differences in the independent variable (Graziano and Raulin 2009). For example, an

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experimenter might add a substance to cells and observe whether adding that substance increases the rate of cell division. In this example, the independent variable is the substance added to the cells and the dependent variable is the rate of cell division.

One of the most important elements of establishing a good experiment is that the system must be well controlled. If controls are not used, it is impossible to state definitively that the independent variable caused a change in the dependent variable. This is because without controls, you do not know whether other variables could be changing and affecting the outcome of the experiment (Graziano and Raulin 2009). For example, what if lab temperature changed at the same time the experimenter added a test substance onto cells? In this case, any change to the dependent variable could be due to the test substance or the change in temperature. Variables that change at the same time as the independent variable are referred to as confounding variables (Graziano and Raulin 2009). These variables can inhibit proper interpretation of results unless they are properly controlled for. This is why researchers set up experiments using the same environmental conditions (i.e., temperature) each time. This is also why other controls are used, including negative and positive controls.

A negative control is a control in which the outcome of the experiment is known to be negative (Graziano and Raulin 2009). For example, if we hypothesize that adding Substance X to cells will increase cell division, a negative control would be growing the cells in the absence of Substance X and assessing the cell division rate for those cells. In this case, the conditions for the negative control would be identical to the conditions for the experimental group. The only difference would be the presence or absence of the independent variable, Substance X. The negative control provides a source of data to which experimental data can be compared (Graziano and Raulin 2009). It allows an experimenter to determine whether changes observed in an experimental group are actually due to the independent variable.

A positive control is a control in which the outcome is expected to be a change in the dependent variable (Graziano and Raulin 2009). For example, in the experiment described previously, a positive control would be to grow the cells in the presence of a carcinogen known to increase the rate of cell division. Once again, the conditions for the positive control would be identical to the conditions for the other groups. The positive control provides a mechanism to ensure that the tool you are using to measure the dependent variable is working properly (Graziano and Raulin 2009). If you do not see a change in the dependent variable in the positive control in an experiment, this suggests that something was wrong with either your experimental set-up or with the tools you are using to collect your data. For example, if the known carcinogen did not increase the rate of cell division, this would suggest that the experimental system is not working as predicted. As a result, results from the experimental condition would be unreliable.

In addition to studying how potential carcinogens affect cells, it is also possible to study how these factors affect organisms. This can also be done using experimental research with proper controls. For example, an animal could be exposed to a potential carcinogen and experimenters could observe whether exposure to that substance leads to the development of tumors within

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that animal. In this case, a negative control could be treating a group of animals identically to the experimental group, with the exception of exposing them to the potential carcinogen. A positive control could be treating a group of animals identically, but exposing them to a known carcinogen instead of to the potential carcinogen of interest.

Experimental research is not the only way that we learn whether substances are carcinogenic. One important reason is that, in many cases, experimental research to assess causation is not ethical when studying humans. Certain questions or approaches are just not ethical with respect to human studies. The Belmont Principles were established in 1979, and continue to be the guidelines used to assess the ethics of research with human subjects (National Commission for the Proptection of Human Subjects of Biomedical and Behavioral Research, Bethesda, MD. 1978). This report describes three fundamental ethical principles that should be used for any human research. The first is respect, which indicates that all individuals should be allowed to make their own decisions and be given the information needed to make an informed and uncoerced decision. The second is beneficence, which indicates that the harm to the study participants has been minimized and the benefit to society is maximized. Finally, the third is justice, which indicates that people should be given an equal and fair opportunity to participate in the research.

As a result of the Belmont Principles, certain experiments with humans are not ethical to conduct. For example, since tobacco smoke is a known carcinogen, setting up an experiment where 500 people are told to smoke two packs a day for a year (experimental group), and 500 people are told not to smoke at all for a year (negative control), is unethical. This type of study would violate the Belmont Principle of beneficence, as it is known that the experimental group would be exposed to a substance that would cause harm to the study participants. Beyond these ethical reasons, human experiments are also sometimes impractical to conduct. For example, it is often impractical to conduct long-term experiments with humans to study long-term exposure to particular environmental factors, or to study diseases that have a long lag time between initial exposure to a particular environmental factor and development of the disease. Some of the reasons these long-term experiments are impractical include that patients are unlikely to agree to participate in such a long term study or to comply with maintaining experimental conditions over long periods of time.

An alternative approach is to use non-experimental (or “observational”) studies to learn what happens when humans are exposed to a particular environmental factor. For example, an observational study can be done in which 500 people who choose to smoke are compared to 500 people who do not smoke. In this case, we are comparing pre-existing groups within the population. Importantly, this observational study cannot be used to determine causation, because it is possible that something additional is different about people who choose to smoke compared with people who choose not to smoke. For example, what if all of the people who chose to smoke were also stressed? It would be impossible to distinguish between smoking and stress as the reason for any observed increase in cancer incidence. As a result, if the people who choose to smoke have a higher incidence of developing cancer, we can only say that there is an association between smoking and cancer development. To overcome this limitation, most

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observational studies attempt to measure as many other factors as possible (confounders) that might contribute to the outcome of interest.

Now that you know a bit more about the types of scientific evidence that support our ability to understand the relationships with environmental factors and cancer, let’s start to explore the studies that focused on exposure to the type of radiation emitted by cell phones, radiofrequency radiation.

Data from Studies of Radiofrequency Radiation ExposureTo understand whether radiofrequency radiation induces changes to cells to make them cancerous, a group of scientists exposed mouse cells to 2.1425 GHz radiofrequency fields at 800 mW/kg continuously for 41 days (Hirose et al. 2008). Of note, according to the World Health Organization, cell phones are thought to operate at a frequency no higher than 2.7 GHz with a peak power no higher than 200 watts (World Health Organization 2011). The study included negative and positive control groups. The negative control group of mouse cells was treated identically to the experimental group, but was not exposed to radiofrequency radiation (Hirose et al. 2008). The positive control group of cells was treated identically to the experimental group, but was exposed to a known carcinogen (Hirose et al. 2008). The researchers looked for the formation of structures (foci) in petri dishes, which only form when cells are transformed into a cancerous phenotype (Hirose et al. 2008). At the end of the study, the experimental dishes looked identical to the negative control dishes (Hirose et al. 2008).

Several groups have conducted studies using rodents in order to assess whether radiofrequency radiation promotes tumor development in rats. In one such study, 500 mice were exposed to 0.9 GHz radiofrequency fields at 4000 mW/kg for one hour per day, seven days a week (Oberto et al. 2007). This study included a group of mice that were treated identically but were not exposed to radiofrequency radiation (Oberto et al. 2007). Mice in the experimental group were no more likely to develop tumors than mice in the control group. Additional rodent studies have confirmed that radiofrequency radiation does not increase the likelihood of tumor development under controlled experimental conditions (National Cancer Institute 2013).

In addition to studies that have been done with cells and animals, epidemiologic studies have been conducted to understand the health impacts of human exposure to radiofrequency radiation. These studies have included occupational studies of those who are frequently exposed to radiofrequency radiation through their jobs. These include US Navy electronics technicians, fire control technicians, and cell phone manufacturing workers. These studies have also included residential exposure from radio and television transmitters. A review of these studies concluded there was no convincing evidence that radiofrequency (RF) exposure causes any adverse health effect (Ahlbom et al. 2004). However, this review acknowledged that the existing studies had limitations, especially that information on the amount of RF the workers had been exposed to was imprecise. As a result of these limitations, the review concluded it was not possible to rule out an association between radiofrequency radiation exposure and adverse health effects (Ahlbom et al. 2004).

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Question 5: How could you experimentally assess whether radiofrequency waves from cell phones are sufficient to allow cells to become cancerous?

Question 6: Based on the information presented so far, do you think there is an association between cell phone use and cancer? Why or why not?

Question 7: You pose the hypothesis that cell phones are associated with brain cancer. To test this hypothesis, you conduct an observational study that enrolls 100,000 people diagnosed with brain cancer and 100,000 people that do not have brain cancer. From these individuals, you gather data on cell phone use. What results from this study would allow you to conclude that cell phone use and cancer are associated?

Part Three: What We Know About Cell Phone Use and Cancer Development in People

Anecdotal Reports of Cancer in Individual Cell Phone UsersNow that we’ve discussed how radiofrequency radiation affects cells, animals and people, what do we know about the effects of exposure to cell phones themselves? In December 2013, Dr. Oz aired a segment about a woman named Tiffany Frantz, who developed breast cancer at the age of 21 (Oz 2013). This young woman carried her cell phone in her bra. She and her mother believe that the cell phone caused her breast cancer. They indicate that Tiffany had no family history of breast cancer, and that she hasn’t inherited the genetic mutations that are attributed to breast cancer. In addition to this anecdote, there have been several cases of famous individuals who have died of brain tumors and were heavy cell phone users. One such case is that of Johnnie Cochran, who was a defense lawyer involved in many high-profile trials, including the O. J. Simpson trial. Mr. Cochran was known to use his cell phone extensively on the same side of the head as where he developed a brain tumor (McClenaghnan 2012). These are examples of anecdotal evidence, or evidence from stories involving individual people.

Data from Epidemiologic StudiesA number of large epidemiologic studies have been done to study whether there is an association between cell phone use and brain cancer. These include case control studies and cohort studies. Case control studies are studies that compare people who have a condition of interest (cases) to people who do not have that condition (controls) to see whether a particular environmental or behavioral factor is found more or less often among people that have the condition of interest (National Cancer Institute 2013). Cohort studies are studies that compare people who were exposed to a particular environmental factor to people who weren’t exposed. These groups are followed up over time to see whether exposure to that factor correlates with an increased or decreased risk of having a particular outcome (National Cancer Institute 2013).

One of the largest case control studies conducted was the Interphone Study (Cardis et al. 2007). This was a study that compared over 5,000 patients with brain tumors to control patients who did not have brain tumors (Cardis et al. 2007). These patients came from 13 different countries (Cardis et al. 2007). Participants were limited to those aged 30–59 to increase the likelihood of

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exposure to cell phones (Cardis et al. 2007). Control participants were matched by age, sex, and study region (Cardis et al. 2007). In other words, if a 39-year-old female from France with a brain tumor was selected for the study, a 39-year-old female from France without a brain tumor would be selected as her matched control. Participants in the study were interviewed to ask about mobile phone use, use of other wireless communication devices, risk factors for brain cancer, medical history, and socioeconomic status (Cardis et al. 2007). This study cost approximately $26.5 million to run (International Agency for Research on Cancer 2010).

In this study, no increased risk in brain tumors was observed with cell phone use (INTERPHONE Study Group 2010). There was no evidence of increased risk observed with longer call times, number of calls, nor years since beginning cell phone use (INTERPHONE Study Group 2010). A modest increased risk in a specific type of brain cancer, glioma, was observed with patients who reported the highest cumulative call time of 1,640 hours or greater (INTERPHONE Study Group 2010). Researchers attributed this finding to biases and error in reporting on the part of these patients (INTERPHONE Study Group 2010). For example, the hours of cell phone use reported by some participants with glioma were thought to be unlikely. The Interphone Study also found no association between the location of a brain tumor and the side of the head where cell phones were typically used (Larjavaara et al. 2011).

The largest cohort study was conducted in Denmark (Frei et al. 2011; Johansen et al. 2001; Schuz et al. 2006). It was a nationwide study of Danish citizens 30 or over that included over 420,000 individuals who had a mobile phone contract before 1995. The study compared incidence of cancer in the cell phone users with incidence of cancer in the overall Danish population (Johansen et al. 2001). Denmark provides a unique opportunity to study cell phone use and cancer incidence in this way, as there is a central population register that has existed in Denmark since 1968 that is used to track health outcomes, gender, age, address, and other factors (Johansen et al. 2001). Using data from Denmark cell phone companies, the investigators were able to match address records from cell phone subscribers to the address records in the central population register (Johansen et al. 2001). These data allowed the investigators to ask questions about health outcomes of cell phone subscribers. This study has been continued and updated twice since the initial results were reported in 2001 (Frei et al. 2011; Schuz et al. 2006). All three publications have demonstrated no increased risks of tumors amongst cell phone users, even those who had used cell phones for 10 years or more (Frei et al. 2011; Johansen et al. 2001; Schuz et al. 2006).

Question 8: Brainstorm some potential problems with anecdotal reports of cancer development.

Question 9: What confounding variables could have contributed to cancer development in the cases of Tiffany Frantz and Johnnie Cochran?

Question 10: Which of the Belmont Principles would be violated by an experiment designed to determine whether cell phones cause cancer in humans?

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Question 11: Based on the information provided, what are the limitations of the described studies?

Question 12: Could these limitations be addressed through better study design?

Question 13: Are there issues that you are interested in with regard to cell phone use and cancer that are not addressed by the described studies? If so, what are they?

Question 14: Based upon what you have read now, do you think there is an association between cell phone use and cancer? Why or why not?

Question 15: Considering the evidence that has been presented through the case thus far, will you change your behavior with regards to your cell phone use? Why or why not?

Activity (Optional): Design a novel, ethical, properly controlled study to evaluate the link between cell phones and cancer. This study could address the limitations in previous studies or address issues that you feel have not yet been addressed by previous studies. What type of study would you choose and why? What are the controls that you would include for your study? How would this study allow you to determine an association between cell phones and a particular type of cancer? Are there any ethical concerns with your study, and if so, how are they being addressed? Why is this approach novel?

Part Four: Funds Available to Support Cancer Research

Data on Available Research FundingIn considering whether or not it is necessary or appropriate to fund additional research on the association between cell phone use and cancer, it is not only important to consider the strength of the currently available data and the limitations of published studies, but also to consider the funds available to support this type of research. Research in the United States is primarily funded by the government. The US government provides budgetary funds to grant funding agencies, such as the National Institutes of Health or National Science Foundation. These agencies solicit grants from academic and clinical scientists. There are funding announcements posted on websites of these funding agencies and scientists compete for funding by writing research proposals that describe their intended work. These grants are reviewed by a panel of experts. These are usually other academic and/or clinical scientists with expertise in the area of research in the proposal. These individuals review each grant to ensure that the proposed science is logical, interesting, and likely to lead to important findings. Each year, grant funding agencies can only fund a limited percentage of the proposals they receive based on their budget. As a result, the panel will compare the grants and choose the ones that seem to be the most promising.

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In fiscal year (FY) 2011, the federal budget dedicated to research and development was approximately $140.0 billion (Sargent 2013). Of these funds, approximately $5.5 billion went to the National Science Foundation (NSF), and approximately $31 billion went to the National Institutes of Health (NIH), the two agencies that are most likely to support research on cell phone use and cancer (Sargent 2013). Within these two agencies, the organizations that would be most likely to fund this research include the National Cancer Institute (NCI), which had a budget of approximately $5 billion in 2012, the National Institute of Environmental Health Sciences (NIEHS), with a budget of $684 million, and the Biological Sciences Directorate of NSF (NSF-BIO), with a budget of $712 million (Sargent 2013). Of note, these funds are intended to support all research relating to cancer biology (NCI), understanding how the environment affects human health (NIEHS), and understanding basic molecular, cell, organismal biology, and environmental science (NSF-BIO).

Within these divisions of NIH and NSF, only a certain amount of this money is designated to supporting new research proposals. The rest is used to continue supporting proposals that were funded in previous fiscal years, to support the administration of that division, and to support other programs such as postdoctoral training programs. In 2013, ~$404 million was spent by the NCI on new research project grants, for a funding rate of ~14% (National Institutes of Health 2014). What this means is that for all of the research funding proposals submitted to NCI, only about 14% were funded. Consider that 1,095 applications were awarded in FY2013, which means that, on average, about $370,000 was awarded per funded grant from the NCI (National Institutes of Health 2014). Note that this $370,000 is typically used over a 3–5 year period to support salaries of the researchers conducting the research, as well as equipment and supplies for doing the research. For NIEHS, the funding rate was about 36% with ~$19 million distributed to 93 awardees, for an average of about $205,000 awarded per funded grant (National Institutes of Health 2014). The funding rate for NSF-BIO was ~18% with over 800 awardees, but data are not clearly available on funds that were distributed to support these awardees (National Science Foundation 2014). Taken together, a little over 2,000 research proposals were funded last year from these three organizations, which represent all of cancer research, research on how the environment affects human health, and research on relevant basic biological sciences.

Question 16: Considering what you now know about the evidence relating to cell phone use and cancer, and about available funding, do you think it is appropriate to fund additional research studies focused on understanding the association between cancer and cell phone use? Why or why not?

Question 17: Research spending by the US government in support of scientific research is currently on the decline. Discuss the impact of a continued decline on cancer research in this country.

Question 18 (Optional): Now refer back to the article you found that supported your original view of whether cell phones cause cancer. Briefly summarize its main conclusion(s). Considering

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everything you have learned about cell phone use and cancer, do you believe this article’s conclusions? Why or why not?

References

Ahlbom, A., A. Green, L. Kheifets, D. Savitz, A. Swerdlow, and International Commission for Non-Ionizing Radiation Protection (ICNIRP) Standing Committee on Epidemiology. 2004. "Epidemiology of Health Effects of Radiofrequency Exposure." Environmental Health Perspectives, 112: 1741–54.

Almeida, C. A., and S. A. Barry. 2011. Cancer: Basic Science and Clinical Aspects. Easton, MA: John Wiley and Sons.

CancerQuest. 2012. "An Introduction to Oncogenes." http://www.cancerquest.org/cancer-genes-oncogenes.html.

Cardis, E., L. Richardson, I. Deltour, B. Armstrong, M. Feychting, C. Johansen, M. Kilkenny, P. McKinney, B. Modan, and S. Sadetzki. 2007. "The INTERPHONE Study: Design, Epidemiological Methods, and Description of the Study Population." European Journal of Epidemiology, 22: 647–64.

Federal Communications Commission. 2013. "Specific Absorption Rate (SAR) for Cellular Telephones." http://www.fcc.gov/encyclopedia/specific-absorption-rate-sar-cellular-telephones.

Frei, P., A. H. Poulsen, C. Johansen, J. H. Olsen, M. Steding-Jessen, and J. Schuz. 2011. "Use of Mobile Phones and Risk of Brain Tumours: Update of Danish Cohort Study." BMJ, 343: d6387.

Futreal, P. A., L. Coin, M. Marshall, T. Down, T. Hubbard, R. Wooster, N. Rahman, and M. R. Stratton. 2004. "A Census of Human Cancer Genes." Nature Reviews. Cancer, 4: 177–83.

Graziano, A., and M. Raulin. 2009. Research Methods: A Process of Inquiry. New York: Pearson.

Hanahan, D., and R. A. Weinberg. 2000. "The Hallmarks of Cancer." Cell, 100: 57–70.

Hirose, H., T. Suhara, N. Kaji, N. Sakuma, M. Sekijima, T. Nojima, and J. Miyakoshi. 2008. "Mobile Phone Base Station Radiation Does Not Affect Neoplastic Transformation in BALB/3T3 Cells." Bioelectromagnetics, 29: 55–64.

International Agency for Research on Cancer. 2011. IARC Classifies Radiofrequency Electromagnetic Fields as Possibly Carcinogenic to Humans. Lyon: World Health Organization.

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———. 2010. Interphone Study Reports on Mobile Phone Use and Brain Cancer Risk. Lyon: World Health Organization.

INTERPHONE Study Group. 2010. "Brain Tumour Risk in Relation to Mobile Telephone Use: Results of the INTERPHONE International Case Control Study." International Journal of Epidemiology, 39: 675–94.

Johansen, C., J. Boice, Jr., J. McLaughlin, and J. Olsen. 2001. Cellular Telephones and Cancer—A Nationwide Cohort Study In Denmark." Journal of the National Cancer Institute, 93: 203–07.

Larjavaara, S., J. Schuz, A. Swerdlow, M. Feychting, C. Johansen, S. Lagorio, T. Tynes, L. Klaeboe, S. R. Tonjer, and M. Blettner et al. 2011. "Location of Gliomas in Relation to Mobile Telephone Use: A Case-Case and Case-Specular Analysis." American Journal of Epidemiology, 174: 2–11.

Linet, M.S., and P. D. Inskip. 2010. "Cellular (Mobile) Telephone Use and Cancer Risk." Reviews on Environmental Health, 25: 51–56.

McClenaghnan, R. 2012. "Do Cell Phones Cause Brain Cancer?" Last updated October 20, 2012. http://www.mangoboss.com/DoCellPhonesCauseBrainCancer.html.

Moulder, J., L. Erdreich, R. Malyapa, J. Merritt, W. Pickard, and Vijayalaxmi. 1999. "Cell Phones and Cancer: What Is the Evidence for a Connection?" Radiation Research, 151: 513–31.

National Cancer Institute. 2014. "What is Cancer?" http://www.cancer.gov/cancertopics/cancerlibrary/what-is-cancer.

———. 2013. "Cell Phones and Cancer Risk." http://www.cancer.gov/cancertopics/factsheet/Risk/cellphones.

National Commission for the Proptection of Human Subjects of Biomedical and Behavioral Research, Bethesda, MD. 1978. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, DC: ERIC Clearinghouse.

National Institutes of Health. 2014. "Success Rates." Last updated January 14, 2014. http://report.nih.gov/success_rates/index.aspx.

National Science Foundation. 2014. "Funding Rates." http://www.nsf.gov/dir/index.jsp?org=BIO.

Oberto, G., K. Rolfo, P. Yu, M. Carbonatto, S. Peano, N. Kuster, S. Ebert, and S. Tofani. 2007. "Carcinogenicity Study of 217 Hz Pulsed 900 MHz Electromagnetic Fields in Pim1 Transgenic Mice." Radiation Research, 168: 316–26.

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Oz, M. 2013. "Keep your Cell Phone out of Your Bra." The Dr. Oz Show, originally aired December 6. Video. http://www.doctoroz.com/episode/why-you-should-keep-your-cell-phone-out-your-bra.

Sanou, B. 2013. The World in 2013: ICT Facts and Figures. Geneva, Switzerland: International Telecommunications Union. Available at: http://www.itu.int/en/ITU-D/Statistics/Documents/facts/ICTFactsFigures2013-e.pdf.

Sargent, J. F., Jr. 2013. Federal Research and Development Funding: FY2013. Washington, DC: Congressional Research Service.

Schuz, J., R. Jacobsen, J. H. Olsen, J. D. Boice, Jr., J. K. McLaughlin, and C. Johansen. 2006. "Cellular Telephone Use and Cancer Risk: Update of a Nationwide Danish Cohort." Journal of the National Cancer Institute, 98: 1707–13.

Sense About Science. 2006. I Don't Know What to Believe? London: Sense About Science. Available at: http://www.senseaboutscience.org/resources.php/16/i-dont-know-what-to-believe.

World Health Organization. 2013. "What Are Electromagnetic Fields?" Available at: ———. 2011. "Electromagnetic Fields and Public Health: Mobile Phones." Reviewed October 2014. http://www.who.int/mediacentre/factsheets/fs193/en/. About the AuthorJennifer S. Stanford is an assistant professor of Biology at Drexel University. Professor Stanford earned a BS in Biology from Elizabethtown College and a PhD in Cell and Developmental Biology from Harvard University. After completing post-doctoral work as the inaugural Curriculum Fellow at Harvard Medical School and serving as the director of Cell Biology in the Biology Department at Drexel as an assistant teaching professor, in 2013, she accepted a tenure track position in Biology Education Research in that department, with a research focus on developing and assessing scalable and sustainable approaches to improve STEM learning.

Professor Stanford has taught medical, dental, graduate, undergraduate biology majors and non-major students. Her courses at all levels emphasize evidence-based reasoning. She has experience with curriculum development including: establishing multiple new graduate and undergraduate courses, creating a new course format (Nanocourses), contributing to the revision of departmental courses and programs, helping to revamp college-level general education curricula, and reviewing undergraduate curricula from across the university to ensure academic standards are met. At Drexel, she engages in learning assessment through the College of Arts and Sciences Assessment Steering Committee, and as a member of the Undergraduate Research Advisory Committee. She is enthusiastic to use her skill set to expand the use of evidence-based reasoning in undergraduate classrooms across the disciplines.

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