What is a Cause?

It is natural for us to ponder the relationship between cause and effect. If one can identify causes, then it is possible to predict future events to some extent. The notion of causation also provides a basis for praise and credit if the effect was desirable or blame if was not.

We all have an intuitive idea of what we think of as a "cause," but how does one define what a cause is? What are the criteria that need to be met in order to say that a factor (or exposure, determinant) is a cause of a particular outcome? Here are several definition:

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Characteristics of a Cause

To be a cause, the factor:

Must precede the effect
Can be either a host or environmental factor (e.g., characteristics, conditions, actions of individuals, events, natural, social or economic phenomena)
May be positive (presence of a causative exposure) or negative (lack of a preventive exposure)

Risk Factors versus Causes

Epidemiologists often use the term "risk factor" to indicate a factor that is associated with a given outcome. However, a risk factor is not necessarily a cause. The term risk factor includes surrogates for underlying causes. For example, consider the following table which summarizes characteristics associated with a high risk of breast cancer and characteristics associated with a low risk.

	High Risk	Low Risk
Country of Birth	North America, Northern Europe	Asia, Africa
Socioeconomic status	High	Low
Marital status	Never married	Ever married

Each of these factors (place of birth, socioeconomic status, and marital status) is associated with an increased risk of breast cancer, but none of these are causes. [Recall Susser's definition that a cause is something that makes a difference; or recall Rothman's definition, i.e., that a cause is an event, condition, or characteristic without which the disease would not have occurred.] These risk factors are surrogates or markers for underlying causes, e.g., populations with a higher prevalence of genetic risk from BRCA1 and BRCA2 alleles, or lower parity which in turn is a marker for unopposed estrogen stimulation of breast tissue.) Being born in northern Europe per se is not a cause; it is a marker for populations that may have a greater genetic predisposition to breast cancer.

It is therefore important to distinguish between risk factors and causes. Nevertheless, before one can wrestle with the difficult question of causation, it is first necessary to establish that a valid association exists. Consequently, if we accept Susser's assertion that a cause is something that makes a difference, one might then ask how to tell if a factor makes a difference. Most epidemiologists would agree that, in a broad sense, this is a two step process.

The evidence must be examined to determine that there is a valid association between an exposure and an outcome. This is achieved by conducting epidemiologic studies and critically reviewing the available studies to determine whether random error or bias or confounding might explain the apparent association.
If it is determined that there is a valid association, then one must wrestle with the question of whether the association was causal. Not all associations are causal. There are no standardized rules for determining whether a relationship is causal.

Answering the question of whether a given factor is a cause or not requires making a judgment. There are no rigid criteria for determining whether a causal relationship exists, although there are guidelines that should be considered. The process of determining whether a causal relationship does in fact exist is called "causal inference".

Given the lack of rigid criteria, debate and disagreement over the evidence is inevitable and positive. However, it also means that the debate can be prolonged for reasons other than scientific dispute, for example, if powerful institutions perceive that there are substantial financial implications that would follow from concluding that there is a causal connection. The existence, sources, and implications of global climate change is perhaps the most prominent current example in which concerns have been raised that commercial interests over the causal association between human activity and atmospheric change have affected the scientific process. The most well-known and well-documented example in recent history was the tobacco industry's effort to deny that the association between cigarette smoking and lung cancer was causal.

Hill's Criteria for Causality

Smoking had long been a contentious issue. Despite its increasing popularity, many had opposed smoking on moral grounds; others claimed that smoking had adverse health effects, but the evidence to support these claims was thin. There had been a remarkable increase in lung cancer in both the US and Britain during the first half of the 20th century, but the cause had not been established. Many attributed the increase to the steady increase in the use of motor vehicles, or the paving of roads, or the steady rise in industry.

Thinking man icon indication a question for the student

When investigators gathered data on the number of motor vehicles in use over time, they found that the increase correlated strongly with the increase in lung cancer mortality. The correlation is evidence of an association between motor vehicle use and lung cancer mortality. Does this indicate that motor vehicle use is a cause of lung cancer mortality?

a. Yes, because there was a "strong" correlation, indicating a strong association.

b. No, because the data on the number of motor vehicles being used was probably grossly inaccurate.

c. No, because the sample size is unknown.

d. No, because these data are from an ecological study, and it is dangerous to conclude that there is a causal relationship from these studies because of the ecological fallacy and the inability to control for many possible confounding factors.

Bradfor Hill In 1939, a German study reported an association between smoking and lung cancer. Then, in the 1940s and 1950s there was a succession of studies that sought to examine the cause of the epidemic of lung cancer that was claiming more and more lives. Richard Doll and Austin Bradford Hill (shown on the right) conducted landmark epidemiologic studies that were important in establishing the strong association between smoking and lung cancer. The first was a case-control study conducted in London area hospitals. The cases were patients with lung cancer, and the controls were age and gender matched patients at the same hospital who had diseases other than cancer. [NOTE text annotation indicator ]

After their case-control study, Doll and Hill launched a prospective cohort study among male physicians in the UK, looking at cause of death as the primary endpoint. The initial findings were published in 1954, with a follow up report in 1958. These studies demonstrated an even stronger association between smoking and lung cancer mortality and also showed that smoking was also significantly associated with other cancers and with a variety of other non-cancerous causes of death including emphysema, chronic bronchitis, TB, atherosclerotic heart disease, stroke, hypertension, and aneurysms.

Despite the strong associations that they found, there was controversy about whether the association was causal. Out of this debate came the notion that causality could not be proven by formulaic consideration of observations; instead, a conclusion of causality was a judgment based on a body of evidence. In 1965 Hill and others proposed certain aspects of evidence that should be considered when trying to draw conclusions about causality. These were not intended to be rigid criteria.

Hill's Criteria

These reports provided the basis for the 1964 US Surgeon General's Report that concluded, "Cigarette smoking is causally related to lung cancer in men; the magnitude of the effect of cigarette smoking far outweighs all other factors." It estimated that moderate smokers had a 10-fold increase in risk of lung cancer, while heavy smokers had a 20-fold increased risk. The report backed pedaled regarding the addictive properties of nicotine concluding that the "tobacco habit should be characterized as an habituation rather than an addiction,...."

The US Surgeon General's report stirred controversy, and even physicians (many of whom were smokers) refused to accept the conclusion that smoking was a cause of lung cancer. In the video below, medical historian Alan Brandt summarizes the reaction to the report and the scientific studies upon which they were based.

Eventually, the epidemiologic studies and the Surgeon General's report did begin to have an impact on public opinion, however A 1958 survey found that only 44 percent of Americans believed smoking caused cancer, but in 1968 78 percent believed that smoking caused lung cancer.

In addition to the tactics described by Alan Brandt in the video, the tobacco industry also steadfastly claimed that there was no proof that cigarettes caused lung cancer. In 1994 the Occupational Health and Safety Administration (OSHA) began a series of hearings regarding a proposed rule on indoor air and the potential harm of environmental tobacco smoke . Part of the hearing was aimed at the more direct question of whether active smoking causes lung cancer. The link below will bring you to a series of responses supplied by tobacco industry scientists when they were asked whether they believe that active smoking causes lung cancer. As you read their responses, consider the following questions:

What distinction do they make between "risk factors" and "cause".
One of the tobacco industry witnesses suggests that lung cancer is multi-factorial. Is this a reasonable possibility?
And, if smoking is multifactorial in etiology, does this mean that tobacco is not a cause?
Can anything be proven to have caused a given case of lung cancer?

Link t the O SHA Testimony (for more excerpts from the hearing, click here).

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