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Diet, breast cancer, and case-control studies
Diet, breast cancer, and case-control
Advantages
studies See page 1351 In this week’s Lancet, Franceschi and colleagues report on the results of a case-control study designed to assess the association between macronutrient intake and breast cancer in a population of Italian women. Case-control studies are well suited for the study of cancer because they are efficient in time and cost (panel). The design eliminates the need for lengthy follow-up and allows for the assessment of exposures encountered many years before diagnosis. Thus, case-control studies are appropriate for studying diseases with long latency. Because subjects are selected on the basis of disease status, data can be collected
on numerous
of interest
variables, and
many
aetiological
expo-
be evaluated. The latter point is particularly advantageous for studies of diet and disease where intake of more than one nutrient may be important. The limitations of case-control studies include the potential for bias in selection of participants and collection of exposure data.’ Selection bias can be introduced when choice of cases and controls is based on exposure status. Low participation rates can introduce bias if , for instance, cases are less likely than the controls to participate and the dietary factor of interest is assciated with case status. Bias could thus be introduced by, for example, differences in educational level if education was associated both with diet and a willingness to participate in the study. In the study by Franceschi et al participation rates were high, with only 4% of cases and controls refusing to participate. Differential recall of diet by cases and controls may also introduce bias. Hypothetically, cases may overreport or underreport their actual intake if they are aware of the exposure-disease relation of interest. Although Franceschi and colleagues purport to show that recall bias may not be important in their study because the women were not health conscious, differential recall of dietary intake between cases and controls may still account for their sures
can
findings. defined population as the cases. The use of hospital-based controls works only if the admission for different diseases came from the same general population (ie, with same referral patterns) and if the control diseases are themselves unrelated to diet. Appropriately the Italian investigators selected controls from patients diagnosed with conditions unrelated, positively or negatively, to diet and who were from the same hospitals as the cases. The accurate measurement of exposure is usually difficult. With diet and cancer the difficulty might be compounded because the exposure period of interest may be many years ago. In addition, there are limitations to assessing dietary intake in free-living populations.2 However, food-frequency questionnaires that have been validated and are reproducible have led to accurate classification of individuals with respect to diet.2 Franceschi et al used a food-frequency questionnaire that has been validated and is reproducible in an Italian population. Having assessed diet only in the 2 years before diagnosis of cancer, they state, correctly, that the results do not reflect the effect of diet many years before breast cancer diagnosis but they are forced to make the plausible assumption that breast cancer has not itself affected diet.
Controls
1346
must come
from the
same
<
of case-control studies
Can study multiple risk factors, and diseases with long latency Efficient in time and cost
uncommon
diseases,
Disadvantages of case-control studies w Seiection of controls can be difficult Expasure data difficult to collect and might be biased Cannat assess incidence directly <* Potential for selection bias * Temporal sequence between exposure and disease may be difficult to establish
Even if diet is measured with a reasonable degree of accuracy, and differential recall by cases and controls can be ruled out, some measurement error may still remain. It may cause overestimation or underestimation of the results or have no effect. Confounding by total energy may also affect the results if energy intake is positively correlated with certain macronutrients and associated with the disease being studied (criteria that must be satisfied to meet the condition of confounding). Franceschi used recent developments in epidemiological and statistical methods to adjust for the effects of total energy intake.2 A well-conducted case-control study that has taken into account all of the methodological concerns can yield valid and informative results. In fact, if cases and controls are selected independently of exposure and controls are sampled randomly from a defined study population from which cases arose (as was the case in the Italian study), it can be shown algebraically that the results are an unbiased estimator of the incidence rate ratio, the measure obtained from a prospective study.3 Nevertheless, it is important to remember that case-control studies always have the potential for bias and that each study should be evaluated individually to determine whether bias influenced the results. Susan A Oliveria, Michael P Osborne Strang Cancer Prevention Center, and Cornell University New York, New 1 2 3
Medical Center,
York, USA
Rothman KJ. Modern epidemiology. Boston: Little, Brown, 1986. Willett W. Nutritional epidemiology. NewYork: Oxford University Press, 1990. Walker AM. Observation and inference: an introduction to the methods of epidemiology. Chesnut Hill, MA: Epidemiology Resources Inc. 1991.
Are
ready for factor V Leiden screening? we
See page 1374 In this issue, Desmarais and colleagues report a study of activated protein C (APC) resistance in unselected patients with pulmonary embolism. Since APC resistance is the commonest cause of venous thrombosis it is quite surprising that the prevalence of APC resistance in patients with confirmed pulmonary embolism is similar to that in patients in whom the pulmonary embolism was excluded. What should we make of these findings and what are the practical applications of the detection of APC resistance ? The basic principle of the APC-resistance test is that the anticoagulant response to APC of a patient’s plasma
Advantages
studies See page 1351 In this week’s Lancet, Franceschi and colleagues report on the results of a case-control study designed to assess the association between macronutrient intake and breast cancer in a population of Italian women. Case-control studies are well suited for the study of cancer because they are efficient in time and cost (panel). The design eliminates the need for lengthy follow-up and allows for the assessment of exposures encountered many years before diagnosis. Thus, case-control studies are appropriate for studying diseases with long latency. Because subjects are selected on the basis of disease status, data can be collected
on numerous
of interest
variables, and
many
aetiological
expo-
be evaluated. The latter point is particularly advantageous for studies of diet and disease where intake of more than one nutrient may be important. The limitations of case-control studies include the potential for bias in selection of participants and collection of exposure data.’ Selection bias can be introduced when choice of cases and controls is based on exposure status. Low participation rates can introduce bias if , for instance, cases are less likely than the controls to participate and the dietary factor of interest is assciated with case status. Bias could thus be introduced by, for example, differences in educational level if education was associated both with diet and a willingness to participate in the study. In the study by Franceschi et al participation rates were high, with only 4% of cases and controls refusing to participate. Differential recall of diet by cases and controls may also introduce bias. Hypothetically, cases may overreport or underreport their actual intake if they are aware of the exposure-disease relation of interest. Although Franceschi and colleagues purport to show that recall bias may not be important in their study because the women were not health conscious, differential recall of dietary intake between cases and controls may still account for their sures
can
findings. defined population as the cases. The use of hospital-based controls works only if the admission for different diseases came from the same general population (ie, with same referral patterns) and if the control diseases are themselves unrelated to diet. Appropriately the Italian investigators selected controls from patients diagnosed with conditions unrelated, positively or negatively, to diet and who were from the same hospitals as the cases. The accurate measurement of exposure is usually difficult. With diet and cancer the difficulty might be compounded because the exposure period of interest may be many years ago. In addition, there are limitations to assessing dietary intake in free-living populations.2 However, food-frequency questionnaires that have been validated and are reproducible have led to accurate classification of individuals with respect to diet.2 Franceschi et al used a food-frequency questionnaire that has been validated and is reproducible in an Italian population. Having assessed diet only in the 2 years before diagnosis of cancer, they state, correctly, that the results do not reflect the effect of diet many years before breast cancer diagnosis but they are forced to make the plausible assumption that breast cancer has not itself affected diet.
Controls
1346
must come
from the
same
<
of case-control studies
Can study multiple risk factors, and diseases with long latency Efficient in time and cost
uncommon
diseases,
Disadvantages of case-control studies w Seiection of controls can be difficult Expasure data difficult to collect and might be biased Cannat assess incidence directly <* Potential for selection bias * Temporal sequence between exposure and disease may be difficult to establish
Even if diet is measured with a reasonable degree of accuracy, and differential recall by cases and controls can be ruled out, some measurement error may still remain. It may cause overestimation or underestimation of the results or have no effect. Confounding by total energy may also affect the results if energy intake is positively correlated with certain macronutrients and associated with the disease being studied (criteria that must be satisfied to meet the condition of confounding). Franceschi used recent developments in epidemiological and statistical methods to adjust for the effects of total energy intake.2 A well-conducted case-control study that has taken into account all of the methodological concerns can yield valid and informative results. In fact, if cases and controls are selected independently of exposure and controls are sampled randomly from a defined study population from which cases arose (as was the case in the Italian study), it can be shown algebraically that the results are an unbiased estimator of the incidence rate ratio, the measure obtained from a prospective study.3 Nevertheless, it is important to remember that case-control studies always have the potential for bias and that each study should be evaluated individually to determine whether bias influenced the results. Susan A Oliveria, Michael P Osborne Strang Cancer Prevention Center, and Cornell University New York, New 1 2 3
Medical Center,
York, USA
Rothman KJ. Modern epidemiology. Boston: Little, Brown, 1986. Willett W. Nutritional epidemiology. NewYork: Oxford University Press, 1990. Walker AM. Observation and inference: an introduction to the methods of epidemiology. Chesnut Hill, MA: Epidemiology Resources Inc. 1991.
Are
ready for factor V Leiden screening? we
See page 1374 In this issue, Desmarais and colleagues report a study of activated protein C (APC) resistance in unselected patients with pulmonary embolism. Since APC resistance is the commonest cause of venous thrombosis it is quite surprising that the prevalence of APC resistance in patients with confirmed pulmonary embolism is similar to that in patients in whom the pulmonary embolism was excluded. What should we make of these findings and what are the practical applications of the detection of APC resistance ? The basic principle of the APC-resistance test is that the anticoagulant response to APC of a patient’s plasma