Methodological Biases in Estimating the Relationship Between Alcohol Consumption and Breast Cancer: The Role of Drinker Misclassification Errors in Meta‐Analytic Results

Abstract

Background While alcohol consumption has been linked to breast cancer in women, few studies have controlled for possible biases created by including former or occasional drinkers in the abstainer reference group. We explored the potential for such misclassification errors as sources of bias in estimates of the alcohol-breast cancer relationship. Methods Meta-analyses of population case-control, hospital case-control, and cohort studies to examine relationships between level of alcohol use and breast cancer morbidity and/or mortality in groups of studies with and without different misclassification errors. Results Of 60 studies identified, only 6 were free of all misclassification errors. The abstainer reference group was biased by the inclusion of former drinkers in 49 studies, occasional drinkers (<10g ethanol per week) in 22 and by both these groups in 18. Occasional drinkers were also mixed with light or hazardous level drinkers in 21 studies. Unbiased estimates of the OR for breast cancer were 1.011 (95% CI: 0.891-1.148) among former drinkers (n = 11) and 1.034 (95% CI: 1.003-1.064) among occasional drinkers (n=17). Hazardous level drinking (>20g<41g ethanol/day) was not significantly associated with breast cancer in studies with occasional drinker bias. However, in studies free from occasional drinker bias, the OR for breast cancer was 1.085 (95% CI: 1.015-1.160) for low level (<21g/day) drinkers (n=17), 1.374 (95% CI: 1.319-1.431) for hazardous level drinkers (n=26) and 1.336 (95% CI: 1.228-1.454) for harmful level (>40g/day) drinkers (n=9). Conclusions While the great majority of studies of the alcohol-breast cancer link include misclassification errors, only misclassification of occasional drinkers was found to bias risk estimates significantly. Estimates based on error free studies confirmed that low, hazardous and harmful levels of alcohol use each significantly increase the risk of breast cancer.

Alcohol Use and Breast Cancer: A Critical Review

“…In the case of breast cancer, this bias leads to a small but significant downward shift in the RR estimates which is caused by the misclassification of occasional drinkers (including people who reduce their alcohol consumption due to declining health [Liang and Chikritzhs, 2013] and people who are in better health than are lifetime abstainers due to factors unrelated to alcohol consumption [Stockwell et al, 2012]). The misclassification of former drinkers was not found to affect estimates of the risk of breast cancer (Zeisser et al, 2014); however, the finding that measuring lifetime alcohol consumption leads to a higher breast cancer RR when compared to measuring more recent alcohol consumption supports the hypothesis that former drinker misclassification bias is a factor when measuring the RR between alcohol and breast cancer. Reference group bias also affects the alcohol-attributable breast cancer estimates presented in the meta-analysis by Bagnardi and colleagues (2015), which meta-analysis does not account for this bias and, thus, the alcohol-attributable burden estimates presented in this study can be seen as a conservative estimate of the actual burden of alcohol-attributable breast cancer.…”

“…Most of the systematic reviews included in this study are affected by reference group bias (Zeisser et al, 2014). In the case of breast cancer, this bias leads to a small but significant downward shift in the RR estimates which is caused by the misclassification of occasional drinkers (including people who reduce their alcohol consumption due to declining health [Liang and Chikritzhs, 2013] and people who are in better health than are lifetime abstainers due to factors unrelated to alcohol consumption [Stockwell et al, 2012]).…”

The relationship between different dimensions of alcohol use and the burden of disease—an update

“…Furthermore, as with other diseases related causally to alcohol consumption, the relative risks for cancer are dependent upon the systematic search strategy, inclusion and exclusion criteria, reference group (and if this includes former drinkers) of the underlying studies 172, 173, 174, use of case–control and/or cohort studies 175 and use of categorical or continuous estimates for alcohol consumption 169 (for relative risk graphs see 176 and Supporting information, Appendix S2). …”

Is alcohol consumption a risk factor for prostate cancer? A systematic review and meta–analysis

“…While many unidentified and uncontrolled factors or biases may have confounded the relationships of interest in these studies, an additional concern is that former and occasional drinkers may be misclassified into the abstaining reference group. Previous studies have showed that such misclassification can bias estimates of health risks from alcohol use, for example, underestimating risks from low–volume drinking [14–19]. Former and occasional drinkers may include people who have stopped or reduced their drinking as they aged and experienced declining health [16, 20].…”