Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis

Abstract

Background. Although individual metabolic risk factors are reported to be associated with breast cancer risk, controversy surrounds risk of breast cancer from metabolic syndrome (MS). We report the first systematic review and meta-analysis of the association between MS and breast cancer risk in all adult females. Methods. Studies were retrieved by searching four electronic reference databases [PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, and ProQuest through June 30, 2012] and cross-referencing retrieved articles. Eligible for inclusion were longitudinal studies reporting associations between MS and breast cancer risk among females aged 18 years and older. Relative risks and 95% confidence intervals were calculated for each study and pooled using random-effects models. Publication bias was assessed quantitatively (Trim and Fill) and qualitatively (funnel plots). Heterogeneity was examined using Q and I (2) statistics. Results. Representing nine independent cohorts and 97,277 adult females, eight studies met the inclusion criteria. A modest, positive association was observed between MS and breast cancer risk (RR: 1.47, 95% CI, 1.15-1.87; z = 3.13; p = 0.002; Q = 26.28, p = 0.001; I (2) = 69.55%). No publication bias was observed. Conclusions. MS is associated with increased breast cancer risk in adult women.

Figure 1

Flow diagram describing the selection of studies. ^*CINAHL: Cumulative Index to Nursing and Allied Health Literature.

Figure 2

Forest plot for metabolic syndrome and breast cancer risk (random-effects model). The black circles represent the weighted risk ratio (RR) for each result from each study, while the horizontal lines represent the lower and upper 95% confidence intervals (CI) for the RR. The black diamond represents the overall pooled RR, while the left and right sides of the diamond represent the lower and upper 95% CI for the pooled RR. For studies that included more than one definition of metabolic syndrome, the following were used: Agnoli et al. (tertile definition), Bosco (time-independent definition), Osaki et al. (modified NCEP 2001 definition), and Ronco et al. (diabetes, overweight, and hypertension definition).

Figure 3

Funnel plot of precision by log risk ratio.

Figure 4

Influence analysis with each result from each study deleted from the random-effects model once. The black circles represent the risk ratio (RR) for each result from each study while the horizontal lines represent the lower and upper 95% confidence interval (CI) for the RR. The black diamond represents the overall pooled result while the left and right sides of the diamond represent the lower and upper 95% CI for the pooled RR. For studies that included more than one definition of metabolic syndrome, the following were used: Agnoli et al. (tertile definition), Bosco (time-independent definition), Osaki et al. (modified NCEP 2001 definition), and Ronco et al. (diabetes, overweight, and hypertension definition).

Figure 5

Cumulative meta-analysis, ranked by year and based on a random-effects model. The black circles represent the cumulative risk ratios (RR) while the horizontal lines represent the lower and upper 95% confidence intervals (CI) for the RR. The black diamond represents the overall pooled RR while the left and right sides of the diamond represent the lower and upper 95% CI for the pooled RR. For those studies that included more than one definition of metabolic syndrome, the following were used: Agnoli et al. (tertile definition), Bosco (time-independent definition), Osaki et al. (modified NCEP 2001 definition), and Ronco et al. (diabetes, overweight, and hypertension definition).