The mediating roles of anthropo-metabolic biomarkers on the association between beverage consumption and breast cancer risk

Abstract

Background: Breast cancer (BC) is the most common malignancy in women, yet the role of beverage consumption in BC risk remains unclear. Additionally, the contribution of anthropo-metabolic biomarkers as mediators is unknown, limiting the development of effective prevention strategies.

Methods: This study included 13,567 participants from the Guangzhou Biobank Cohort Study (GBCS), where beverage consumption was assessed at baseline using a food frequency questionnaire. BC cases were identified through cancer registry linkage over a mean follow-up of 14.8 years. Mendelian randomization (MR) analyses were performed to evaluate the causal effects of beverage consumption on BC risk, with a two-step MR approach used to estimate mediation effects.

Results: During follow-up, 243 BC cases were identified. Weekly consumption of ≥ 1 portion of sugar sweetened beverages (SSB), versus < 1 portion, was significantly associated with a higher risk of BC (hazard ratio [HR] 1.58, 95% confidence interval [CI] 1.12-2.23). This association was partly mediated by body mass index (proportion mediated [PM] 4.2%, 95% CI 0.9-17.1%) and uric acid (PM 18.8%, 95% CI 1.5-77.5%). Weekly consumption of > 6 portions of dairy-based milk was associated with a non-significantly higher BC risk (HR 1.41, 95% CI 0.99-2.03), while 3-6 portions of soy milk were associated with a lower BC risk (HR 0.31, 95% CI 0.10-0.98). No significant associations were found for pure fruit juice, coffee, tea, or alcoholic drinks. MR analyses supported the detrimental effect of SSB on BC risk, with high-density lipoprotein cholesterol, polyunsaturated fatty acids to total fatty acids (TFAs) ratio, and omega-6 fatty acids to TFAs ratio mediating 2.44%, 2.73%, and 3.53% of the association, respectively.

Conclusion: This study suggested that SSB consumption was a risk factor for BC and identified key anthropo-metabolic biomarkers mediating this relationship. Reducing SSB consumption and addressing associated metabolic pathways may offer effective strategies for BC prevention.

Keywords: Anthropo-metabolic biomarkers; Beverage consumption; Breast cancer prevention; Mediation; Sugar sweetened beverages.

Fig. 1

Mediating effects of the association between sugar sweetened beverages and risk of breast cancer by anthropo-metabolic markers in the Guangzhou Biobank Cohort Study. Abbreviations: CI, confidence interval; HR, hazard ratio; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol. ^aAdjusted for age, education level, occupation, annual personal income, smoking status, alcohol use, physical activity, age at menarche and menopause, parity and breastfeeding history, oral contraceptive use, hormone replacement therapy, self-reported health status, family history of breast cancer, and daily dietary energy intake. *P < 0.05; **P < 0.01; ***P < 0.001

Fig. 2

Mediation analysis on the causal association between sugar sweetened beverages and breast cancer using two-step Mendelian randomization. Abbreviations: CI, confidence interval; OR, odds ratio; LDL, low-density lipoprotein; HDL-C, high-density lipoprotein cholesterol; TFAs, total fatty acids. .^aThe β/OR and 95% CI were estimated using two-sample univariable Mendelian randomization analysis, with inverse-variance weighted as the main method. *P < 0.05; **P < 0.01