Details

Autor(en) / Beteiligte

• Chen, Fa
• Wen, Wanqing
• Long, Jirong
• Shu, Xiang
• Yang, Yaohua
• Shu, Xiao‐Ou
• Zheng, Wei

Titel

Mendelian randomization analyses of 23 known and suspected risk factors and biomarkers for breast cancer overall and by molecular subtypes

Ist Teil von

• International journal of cancer, 2022-08, Vol.151 (3), p.372-380

Ort / Verlag

Hoboken, USA: John Wiley & Sons, Inc

Erscheinungsjahr

2022

Link zum Volltext

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• Many risk factors have been identified for breast cancer. The potential causality for some of them remains uncertain, and few studies have comprehensively investigated these associations by molecular subtypes. We performed a two‐sample Mendelian randomization (MR) study to evaluate potential causal associations of 23 known and suspected risk factors and biomarkers with breast cancer risk overall and by molecular subtypes using data from the Breast Cancer Association Consortium. The inverse‐variance weighted method was used to estimate odds ratios (OR) and 95% confidence interval (CI) for association of each trait with breast cancer risk. Significant associations with breast cancer risk were found for 15 traits, including age at menarche, age at menopause, body mass index, waist‐to‐hip ratio, height, physical activity, cigarette smoking, sleep duration, and morning‐preference chronotype, and six blood biomarkers (estrogens, insulin‐like growth factor‐1, sex hormone‐binding globulin [SHBG], telomere length, HDL‐cholesterol and fasting insulin). Noticeably, an increased circulating SHBG was associated with a reduced risk of estrogen receptor (ER)‐positive cancer (OR = 0.83, 95% CI: 0.73‐0.94), but an elevated risk of ER‐negative (OR = 1.12, 95% CI: 0.93‐1.36) and triple negative cancer (OR = 1.19, 95% CI: 0.92‐1.54) (Pheterogeneity = 0.01). Fasting insulin was most strongly associated with an increased risk of HER2‐negative cancer (OR = 1.94, 95% CI: 1.18‐3.20), but a reduced risk of HER2‐enriched cancer (OR = 0.46, 95% CI: 0.26‐0.81) (Pheterogeneity = 0.006). Results from sensitivity analyses using MR‐Egger and MR‐PRESSO were generally consistent. Our study provides strong evidence supporting potential causal associations of several risk factors for breast cancer and suggests potential heterogeneous associations of SHBG and fasting insulin levels with subtypes of breast cancer. What's new? Many risk factors have been identified for breast cancer in observational studies. But the potential causality for some of these associations has not yet been established, and few studies have comprehensively investigated these associations by molecular subtype. This large two‐sample Mendelian randomization study supports potential causal associations for 15 risk factors and blood biomarkers with the risk of breast cancer. The results also show that the association of breast cancer risk with certain risk factors and biomarkers may differ by estrogen receptor status and intrinsic subtype, highlighting the heterogeneous nature of this disease.