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P46 Body shape phenotypes and breast cancer risk: a Mendelian randomization analysis

孟德尔随机化 乳腺癌 体质指数 癌症 医学 肿瘤科 内科学 优势比 人体测量学 全基因组关联研究 腰臀比 腰围 生物 遗传学 基因型 单核苷酸多态性 遗传变异 基因
作者
Laia Peruchet Noray,Niki Dimou,Anja M. Sedlmeier,Béatrice Fervers,Isabelle Romieu,Vivian Viallon,Marc J. Gunter,Pietro Ferrari,Robert Carreras-Torres,Heinz Freisling
标识
DOI:10.1136/jech-2022-ssmabstracts.140
摘要

Background

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among women. Previous observational and Mendelian randomization studies have linked different anthropometric traits to breast cancer risk, with inconsistent results. We aimed to investigate whether body shape defined by combining multiple anthropometric traits (body mass index, height, weight, waist-to-hip ratio (WHR), waist and hip circumference) is causally associated with overall breast cancer risk and its sub-types (luminal A, luminal B, HER2+, triple negative and luminal B/HER2 negative).

Methods

We performed a two-sample Mendelian randomization (MR) analysis using summary-level data from previous genome-wide association studies. First, summary statistics for 188 common genetic variants robustly linked to three body shapes were extracted. The three body shape phenotypes reflected the first three principal components (PC1, PC2 and PC3) on six anthropometric traits, thus providing independent dimensions of body shape. Second, summary statistics for the association of these genetic variants and risk of breast cancer were obtained from 133,384 cases and 113,789 controls of European descent in the Breast Cancer Association Consortium (BCAC). Finally, fixed-effects inverse variance weighted (IVW) MR analyses and several sensitivity analyses were performed to assess the risk of breast cancer associated with body shape phenotypes.

Results

The body shape principal component 1 (PC1) indicative of overall adiposity was inversely associated with breast cancer risk (IVWrandom-effectsodds ratio (OR) per each standard deviation (1SD) increase of body shape PC1 = 0.89 [95% confidence interval 0.81–0.98]; p = 0.016). PC2 (tall individuals with low WHR) was weakly positively associated with overall breast cancer risk (IVWrandom-effects OR = 1.05 [95% confidence interval 0.98–1.12]; p-value = 0.135), but with a confidence interval including the null. PC3 (tall individuals with large WHR) was not associated with overall breast cancer risk (IVWrandom-effects OR = 1.04 [95% confidence interval 0.89–1.21]; p = 0.619). Some of these associations differed by breast cancer sub-types. For instance, PC2 was positively associated with risk of luminal A breast cancer sub-type (IVWrandom-effects OR = 1.09 [95% confidence interval 1.01–1.18]; p-value = 0.02).

Conclusion

Our study provides evidence for potential causal associations between body shape and breast cancer risk and breast cancer sub-types highlighting the importance to also assess body morphology holistically.

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