Zusammenfassung
Simple Summary Investigating body shapes may offer novel insights into the role of adiposity and body size in breast cancer development. We derived three distinct body shapes from combinations of height, weight, body mass index (BMI), waist and hip circumference, and waist-to-hip ratio (WHR) by a principal component analysis. We then used genetic variants linked to these body shapes and ...
Zusammenfassung
Simple Summary Investigating body shapes may offer novel insights into the role of adiposity and body size in breast cancer development. We derived three distinct body shapes from combinations of height, weight, body mass index (BMI), waist and hip circumference, and waist-to-hip ratio (WHR) by a principal component analysis. We then used genetic variants linked to these body shapes and investigated associations with breast cancer risk. A body shape characterizing general adiposity was associated with a lower breast cancer risk, however this is likely because the genetic variants predicting this body shape reflect body fatness during childhood and adolescence rather than during later adulthood. A body shape characterizing tall women with a low WHR was weakly associated with a higher breast cancer risk. A body shape characterizing tall women with a large WHR was not associated with breast cancer risk. These findings can spur wider application in cancer research and possibly risk stratification. Observational and genetic studies have linked different anthropometric traits to breast cancer (BC) risk, with inconsistent results. We aimed to investigate the association between body shape defined by a principal component (PC) analysis of anthropometric traits (body mass index [BMI], height, weight, waist-to-hip ratio [WHR], and waist and hip circumference) and overall BC risk and by tumor sub-type (luminal A, luminal B, HER2+, triple negative, and luminal B/HER2 negative). We performed two-sample Mendelian randomization analyses to assess the association between 188 genetic variants robustly linked to the first three PCs and BC (133,384 cases/113,789 controls from the Breast Cancer Association Consortium (BCAC)). PC1 (general adiposity) was inversely associated with overall BC risk (0.89 per 1 SD [95% CI: 0.81-0.98]; p-value = 0.016). PC2 (tall women with low WHR) was weakly positively associated with overall BC risk (1.05 [95% CI: 0.98-1.12]; p-value = 0.135), but with a confidence interval including the null. PC3 (tall women with large WHR) was not associated with overall BC risk. Some of these associations differed by BC sub-types. For instance, PC2 was positively associated with a risk of luminal A BC sub-type (1.09 [95% CI: 1.01-1.18]; p-value = 0.02). To clarify the inverse association of PC1 with breast cancer risk, future studies should examine independent risk associations of this body shape during childhood/adolescence and adulthood.
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