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J Natl Cancer Inst. 2020 Jan 3. pii: djz241. doi: 10.1093/jnci/djz241. [Epub ahead of print]

Genetic factors, adherence to healthy lifestyle behavior, and risk of invasive breast cancer among women in the UK Biobank.

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Albert Einstein College of Medicine, Bronx, NY.



Breast cancer is considered to result from a combination of genetic and lifestyle-related factors, but the degree to which an overall healthy lifestyle may attenuate the impact of multiple genetic variants on invasive breast cancer risk remains equivocal.


Using Cox proportional hazards regression models, we examined the association of a modified healthy lifestyle index (HLI) with risk of invasive breast cancer by genetic risk group among 146,326 women from the UK Biobank. We generated an HLI score based on a combination of diet, physical activity, smoking, alcohol consumption and anthropometry, and a polygenic risk score (PRS) using 304 breast cancer-associated genetic loci.


Among premenopausal and postmenopausal women, a favorable lifestyle (highest tertile) was associated with 22% and 31% reductions in invasive breast cancer risk, respectively (HRhigh vs low: 0.78, 95% CI = 0.64 to 0.94 and 0.69, 0.63 to 0.77), while a high PRS (highest tertile) was associated with more than a doubling in the risk in both groups. For premenopausal women, the greatest risk reduction in association with the HLI was seen among those with a high PRS (HRhigh vs low: 0.73, 95% CI = 0.75 to 0.95). In postmenopausal women, those with a favorable lifestyle had 30%, 29% and 32% reductions in risk of invasive breast cancer in the low, intermediate and high PRS groups, respectively (HRhigh vs low: 0.70, 95% CI = 0.56 to 0.88, 0.71, 0.59 to 0.84 and 0.68, 0.59 to 0.78, respectively). There was an additive but not multiplicative interaction between the HLI score and PRS for postmenopausal and, to a lesser extent, premenopausal women.


Our findings support the view that an overall healthy lifestyle may attenuate the impact of genetic factors on invasive breast cancer risk among women of European ancestry.


UK Biobank; alcohol; body fat; breast cancer; diet; genes; lifestyle; physical activity; smoking


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