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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.

Author information

1
Albert Einstein College of Medicine, Bronx, NY.

Abstract

BACKGROUND:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

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

PMID:
31899501
DOI:
10.1093/jnci/djz241

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