TY - JOUR
T1 - Genetic factors, adherence to healthy lifestyle behavior, and risk of invasive breast cancer among women in the UK biobank
AU - Arthur, Rhonda S.
AU - Wang, Tao
AU - Xue, Xiaonan
AU - Kamensky, Victor
AU - Rohan, Thomas E.
N1 - Publisher Copyright:
© 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.
PY - 2020/9/1
Y1 - 2020/9/1
N2 - 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 (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas 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; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 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.
AB - 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 (hazard ratio [HR]high vs low = 0.78, 95% confidence interval [CI] = 0.64 to 0.94; HRhigh vs low = 0.69, 95% CI = 0.63 to 0.77, respectively), whereas 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; HRhigh vs low = 0.71, 95% CI = 0.59 to 0.84; and HRhigh vs low = 0.68, 95% CI = 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.
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U2 - 10.1093/jnci/djz241
DO - 10.1093/jnci/djz241
M3 - Article
C2 - 31899501
AN - SCOPUS:85086008854
VL - 112
SP - 893
EP - 901
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 9
ER -