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Joint association of mammographic density adjusted for age and body mass index and polygenic risk score with breast cancer risk.


ABSTRACT: BACKGROUND:Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk. METHODS:Using 3628 breast cancer cases and 5126 controls of European ancestry from eight case-control studies, we evaluated joint associations of a 77-single nucleotide polymorphism (SNP) PRS and quantitative mammographic density measures with breast cancer. Mammographic percent density and absolute dense area were evaluated using thresholding software and examined as residuals after adjusting for age, 1/BMI, and study. PRS and adjusted density phenotypes were modeled both continuously (per 1 standard deviation, SD) and categorically. We fit logistic regression models and tested the null hypothesis of multiplicative joint associations for PRS and adjusted density measures using likelihood ratio and global and tail-based goodness of fit tests within the subset of six cohort or population-based studies. RESULTS:Adjusted percent density (odds ratio (OR)?=?1.45 per SD, 95% CI 1.38-1.52), adjusted absolute dense area (OR?=?1.34 per SD, 95% CI 1.28-1.41), and the 77-SNP PRS (OR?=?1.52 per SD, 95% CI 1.45-1.59) were associated with breast cancer risk. There was no evidence of interaction of the PRS with adjusted percent density or dense area on risk of breast cancer by either the likelihood ratio (P?>?0.21) or goodness of fit tests (P?>?0.09), whether assessed continuously or categorically. The joint association (OR) was 2.60 in the highest categories of adjusted PD and PRS and 0.34 in the lowest categories, relative to women in the second density quartile and middle PRS quintile. CONCLUSIONS:The combined associations of the 77-SNP PRS and adjusted density measures are generally well described by multiplicative models, and both risk factors provide independent information on breast cancer risk.

SUBMITTER: Vachon CM 

PROVIDER: S-EPMC6532188 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Joint association of mammographic density adjusted for age and body mass index and polygenic risk score with breast cancer risk.

Vachon Celine M CM   Scott Christopher G CG   Tamimi Rulla M RM   Thompson Deborah J DJ   Fasching Peter A PA   Stone Jennifer J   Southey Melissa C MC   Winham Stacey S   Lindström Sara S   Lilyquist Jenna J   Giles Graham G GG   Milne Roger L RL   MacInnis Robert J RJ   Baglietto Laura L   Li Jingmei J   Czene Kamila K   Bolla Manjeet K MK   Wang Qin Q   Dennis Joe J   Haeberle Lothar L   Eriksson Mikael M   Kraft Peter P   Luben Robert R   Wareham Nick N   Olson Janet E JE   Norman Aaron A   Polley Eric C EC   Maskarinec Gertraud G   Le Marchand Loic L   Haiman Christopher A CA   Hopper John L JL   Couch Fergus J FJ   Easton Douglas F DF   Hall Per P   Chatterjee Nilanjan N   Garcia-Closas Montse M  

Breast cancer research : BCR 20190522 1


<h4>Background</h4>Mammographic breast density, adjusted for age and body mass index, and a polygenic risk score (PRS), comprised of common genetic variation, are both strong risk factors for breast cancer and increase discrimination of risk models. Understanding their joint contribution will be important to more accurately predict risk.<h4>Methods</h4>Using 3628 breast cancer cases and 5126 controls of European ancestry from eight case-control studies, we evaluated joint associations of a 77-si  ...[more]

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