Generalizability of Polygenic Risk Scores for Breast Cancer Among Women With European, African, and Latinx Ancestry

Liu, Cong; Zeinomar, Nur; Chung, Wendy K.; Kiryluk, Krzysztof; Gharavi, Ali G.; Hripcsak, George; Crew, Katherine D.; Shang, Ning; Khan, Atlas; Fasel, David; Jarvik, Gail P.; Rowley, Robb; Justice, Ann E.; Rahm, Alanna Kulchak; Fullerton, Stephanie M.; Smoller, Jordan W.; Larson, Eric B.; Crane, Paul K.; Dikilitas, Ozan; Wiesner, Georgia L.; Bick, Alexander; Terry, Mary Beth; Weng, Chunhua

doi:10.1001/jamanetworkopen.2021.19084

Cited by 38 publications

(48 citation statements)

References 39 publications

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“…The network highlights how risk stratification has improved with the use of comprehensive models incorporating genetic and epidemiological risk factors and mammographic breast density, which have shown an excellent calibration for the European, Hispanic and African-American population [7]. Recent studies report that PRS models derived from women with European ancestry for breast cancer risk generalized well for women with European and Latina ancestries and to a lesser degree to women with African ancestry where further studies with larger sample size are needed [47,48]. Although research is still ongoing to assess the clinical utility of PRS for population screening programs, Yanes et al point out that polygenic testing is already being implemented in specialist familial cancer clinics to provide additional information for women with family history and uninformative genetic test results [7].…”

Section: Barriers and Facilitators Related To Implementing A Risk-bas...mentioning

confidence: 99%

Views of health professionals on risk-based breast cancer screening and its implementation in the Spanish National Health System: A qualitative discussion group study

et al. 2022

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Background With the aim of increasing benefits and decreasing harms, risk-based breast cancer screening has been proposed as an alternative to age-based screening. This study explores barriers and facilitators to implementing a risk-based breast cancer screening program from the perspective of health professionals, in the context of a National Health Service. Methods Socio-constructivist qualitative research carried out in Catalonia (Spain), in the year 2019. Four discussion groups were conducted, with a total of 29 health professionals from primary care, breast cancer screening programs, hospital breast units, epidemiology units, and clinical specialties. A descriptive-interpretive thematic analysis was performed. Results Identified barriers included resistance to reducing the number of screening exams for low-risk women; resistance to change for health professionals; difficulties in risk communication; lack of conclusive evidence of the benefits of risk-based screening; limited economic resources; and organizational transformation. Facilitators include benefits of risk-based strategies for high and low-risk women; women’s active role in their health care; proximity of women and primary care professionals; experience of health professionals in other screening programs; and greater efficiency of a risk-based screening program. Organizational and administrative changes in the health system, commitment by policy makers, training of health professionals, and educational interventions addressed to the general population will be required. Conclusions Despite the expressed difficulties, participants supported the implementation of risk-based screening. They highlighted its benefits, especially for women at high risk of breast cancer and those under 50 years of age, and assumed a greater efficiency of the risk-based program compared to the aged-based one. Future studies should assess the efficiency and feasibility of risk-based breast cancer screening for its transfer to clinical practice.

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Section: Barriers and Facilitators Related To Implementing A Risk-bas...mentioning

confidence: 99%

Views of health professionals on risk-based breast cancer screening and its implementation in the Spanish National Health System: A qualitative discussion group study

et al. 2022

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“…The effect sizes may differ among populations, for example due to differences in linkage disequilibrium structure. This has been shown for PRS313, for which somewhat smaller effect sizes have been estimated in Asian and African-American populations [10][11][12][13] . In addition, the mean PRS can vary significantly by population PRS313 has a higher mean in both Asian and African-American populations than in Europeans.…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 69%

Incorporating alternative Polygenic Risk Scores into the BOADICEA breast cancer risk prediction model

Mavaddat

Ficorella

Carver

et al. 2022

Preprint

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Background: The multifactorial risk prediction model BOADICEA enables identification of women at higher or lower risk of developing breast cancer. BOADICEA models genetic susceptibility in terms of the effects of rare variants in breast cancer susceptibility genes and a polygenic component, decomposed into an unmeasured and a measured component - the polygenic risk score (PRS). The current version was developed using a 313 SNP PRS. Here, we evaluated approaches to incorporating this PRS and alternative PRS in BOADICEA. Methods: The mean, standard deviation (SD), and proportion of the overall polygenic component explained by the PRS (α2) need to be estimated. α was estimated using logistic regression, where the age-specific log-relative risk is constrained to be a function of the age-dependent polygenic relative risk in BOADICEA; and using a retrospective likelihood (RL) approach that models, in addition, the unmeasured polygenic component. Results: Parameters were computed for 11 PRS, including 6 variations of the 313 SNP PRS used in clinical trials and implementation studies. The logistic regression approach underestimates α as compared with the RL estimates. The RL α estimates were very close to those obtained by assuming proportionality to the odds ratio per 1 SD, with the constant of proportionality estimated using the 313 SNP PRS. Small variations in the SNPs included in the PRS can lead to large differences in the mean. Conclusions: BOADICEA can be readily adapted to different PRS in a manner that maintains consistency of the model. Impact: The methods described enable comprehensive breast cancer risk assessment.

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“…Polygenic risk scores (PRSs) have advanced substantially in recent years and are widely used as an informative genetic measure for discriminating subpopulations at high risk of site-specific cancers 6,7,54,55,56,57,58,59,60,61,62,63 . Our recent work also constructed a PRS to stratify risk of lung cancer 6 .…”

Section: Discussionmentioning

confidence: 99%

Interplay between mosaic chromosomal alterations and polygenic risk score increases risk of non-small cell lung cancer

Qin

Chen

Liu

et al. 2022

Preprint

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We investigated autosomal mosaic chromosomal alterations (mCAs) in 10,248 non-small cell lung cancer (NSCLC) cases and 9,298 cancer-free controls of Chinese ancestry. Mosaic loss and copy-neutral loss of heterozygosity were associated with an increased risk of NSCLC, while mosaic gain was associated with a decreased risk of NSCLC, especially those spanning telomeres. The increased cell fraction of mCAs was also correlated with an increasing NSCLC risk in the affected individuals. Both multiplicative and additive interactions were observed between polygenic risk score (PRS) and the presence of mosaic loss, where carriers of mosaic loss events with cell fractions ≥5% among the high genetic risk group had the greatest risk for developing NSCLC. These findings suggest that mCA events may act as a new endogenous indicator for risk of NSCLC and have the potential to be jointly used with PRS to optimize risk stratification of NSCLC.

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Generalizability of Polygenic Risk Scores for Breast Cancer Among Women With European, African, and Latinx Ancestry

Cited by 38 publications

References 39 publications

Views of health professionals on risk-based breast cancer screening and its implementation in the Spanish National Health System: A qualitative discussion group study

Views of health professionals on risk-based breast cancer screening and its implementation in the Spanish National Health System: A qualitative discussion group study

Incorporating alternative Polygenic Risk Scores into the BOADICEA breast cancer risk prediction model

Interplay between mosaic chromosomal alterations and polygenic risk score increases risk of non-small cell lung cancer

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