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Advancing equity in colorectal cancer genetic risk prediction through expansion of racial/ethnic minority representation

Award Number: R01CA244588
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary / Abstract As colorectal cancer (CRC) remains one of the leading causes of cancer death new approaches are of vital importance to make critical inroads in reducing the burden of this lethal disease. Precision medicine holds enormous promise as advances in genomic research that were previously unimaginable now offer vast commercial potential and are rapidly being moved into clinical practice, even though critical questions remain to be addressed. Polygenic risk scores (PRS) that aggregate common genetic risk variants into a single score to predict disease are a key example. Broad accessibility, plummeting genotyping costs, and the need to account for the patient's individual risk profile to improve screening have provided transformative opportunities in personalized prevention. However, wide-scale clinical adoption of PRS raises key ethical and scientific challenges. Arguably one of the most critical challenge is the fact that current PRS are substantially more effective in predicting risk in individuals of European ancestry compared with other populations due to the Euro- centric bias in genetic research. Accordingly, we need to develop an unbiased PRS that predicts CRC risk in all major racial/ethnic groups. However, this is only the first step towards implementation, which also requires the evaluation of the optimal risk-stratified screening approach and development of risk communication tool among others. To address these needs, we will develop and validate an unbiased PRS for CRC across ethnic/racial minority groups to inform risk-stratified CRC screening (Aim 1a). We will augment the PRS with an environmental/ lifestyle risk score (ERS) to account for other risk factors (Aim 1b) and examine differential effects by age of onset (Aim 1c), given the alarming increase of early onset CRC. In Aim 2a we will determine the optimal CRC screening strategy given an individual's risk defined in Aim 1 using our microsimulation modeling by incorporating differences in CRC incidence and mortality rates by age, sex and race/ethnicity, and in risk factor distributions across racial/ethnic groups. In Aim 2b we will evaluate the cost-effectiveness of risk stratified screening compared with current screening guidelines. Finally, we will develop a risk communication tool (Aim 3a) and investigate potential dissemination issues of risk-stratified CRC screening across ethnic/racial minority groups (Aim 3b). Our trans-disciplinary research team, which includes a community advisory board, is uniquely set up to address these critical questions as we 1) have brought together all known racially/ethnically diverse CRC studies totaling to over 120,000 CRC cases and controls, 2) have strong expertise in developing comprehensive genetic and environmental risk scores in racially/ethnically diverse populations, 3) lead one of the most comprehensive decision models for cost-effectiveness analysis which has consistently been used to inform US screening guidelines and 4) have expertise in implementation science for genetic research in minorities. Addressing all aims is critical to avoid a sequential science in this rapidly moving field of precision medicine.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $643,405 )
2023	2023	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	5	6/21/2023	NON-COMPETING CONTINUATION	$643,405
														Subtotal = $643,405

Issue Date FY: 2022 ( Subtotal = $683,865 )
2022	2022	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	005	4	8/22/2022	NON-COMPETING CONTINUATION	$683,865
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	004	3	7/29/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$77,869
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	003	2	7/29/2022	NON-COMPETING CONTINUATION	-$1
2022	2021	FRED HUTCHINSON CANCER CENTER	1100 FAIRVIEW AVE N	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	001	3	6/14/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$709,766
2022	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	2	6/14/2022	NON-COMPETING CONTINUATION	-$709,766
2022	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	002	1	7/29/2022	NEW	-$77,868
														Subtotal = $683,865

Issue Date FY: 2021 ( Subtotal = $709,767 )
2021	2021	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	2	6/17/2021	NON-COMPETING CONTINUATION	$709,767
														Subtotal = $709,767

Issue Date FY: 2020 ( Subtotal = $797,274 )
2020	2020	FRED HUTCHINSON CANCER RESEARCH CENTER	1100 FAIRVIEW AVE N J6-300	SEATTLE	WA	98109	KING	USA	Cancer Cause and Prevention Research	000	1	6/4/2020	NEW	$797,274
														Subtotal = $797,274

Grand Total All Awards = $2,834,311

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Advancing equity in colorectal cancer genetic risk prediction through expansion of racial/ethnic minority representation

Award Number: R01CA244588

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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