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FOCUSED GENOMIC DISSECTION OF THE PROSTATE CANCER RISK VARIANT ON CHROMOSOME 8Q24

Award Number: R01CA129991
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/07/2007
PERIOD OF PERFORMANCE END DATE: 05/31/2011

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FOCUSED GENOMIC DISSECTION OF THE PROSTATE CANCER RISK VARIANT ON CHROMOSOME 8Q24 - Prostate cancer is the most commonly diagnosed male malignancy in the US with an estimated 33% of all new male cancer diagnoses and 9% of all cancer deaths in 2006. Progress in finding reproducible prostate cancer risk variants has been slow even though family and twin studies show that there is a significant genetic component to the disease. Using a combination of linkage and association analysis, we identified a common genetic variant on chromosome 8q24 that is significantly associated with an increased risk of prostate cancer. Importantly, we have replicated our findings in two populations of European origin and one African American. The variant explains about 8% of prostate cancer risk in populations of European ancestry but up to 16% of the risk in African Americans and may partly explain the higher incidence of prostate cancer in this group. Our findings have now been replicated in Japanese American, Native Hawaiian, Latino American and European American prostate cancer case-control series lending additional support to the presence of risk variants in this region that are important in a wide spectrum of populations. The association signal is located within a linkage disequilibrium block on Chr8q24. This genomic region contains no known genes but is frequently gained or amplified in prostate cancer as well as other cancer types. To delineate the functional consequences of carrying the at risk variant(s) we propose to thoroughly analyze a 2 Mb region on Chr8q24 centered on the genomic region containing the markers that associate significantly to prostate cancer. We will use several complementary high-resolution array based technologies to uncover transcripts, copy number variants and methylated sites in the Chr8q24 region and relate these to the prostate cancer risk variant(s). We thus propose to take the first steps towards identifying the underlying functional prostate cancer risk factor on Chr8q24 and begin to explain why carriers are at an increased risk of developing prostate cancer. A better understanding of the prostate cancer risk factor on Chr8q24 is important for several reasons. First, it will increase our knowledge of how possibly minor differences in normal cellular physiology can over time lead to prostate cancer. Second, this information may unveil new cellular mechanisms that affect predisposition to prostate cancer and possibly other cancer types. Last, but not least, increased knowledge about the functional aspects of predisposition to prostate cancer may lead to the development of new methods for diagnosing and treating the disease.


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: 2011 ( Subtotal = $0 )
2011	2009	DECODE GENETICS EHF	STURLUGOTU 8	REYKJAVIK				ISL	Cancer Cause and Prevention Research	001	4	2/28/2011	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$196,509
2011	2009	DECODE GENETICS INC	STURLUGATTA 8	ICELAND				ISL	Cancer Cause and Prevention Research	000	3	2/28/2011	NON-COMPETING CONTINUATION	-$196,509
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $196,509 )
2009	2009	DECODE GENETICS INC	STURLUGATTA 8	ICELAND				ISL	Cancer Cause and Prevention Research	001	3	9/1/2009	NON-COMPETING CONTINUATION	$196,509
2009	2008	DECODE GENETICS INC	STURLUGATTA 8	ICELAND				ISL	Cancer Cause and Prevention Research	000	2	1/6/2009	NON-COMPETING CONTINUATION	$0
														Subtotal = $196,509

Issue Date FY: 2007 ( Subtotal = $353,816 )
2007	2007	DECODE GENETICS INC	STURLUGATTA 8	ICELAND				ISL	Cancer Cause and Prevention Research	000	1	9/7/2007	NEW	$353,816
														Subtotal = $353,816

Grand Total All Awards = $550,325

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FOCUSED GENOMIC DISSECTION OF THE PROSTATE CANCER RISK VARIANT ON CHROMOSOME 8Q24

Award Number: R01CA129991

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/07/2007

PERIOD OF PERFORMANCE END DATE: 05/31/2011

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