Dataset Information

Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.

ABSTRACT: Five genetic variants along chromosomes 8q24 and 17q have a cumulative association with prostate cancer risk. Our research group previously reported an association between these variants and clinicopathological characteristics. More recently 4 additional prostate cancer susceptibility variants were identified on chromosomes 2p15, 10q11, 11q13 and Xp11. We performed cumulative risk assessment incorporating all 9 genetic variants and determined the relationship of the new variants to clinicopathological tumor features.The genotype of 9 variants was determined in 687 men of European ancestry who underwent radical prostatectomy from 2002 to 2008 and in 777 healthy volunteer controls. We compared the incidence of these variants in prostate cancer cases and controls, and assessed their cumulative risk. We also determined the relationship of carrier status for the 4 new variants and clinicopathological tumor features.Prostate cancer cases had an increased incidence of all 9 risk variants compared to controls. A cumulative model including the 9 single nucleotide polymorphisms provided greater prostate cancer risk stratification than a model restricted to the original 5 single nucleotide polymorphisms described. Specifically men with 6 or more variants were at greater than 6-fold increased risk for prostate cancer. Although 2p15 and 11q13 carriers were more likely to have aggressive features, other clinicopathological features were similar in carriers and noncarriers.Genetic variants located in 9 regions have a cumulative association with prostate cancer risk. Identification of an increasing number of single nucleotide polymorphisms may provide greater understanding of their combined relationship with CaP risk and disease aggressiveness.

SUBMITTER: Helfand BT

PROVIDER: S-EPMC3164535 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.

Helfand Brian T BT Fought Angela J AJ Loeb Stacy S Meeks Joshua J JJ Kan Donghui D Catalona William J WJ

The Journal of urology 20100617 2

<h4>Purpose</h4>Five genetic variants along chromosomes 8q24 and 17q have a cumulative association with prostate cancer risk. Our research group previously reported an association between these variants and clinicopathological characteristics. More recently 4 additional prostate cancer susceptibility variants were identified on chromosomes 2p15, 10q11, 11q13 and Xp11. We performed cumulative risk assessment incorporating all 9 genetic variants and determined the relationship of the new variants ...[more]

PMID: 20620408

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Project description:Colorectal cancer (CRC) has a substantial heritable component. Common genetic variation has been shown to contribute to CRC risk. A study was conducted in a large multi-population study to assess the feasibility of CRC risk prediction using common genetic variant data combined with other risk factors. A risk prediction model was built and applied to the Scottish population using available data.Nine populations of European descent were studied to develop and validate CRC risk prediction models. Binary logistic regression was used to assess the combined effect of age, gender, family history (FH) and genotypes at 10 susceptibility loci that individually only modestly influence CRC risk. Risk models were generated from case-control data incorporating genotypes alone (n=39,266) and in combination with gender, age and FH (n=11,324). Model discriminatory performance was assessed using 10-fold internal cross-validation and externally using 4187 independent samples. The 10-year absolute risk was estimated by modelling genotype and FH with age- and gender-specific population risks.The median number of risk alleles was greater in cases than controls (10 vs 9, p<2.2 × 10(-16)), confirmed in external validation sets (Sweden p=1.2 × 10(-6), Finland p=2 × 10(-5)). The mean per-allele increase in risk was 9% (OR 1.09; 95% CI 1.05 to 1.13). Discriminative performance was poor across the risk spectrum (area under curve for genotypes alone 0.57; area under curve for genotype/age/gender/FH 0.59). However, modelling genotype data, FH, age and gender with Scottish population data shows the practicalities of identifying a subgroup with >5% predicted 10-year absolute risk.Genotype data provide additional information that complements age, gender and FH as risk factors, but individualised genetic risk prediction is not currently feasible. Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into CRC risk categories, thereby informing targeted prevention and surveillance.

Dataset Information

Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.

Publications

Genetic prostate cancer risk assessment: common variants in 9 genomic regions are associated with cumulative risk.

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