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Impact of common genetic variants and other risk factors on colorectal cancer risk

A study in the latest issue of Gut investigates the cumulative impact of common genetic variants and other risk factors on colorectal cancer risk.

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Colorectal cancer has a substantial heritable component.

Common genetic variation has been shown to contribute to colorectal cancer risk.

Dr Malcolm Dunlop and colleagues from the United Kingdom conducted a large multi-population study to assess the feasibility of colorectal cancer 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.

The team studied 9 populations of European descent to develop and validate colorectal cancer risk prediction models.

The team of doctors assessed the combined effect of age, gender, family history and genotypes at 10 susceptibility loci that individually only modestly influence colorectal cancer risk.

Risk models were generated from case-control data incorporating genotypes alone, and in combination with gender, age and family history.

Mean per-allele increase in risk was 9%
Gut

The doctors assessed that model discriminatory performanced using 10-fold internal cross-validation and externally using 4187 independent samples.

The 10-year absolute risk was estimated by modelling genotype and family history with age- and gender-specific population risks.

The research team noted that results in the median number of risk alleles was greater in cases than controls, confirmed in external validation sets.

The research team found that mean per-allele increase in risk was 9%.

Discriminative performance was poor across the risk spectrum.

Modelling genotype data, family history, age and gender with Scottish population data shows the practicalities of identifying a subgroup with more than 5% predicted 10-year absolute risk.

Dr Dunlop's team commented "Genotype data provide additional information that complements age, gender and family history as risk factors, but individualized genetic risk prediction is not currently feasible."

"Nonetheless, the modelling exercise suggests public health potential since it is possible to stratify the population into colorectal cancer risk categories, thereby informing targeted prevention and surveillance."

Gut 2013: 62: 871-881
11 June 2013

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