How do researchers manage genetic results in practice? The experience of the multinational Colon Cancer Family Registry.

There is consensus internationally that research participants should be offered the opportunity to receive clinically relevant genetic information identified through research, but there is little empirical peer-reviewed work documenting this process. We report the experience of conducting genetic research with nearly 35,000 participants in the Colon Cancer Family Registry, based in the USA, Canada, Australia, and New Zealand. Investigators from six multinational sites provided information about disclosure protocols, implementation, and uptake of genetic results and made suggestions to inform practice.

A novel recurrent mutation in MITF predisposes to familial and sporadic melanoma.

So far, two genes associated with familial melanoma have been identified, accounting for a minority of genetic risk in families. Mutations in CDKN2A account for approximately 40% of familial cases, and predisposing mutations in CDK4 have been reported in a very small number of melanoma kindreds. Here we report the whole-genome sequencing of probands from several melanoma families, which we performed in order to identify other genes associated with familial melanoma.

Genome-wide association study identifies a new melanoma susceptibility locus at 1q21.3.

We performed a genome-wide association study of melanoma in a discovery cohort of 2,168 Australian individuals with melanoma and 4,387 control individuals. In this discovery phase, we confirm several previously characterized melanoma-associated loci at MC1R, ASIP and MTAP-CDKN2A. We selected variants at nine loci for replication in three independent case-control studies (Europe: 2,804 subjects with melanoma, 7,618 control subjects; United States 1: 1,804 subjects with melanoma, 1,026 control subjects; United States 2: 585 subjects with melanoma, 6,500 control subjects).

Population-based, case-control-family design to investigate genetic and environmental influences on melanoma risk: Australian Melanoma Family Study.

Discovering and understanding genetic risk factors for melanoma and their interactions with phenotype, sun exposure, and other risk factors could lead to new strategies for melanoma control. This paper describes the Australian Melanoma Family Study, which uses a multicenter, population-based, case-control-family design. From 2001 to 2005, the authors recruited 1,164 probands including 629 cases with histopathologically confirmed, first-primary cutaneous melanoma diagnosed before age 40 years, 240 population-based controls frequency matched for age, and 295 spouse/friend controls.

Is uptake of genetic testing for colorectal cancer influenced by knowledge of insurance implications?

Objective: To assess whether knowledge of insurance implications influenced uptake of genetic testing by participants in a research study of the causes of colorectal cancer.

Design, Setting And Participants: Analysis of uptake of genetic testing by participants in the population-based Victorian Colorectal Cancer Family Study during two periods: from 1999 to 2003, when participants were not informed of any potential effect of genetic testing conducted during the study on their eligibility for new insurance policies; and from 2003 to 2006, when the protocol was changed to provide participants with information on the potential effect of genetic testing on insurance eligibility.

Main Outcome Measure: Uptake of genetic testing for germline mutations in DNA mismatch repair (MMR) genes at a family cancer clinic.

Common sequence variants on 20q11.22 confer melanoma susceptibility.

We conducted a genome-wide association pooling study for cutaneous melanoma and performed validation in samples totaling 2,019 cases and 2,105 controls. Using pooling, we identified a new melanoma risk locus on chromosome 20 (rs910873 and rs1885120), with replication in two further samples (combined P < 1 x 10(-15)). The per allele odds ratio was 1.