CYP2C19*2 polymorphism is associated with increased survival in breast cancer patients using tamoxifen.

Aims: Variant alleles of the CYP2C19 gene were recently associated with survival in breast cancer patients on tamoxifen therapy. CYP2C19 is one of the enzymes involved in the metabolism of tamoxifen into active metabolites. We investigated the hypothesis that CYP2C19*2 and *3 variants, known for their lack of enzyme activity, are associated with an increased breast cancer mortality rate in patients using tamoxifen.

Risk factors for single and multiple basal cell carcinomas.

Objective: To investigate the incidence of single and multiple basal cell carcinoma (BCC) lesions and associated risk factors.

Design: A prospective, population-based cohort study (from January 1, 1990, through December 31, 2007).

Setting: Two cohorts of 10 994 Dutch people, 55 years or older, were studied in 1990 (first cohort) and 1999 (second cohort).

Variation in the CYP2D6 gene is associated with a lower serum sodium concentration in patients on antidepressants.

Aim: To study the effect of the CYP2D6*4 polymorphism on serum sodium concentration in users of antidepressants [selective serotonin reuptake inhibitors and tricyclic antidepressants (TCAs)].

Methods: In this population-based cohort study, all subjects in the Rotterdam Study were included who used an antidepressant at baseline and from whom a blood sample was available in which CYP2D6 genotype and serum sodium concentration could be determined (n= 76). Multivariate linear regression was used to study the association between CYP2D6*4 and serum sodium concentration.

The CYP2D6*4 polymorphism affects breast cancer survival in tamoxifen users.

Cytochrome P450 2D6 (CYP2D6) plays an important role in the formation of endoxifen, the active metabolite of tamoxifen. In this study the association between the most prevalent CYP2D6 null-allele in Caucasians (CYP2D6*4) and breast cancer mortality was examined among all incident users of tamoxifen in a population-based cohort study. Breast cancer mortality was significantly increased in patients with the * 4/*4 genotype (HR = 4.

Influence of the CYP2D6*4 polymorphism on dose, switching and discontinuation of antidepressants.

What Is Already Known About This Subject: * Most antidepressants are metabolized by CYP2D6. The variant allele CYP2D6*4 is the main polymorphism resulting in reduced enzyme activity in Caucasians. * Reduced enzyme activity potentially leads to increased toxicity of antidepressants, but the relevance of genotyping for clinical practice is unclear.