We read with interest the important findings of Goldacre et al (Reference Goldacre, Kurina and Wotton2005) on the association between schizophrenia and cancer morbidity. Compared with the general population, they found a reduced rate of cancer of the colon in the schizophrenia cohort (adjusted rate ratio 0.72, 95% CI 0.50–1.01) with a trend towards significance (P=0.06). Rates of rectal cancer were significantly reduced in people with schizophrenia (rate ratio 0.57, 95% CI 0.33–0.93, P=0.03). In their discussion, they emphasised the reduced rate of skin cancer in the schizophrenia cohort (rate ratio 0.56, 95% CI 0.36–0.83, P=0.004).
Recent studies suggest that abnormal insulin-like growth factor-2 (IGF-2) imprinting is aetiological in the development of colorectal cancer (Reference JirtleJirtle, 2004). Genomic imprinting occurs following epigenetic modification of the germ line, which results in parent-of-origin dependent, monoallelic gene expression in somatic cells. Epigenetic changes in the genome are stable but reversible alterations in a CpG dinucleotide or histones, for example through changes in methylation. The genome of colonic epithelium from patients with colorectal cancer is hypomethylated compared with normal colonic epithelia (Reference Feinberg and VogelsteinFeinberg & Vogelstein, 1983). Hypomethylation results in the loss of IGF-2 imprinting. We proposed abnormal imprinting (deletion of paternally expressed IGF-2) as a possible mechanism associated with schizophrenia risk (Reference AbelAbel, 2004). Early nutritional influences (prenatal/maternal) may stimulate changes in cytosine methylation to which imprinted genes such as IGF-2 seem susceptible. Early nutrition may influence susceptibility not only to adult obesity, diabetes and cardiovascular disease (Reference Waterland and JirtleWaterland & Jirtle, 2004) but also to schizophrenia. This suggests that early nutritional interventions aimed at preventing chronic disease are an exciting possibility in schizophrenia. This view is supported by Dutch and more recent Chinese data which indicated that rates of schizophrenia doubled following prenatal exposure to famine (Reference St Clair, Xu and WangSt Clair et al, 2005).
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