Characterisation of CYP2C8, CYP2C9 and CYP2C19 polymorphisms in a Ghanaian population

<p>Abstract</p> <p>Background</p> <p>Genetic influences on drug efficacy and tolerability are now widely known. Pharmacogenetics has thus become an expanding field with great potential for improving drug efficacy and reducing toxicity. Many pharmacologically-relevant polymorphisms do show variability among different populations. Knowledge of allelic frequency distribution within specified populations can be useful in explaining therapeutic failures, identifying potential risk groups for adverse drug reactions (ADRs) and optimising doses for therapeutic efficacy. We sought to determine the prevalence of clinically relevant Cytochrome P450 (<it>CYP) 2C8</it>, <it>CYP2C9</it>, and <it>CYP2C19 </it>variants in Ghanaians. We compared the data with other ethnic groups and further investigated intra country differences within the Ghanaian population to determine its value to pharmacogenetics studies.</p> <p>Methods</p> <p>RFLP assays were used to genotype <it>CYP2C8 </it>(<it>*2</it>, <it>*3</it>, <it>*4</it>) variant alleles in 204 unrelated Ghanaians. <it>CYP2C9*2 </it>and <it>CYP2C19 </it>(<it>*2 </it>and <it>*3</it>) variants were determined by single-tube tetra-primer assays while <it>CYP2C9 </it>(<it>*3, *4, *5 </it>and <it>*11</it>) variants were assessed by direct sequencing.</p> <p>Results</p> <p>Allelic frequencies were obtained for <it>CYP2C8*2 </it>(17%), <it>CYP2C8*3 </it>(0%), <it>CYP2C8*4 </it>(0%), <it>CYP2C9*2 </it>(0%), <it>CYP2C9*3 </it>(0%), <it>CYP2C9*4 </it>(0%), <it>CYP2C9</it>*5 (0%), <it>CYP2C9*11 </it>(2%), <it>CYP2C19*2 </it>(6%) and <it>CYP2C19*3 </it>(0%).</p> <p>Conclusion</p> <p>Allele frequency distributions for <it>CYP2C8</it>, <it>CYP2C9 </it>and <it>CYP2C19 </it>among the Ghanaian population are comparable to other African ethnic groups but significantly differ from Caucasian and Asian populations. Variant allele frequencies for <it>CYP2C9 </it>and <it>CYP2C19 </it>are reported for the first time among indigenous Ghanaian population.</p

Family history of cancer and the risk of squamous cell carcinoma of oesophagus: A case-control study in Kashmir, India

Background: Only a few studies have examined the association between family history of cancer (FHC) and the risk of oesophageal squamous cell carcinoma (ESCC) in high incidence areas of ESCC. We conducted a case-control study to evaluate the relationship between FHC and ESCC risk in Kashmir, India, with analysis of detailed epidemiological data and information on multiple gene polymorphisms.Methods: We collected detailed information on FHC and a number of socio-demographic and lifestyle factors, and also obtained blood samples for genetic analysis from 703 histopathologically confirmed ESCC cases and 1664 individually matched controls. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (95% CIs).Results: Participants who had FHC showed a strong association with ESCC risk, and the risk was stronger when first-degree relatives (FDRs) had FHC (OR=6.8; 95% CI=4.6-9.9). Having a sibling with a cancer showed the strongest association (OR=10.8; 95% CI=6.0-19.3), but having a child with a cancer was not associated with ESCC risk. A history of any cancer in the spouse was also associated with ESCC risk (OR=4.1; 95% CI=1.6-10.2). Those with two or more relatives with FHC were at a higher risk of ESCC. After restricting FHC to familial ESCC only, the above associations were strengthened, except when spouses were affected with ESCC (OR=2.5; 95% CI=0.7-8.9). When we examined the associations between several single-nucleotide polymorphisms and ESCC in those with and without FHC, the associations of variant genotypes in cytochrome P450 (CYP) 2C19 and CYP2D6 and the wild genotype of CYP2E1 with ESCC were much stronger in those with FHC. The FHC had an additive interaction with several risk factors of ESCC in this population.Conclusion: Our results showed that FHC was strongly associated with ESCC risk in Kashmir. It seems both genetic factors and shared environment are involved in this association. © 2015 Cancer Research UK. All rights reserved