Warfarin pharmacogenetics in a black Zimbabwean cohort: an observational prospective study.

Aim: A prospective observational study was conducted to evaluate the feasibility of implementing clinical guidelines for warfarin dosing in black Zimbabwean patients. Methods: CYP2C9*5, CYP2C9*6, CYP2C9*8 and CYP2C9*11 and VKORC1 c. 1639 G>A variations were observed in 62 study patients. Results & Conclusion: Overall, 39/62 (62.90%) participants did not receive a warfarin starting dose as would have been recommended by Clinical Pharmacogenetics Implementation Consortium guidelines. US FDA and Dutch Pharmacogenetics Working Group guidelines are based on CYP2C9*2 and CYP2C9*3 only, hence, unlikely useful in this cohort, where such variants were not detected. Clinical Pharmacogenetics Implementation Consortium guidelines, on the other hand, have a specific recommendation on the African-specific variants CYP2C9*5, CYP2C9*6 and CYP2C9*11, and are hence suitable for implementation in Zimbabwe and would help optimize warfarin doses in patients in the study cohort.

Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases.

BACKGROUND: Approximately 25% of colorectal cancer patients in sub-Saharan Africa are younger than 40 years, and hereditary factors may contribute. We investigated the frequency and patterns of inherited colorectal cancer among black Zimbabweans. METHODS: A population-based cross-sectional study of ninety individuals with a new diagnosis of colorectal cancer was carried out in Harare, Zimbabwe between November 2012 and December 2015. Phenotypic data was obtained using interviewer administered questionnaires, and reviewing clinical and pathology data. Cases were screened for mismatch repair deficiency by immunohistochemistry and/or microsatellite instability testing, and for MLH1, MSH2 and EPCAM deletions using multiplex ligation-dependent probe amplification. Next generation sequencing using a 16-gene panel was performed for cases with phenotypic features consistent with familial colorectal cancer. Variants were assessed for pathogenicity using the mean allele frequency, phenotypic features and searching online databases. RESULTS: Three Lynch syndrome cases were identified: MSH2 c.2634G>A pathogenic mutation, c.(1896+1_1897-1)_(*193_?)del , and one fulfilling the Amsterdam criteria, with MLH1 and PMS2 deficiency, but no identifiable pathogenic mutation. Two other cases had a strong family history of cancers, but the exact syndrome was not identified. The prevalence of Lynch syndrome was 3·3% (95% CI 0·7-9·4), and that of familial colorectal cancer was 5·6% (95% CI, 1·8-12·5). CONCLUSIONS: Identifying cases of inherited colorectal cancer in sub-Saharan Africa is feasible, and our findings can inform screening guidelines appropriate to this setting.

A case-control study of risk factors for colorectal cancer in an African population.

The interplay between hereditary and environmental factors in the causation of colorectal cancer in sub-Saharan Africa is poorly understood. We carried out a community based case-control study to identify the risk factors associated with colorectal cancer in Zimbabwe. We recruited 101 cases of colorectal cancer and 202 controls, matched for age, sex and domicile. Potential risk factors including family history, socioeconomic status, urbanization, diabetes mellitus and previous schistosomiasis were evaluated. Conditional logistic regression was used to estimate the odds ratios associated with the different factors. Cases were more likely to have a tertiary education (32.7 vs. 13.4%, P<0.001) and a higher income (18.8 vs. 6.9%, P=0.002). After multivariate analysis, diabetes mellitus [odds ratio (OR): 5.3; 95% confidence interval (CI): 1.4-19.9; P=0.012], previous urban domicile (OR: 2.8; 95% CI: 1.0-7.8; P=0.042), previous schistosomiasis (OR: 2.4; 95% CI: 1.4-4.2; P=0.001) and cancer in a first-degree relative (OR: 2.4; 95% CI: 1.2-4.8; P=0.018) were associated independently with colorectal cancer. Our findings suggest that family history, diabetes mellitus, previous schistosomiasis and approximation to a western lifestyle are the predominant associations with colorectal cancer in Africans. This offers opportunities for targeted prevention and hypothesis-driven research into the aetiology of colorectal cancer in this population.

Dietary patterns and colorectal cancer risk in Zimbabwe: A population based case-control study.

BACKGROUND: The rising incidence of colorectal cancer in sub-Saharan Africa may be partly caused by changing dietary patterns. We sought to establish the association between dietary patterns and colorectal cancer in Zimbabwe. METHODS: One hundred colorectal cancer cases and 200 community-based controls were recruited. Data were collected using a food frequency questionnaire, and dietary patterns derived by principal component analysis. Generalised linear and logistic regression models were used to assess the associations between dietary patterns, participant characteristics and colorectal cancer. RESULTS: Three main dietary patterns were identified: traditional African, urbanised and processed food. The traditional African diet appeared protective against colorectal cancer (Odds Ratio (OR) 0.35; 95% Confidence Interval (CI), 0.21 - 0.58), which had no association with the urban (OR 0.68; 95% CI, 0.43-1.08), or processed food (OR 0.91; 0.58-1.41) patterns. The traditional African diet was associated with rural domicile, (OR 1.26; 95% CI, 1.00-1.59), and a low income (OR1.48; 95% CI, 1.06-2.08). The urbanised diet was associated with urban domicile (OR 1.70; 95% CI, 1.38-2.10), secondary (OR 1.30; 95% CI, 1.07-1.59) or tertiary education (OR 1.48; 95% CI, 1.11-1.97), and monthly incomes of $201-500 (OR 1.30; 95% CI, 1.05-1.62), and the processed food pattern with tertiary education (OR 1.42; 95% CI, 1.05-1.92), and income >$1000/month (OR 1.48; 95% CI, 1.02-2.15). CONCLUSION: A shift away from protective, traditional African dietary patterns may partly explain the rising incidence of colorectal cancer in sub-Saharan Africa.

The incidence and histo-pathological characteristics of colorectal cancer in a population based cancer registry in Zimbabwe.

BACKGROUND: Data on colorectal cancer (CRC) in sub-Saharan Africa is mainly based on hospital series which suggest low incidence and frequent early onset cancers. This study characterises colorectal cancer in a population-based cancer registry in Zimbabwe. METHODS: Cases of CRC recorded by the Zimbabwe National Cancer Registry between 2003 and 2012 were analysed. Demographic and pathological characteristics were compared according to ethnicity and age. Trends in age standardised incidence rates (ASR) were determined. RESULTS: There were 886 and 216 cases of CRC among black Africans and Caucasians respectively, and 26% of the black Africans were younger than 40 years. Signet ring cell carcinomas were more common among black Africans compared to Caucasians (4% vs 1%, p=0.027). ASR increased by 1.9%/year and 3.9%/year among black African males and females respectively. CONCLUSION: CRC incidence is rising among black Africans and has unique demographic and pathological characteristics.