Characteristics, management, and outcomes of patients with hepatocellular carcinoma in Africa: a multicountry observational study from the Africa Liver Cancer Consortium.

BACKGROUND: Hepatocellular carcinoma is a leading cause of cancer-related death in Africa, but there is still no comprehensive description of the current status of its epidemiology in Africa. We therefore initiated an African hepatocellular carcinoma consortium aiming to describe the clinical presentation, management, and outcomes of patients with hepatocellular carcinoma in Africa. METHODS: We did a multicentre, multicountry, retrospective observational cohort study, inviting investigators from the African Network for Gastrointestinal and Liver Diseases to participate in the consortium to develop hepatocellular carcinoma research databases and biospecimen repositories. Participating institutions were from Cameroon, Egypt, Ethiopia, Ghana, Ivory Coast, Nigeria, Sudan, Tanzania, and Uganda. Clinical information-demographic characteristics, cause of disease, liver-related blood tests, tumour characteristics, treatments, last follow-up date, and survival status-for patients diagnosed with hepatocellular carcinoma between Aug 1, 2006, and April 1, 2016, were extracted from medical records by participating investigators. Because patients from Egypt showed differences in characteristics compared with patients from the other countries, we divided patients into two groups for analysis; Egypt versus other African countries. We undertook a multifactorial analysis using the Cox proportional hazards model to identify factors affecting survival (assessed from the time of diagnosis to last known follow-up or death). FINDINGS: We obtained information for 2566 patients at 21 tertiary referral centres (two in Egypt, nine in Nigeria, four in Ghana, and one each in the Ivory Coast, Cameroon, Sudan, Ethiopia, Tanzania, and Uganda). 1251 patients were from Egypt and 1315 were from the other African countries (491 from Ghana, 363 from Nigeria, 277 from Ivory Coast, 59 from Cameroon, 51 from Sudan, 33 from Ethiopia, 21 from Tanzania, and 20 from Uganda). The median age at which hepatocellular carcinoma was diagnosed significantly later in Egypt than the other African countries (58 years [IQR 53-63] vs 46 years [36-58]; p<0·0001). Hepatitis C virus was the leading cause of hepatocellular carcinoma in Egypt (1054 [84%] of 1251 patients), and hepatitis B virus was the leading cause in the other African countries (597 [55%] of 1082 patients). Substantially fewer patients received treatment specifically for hepatocellular carcinoma in the other African countries than in Egypt (43 [3%] of 1315 vs 956 [76%] of 1251; p<0·0001). Among patients with survival information (605 [48%] of 1251 in Egypt and 583 [44%] of 1315 in other African countries), median survival was shorter in the other African countries than in Egypt (2·5 months [95% CI 2·0-3·1] vs 10·9 months [9·6-12·0]; p<0·0001). Factors independently associated with poor survival were: being from an African countries other than Egypt (hazard ratio [HR] 1·59 [95% CI 1·13-2·20]; p=0·01), hepatic encephalopathy (2·81 [1·72-4·42]; p=0·0004), diameter of the largest tumour (1·07 per cm increase [1·04-1·11]; p<0·0001), log α-fetoprotein (1·10 per unit increase [1·02-1·20]; p=0·0188), Eastern Cooperative Oncology Group performance status 3-4 (2·92 [2·13-3·93]; p<0·0001) and no treatment (1·79 [1·44-2·22]; p<0·0001). INTERPRETATION: Characteristics of hepatocellular carcinoma differ between Egypt and other African countries. The proportion of patients receiving specific treatment in other African countries was low and their outcomes were extremely poor. Urgent efforts are needed to develop health policy strategies to decrease the burden of hepatocellular carcinoma in Africa. FUNDING: None.

HER-2/neu Ile655Val polymorphism and the risk of breast cancer.

Genetic alterations of the proto-oncogene human epidermal growth factor receptor (HER-2/neu) have been shown to induce malignant transformation and metastasis. Genotyping studies have addressed the association of codon 655 isoleucine to valine polymorphism located in the transmembrane coding region and the risk of breast cancer, but the results are inconsistent. In this study, we investigated the association of HER-2/neu Ile655Val polymorphism and the risk of breast cancer in a Sudanese population. In addition, the joint effects of HER-2/neu variants and our previously reported ESR1C325G polymorphism were tested for their association with breast cancer risk. Candidate single nucleotide polymorphism (SNP) in HER-2/neu Ile655Val [db SNP rs1136200] was genotyped in breast cancer patients and in healthy controls that were randomly selected from the same age group as the patients. Genotyping was performed using a high-throughput allelic discrimination method using real-time PCR, and data on clinical features and demographic details were collected. Associations between genotype and breast cancer were assessed by means of logistic regression. The prevalence of Val/Val genotype was similar in patients of breast cancer and control subjects. In comparison with the Ile/Ile genotype, the Ile/Val had a borderline significantly (P= 0.06) higher risk of breast cancer (OR = 2.95, 95% CI: 0.97-8.96). Regarding the genotypic and allelic frequencies stratified by age and menopausal status, there were no significant associations. A significantly higher risk of breast cancer was observed among homozygous carriers of ESR1325 CC genotype and heterozygous carriers of HER-2/neu655 Ile/Val genotype (P= 0.05; adjusted OR = 4.9, 95% CI: 1.0-24). The association of HER-2/neu Ile655Val polymorphism and the risk of breast cancer was borderline significant with the heterozygous carrier being at higher risk. However, the frequency of different polymorphic variants varies with ethnicity. The results of this study suggest that a significant gene-gene interaction between ESR1325C (previously reported) and HER-2/neu Ile655Val variants may jointly contribute to a higher risk of breast cancer.

Estrogen receptor alpha gene polymorphism and breast cancer.

Estrogen and estrogen receptors play important roles in the proliferation and development of breast cancer. Several genetic alterations identified in the estrogen receptor alpha gene (ESR1) are thought to influence the expression or function of this protein, and many have been evaluated for their role in breast cancer predisposition. The aim of this study was to evaluate the role of the C325G single nucleotide polymorphism (SNP) in the ESR1 in predisposition to breast cancer. The candidate SNP C325G in ESR1, exon 4 was genotyped in breast cancer patients and in healthy controls that were age and sex matched. Genotyping was performed using both single-stranded conformational polymorphism (SSCP) and a higher throughput allelic discrimination method using real-time PCR. Data on clinical features and demographic details were collected. Significant association of breast cancer risk was shown in the subgroup of women 50 years and younger who had the C allele (OR: 2.28, 95% CI: 1.10-4.72) (P= 0.03). However, the overall susceptibility to breast cancer was not significant, although all estimates were in the direction of a higher risk in women with CC genotypes. This study found significant evidence that polymorphism within the low penetrance ESR1 is associated with breast cancer susceptibility in women of 50 years or younger. There is also an indication that G allele is protective (compared to C allele).