Comparability, diagnostic validity and completeness of Nigerian cancer registries.

BACKGROUND: Like many countries in Africa, Nigeria is improving the quality and coverage of its cancer surveillance. This work is essential to address this growing category of chronic diseases, but is made difficult by economic, geographic and other challenges. PURPOSE: To evaluate the completeness, comparability and diagnostic validity of Nigeria's cancer registries. METHODS: Completeness was measured using children's age-specific incidence (ASI) and an established metric based on a modified Poisson distribution with regional comparisons. We used a registry questionnaire as well as percentages of death-certificate-only cases, morphologically verified cases, and case registration errors to examine comparability and diagnostic validity. RESULTS: Among the children's results, we found that over half of all cancers were non-Hodgkin lymphoma. There was also evidence of incompleteness. Considering the regional completeness comparisons, we found potential evidence of cancer-specific general incompleteness as well as what appears to be incompleteness due to inability to diagnose specific cancers. We found that registration was generally comparable, with some exceptions. Since autopsies are not common across Nigeria, coding for both them and death-certificate-only cases was also rare. With one exception, registries in our study had high rates of morphological verification of female breast, cervical and prostate cancers. CONCLUSIONS: Nigeria's registration procedures were generally comparable to each other and to international standards, and we found high rates of morphological verification, suggesting high diagnostic validity. There was, however, evidence of incompleteness.

Global patterns of prostate cancer incidence, aggressiveness, and mortality in men of african descent.

Prostate cancer (CaP) is the leading cancer among men of African descent in the USA, Caribbean, and Sub-Saharan Africa (SSA). The estimated number of CaP deaths in SSA during 2008 was more than five times that among African Americans and is expected to double in Africa by 2030. We summarize publicly available CaP data and collected data from the men of African descent and Carcinoma of the Prostate (MADCaP) Consortium and the African Caribbean Cancer Consortium (AC3) to evaluate CaP incidence and mortality in men of African descent worldwide. CaP incidence and mortality are highest in men of African descent in the USA and the Caribbean. Tumor stage and grade were highest in SSA. We report a higher proportion of T1 stage prostate tumors in countries with greater percent gross domestic product spent on health care and physicians per 100,000 persons. We also observed that regions with a higher proportion of advanced tumors reported lower mortality rates. This finding suggests that CaP is underdiagnosed and/or underreported in SSA men. Nonetheless, CaP incidence and mortality represent a significant public health problem in men of African descent around the world.

Chromosome 8q24 variants are associated with prostate cancer risk in a high risk population of African ancestry.

BACKGROUND: Earlier studies on the role of germline variations in the disproportionate higher burden of prostate cancer in men of African ancestry have been largely unrewarding. However, the successful replication of recent genome-wide association findings implicating some regions of chromosome 8q24 in the disparate prostate cancer susceptibility in men of European and African ancestry have been encouraging. This case-control study was designed to evaluate the association between germline variations in chromosome 8q24 and prostate cancer risk in Afro-Caribbean Tobago men, a population of predominantly West African ancestry. METHODS: High molecular weight genomic DNA was isolated from blood clots using Qiagen kits. Genotyping was performed on genomic DNA using a pre-designed TaqMan SNP assay according to the manufacture's protocol on a 7900HT Fast Real-Time PCR system (Applied Biosystems, Foster City, CA). RESULTS: SNP rs16901979 in region 2 was associated with significantly increased risk of prostate cancer (OR = 1.41, 95% confidence interval [CI] 1.02-1.95, P = 0.04) with the risk stronger in men with early-onset prostate cancer (OR = 2.37, 95% CI 1.40-3.99, P = 0.001). There was a tendency towards significantly increased risk for SNPs rs1447295 and rs6983267 in men with early-onset prostate cancer. CONCLUSIONS: The replication of the association of chromosome 8q24 variants with increased prostate cancer risk in Tobago men and the higher frequency of the risk alleles in controls in populations of African ancestry further strengthens the possible role of this genomic region in the disproportionate higher burden of prostate cancer in men of African ancestry.

Leptin levels and leptin receptor polymorphism frequency in healthy populations.

BACKGROUND: The leptin receptor gene (LEPR) polymorphism Q223R is one of the most common in the general population, and is thought to be associated with an impaired signaling capacity of the leptin receptor and with higher mean circulating levels of leptin. Leptin is a hormone primarily produced in adipose tissue. Increased levels of leptin have been positively correlated with obesity. We have determined the frequency of the leptin receptor polymorphism (LEPR Q223R) in healthy populations from various ethnic groups, and compared plasma leptin levels across the LEPR Q223R polymorphism in healthy African-Caribbean and Caucasian women. RESULTS: The study population consists of 1,418 healthy subjects from various ethnic groups. The LEPR Q223R homozygous variant was observed overall in 19% of subjects (n = 1,418), with significant differences based on self reported ethnicity: the proportion of subjects with the homozygous variant was lower in Caucasians (14%, n = 883) than in African-Caribbean (n = 194), African-American (n = 36) and Asian/other ethnic groups (n = 26), (35%, 33% and 34.6% respectively); the frequency in Africans (20%), was similar to the overall study population. The mean +/- standard deviation (SD), circulating leptin levels for African-Caribbean women was 44.7 +/- 31.4 ng/ml, while for Caucasian women the mean was 42.4 +/- 34.8 ng/ml. Adjusted circulating leptin levels in post-menopausal Caucasian women who were LEPR Q223R homozygous variant were marginally statistically significantly higher than in women with the wild-type genotype (p = 0.098). No significant differences in leptin levels by genotype were observed for African-Caribbean women, (heterozygous: p = 0.765, homozygous variant: p = 0.485). CONCLUSION: These findings suggest an association between mean circulating leptin levels and the LEPR Q223R genotype among post-menopausal Caucasian women.

Cytochrome P450 1B1 Val432Leu polymorphism and breast cancer risk in Nigerian women: a case control study.

BACKGROUND: Cytochrome P450 1B1 (CYP1B1) is active in the metabolism of estrogens to reactive catechols and of different procarcinogens. Several studies have investigated the relationship between genetic polymorphisms of CYP1B1 and breast cancer risk with inconsistent results. A G --> C transversion polymorphism in the heme-binding region in codon 432 of the gene results in amino acid change (Val --> Leu); the Leu allele display increased catalytic efficiency for 4-hydroxylation of estradiol in some experimental systems. METHODS: In this study, we utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to assess the relationship between this polymorphism and breast cancer risk in a case control study including 250 women with breast cancer and 250 controls from four University Teaching Hospitals in Southern Nigeria. RESULTS: Heterozygosity for the CYP1B1 M1 genotype (CYP1B1 M1 [Val/Leu]) was associated with a significant 59% increased risk of breast cancer (OR = 1.59, 95% CI 1.01-2.58) while homozygosity for the genotype (CYP1B1 M1 [Leu/Leu]) conferred a non-significant 51% increased risk of breast cancer. These risk profiles were modified in subgroup analysis. In premenopausal women, harboring at least one CYP1B1 (Leu) allele conferred a significant two-fold increased risk of breast cancer (OR = 2.04, 95% CI 1.10-3.78). No significant association was observed in postmenopausal women (OR = 1.08, 95% CI 0.57-2.04). CONCLUSION: Our results suggest that the codon 432 polymorphism of the CYP1B1 gene is associated with increased risk of breast cancer and is particularly involved in breast cancer risk in premenopausal women of African descent.

Leptin receptor Gln223Arg polymorphism and breast cancer risk in Nigerian women: a case control study.

BACKGROUND: Leptin, a 16 kDa polypeptide hormone, implicated in various physiological processes, exerts its action through the leptin receptor, a member of the class I cytokine receptor family. Both leptin and leptin receptor have recently been implicated in processes leading to breast cancer initiation and progression in animal models and humans. An A to G transition mutation in codon 223 in exon 6 of the leptin receptor gene, resulting in glutamine to arginine substitution (Gln223Arg), lies within the first of two putative leptin-binding regions and may be associated with impaired signaling capacity of the leptin receptor. This study was designed to assess the role of this polymorphism in breast cancer susceptibility in Nigerian women. METHODS: We utilized a polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay to evaluate the association between the Gln223Arg polymorphism of the leptin receptor gene and breast risk in Nigeria in a case control study involving 209 women with breast cancer and 209 controls without the disease. Study participants were recruited from surgical outpatient clinics and surgical wards of four University Teaching Hospitals located in Midwestern and southeastern Nigeria between September 2002 and April 2004. RESULTS: Premenopausal women carrying at least one LEPR 223Arg allele were at a modestly increased risk of breast cancer after adjusting for confounders (OR = 1.8, 95% confidence interval [CI] 1.0-3.2, p = 0.07). There was no association with postmenopausal breast cancer risk (OR = 0.9, 95% CI 0.4-1.8, p = 0.68). CONCLUSION: Our results suggest that the LEPR Gln223Arg polymorphism in the extracellular domain of the LEPR receptor gene is associated with a modestly increased risk of premenopausal breast cancer in Nigerian women.

African-Caribbean cancer consortium for the study of viral, genetic and environmental cancer risk factors.

This is a short summary of a meeting of the "African-Caribbean Cancer Consortium", jointly organized by the University of Pittsburgh, Department of Epidemiology and the University of Pittsburgh Cancer Institute, held in Montego Bay, Jamaica as a satellite meeting at the Caribbean Health Research Council, 52nd Annual Council and Scientific meeting on May 4, 2007.

Anthropometry and breast cancer risk in Nigerian women.

The recent upsurge in global obesity and the recognition of the role of metabolic syndrome and other correlates of obesity in the etiology of breast cancer and other chronic diseases has created the impetus for renewed interest in the role of anthropometric measures in breast cancer risk. This case-control study was designed to evaluate the role of anthropometric variables in breast cancer susceptibility in an indigenous sub-Saharan African population drawn from midwestern and southeastern Nigeria, a population grossly underreported in the global epidemiologic literature. Study participants were 250 women with breast cancer who were receiving treatment in the surgical outpatient clinics and surgical wards of four university teaching hospitals located in midwestern and southeastern Nigeria, while the controls were 250 age-matched women without breast cancer or other malignant diseases being treated for other surgical diseases in the same institutions between September 2002 and April 2004. Waist:hip ratio (WHR) was associated with a significant 2.5-fold increased risk of premenopausal breast cancer (odds ratio [OR] = 2.56, 95% confidence interval [CI] 1.48-4.41] and a 2-fold increased risk of postmenopausal breast cancer (OR = 2.00, 95% CI 1.04-2.53). Increasing height conferred a modestly nonsignificant increased risk of premenopausal breast cancer (OR = 1.59, 95% CI 0.98-2.58). The study showed that WHR is a significant predictor of breast cancer risk in Nigerian women and measures to sustain increased physical activity and ensure healthy dietary practices are recommended to reduce the burden of obesity in the population.

Case-control study of risk factors for breast cancer in Nigerian women.

This study evaluated the potential risk factors for breast cancer in Nigerian women using a case-control design of 250 women with breast cancer and their age-matched female controls. Both cases and controls were recruited from 4 University Teaching Hospitals in Midwestern and Southeastern Nigeria. Data on the clinical and epidemiological characteristics were collected using interviewer-administered structured questionnaires. The mean age of the cases and controls were 46.1 and 47.1 years, respectively. Fifty-seven percent of the cases were premenopausal while 43% were postmenopausal. The association of risk factors with breast cancer was assessed using conditional logistic regression. Positive family history of breast cancer in first- and second-degree relatives (Odds ratio [OR] = 8.07, 95% confidence interval [CI], 1.003, 64.95, p = 0.04), education of high school level and above (OR = 1.35, 95% CI 1.04, 1.74, p = 0.0205), age at first fullterm pregnancy (FFTP) greater than 20 years (OR = 1.32 95% CI 1.01, 1.71, p = 0.0413) and waist/hip ratio (WHR) (OR = 1.98, 95% CI 1.27, 3.10, p = 0.0026) were associated with increased risk of breast cancer in the final multiple conditional logistic regression model. The findings from this study have shown that sociodemographic characteristics, reproductive variables and anthropometric measures are significant predictors of breast cancer risk in Nigerian women.

Simple tandem repeat (TTTA)n polymorphism in CYP19 (aromatase) gene and breast cancer risk in Nigerian women.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer related deaths in women worldwide. The incidence of the disease is increasing globally and this increase is occurring at a faster rate in population groups that hirtherto enjoyed low incidence. This study was designed to evaluate the role of a simple tandem repeat polymorphism (STRP) in the aromatase (CYP19) gene in breast cancer susceptibility in Nigerian women, a population of indigenous sub-Saharan African ancestry. METHODS: A case-control study recruiting 250 women with breast cancer and 250 women without the disease from four University Teaching Hospitals in Southern Nigeria was carried out between September 2002 and April 2004. Participants were recruited from the surgical outpatient clinics and surgical wards of the Nigerian institutions. A polymerase chain reaction (PCR)-based assay was employed for genotyping and product sizes were detected with an ABI 3730 DNA Analyzer. RESULTS: Conditional logistic regression analysis revealed that harboring the putative high risk genotypes conferred a 29% increased risk of breast cancer when all women in the study were considered (Odds ratio [OR] = 1.29, 95% confidence interval [CI] 0.83-2.00), although this association was not statistically significant. Subgroup analysis based on menopausal status showed similar results among premenopausal women (OR = 1.35, 95% CI 0.76-2.41 and postmenopausal women (OR = 1.27, 95% CI 0.64-2.49). The data also demonstrated marked differences in the distribution of (TTTA)n repeats in Nigerian women compared with other populations. CONCLUSION: This study has shown that harboring 10 or more repeats of the microsatellite (TTTA)n repeats of the CYY19 gene is associated with a modest increased risk of breast cancer in Nigerian women.