Mosquito control exposures and breast cancer risk: analysis of 1071 cases and 2096 controls from the Ghana Breast Health Study.

Epidemiologic data on insecticide exposures and breast cancer risk are inconclusive and mostly from high-income countries. Using data from 1071 invasive pathologically confirmed breast cancer cases and 2096 controls from the Ghana Breast Health Study conducted from 2013 to 2015, we investigated associations with mosquito control products to reduce the spread of mosquito-borne diseases, such as malaria. These mosquito control products were insecticide-treated nets, mosquito coils, repellent room sprays, and skin creams for personal protection against mosquitos. Multivariable and polytomous logistic regression models were used to estimate odds ratios (ORadj) and 95% confidence intervals (CI) with breast cancer risk-adjusted for potential confounders and known risk factors. Among controls, the reported use of mosquito control products were mosquito coils (65%), followed by insecticide-treated nets (56%), repellent room sprays (53%), and repellent skin creams (15%). Compared to a referent group of participants unexposed to mosquito control products, there was no significant association between breast cancer risk and mosquito coils. There was an association in breast cancer risk with reported use of insecticide-treated nets; however, that association was weak and not statistically significant. Participants who reported using repellent sprays were at elevated risks compared to women who did not use any mosquito control products, even after adjustment for all other mosquito control products (OR = 1.42, 95% CI=1.15-1.75). We had limited power to detect an association with repellent skin creams. Although only a few participants reported using repellent room sprays weekly/daily or < month-monthly, no trends were evident with increased frequency of use of repellent sprays, and there was no statistical evidence of heterogeneity by estrogen receptor (ER) status (p-het > 0.25). Our analysis was limited when determining if an association existed with repellent skin creams; therefore, we cannot conclude an association. We found limited evidence of risk associations with widely used mosquito coils and insecticide-treated nets, which are reassuring given their importance for malaria prevention. Our findings regarding specific breast cancer risk associations, specifically those observed between repellent sprays, require further study.

Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study.

BACKGROUND: Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study. METHODS: Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case-control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders. RESULTS: Measured BMI (≥ 30 vs. 18.5-24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57-93.53) vs. 50.89 (43.47-59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47-36.07) vs. 13.26 (10.37-16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women. CONCLUSIONS: We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.

The oral microbiome and breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in the Ghana Breast Health Study.

The oral microbiome, like the fecal microbiome, may be related to breast cancer risk. Therefore, we investigated whether the oral microbiome was associated with breast cancer and nonmalignant breast disease, and its relationship with the fecal microbiome in a case-control study in Ghana. A total of 881 women were included (369 breast cancers, 93 nonmalignant cases and 419 population-based controls). The V4 region of the 16S rRNA gene was sequenced from oral and fecal samples. Alpha-diversity (observed amplicon sequence variants [ASVs], Shannon index and Faith's Phylogenetic Diversity) and beta-diversity (Bray-Curtis, Jaccard and weighted and unweighted UniFrac) metrics were computed. MiRKAT and logistic regression models were used to investigate the case-control associations. Oral sample alpha-diversity was inversely associated with breast cancer and nonmalignant breast disease with odds ratios (95% CIs) per every 10 observed ASVs of 0.86 (0.83-0.89) and 0.79 (0.73-0.85), respectively, compared to controls. Beta-diversity was also associated with breast cancer and nonmalignant breast disease compared to controls (P ≤ .001). The relative abundances of Porphyromonas and Fusobacterium were lower for breast cancer cases compared to controls. Alpha-diversity and presence/relative abundance of specific genera from the oral and fecal microbiome were strongly correlated among breast cancer cases, but weakly correlated among controls. Particularly, the relative abundance of oral Porphyromonas was strongly, inversely correlated with fecal Bacteroides among breast cancer cases (r = -.37, P ≤ .001). Many oral microbial metrics were strongly associated with breast cancer and nonmalignant breast disease, and strongly correlated with fecal microbiome among breast cancer cases, but not controls.

Associations of fecal microbial profiles with breast cancer and nonmalignant breast disease in the Ghana Breast Health Study.

The gut microbiota may play a role in breast cancer etiology by regulating hormonal, metabolic and immunologic pathways. We investigated associations of fecal bacteria with breast cancer and nonmalignant breast disease in a case-control study conducted in Ghana, a country with rising breast cancer incidence and mortality. To do this, we sequenced the V4 region of the 16S rRNA gene to characterize bacteria in fecal samples collected at the time of breast biopsy (N = 379 breast cancer cases, N = 102 nonmalignant breast disease cases, N = 414 population-based controls). We estimated associations of alpha diversity (observed amplicon sequence variants [ASVs], Shannon index, and Faith's phylogenetic diversity), beta diversity (Bray-Curtis and unweighted/weighted UniFrac distance), and the presence and relative abundance of select taxa with breast cancer and nonmalignant breast disease using multivariable unconditional polytomous logistic regression. All alpha diversity metrics were strongly, inversely associated with odds of breast cancer and for those in the highest relative to lowest tertile of observed ASVs, the odds ratio (95% confidence interval) was 0.21 (0.13-0.36; Ptrend < .001). Alpha diversity associations were similar for nonmalignant breast disease and breast cancer grade/molecular subtype. All beta diversity distance matrices and multiple taxa with possible estrogen-conjugating and immune-related functions were strongly associated with breast cancer (all Ps < .001). There were no statistically significant differences between breast cancer and nonmalignant breast disease cases in any microbiota metric. In conclusion, fecal bacterial characteristics were strongly and similarly associated with breast cancer and nonmalignant breast disease. Our findings provide novel insight into potential microbially-mediated mechanisms of breast disease.

Prostate tumors of native men from West Africa show biologically distinct pathways-A comparative genomic study.

BACKGROUND: Native African men (NAM) experience a disproportionate burden of prostate cancer (PCa) and have higher mortality rates compared to European American men (EAM). While socioeconomic status has been implicated as a driver of this disparity, little is known about the genomic mechanisms and distinct biological pathways that are associated with PCa of native men of African origin. METHODS: To understand biological factors that contribute to this disparity we utilized a total of 406 multi-institutional localized PCa samples, collected by Men of African Descent and Carcinoma of the Prostate biospecimen network and Moffitt Cancer Center/University of Pennsylvania Health science system. We performed comparative genomics and immunohistochemistry to identify the biomarkers that are highly enriched in NAM from west Africa and compared them with African American Men (AAM) and EAM. Quantified messenger RNA expression and Median H scores based on immune reactivity of staining cells, were compared using Mann Whitney test. For gene expression analysis, p values were further adjusted for multiple comparisons using false discovery rates. RESULTS: Immunohistochemical analysis on selected biomarkers showed a consistent association between ETS related gene (ERG) status and race with 83% of NAM exhibiting tumors that lacked TMPRSS2-ERG translocation (ERGnegative ) as compared to AAM (71%) and EAM (52%). A higher proportion of NAM (29%) were also found to be double negative (ERGnegative and PTENLoss ) as compared to AAM (6%) and EAM (7%). NAM tumors had significantly higher immunoreactivity (H-score) for PSMA, and EZH2, whereas they have lower H-score for PTEN, MYC, AR, RB and Racemase, (all p < .05). Comparative genomics revealed that NAM had significant transcriptomic variability in AR-activity score. In pathways enrichment analysis NAM tumors exhibited the enrichment of proinflammatory pathways including cytokine, interleukins, inflammatory response, and nuclear factor kappa B signaling. CONCLUSIONS: Prostate tumors in NAM are genomically distinct and are characterized by the dysregulation of several biomarkers. Furthermore, these tumors are also highly enriched for the major proinflammatory pathways. These distinct biological features may have implications for diagnosis and response to targeted therapy among Black men, globally.

Outcomes of patients with cervical cancer treated with low- or high-dose rate brachytherapy after concurrent chemoradiation.

OBJECTIVE: The majority of patients with cervical cancer in Ghana present with locally advanced disease. In October 2014, high-dose rate (HDR) brachytherapy was introduced at the National Center for Radiotherapy, Accra after years of using low-dose rate (LDR) brachytherapy. The aim of this study was to compare the treatment outcomes of patients treated with LDR versus HDR brachytherapy. METHODS: Patients with cervical cancer treated from January 2008 to December 2017 were reviewed. Those with stage IB-IIIB who received chemoradiation plus brachytherapy were included in the study. Post-operative patients and those with stage IV were excluded. The study end points were local control, disease-free survival, and overall survival at 2 years. Endpoints were estimated using the Kaplan-Meier method. Comparisons between treatment groups were performed using the log-rank test and Cox proportional hazards model. RESULTS: We included 284 LDR and 136 HDR brachytherapy patients. For stages IB, IIA, IIB, IIIA and IIIB disease, the 2-year local control for LDR versus HDR brachytherapy was 63% and 61% (p=0.35), 86% and 90% (p=0.68), 86% and 88% (p=0.83), 66% and 60% (p=0.56), and 77% and 40% (p=0.005), respectively. The 2-year disease-free survival for LDR versus HDR brachytherapy was 64% and 61% (p=0.50), 81% and 69% (p=0.18), 81% and 80% (p=0.54), 62% and 33% (p=0.82), and 71% and 30% (p=0.001) for stages IB, IIA, IIB, IIIA, and IIIB, respectively. The 2-year overall survival for LDR versus HDR brachytherapy was 94% and 93% (p=0.92), 98% and 68% (p=0.21), 89% and 88% (p=0.60), and 88% and 82% (p=0.34) for stages IB, IIA, IIB, and IIIB disease, respectively. CONCLUSION: There was no difference between LDR and HDR brachytherapy in local control and disease-free survival for all stages of disease, except in stage IIIB. These findings highlight the need to refine this brachytherapy technique for this group of patients.

Reproductive factors and risk of breast cancer by tumor subtypes among Ghanaian women: A population-based case-control study.

Higher proportions of early-onset and estrogen receptor (ER) negative cancers are observed in women of African ancestry than in women of European ancestry. Differences in risk factor distributions and associations by age at diagnosis and ER status may explain this disparity. We analyzed data from 1,126 cases (aged 18-74 years) with invasive breast cancer and 2,106 controls recruited from a population-based case-control study in Ghana. Odds ratios (OR) and 95% confidence intervals (CI) were estimated for menstrual and reproductive factors using polytomous logistic regression models adjusted for potential confounders. Among controls, medians for age at menarche, parity, age at first birth, and breastfeeding/pregnancy were 15 years, 4 births, 20 years and 18 months, respectively. For women ≥50 years, parity and extended breastfeeding were associated with decreased risks: >5 births vs. nulliparous, OR 0.40 (95% CI 0.20-0.83) and 0.71 (95% CI 0.51-0.98) for ≥19 vs. <13 breastfeeding months/pregnancy, which did not differ by ER. In contrast, for earlier onset cases (<50 years) parity was associated with increased risk for ER-negative tumors (p-heterogeneity by ER = 0.02), which was offset by extended breastfeeding. Similar associations were observed by intrinsic-like subtypes. Less consistent relationships were observed with ages at menarche and first birth. Reproductive risk factor distributions are different from European populations but exhibited etiologic heterogeneity by age at diagnosis and ER status similar to other populations. Differences in reproductive patterns and subtype heterogeneity are consistent with racial disparities in subtype distributions.

Skin lighteners and hair relaxers as risk factors for breast cancer: results from the Ghana breast health study.

Skin lighteners and hair relaxers, both common among women of African descent, have been suggested as possibly affecting breast cancer risk. In Accra and Kumasi, Ghana, we collected detailed information on usage patterns of both exposures among 1131 invasive breast cancer cases and 2106 population controls. Multivariate analyses estimated odds ratios (ORs) and 95% confidence intervals (CIs) after adjustment for breast cancer risk factors. Control usage was 25.8% for ever use of skin lighteners and 90.0% for use of hair relaxers for >1 year. The OR for skin lighteners was 1.10 (95% CI 0.93-1.32), with higher risks for former (1.21, 0.98-1.50) than current (0.96, 0.74-1.24) users. No significant dose-response relations were seen by duration, age at first use or frequency of use. In contrast, an OR of 1.58 (95% CI 1.15-2.18) was associated with use of hair relaxers, with higher risks for former (2.22, 1.56-3.16) than current (1.39, 1.00-1.93) users. Although numbers of burns were inconsistently related to risk, associations increased with duration of use, restricted to women who predominately used non-lye products (P for trend < 0.01). This was most pronounced among women with few children and those with smaller tumors, suggesting a possible role for other unmeasured lifestyle factors. This study does not implicate a substantial role for skin lighteners as breast cancer risk factors, but the findings regarding hair relaxers were less reassuring. The effects of skin lighteners and hair relaxers on breast cancer should continue to be monitored, especially given some biologic plausibility for their affecting risk.

Design considerations for identifying breast cancer risk factors in a population-based study in Africa.

Although breast cancer is becoming more prevalent in Africa, few epidemiologic studies have been undertaken and appropriate methodologic approaches remain uncertain. We therefore conducted a population-based case-control study in Accra and Kumasi, Ghana, enrolling 2,202 women with lesions suspicious for breast cancer and 2,161 population controls. Biopsy tissue for cases prior to neoadjuvant therapy (if given), blood, saliva and fecal samples were sought for study subjects. Response rates, risk factor prevalences and odds ratios for established breast cancer risk factors were calculated. A total of 54.5% of the recruited cases were diagnosed with malignancies, 36.0% with benign conditions and 9.5% with indeterminate diagnoses. Response rates to interviews were 99.2% in cases and 91.9% in controls, with the vast majority of interviewed subjects providing saliva (97.9% in cases vs. 98.8% in controls) and blood (91.8% vs. 82.5%) samples; lower proportions (58.1% vs. 46.1%) provided fecal samples. While risk factor prevalences were unique as compared to women in other countries (e.g., less education, higher parity), cancer risk factors resembled patterns identified elsewhere (elevated risks associated with higher levels of education, familial histories of breast cancer, low parity and larger body sizes). Subjects with benign conditions were younger and exhibited higher socioeconomic profiles (e.g., higher education and lower parity) than those with malignancies, suggesting selective referral influences. While further defining breast cancer risk factors in Africa, this study showed that successful population-based interdisciplinary studies of cancer in Africa are possible but require close attention to diagnostic referral biases and standardized and documented approaches for high-quality data collection, including biospecimens.

Factors contributing to delays in diagnosis of breast cancers in Ghana, West Africa.

BACKGROUND: Late diagnoses and poor prognoses of breast cancer are common throughout Africa. METHODS: To identify responsible factors, we utilized data from a population-based case-control study involving 1184 women with breast malignancies conducted in three hospitals in Accra and Kumasi, Ghana. Interviews focused on potential breast cancer risk factors as well as factors that might contribute to presentation delays. We calculated odds ratios (OR) and 95% confidence intervals (CI) comparing malignances with biopsy masses larger than 5 cm. (62.4% of the 1027 cases with measurable lesions) to smaller lesions. RESULTS: In multivariate analyses, strong predictors of larger masses were limited education (OR 1.96, 95% CI 1.32-2.90