Cancer Risk Studies and Priority Areas for Cancer Risk Appraisal in Uganda.

Background: Research into aetiologies and prevention of the commonest cancers and implementation of primary and secondary prevention can reduce cancer risk and improve quality of life. Moreover, monitoring the prevalence of cancer risk factors in a specific population helps guide cancer prevention and early detection efforts and national cancer control programming. Objective: This article aims to provide the scope and findings of cancer risk studies conducted in Uganda to guide researchers, health-care professionals, and policymakers. Methods: Between November 2019 to January 2020, we searched peer-reviewed published articles in Pubmed, EMBASE and Cochrane Library (Cochrane central register of controlled trials-CENTRAL). We followed the recommendation of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - the PRISMA. The primary focus was to identify cancer risk and prevention studies conducted in Uganda and published in peer-reviewed journals from January 2000 and January 2020. We used key Boolean search terms with their associated database strings. Results: We identified 416 articles, screened 269 non-duplicate articles and obtained 77 full-text articles for review. Out of the 77 studies, we identified one (1%) randomized trial, two (2.5%) retrospective cohort studies and 14 (18%) case-control studies, 46 (60%) cross-sectional studies, five (6.4%) ecological studies, three panel studies (4%) and six (8%) qualitative studies. Cervical cancer was the most studied type of cancer in Uganda (23.4%, n = 18 studies), followed by lymphomas - both Hodgkin and Non-Hodgkin sub-types (20.7%), n = 16 studies) and breast cancer (15.6%, n = 12 studies). In lymphoma studies, Burkitt lymphoma was the most studied type of lymphoma (76%, n = 13 studies). The studies concentrated on specific cancer risk awareness, risk perceptions, attitudes, uptake of screening, uptake of human papillomavirus vaccination, the prevalence of some of the known cancer risk factors and obstacles to accessing screening services. Conclusion: The unmet need for comprehensive cancer risk and prevention studies is enormous in Uganda. Future studies need to comprehensively investigate the known and putative cancer risk factors and prioritize the application of the higher-hierarchy evidence-generating epidemiological studies to guide planning of the national cancer control program.

Effects of Coffee, Black Tea and Green Tea Consumption on the Risk of Non-Hodgkin's Lymphoma: A Systematic Review and Dose-Response Meta-Analysis of Observational Studies.

Aim: Several studies have evaluated the association between coffee, black and green tea consumption and non-Hodgkin's lymphoma (NHL) risk, while the results were inconsistent. We conducted a dose-response meta-analysis of available observational studies to assess the association among coffee, black and green tea intake and the risk of NHL in the general population. Methods: Studies published up to August 2018 were identified on the basis of a literature search in PubMed, ISI Web of Science, Scopus and Cochrane databases using Mesh and non-Mesh relevant keywords. Relative risks (RRs) with 95% confidence intervals (CIs) and the dose-response relationships were calculated using random-effects models. Results: In the meta-analysis of 19 effect sizes (315,972 participants with 4,914 cases of NHL), we found that higher green tea intake was associated with a 39% reduced risk of NHL (pooled RR = 0.61; 95% CIs = 0.38-0.99, I2=60.4%, pheterogeneity=0.080) in high- versus low-intake meta-analysis. No association was observed between coffee intake (pooled RR = 1.21; 95% CIs = 0.97-1.50, I2=52.6%, pheterogeneity < 0.05), black tea intake (pooled RR = 1.01; 95% CI = 0.82-1.24, I2=0%, pheterogeneity=0.875) and risk of NHL in high- versus low-intake meta-analysis. Conclusions: Findings from this dose-response meta-analysis suggest that green tea intake may be associated with reduced risk of NHL.

Trans fatty acid intake is associated with increased risk and n3 fatty acid intake with reduced risk of non-hodgkin lymphoma.

We evaluated the association of dietary fat and protein intake with risk of non-Hodgkin lymphoma (NHL) in a clinic-based study in 603 cases (including 218 chronic lymphocytic leukemia/small lymphocytic lymphoma, 146 follicular lymphoma, and 105 diffuse large B-cell lymphoma) and 1007 frequency-matched controls. Usual diet was assessed with a 128-item food-frequency questionnaire. Unconditional logistic regression was used to estimate ORs and 95% CIs, and polytomous logistic regression was used to assess subtype-specific risks. trans Fatty acid (TFA) intake was positively associated with NHL risk [OR = 1.60 for highest vs. lowest quartile (95% CI = 1.18, 2.15); P-trend = 0.0014], n3 (ω3) fatty acid intake was inversely associated with risk [OR = 0.48 (95% CI = 0.35, 0.65); P-trend < 0.0001], and there was no association with total, animal, plant-based, or saturated fat intake. When examining intake of specific foods, processed meat [OR = 1.37 (95% CI = 1.02, 1.83); P-trend = 0.03], milk containing any fat [OR = 1.47 (95% CI = 1.16, 1.88); P-trend = 0.0025], and high-fat ice cream [OR = 4.03 (95% CI = 2.80, 5.80); P-trend < 0.0001], intakes were positively associated with risk, whereas intakes of fresh fish and total seafood [OR = 0.61 (95% CI = 0.46, 0.80); P-trend = 0.0025] were inversely associated with risk. Overall, there was little evidence for NHL subtype-specific heterogeneity. In conclusion, diets high in TFAs, processed meats, and higher fat dairy products were positively associated with NHL risk, whereas diets high in n3 fatty acids and total seafood were inversely associated with risk.

Intake of vitamins D and A and calcium and risk of non-Hodgkin lymphoma: San Francisco Bay Area population-based case-control study.

Several nutrients identified as potentially cancer protective have been inconsistently associated with non-Hodgkin lymphoma (NHL) risk. Dietary history data, including use of vitamin supplements, were collected using a semiquantitative food frequency questionnaire administered during in-person interviews with 4,133 participants (2,052 cases, 2,081 controls) in a San Francisco Bay Area population-based case-control study. Data were used to determine the association of intake levels of vitamins D and A and calcium with risk of NHL and NHL subtypes. Odds ratios (OR) and 95% confidence intervals (CI) were computed as estimates of relative risk using adjusted unconditional logistic regression. Increasing vitamin D intake from food and supplements was positively associated with NHL risk in men (5th quintile: OR = 1.6, 95% CI = 1.0-2.4, P(trend) = 0.07) and with diffuse large B-cell lymphoma (DLBCL) in women and men (5th quintile: OR = 1.6, 95% CI = 1.0-2.5, P(trend) = 0.02); that was largely due to the effect in men (P(trend) = 0.03). These results do not support a strong role for vitamin D intake with NHL risk, with the exception of a potential association for DLBCL risk in men. Our results should be interpreted conservatively until further investigation in larger pooled studies can be conducted to better assess the role of vitamin D intake in lymphomagenesis.

Food-frequency questionnaire-based estimates of total antioxidant capacity and risk of non-Hodgkin lymphoma.

Antioxidants, primarily from fruits and vegetables, have been hypothesized to protect against non-Hodgkin lymphoma (NHL). The oxygen radical absorbance capacity (ORAC) assay, which measures total antioxidant capacity of individual foods and accounts for synergism, can be estimated using a food-frequency questionnaire (FFQ). We tested the hypothesis that higher intake of antioxidant nutrients from foods, supplements and FFQ-based ORAC values are associated with a lower risk of NHL in a clinic-based study of 603 incident cases and 1,007 frequency-matched controls. Diet was assessed with a 128-item FFQ. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals adjusted for age, sex, residence and total energy. Dietary intake of α-tocopherol (OR=0.50; p-trend=0.0002), ß-carotene (OR=0.58; p-trend=0.0005), lutein/zeaxanthin (OR=0.62; p-trend=0.005), zinc (OR=0.54; p-trend=0.003) and chromium (OR=0.68; p-trend=0.032) was inversely associated with NHL risk. Inclusion of supplement use had little impact on these associations. Total vegetables (OR=0.52; p-trend<0.0001), particularly green leafy (OR=0.52; p-trend<0.0001) and cruciferous (OR=0.68; p-trend=0.045) vegetables, were inversely associated with NHL risk. NHL risk was inversely associated with both hydrophilic ORAC (OR=0.61, p-trend=0.003) and lipophilic ORAC (OR=0.48, p-trend=0.0002), although after simultaneous adjustment for other antioxidants or total vegetables, only the association for lipophilic ORAC remained significant. There was no striking heterogeneity in results across the common NHL subtypes. Higher antioxidant intake as estimated by the FFQ-ORAC, particularly the lipophilic component, was associated with a lower NHL risk after accounting for other antioxidant nutrients and vegetable intake, supporting this as potentially useful summary measure of total antioxidant intake.

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers.

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

Antioxidant intake from fruits, vegetables and other sources and risk of non-Hodgkin's lymphoma: the Iowa Women's Health Study.

Antioxidant nutrients found in fruits, vegetables and other foods are thought to inhibit carcinogenesis and to influence immune status. We evaluated the association of these factors with risk of non-Hodgkin's lymphoma (NHL) overall and for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma specifically in a prospective cohort of 35,159 Iowa women aged 55-69 years when enrolled at baseline in 1986. Diet was ascertained using a validated semiquantitative food frequency questionnaire. Through 2005, 415 cases of NHL (including 184 DLBCL and 90 follicular) were identified. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusting for age and total energy. The strongest associations of antioxidants with risk of NHL (RR for highest versus lowest quartile; p for trend) were observed for dietary vitamin C (RR = 0.78; p = 0.044), alpha-carotene (RR = 0.71; p = 0.015), proanthocyanidins (RR = 0.70; p = 0.0024) and dietary manganese (RR = 0.62; p = 0.010). There were no associations with multivitamin use or supplemental intake of vitamins C, E, selenium, zinc, copper or manganese. From a food perspective, greater intake of total fruits and vegetables (RR = 0.69; p = 0.011), yellow/orange (RR = 0.72; p = 0.015) and cruciferous (RR = 0.82; p = 0.017) vegetables, broccoli (RR = 0.72; p = 0.018) and apple juice/cider (RR = 0.65; p = 0.026) were associated with lower NHL risk; there were no strong associations for other antioxidant-rich foods, including whole grains, chocolate, tea or nuts. Overall, these associations were mainly observed for follicular lymphoma and were weaker or not apparent for DLBCL. In conclusion, these results support a role for vegetables, and perhaps fruits and associated antioxidants from food sources, as protective factors against the development of NHL and follicular lymphoma in particular.

Vitamin D and non-Hodgkin lymphoma risk in adults: a review.

Animal and human studies support a protective effect of vitamin D sufficiency related to malignancy by uncovering paracrine and autocrine effects of extra-renal 25-hydroxyvitamin D (25(OH)D) activation including regulation of cell cycle proliferation, apoptosis induction, and increased cell differentiation signaling. Recent epidemiologic studies demonstrate a reduction in non-Hodgkin lymphoma (NHL) risk with increased sunlight exposure. As sunlight is a major vitamin D source, it has been suggested that vitamin D status may mediate this observed association. This review provides a comprehensive discussion of the current epidemiologic evidence with regard to the investigation of an association between vitamin D status and NHL risk.

Pesticides, soft-tissue sarcoma and non-Hodgkin lymphoma--historical aspects on the precautionary principle in cancer prevention.

BACKGROUND: After the 2(nd) World War a long range of chemical agents have been introduced on the market, both in Sweden and most other countries. From the 1950's several pesticides gained increasing use in agriculture and forestry. In the 1970's public concern increased in Sweden especially regarding use of phenoxy herbicides to combat deciduous wood, although statements from different authorities were reassuring of the safety. MATERIALS AND METHODS: At the end of the 1970's the author and his colleagues published the first scientific evidence of an association between exposure to phenoxyacetic acids, chlorophenols and certain malignant tumours, i.e., soft-tissue sarcoma and malignant lymphoma. The study subjects were also exposed to contaminating dioxins such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Later studies showed also an association between certain persistent organic pollutants such as polychlorinated biphenyls and non-Hodgkin lymphoma (NHL) with an interaction with titers of antibodies to Epstein-Barr virus early antigen. These results have been corroborated in other studies. DISCUSSION: Over the years industry and its allied experts have attacked our studies, but in 1997 IARC classified TCDD as a human carcinogen, Group I. The increasing incidence of NHL in Sweden levelled off about 1990. The author postulated that the regulation or ban of the use of chlorophenols, certain phenoxy herbicides and some persistent organic pollutants in Sweden back in the 1970s has contributed to the now decreasing incidence of NHL. Unfounded criticism from industry experts may prohibit the precautionary principle and early warnings of cancer risk can be ignored. Cancer risks by certain chlorinated phenols may serve as a model of how the precautionary principle should be used by taking early warnings seriously.

Drug evaluation: FavId, a patient-specific idiotypic vaccine for non-Hodgkin's lymphoma.

Favrille Inc is developing FavIld, a patient-specific immunotherapy combining tumor-specific idiotype protein and keyhole limpet hemocyanin, for the potential treatment of lymphoma. A phase III clinical trial in follicular B-cell non-Hodgkin's lymphoma is underway.

Vegetables, fruit, and antioxidant-related nutrients and risk of non-Hodgkin lymphoma: a National Cancer Institute-Surveillance, Epidemiology, and End Results population-based case-control study.

BACKGROUND: Factors related to DNA damage and altered immunologic responses, such as reactive oxygen species production, are associated with the risk of non-Hodgkin lymphoma (NHL). OBJECTIVE: The aim was to evaluate NHL risk with intakes of vegetables, fruit, and nutrients involved in antioxidant activities. DESIGN: Incident case subjects aged 20-74 y were identified between 1998 and 2000 from a National Cancer Institute-sponsored study by using four Surveillance, Epidemiology, and End Results registries. Control subjects, who were selected by random dialing (< 65 y) and from Medicare files (> or = 65 y), were matched to cases by age, center, race, and sex. Of 1321 case and 1057 control subjects who enrolled, dietary data were collected on a subset (466 cases and 391 controls). Carotenoid intakes were estimated by using updated values from the US Department of Agriculture nutrient databases. Unconditional logistic regression models were used to estimate odds ratios (ORs) and 95% CIs. RESULTS: NHL risk was inversely associated with higher number of weekly servings of all vegetables (multivariable OR for highest compared with lowest quartile: 0.58; 95% CI: 0.35, 0.95; P for trend = 0.04), green leafy vegetables (OR: 0.59; 95% CI: 0.36, 0.96; P for trend = 0.01), and cruciferous vegetables (OR: 0.62; 95% CI: 0.39, 1.00; P for trend = 0.05) and with higher daily intakes of lutein and zeaxanthin (OR: 0.54; 95% CI: 0.32, 0.91; P for trend = 0.06) and zinc (OR: 0.58; 95% CI: 0.36, 0.91; P for trend = 0.02). An effect modification by exercise and NHL subtype was observed with some food groups and nutrients. CONCLUSION: Higher intakes of vegetables, lutein and zeaxanthin, and zinc are associated with a lower NHL risk.

The epidemiology of selenium and human cancer.

The relation between the trace element selenium and the etiology of cancer in humans remains elusive and intriguing, despite the number of epidemiologic studies published on the topic. We address some methodologic issues, such as misclassification of exposure, particularly to single selenium compounds, effect modification, confounding, and other sources of bias, which may explain the inconsistencies in the literature. We also review the results of cohort studies, which have yielded either inverse or null or direct associations between selenium exposure and subsequent cancer risk. To date, no beneficial effect on cancer incidence at major sites, including prostate cancer, has emerged from the Finnish program begun in 1984 to increase the average selenium intake in its population. Populations exposed to unusually high or low levels of environmental selenium might offer unique opportunities to investigate if selenium exposure is related to the etiology of human cancer.