Capitalizing on success against childhood HIV/AIDS in Botswana: Towards a comprehensive healthcare policy for pediatric oncology in Botswana

Pediatric HIV/AIDS in sub-Saharan Africa has been a major public health crisis with an estimated 3.5 million children infected. Baylor International Pediatric AIDS Initiative (BIPAI) has created a network of centers providing care and treatment for these children in several countries. In Botswana, where the first BIPAI center in Africa was opened, childhood mortality from HIV/AIDS is now less than 1%. Botswana is a middle-income country that previously held the highest HIV prevalence rate in the world. Efforts against HIV/AIDS have resulted in the building of a strong medical infrastructure with clear success against pediatric HIV/AIDS. The WHO predicts the next global health crisis will be cancer. Given the increased incidence of cancer in the setting of HIV/AIDS, Botswana has already implemented strategies to combat HIV-related malignancies in adults, but efforts in pediatrics have been lagging. This policy paper describes the importance of building on success against pediatric HIV/AIDS and extending this success to pediatric cancer in general. Specifically, it outlines a comprehensive pediatric cancer policy for the education and training of health professionals, the development of a pediatric cancer program, a pediatric cancer registry, public awareness efforts, and an appropriate, country specific pediatric cancer research agenda.^

Dietary patterns and risk of pancreatic cancer in a hospital-based case-control study

Background. It is important to understand the association between diet and risk of pancreatic cancer in order to better understand the etiology of pancreatic cancer.^ Objectives. Describe the dietary patterns of cases of adenocarcinoma of the pancreas and non-cancer controls and evaluate the odds of having a healthy eating pattern among cases and non-cancer controls.^ Design and Methods. An ongoing hospital-based case-control study was conducted in Houston, Texas from 2000-2008 with 678 pancreatic adenocarcinoma cases and 724 controls. Participants completed a food frequency questionnaire and a risk factor questionnaire. Dietary patterns were derived by principal component analysis and associations between dietary patterns and pancreatic cancer risk were assessed using unconditional logistic regression.^ Results. Two dietary patterns were derived: fruit-vegetable and high fat-meat. There were no statistically significant associations between the fruit-vegetable pattern and pancreatic cancer. An inverse association was seen between the high fat-meat pattern and pancreatic cancer risk when comparing those in the upper intake quintile to those scoring in the lowest quintile after adjusting for demographic and risk factor variables (OR=0.67, p=0.03). In sex-stratified analysis adjusted for demographic and risk factor variables, females scoring in the upper intake quintile of the fruit-vegetable pattern had a 49% lower risk of pancreatic cancer compared to females scoring in the lowest quintile (OR=0.51, p=0.03). An inverse relationship was also seen for the high fat-meat pattern when comparing females in the upper intake quintile to females in the lowest quintile (OR=0.50, p=0.03). In males, neither dietary pattern was significantly associated with pancreatic cancer.^ Conclusions. The current findings for the fruit-vegetable pattern are similar to those of previous studies and support the hypothesis that there is an inverse association between a “healthy” diet (comprised of fruits, vegetables, and whole grains) and risk of having pancreatic cancer (in females only). However, the inverse relationship with the high fat-meat pattern and risk of pancreatic cancer is contrary to other results. Further research on dietary patters and pancreatic cancer risk may lead to better understanding of the etiologic cause of pancreatic cancer.^

A nested case-control study of radiation exposure and brain cancer incidence in the United States Air Force

A nested case-control study design was used to investigate the relationship between radiation exposure and brain cancer risk in the United States Air Force (USAF). The cohort consisted of approximately 880,000 men with at least 1 year of service between 1970 and 1989. Two hundred and thirty cases were identified from hospital discharge records with a diagnosis of primary malignant brain tumor (International Classification of Diseases, 9th revision, code 191). Four controls were exactly matched with each case on year of age and race using incidence density sampling. Potential career summary extremely low frequency (ELF) and microwave-radiofrequency (MWRF) radiation exposures were based upon the duration in each occupation and an intensity score assigned by an expert panel. Ionizing radiation (IR) exposures were obtained from personal dosimetry records.^ Relative to the unexposed, the overall age-race adjusted odds ratio (OR) for ELF exposure was 1.39, 95 percent confidence interval (CI) 1.03-1.88. A dose-response was not evident. The same was true for MWRF, although the OR = 1.59, with 95 percent CI 1.18-2.16. Excess risk was not found for IR exposure (OR = 0.66, 45 percent CI 0.26-1.72).^ Increasing socioeconomic status (SES), as identified by military pay grade, was associated with elevated brain tumor risk (officer vs. enlisted personnel age-race adjusted OR = 2.11, 95 percent CI 1.98-3.01, and senior officers vs. all others age-race adjusted OR = 3.30, 95 percent CI 2.0-5.46). SES proved to be an important confounder of the brain tumor risk associated with ELF and MWRF exposure. For ELF, the age-race-SES adjusted OR = 1.28, 95 percent CI 0.94-1.74, and for MWRF, the age-race-SES adjusted OR = 1.39, 95 percent CI 1.01-1.90.^ These results indicate that employment in Air Force occupations with potential electromagnetic field exposures is weakly, though not significantly, associated with increased risk for brain tumors. SES appeared to be the most consistent brain tumor risk factor in the USAF cohort. Other investigators have suggested that an association between brain tumor risk and SES may arise from differential access to medical care. However, in the USAF cohort health care is universally available. This study suggests that some factor other than access to medical care must underlie the association between SES and brain tumor risk. ^

Genetic susceptibility, cigarette smoking, and wood dust exposure in lung cancer: Case control analyses

This case control study was conducted to assess the association between lung cancer risk, mutagen sensitivity (a marker of cancer susceptibility), and a putative lung carcinogen, wood dust exposure. There were 165 cases (98 African-Americans, 67 Mexican-Americans) with newly diagnosed, previously untreated lung cancer, and 239 controls, frequency-matched on age, sex, and ethnicity.^ Mutagen sensitivity ($\ge$1 break/cell) was associated with a statistically significant elevated risk for lung cancer (odds ratio (OR) = 4.1, 95% confidence limits (CL) = 2.3,7.2). Wood dust exposure was also a significant predictor of risk (OR = 2.8, 95% CL = 1.2,6.6) after controlling for smoking and mutagen sensitivity. When stratified by ethnicity, wood dust exposure was a significant risk factor for African-Americans (OR = 4.0, 95% CL = 1.4,11.5), but not for Mexican-Americans (OR = 1.5, 95% CL = 0.3,7.1). Stratified analysis suggested a greater than multiplicative interaction between wood dust exposure and both mutagen sensitivity and smoking.^ The cases had significantly more breaks on chromosomes 4 and 5 than the controls did with ORs of 4.9 (95% CL = 2.0, 11.7) and 3.9 (95% CL = 1.6, 9.3), respectively. Breaks at 4p14, 4q27, 4q31, 5q21-22, 5q31, and 5q33 were significantly more common in lung cancer patients than in controls. Lung cancer risk had a dose-response relationship with breaks on chromosomes 4 and 5. Cigarette smoking had a strong interaction with breaks on chromosomes 2, 4, and 5.^ In a molecular cytogenetic study, using chromosome painting and G-banding, we showed that: (1) the proportion of chromosome 5 abnormalities surviving as chromosome-type aberrations remained significantly higher in cells of lung cancer cases (14%) than in controls (5%) (P $<$ 0.001). However, no significant differences were detected in chromosome 4 abnormalities between cases and controls; (2) the proportion of chromosome 5q13-22 abnormalities was 5.3% in the cases and 0.7% in the controls (P $<$ 0.001). 5q13-22 regions represented 40% of all abnormalities on chromosome 5 in the cases and only 14% in the controls.^ This study suggests that mutagen sensitivity, wood dust exposure, and cigarette smoking were independent risk factors for lung cancer, and the susceptibility of particular chromosome loci to mutagenic damage may be a genetic marker for specific types of lung cancer. ^

LUNG CANCER AMONG TEXAS MALE OIL REFINERY WORKERS, 1976 - 1980 (CASE-CONTROL STUDY)

The apparent excess in the rate of lung cancer among the population of Texas coastal counties has prompted this study. The main objective was to assess the risk of lung cancer among employees of oil refining industries. Data collected by UTSPH and NCI were used for this research. A non significant overall low risk of lung cancer was observed among workers ever employed in oil refining (COR = 0.84). A lower but not significant risk of lung cancer was detected among the same workers when classified by their usual industry of employment (COR = 0.77). An overall non significant crosstime decline in the risk of lung cancer was observed among most of the occupational groups within the oil refining industry, with the exception of professional/technical and clerical/sales occupations where a non significant crosstime increase in the risk was observed. ^

THE RELATIONSHIP BETWEEN SERUM CHOLESTEROL AND CANCER INCIDENCE IN THE POPULATION OF THE HYPERTENSION DETECTION AND FOLLOW-UP PROGRAM

The relationship between serum cholesterol and cancer incidence was investigated in the population of the Hypertension Detection and Follow-up Program (HDFP). The HDFP was a multi-center trial designed to test the effectiveness of a stepped program of medication in reducing mortality associated with hypertension. Over 10,000 participants, ages 30-69, were followed with clinic and home visits for a minimum of five years. Cancer incidence was ascertained from existing study documents, which included hospitalization records, autopsy reports and death certificates. During the five years of follow-up, 286 new cancer cases were documented. The distribution of sites and total number of cases were similar to those predicted using rates from the Third National Cancer Survey. A non-fasting baseline serum cholesterol level was available for most participants. Age, sex, and race specific five-year cancer incidence rates were computed for each cholesterol quartile. Rates were also computed by smoking status, education status, and percent ideal weight quartiles. In addition, these and other factors were investigated with the use of the multiple logistic model.^ For all cancers combined, a significant inverse relationship existed between baseline serum cholesterol levels and cancer incidence. Previously documented associations between smoking, education and cancer were also demonstrated but did not account for the relationship between serum cholesterol and cancer. The relationship was more evident in males than females but this was felt to represent the different distribution of occurrence of specific cancer sites in the two sexes. The inverse relationship existed for all specific sites investigated (except breast) although a level of statistical significance was reached only for prostate carcinoma. Analyses after exclusion of cases diagnosed during the first two years of follow-up still yielded an inverse relationship. Life table analysis indicated that competing risks during the period of follow-up did not account for the existence of an inverse relationship. It is concluded that a weak inverse relationship does exist between serum cholesterol for many but not all cancer sites. This relationship is not due to confounding by other known cancer risk factors, competing risks or persons entering the study with undiagnosed cancer. Not enough information is available at the present time to determine whether this relationship is causal and further research is suggested. ^

Association of TNF-alpha genetic variants with HPV-associated oral cancer risk---a case-control study

The incidence of OSCC in younger population and in those who never smoked or drank has increased since the last decade. This increase may be attributable to increase of infection with HPV. The pro-inflammatory cytokine TNF-&agr; has the role in the pathogenesis of chronic inflammatory diseases and was found to control HPV infection in cervical cancer studies. Our study aimed to investigate the association between the four polymorphisms located in TNF-&agr; promoter region, -308(rs1800629), -857(rs1799724), -863(rs1800630) and -1031(rs1799964), and the risk of HPV-related OSCC. In this hospital-based case-control study, 325 cases and 335 controls were included. We found that HPV 16 seropositivity was associated with an increased risk of oral cancer (OR = 3.1, 95% CI, 2.1–4.6). Each of the polymorphism showed to increase the risk of HPV-related OSCC. And after combining the risk genotypes and using the low-risk group (0–1 combined risk genotypes) and HPV16 seronegativity as the reference group, only the high-risk groups (3–4 combined risk genotypes) and HPV16 seronegativity were associated with a low OR of 1.8 (95% CI, 1.1–2.8), while the low-risk and high-risk groups and HPV16 seropositivity were significantly associated with a higher OR of 2.7 (95% CI, 1.3–5.8) and 8.5 (95% CI, 3.7–19.4), respectively. In addition, the joint effects were greater among the young subjects (aged<50), males, never smokers or never drinkers, and patients with oropharyngeal cancer. Overall, the four TNF-&agr; polymorphisms, individually or collectively, would result in a significantly increased risk for HPV16-associated oral cancer in a non-Hispanic white population. More large sized studies are needed for future investigation.^

The Colic Clinic---a comprehensive program evaluation

Child abuse correlated with excessive infant crying affects millions of families each year, with consequences of the abuse lasting a lifetime. The University Of Texas School Of Medicine's Colic Clinic is currently in the early stages of testing Dr. Harvey Karp's combinatorial soothing technique for infants called "The Happiest Baby on the Block". In order to gauge the program's potential effectiveness, the Colic Clinic Protocol was examined in order to assess the applicability of the intervention to known causal factors of child abuse associated with excessive infant crying. ^ This evaluation also carried out an anticipated cost-benefit breakout analysis for the implementation of the intervention for 100 children and compared the cost of the program implementation to the cost associated with a single instance of child abuse. The analysis revealed that while accounting for materials, advertising, salaried personnel and other overhead expenses, the cost to implement the intervention was less than half the cost of the medical treatment associated with a single victim of whiplash-shaken infant syndrome. ^ Although the program is still in its early evaluative phase, the future implications of this work are extensive. If this intervention is revealed to be relevant and cost effective, it will precipitate sweeping changes in medical education and training, public health detection and prevention programs, and law enforcement.^

Association of processed red meat and prostate cancer stage in Mexican-Americans: A population based case-control study

Objective: The objective of this study is to investigate the association between processed and unprocessed red meat consumption and prostate cancer (PCa) stage in a homogenous Mexican-American population. Methods: This population-based case-control study had a total of 582 participants (287 cases with histologically confirmed adenocarcinoma of the prostate gland and 295 age and ethnicity-matched controls) that were all residing in the Southeast region of Texas from 1998 to 2006. All questionnaire information was collected using a validated data collection instrument. Statistical Analysis: Descriptive analyses included Student's t-test and Pearson's Chi-square tests. Odds ratios and 95% confidence intervals were calculated to quantify the association between nutritional factors and PCa stage. A multivariable model was used for unconditional logistic regression. Results: After adjusting for relevant covariates, those who consume high amounts of processed red meat have a non-significant increased odds of being diagnosed with localized PCa (OR = 1.60 95% CI: 0.85 - 3.03) and total PCa (OR = 1.43 95% CI: 0.81 - 2.52) but not for advanced PCa (OR = 0.91 95% CI: 1.37 - 2.23). Interestingly, high consumption of carbohydrates shows a significant reduction in the odds of being diagnosed with total PCa and advanced PCa (OR = 0.43 95% CI: 0.24 - 0.77; OR = 0.27 95% CI: 0.10 - 0.71, respectively). However, consuming high amounts of energy from protein and fat was shown to increase the odds of being diagnosed with advanced PCa (OR = 4.62 95% CI: 1.69 - 12.59; OR = 2.61 95% CI: 1.04 - 6.58, respectively). Conclusion: Mexican-Americans who consume high amounts of energy from protein and fat had increased odds of being diagnosed with advanced PCa, while high amounts of carbohydrates reduced the odds of being diagnosed with total and advanced PCa.^