Selenium for preventing cancer

BACKGROUND This review is an update of the first Cochrane publication on selenium for preventing cancer (Dennert 2011).Selenium is a metalloid with both nutritional and toxicological properties. Higher selenium exposure and selenium supplements have been suggested to protect against several types of cancers. OBJECTIVES Two research questions were addressed in this review: What is the evidence for:1. an aetiological relation between selenium exposure and cancer risk in humans? and2. the efficacy of selenium supplementation for cancer prevention in humans? SEARCH METHODS We conducted electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, 2013, Issue 1), MEDLINE (Ovid, 1966 to February 2013 week 1), EMBASE (1980 to 2013 week 6), CancerLit (February 2004) and CCMed (February 2011). As MEDLINE now includes the journals indexed in CancerLit, no further searches were conducted in this database after 2004. SELECTION CRITERIA We included prospective observational studies (cohort studies including sub-cohort controlled studies and nested case-control studies) and randomised controlled trials (RCTs) with healthy adult participants (18 years of age and older). DATA COLLECTION AND ANALYSIS For observational studies, we conducted random effects meta-analyses when five or more studies were retrieved for a specific outcome. For RCTs, we performed random effects meta-analyses when two or more studies were available. The risk of bias in observational studies was assessed using forms adapted from the Newcastle-Ottawa Quality Assessment Scale for cohort and case-control studies; the criteria specified in the Cochrane Handbook for Systematic Reviews of Interventions were used to evaluate the risk of bias in RCTs. MAIN RESULTS We included 55 prospective observational studies (including more than 1,100,000 participants) and eight RCTs (with a total of 44,743 participants). For the observational studies, we found lower cancer incidence (summary odds ratio (OR) 0.69, 95% confidence interval (CI) 0.53 to 0.91, N = 8) and cancer mortality (OR 0.60, 95% CI 0.39 to 0.93, N = 6) associated with higher selenium exposure. Gender-specific subgroup analysis provided no clear evidence of different effects in men and women (P value 0.47), although cancer incidence was lower in men (OR 0.66, 95% CI 0.42 to 1.05, N = 6) than in women (OR 0.90, 95% CI 0.45 to 1.77, N = 2). The most pronounced decreases in risk of site-specific cancers were seen for stomach, bladder and prostate cancers. However, these findings have limitations due to study design, quality and heterogeneity that complicate interpretation of the summary statistics. Some studies suggested that genetic factors may modify the relation between selenium and cancer risk-a hypothesis that deserves further investigation.In RCTs, we found no clear evidence that selenium supplementation reduced the risk of any cancer (risk ratio (RR) 0.90, 95% CI 0.70 to 1.17, two studies, N = 4765) or cancer-related mortality (RR 0.81, 95% CI 0.49 to 1.32, two studies, N = 18,698), and this finding was confirmed when the analysis was restricted to studies with low risk of bias. The effect on prostate cancer was imprecise (RR 0.90, 95% CI 0.71 to 1.14, four studies, N = 19,110), and when the analysis was limited to trials with low risk of bias, the interventions showed no effect (RR 1.02, 95% CI 0.90 to 1.14, three studies, N = 18,183). The risk of non-melanoma skin cancer was increased (RR 1.44, 95% CI 0.95 to 1.17, three studies, N = 1900). Results of two trials-the Nutritional Prevention of Cancer Trial (NPCT) and the Selenium and Vitamin E Cancer Trial (SELECT)-also raised concerns about possible increased risk of type 2 diabetes, alopecia and dermatitis due to selenium supplements. An early hypothesis generated by NPCT that individuals with the lowest blood selenium levels at baseline could reduce their risk of cancer, particularly of prostate cancer, by increasing selenium intake has not been confirmed by subsequent trials. As the RCT participants were overwhelmingly male (94%), gender differences could not be systematically assessed. AUTHORS' CONCLUSIONS Although an inverse association between selenium exposure and the risk of some types of cancer was found in some observational studies, this cannot be taken as evidence of a causal relation, and these results should be interpreted with caution. These studies have many limitations, including issues with assessment of exposure to selenium and to its various chemical forms, heterogeneity, confounding and other biases. Conflicting results including inverse, null and direct associations have been reported for some cancer types.RCTs assessing the effects of selenium supplementation on cancer risk have yielded inconsistent results, although the most recent studies, characterised by a low risk of bias, found no beneficial effect on cancer risk, more specifically on risk of prostate cancer, as well as little evidence of any influence of baseline selenium status. Rather, some trials suggest harmful effects of selenium exposure. To date, no convincing evidence suggests that selenium supplements can prevent cancer in humans.

Polycyclic aromatic compounds (PAHs and oxygenated PAHs) and trace metals in fish species from Ghana (West Africa): Bioaccumulation and health risk assessment

We report the concentrations of 28 PAHs, 15 oxygenated PAHs (OPAHs) and 11 trace metals/metalloids (As, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, Se, and Zn) in muscle and gut + gill tissues of demersal fishes (Drapane africana, Cynoglossus senegalensis and Pomadasys peroteti) from three locations along the coast of the Gulf of Guinea (Ghana). The concentrations of ∑ 28PAHs in muscle tissues averaged 192 ng g− 1 dw (range: 71–481 ng g− 1 dw) and were not statistically different between locations. The concentrations of ∑ 28 PAHs were higher in guts + gills than in muscles. The PAH composition pattern was dominated by low molecular weight compounds (naphthalene, alkyl-naphthalenes and phenanthrene). All fish tissues had benzo[a]pyrene concentrations lower than the EU limit for food safety. Excess cancer risk from consumption of some fish was higher than the guideline value of 1 × 10− 6. The concentrations of ∑ 15 OPAHs in fish muscles averaged 422 ng g− 1 dw (range: 28–1715 ng g− 1dw). The ∑ 15 OPAHs/∑ 16 US-EPA PAHs concentration ratio was > 1 in 68% of the fish muscles and 100% of guts + gills. The log-transformed concentrations of PAHs and OPAHs in muscles, guts + gills were significantly (p < 0.05) correlated with their octanol–water partitioning coefficients, strongly suggesting that equilibrium partitioning from water/sediment into fish tissue was the main mechanism of bioaccumulation. The trace metal concentrations in the fish tissues were in the medium range when compared to fish from other parts of the world. The concentrations of some trace metals (Cd, Cu, Fe, Mn, Zn) were higher in guts + gills than in muscle tissues. The target hazard quotients for metals were < 1 and did not indicate a danger to the local population. We conclude that the health risk arising from the consumption of the studied fish (due to their PAHs and trace metals content) is minimal.

A Drosophila XPD model links cell cycle coordination with neuro-development and suggests links to cancer

XPD functions in transcription, DNA repair and in cell cycle control. Mutations in human XPD (also known as ERCC2) mainly cause three clinical phenotypes: xeroderma pigmentosum (XP), Cockayne syndrome (XP/CS) and trichothiodystrophy (TTD), and only XP patients have a high predisposition to developing cancer. Hence, we developed a fly model to obtain novel insights into the defects caused by individual hypomorphic alleles identified in human XP-D patients. This model revealed that the mutations that displayed the greatest in vivo UV sensitivity in Drosophila did not correlate with those that led to tumor formation in humans. Immunoprecipitations followed by targeted quantitative MS/MS analysis showed how different xpd mutations affected the formation or stability of different transcription factor IIH (TFIIH) subcomplexes. The XP mutants most clearly linked to high cancer risk, Xpd R683W and R601L, showed a reduced interaction with the core TFIIH and also an abnormal interaction with the Cdk-activating kinase (CAK) complex. Interestingly, these two XP alleles additionally displayed high levels of chromatin loss and free centrosomes during the rapid nuclear division phase of the Drosophila embryo. Finally, the xpd mutations showing defects in the coordination of cell cycle timing during the Drosophila embryonic divisions correlated with those human mutations that cause the neurodevelopmental abnormalities and developmental growth defects observed in XP/CS and TTD patients.

Childhood cancer and residential exposure to highways: a nationwide cohort study.

Children living near highways are exposed to higher concentrations of traffic-related carcinogenic pollutants. Several studies reported an increased risk of childhood cancer associated with traffic exposure, but the published evidence is inconclusive. We investigated whether cancer risk is associated with proximity of residence to highways in a nation-wide cohort study including all children aged <16 years from Swiss national censuses in 1990 and 2000. Cancer incidence was investigated in time to event analyses (1990-2008) using Cox proportional hazards models and incidence density analyses (1985-2008) using Poisson regression. Adjustments were made for socio-economic factors, ionising background radiation and electromagnetic fields. In time to event analysis based on 532 cases the adjusted hazard ratio for leukaemia comparing children living <100 m from a highway with unexposed children (≥500 m) was 1.43 (95 % CI 0.79, 2.61). Results were similar in incidence density analysis including 1367 leukaemia cases (incidence rate ratio (IRR) 1.57; 95 % CI 1.09, 2.25). Associations were similar for acute lymphoblastic leukaemia (IRR 1.64; 95 % CI 1.10, 2.43) and stronger for leukaemia in children aged <5 years (IRR 1.92; 95 % CI 1.22, 3.04). Little evidence of association was found for other tumours. Our study suggests that young children living close to highways are at increased risk of developing leukaemia.

Primary lung cancer after breast cancer: The role of radiation therapy and cigarette smoking

The magnitude of the interaction between cigarette smoking, radiation therapy, and primary lung cancer after breast cancer remains unresolved. This case control study further examines the main and joint effects of cigarette smoking and radiation therapy (XRT) among breast cancer patients who subsequently developed primary lung cancer, at The University of Texas M. D. Anderson Cancer Center (MDACC) in Houston, Texas. Cases (n = 280) were women diagnosed with primary lung cancer between 1955 and 1970, between 30–89 years of age, who had a prior history of breast cancer, and were U.S. residents. Controls (n = 300) were randomly selected from 37,000 breast cancer patients at MDACC and frequency matched to cases on age at diagnosis (in 5-year strata), ethnicity, year of breast cancer diagnosis (in 5-year strata), and had survived at least as long as the time interval for lung cancer diagnosis in the cases. Stratified analysis and unconditional logistic regression modeling were used to calculate the main and joint effects of cigarette smoking and radiation treatment on lung cancer risk. Medical record review yielded smoking information on 93% of cases and 84% of controls, and among cases 45% received XRT versus 44% of controls. Smoking increased the odds of lung cancer in women who did not receive XRT (OR = 6.0, 95%CI, 3.5–10.1) whereas XRT was not associated with increased odds (OR = 0.5, 95%CI, 0.2–1.1) in women who did not smoke. Overall the odds ratio for both XRT and smoking together compared with neither exposure was 9.00 (9 5% CI, 5.1–15.9). Similarly, when stratifying on laterality of the lung cancer in relation to the breast cancer, and when the time interval between breast and lung cancers was >10 years, there was an increased odds for both smoking and XRT together for lung cancers on the same side as the breast cancer (ipsilateral) (OR = 11.5, 95% CI, 4.9–27.8) and lung cancers on the opposite side of the breast cancer (contralateral) (OR= 9.6, 95% CI, 2.9–0.9). After 20 years the odds for the ipsilateral lung were even more pronounced (OR = 19.2, 95% CI, 4.2–88.4) compared to the contralateral lung (OR = 2.6, 95% CI, 0.2–2.1). In conclusion, smoking was a significant independent risk factor for lung cancer after breast cancer. Moreover, a greater than multiplicative effect was observed with smoking and XRT combined being especially evident after 10 years for both the ipsilateral and contralateral lung and after 20 years for the ipsilateral lung. ^

Modifier genes and susceptibility to colorectal cancer in individuals with Lynch syndrome

Lynch syndrome, is caused by inherited germ-line mutations in the DNA mismatch repair genes resulting in cancers at an early age, predominantly colorectal (CRC) and endometrial cancers. Though the median age at onset for CRC is about 45 years, disease penetrance varies suggesting that cancer susceptibility may be modified by environmental or other low-penetrance genes. Genetic variation due to polymorphisms in genes encoding metabolic enzymes can influence carcinogenesis by alterations in the expression and activity level of the enzymes. Variation in MTHFR, an important folate metabolizing enzyme can affect DNA methylation and DNA synthesis and variation in xenobiotic-metabolizing enzymes can affect the metabolism and clearance of carcinogens, thus modifying cancer risk. ^ This study examined a retrospective cohort of 257 individuals with Lynch syndrome, for polymorphisms in genes encoding xenobiotic-metabolizing enzymes-- CYP1A1 (I462V and MspI), EPHX1 (H139R and Y113H), GSTP1 (I105V and A114V), GSTM1 and GSTT1 (deletions) and folate metabolizing enzyme--MTHFR (C677T and A1298C). In addition, a series of 786 cases of sporadic CRC were genotyped for CYP1A1 I462V and EPHX1 Y113H to assess gene-gene interaction and gene-environment interaction with smoking in a case-only analysis. ^ Prominent findings of this study were that the presence of an MTHFR C677T variant allele was associated with a 4 year later age at onset for CRC on average and a reduced age-associated risk for developing CRC (Hazard ratio: 0.55; 95% confidence interval: 0.36–0.85) compared to the absence of any variant allele in individuals with Lynch syndrome. Similarly, Lynch syndrome individuals heterozygous for CYP1A1 I462V A>G polymorphism developed CRC an average of 4 years earlier and were at a 78% increased age-associated risk (Hazard ratio for AG relative to AA: 1.78; 95% confidence interval: 1.16-2.74) than those with the homozygous wild-type genotype. Therefore these two polymorphisms may be additional susceptibility factors for CRC in Lynch syndrome. In the case-only analysis, evidence of gene-gene interaction was seen between CYP1A1 I462V and EPHX1 Y113H and between EPHX1 Y113H and smoking suggesting that genetic and environmental factors may interact to increase sporadic CRC risk. Implications of these findings are the ability to identify subsets of high-risk individuals for targeted prevention and intervention. ^

Psychosocial measures reported by parents in studies of skin cancer prevention

Background. Because it is important to minimize children's sun exposure to reduce skin cancer risk, much of the extensive skin cancer prevention literature consists of studies of children's sun protection, sun avoidance and ultraviolet radiation (UVR) exposure. Little attention has been focused on the measurement of psychosocial constructs in these studies. Identification of the psychosocial correlates or determinants of children's skin cancer risk or risk-reduction behavior is critical to more fully understand and predict behavior. Furthermore, psychosocial variables may be influenced by interventions to reduce risk. Thus, it is important to examine the psychosocial measures used in studies of children's skin cancer prevention. Information on the validity and reliability of psychosocial measures may increase confidence in study findings based on these measures. In particular, self-efficacy and barriers are key constructs in several major theoretical frameworks and parental measures have been associated with children's sun protection. However, there is conceptual overlap of self-efficacy and barriers measures and little is known about the psychometric properties of these measures.^ Study Aims and Methods. The overall goal of this dissertation was to examine the measurement of psychosocial constructs relevant to children's skin cancer prevention. Because children depend primarily on their parents for skin cancer prevention, measures of parents' psychosocial constructs are the focus. Study 1 was a systematic review of parental psychosocial measures used in studies of children's sun protection, sun avoidance and UVR exposure. The specific aims of Study 1 were to (1) describe psychosocial measures reported by parents, including available information on the psychometric properties of these measures and their use in analyses and (2) provide recommendations for the development, refinement and standardized reporting of measures. ^ Study 2 examined the psychometric properties of measures of parental self-efficacy and barriers regarding children's sun protection. Melanoma patients (N=205) who were parents of children ≤ 12 years of age completed a telephone interview that included self-efficacy and barriers measures specific to sunscreen, clothing, shade and limiting time outdoors. The specific aims of Study 2 were to (1) use a confirmatory factor analytic approach to examine the factorial validity of parental self-efficacy and barriers measures, (2) examine the convergent and discriminant validity of behavior-specific measures of self-efficacy and barriers and (3) assess the reliability of item and scale measures.^ Results. In Study 1, a search of standard databases yielded 48 eligible studies. Most studies assessed only one or two psychosocial constructs. Knowledge was measured most frequently. There was little discussion of measure source, development, theoretical background or psychometric properties, besides internal consistency reliability. There was conceptual overlap of some measures. In Study 2, confirmatory factor analytic findings supported the factorial validity of the self-efficacy and barriers measures. When all eight self-efficacy and barriers measures were included in the same model, a modified eight-factor model adequately fit the data, providing preliminary evidence that the measures are distinct. Measure associations supported the convergent validity of all measures and the discriminant validity of most measures. The self-efficacy and barriers measures were reliable.^ Conclusions. Recommendations based on the literature review include developing and refining psychosocial measures based on theory. Describing a measure's theoretical basis and psychometric properties would facilitate critical evaluation. Standardized reporting of source, development, theory, construct, items and analytic role would facilitate comparison of findings, continual refinement and future applications of measures. In the validation study, self-efficacy and barriers measures were examined in a sample of parents with a personal history of melanoma. Findings suggested that these measures are valid and reliable for use in studies of children's sun protection. There was preliminary evidence that these measures are distinct but additional study is needed. ^

Genetic variations in the PI3K-AKT-mTOR pathway and bladder cancer susceptibility and clinical outcomes

Bladder cancer is the fourth most common cancer in men in the United States. There is compelling evidence supporting that genetic variations contribute to the risk and outcomes of bladder cancer. The PI3K-AKT-mTOR pathway is a major cellular pathway involved in proliferation, invasion, inflammation, tumorigenesis, and drug response. Somatic aberrations of PI3K-AKT-mTOR pathway are frequent events in several cancers including bladder cancer; however, no studies have investigated the role of germline genetic variations in this pathway in bladder cancer. In this project, we used a large case control study to evaluate the associations of a comprehensive catalogue of SNPs in this pathway with bladder cancer risk and outcomes. Three SNPs in RAPTOR were significantly associated with susceptibility: rs11653499 (OR: 1.79, 95%CI: 1.24–2.60), rs7211818 (OR: 2.13, 95%CI: 1.35–3.36), and rs7212142 (OR: 1.57, 95%CI: 1.19–2.07). Two haplotypes constructed from these 3 SNPs were also associated with bladder cancer risk. In combined analysis, a significant trend was observed for increased risk with an increase in the number of unfavorable genotypes (P for trend<0.001). Classification and regression tree analysis identified potential gene-environment interactions between RPS6KA5 rs11653499 and smoking. In superficial bladder cancer, we found that PTEN rs1234219 and rs11202600, TSC1 rs7040593, RAPTOR rs901065, and PIK3R1 rs251404 were significantly associated with recurrence in patients receiving BCG. In muscle invasive and metastatic bladder cancer, AKT2 rs3730050, PIK3R1 rs10515074, and RAPTOR rs9906827 were associated with survival. Survival tree analysis revealed potential gene-gene interactions: patients carrying the unfavorable genotypes of PTEN rs1234219 and TSC1 rs704059 exhibited a 5.24-fold (95% CI: 2.44–11.24) increased risk of recurrence. In combined analysis, with the increasing number of unfavorable genotypes, there was a significant trend of higher risk of recurrence and death (P for trend<0.001) in Cox proportional hazard regression analysis, and shorter event (recurrence and death) free survival in Kaplan-Meier estimates (P log rank<0.001). This study strongly suggests that genetic variations in PI3K-AKT-mTOR pathway play an important role in bladder cancer development. The identified SNPs, if validated in further studies, may become valuable biomarkers in assessing an individual's cancer risk, predicting prognosis and treatment response, and facilitating physicians to make individualized treatment decisions. ^

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. ^

DIETARY RELATIONSHIPS TO FATAL BREAST CANCER AMONG SEVENTH-DAY ADVENTISTS

Laboratory experiments in animals, correlational and migrant studies in humans suggest a role for diet in the etiology of breast cancer. Data gathered from individuals via case-control studies are less consistent. Seventh-day Adventist women experience lower mortality from breast cancer than comparable U.S. populations and this decrease is thought to be, at least in part, related to dietary practices (half are vegetarian). In 1960, 25,000 California Seventh-day Adventists completed a questionnaire which included a 21 item food frequency section. Cancer mortality in this population was monitored between 1960 and 1980 and the relationship of high fat food intake and fatal breast cancer was evaluated. Although established risk factors for breast cancer were observed in this population (e.g. age at menarche, age at first pregnancy, age at menopause and obesity) consumption of high fat foods were not observed to exert a strong influence on fatal breast cancer risk. Odds ratios (O.R.) for fatal breast cancer among non-vegetarians was 1.2. Increasing meat consumption bore little relation to risk; O.R. = 1.0, 1.2, 1.1 for consumption categories of none/occasional, 1-3 days/week and 4+ days/week respectively. Nor did the consumption of other high fat foods of animal origin (e.g. butter, cheese, milk, eggs) show any relationship to risk. These results remained unchanged after simultaneously controlling for the effect of other, potentially confounding variables (menstrual characteristics, obesity) via logistic regression analysis. ^

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. ^

AN ASSESSMENT OF THE RELATION OF CANCER MORTALITY RATES AND SOURCES OF DRINKING WATER IN TEXAS

The geographic distribution of average annual age-adjusted mortality rates (1964-1976) for four types of cancer (all cancer sites combined, gastrointestinal, urinary, and lung cancer) were compared by sources of drinking water for 254 Texas counties and county rural areas and 301 Texas cities. Exposure variables considered were surface versus ground water, public water supplies versus individuals wells, and trihalomethane levels in municipal water supplies. Each general source of "surface" and "ground" water was further divided by aggregating ground water using areas by aquifers and surface water using study areas by river basins. Potential confounding variables taken into account included median education, employment in cancer risk industries, population mobility, ethnicity, and urbanicity. A pattern of higher and lower cancer mortality rates was found for populations using some aquifers and river basins. Further study is required to determine whether the differences in cancer mortality rates that were observed are related to drinking water content or are coincidental with differences in personal characteristics which could not be taken into account in this ecologic study design. ^

OCCUPATIONAL CAUSES OF LUNG CANCER IN NEW MEXICO'S ANGLOS AND HISPANICS

Although, elevated risk for lung cancer has been associated with certain industries and occupations in previous studies, the lack of cigarette smoking information in many of these investigations resulted in estimates that could not be adjusted for the effects of smoking. To determine lung cancer risk due to occupation and smoking, for New Mexico's Anglos and Hispanics, a population-based case-control study was conducted. Incident cases diagnosed 1980-1982, and controls from the general population, were interviewed for lifetime occupational and smoking histories. Specific high risk industries and occupations were identified in advance and linked with industrial and occupational codes for hypotheses-testings. Significantly elevated risks were found for welders (RR = 3.5) and underground miners (RR = 2.0) with adjustment for smoking. Because shipbuilding was the industry of employment for only five of the 18 cases who were welders, exposures other than asbestos could be causal agents. Among the underground for only five of the 18 cases who were welders, exposures other than asbestos could be causal agents. Among the underground miners, uranium, copper, lead and zinc, coal, and potash mining industries were represented. Low prevalence of employment in some of the industries and occupations of interest resulted in inconclusive results. ^

Colorectal cancer: An insight on dietary factors

Aim. To assess the relationships between dietary factors and colorectal cancer risk. ^ Methods. We looked at all the systematic reviews published in last ten years on the topic. ^ Results. For fruits-vegetables some studies1 were significant for heterogeneity and others2 were not. In study by Aune at al3 only fruits were significant, although all the studies had protective RR between 0.90 to 0.94. For folate only case-control group of studies, the study by Sanjoaquin et al4 was significant with p heterogeneity being 0.01 and all of them had protective effect with RR between 0.75 to 0.95, for dietary as well as total folate. For fiber study by Park et al5 p was insignificant at 0.14 an RR was 0.84. Vitamin B6 study by Larsson et al6 had significant p with RR 0.90. For dietary fat both Alexander7 and Liu8 concluded that there is insufficient evidence that dietary fat is an independent causative risk factor. Only one study by Norat et al9 out of three was able to achieve significant p heterogeneity for meat. All the studies reported RR between 1.14 to 1.35, clearly implicating meat as culprit for increasing the risk of colorectal cancer. ^ Conclusions. We would recommend the use of fruits and vegetables to be protective against colorectal cancer. Also meat consumption increases the risk of colorectal cancer.^ *Please refer to dissertation for references/footnotes.^