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Larry C. Clark

Bio: Larry C. Clark is an academic researcher from University of Arizona. The author has contributed to research in topics: Cancer & Prostate cancer. The author has an hindex of 32, co-authored 51 publications receiving 7834 citations.


Papers
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Journal ArticleDOI
25 Dec 1996-JAMA
TL;DR: Results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites and require confirmation in an independent trial of appropriate design before new public health recommendations regarding seenium supplementation can be made.
Abstract: Objective. —To determine whether a nutritional supplement of selenium will decrease the incidence of cancer. Design. —A multicenter, double-blind, randomized, placebo-controlled cancer prevention trial. Setting. —Seven dermatology clinics in the eastern United States. Patients. —A total of 1312 patients (mean age, 63 years; range, 18-80 years) with a history of basal cell or squamous cell carcinomas of the skin were randomized from 1983 through 1991. Patients were treated for a mean (SD) of 4.5 (2.8) years and had a total follow-up of 6.4 (2.0) years. Interventions. —Oral administration of 200 μg of selenium per day or placebo. Main Outcome Measures. —The primary end points for the trial were the incidences of basal and squamous cell carcinomas of the skin. The secondary end points, established in 1990, were all-cause mortality and total cancer mortality, total cancer incidence, and the incidences of lung, prostate, and colorectal cancers. Results. —After a total follow-up of 8271 person-years, selenium treatment did not significantly affect the incidence of basal cell or squamous cell skin cancer. There were 377 new cases of basal cell skin cancer among patients in the selenium group and 350 cases among the control group (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28), and 218 new squamous cell skin cancers in the selenium group and 190 cases among the controls (RR, 1.14; 95% CI, 0.93-1.39). Analysis of secondary end points revealed that, compared with controls, patients treated with selenium had a nonsignificant reduction in all-cause mortality (108 deaths in the selenium group and 129 deaths in the control group [RR, 0.83; 95% CI, 0.63-1.08]) and significant reductions in total cancer mortality (29 deaths in the selenium treatment group and 57 deaths in controls [RR, 0.50; 95% CI, 0.31-0.80]), total cancer incidence (77 cancers in the selenium group and 119 in controls [RR, 0.63; 95% CI, 0.47-0.85]), and incidences of lung, colorectal, and prostate cancers. Primarily because of the apparent reductions in total cancer mortality and total cancer incidence in the selenium group, the blinded phase of the trial was stopped early. No cases of selenium toxicity occurred. Conclusions. —Selenium treatment did not protect against development of basal or squamous cell carcinomas of the skin. However, results from secondary end-point analyses support the hypothesis that supplemental selenium may reduce the incidence of, and mortality from, carcinomas of several sites. These effects of selenium require confirmation in an independent trial of appropriate design before new public health recommendations regarding selenium supplementation can be made.

2,780 citations

Journal ArticleDOI
01 May 1998-BJUI
TL;DR: Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenum-treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well-controlled prevention trials.
Abstract: Objective To test if supplemental dietary selenium is associated with changes in the incidence of prostate cancer. Patients and method A total of 974 men with a history of either a basal cell or squamous cell carcinoma were randomized to either a daily supplement of 200 μg of selenium or a placebo. Patients were treated for a mean of 4.5 years and followed for a mean of 6.5 years. Results Selenium treatment was associated with a significant (63%) reduction in the secondary endpoint of prostate cancer incidence during 1983–93. There were 13 prostate cancer cases in the selenium-treated group and 35 cases in the placebo group (relative risk, RR=0.37, P=0.002). Restricting the analysis to the 843 patients with initially normal levels of prostate-specific antigen (≤4 ng/mL), only four cases were diagnosed in the selenium-treated group and 16 cases were diagnosed in the placebo group after a 2 year treatment lag, (RR=0.26 P=0.009). There were significant health benefits also for the other secondary endpoints of total cancer mortality, and the incidence of total, lung and colorectal cancer. There was no significant change in incidence for the primary endpoints of basal and squamous cell carcinoma of the skin. In light of these results, the ‘blinded’ phase of this trial was stopped early. Conclusions Although selenium shows no protective effects against the primary endpoint of squamous and basal cell carcinomas of the skin, the selenium-treated group had substantial reductions in the incidence of prostate cancer, and total cancer incidence and mortality that demand further evaluation in well-controlled prevention trials.

657 citations

Journal Article
TL;DR: The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence, although not all site-specific cancers exhibited a reduction in incidence.
Abstract: The Nutritional Prevention of Cancer Trial was a randomized, clinical trial designed to evaluate the efficacy of selenium as selenized yeast (200 microg daily) in preventing the recurrence of nonmelanoma skin cancer among 1312 residents of the Eastern United States. Original secondary analyses through December 31, 1993 showed striking inverse associations between treatment and the incidence of total [hazard ratio (HR) = 0.61, 95% confidence interval (CI) = 0.46-0.82], lung, prostate, and colorectal cancer and total cancer mortality. This report presents results through February 1, 1996, the end of blinded treatment. Effect modification by baseline characteristics is also evaluated. The effects of treatment overall and within subgroups of baseline age, gender, smoking status, and plasma selenium were examined using incidence rate ratios and Cox proportional hazards models. Selenium supplementation reduced total (HR = 0.75, 95% CI = 0.58-0.97) and prostate (HR = 0.48, 95% CI = 0.28-0.80) cancer incidence but was not significantly associated with lung (HR = 0.74, 95% CI = 0.44-1.24) and colorectal (HR = 0.46, 95% CI = 0.21-1.02) cancer incidence. The effects of treatment on other site-specific cancers are also described. The protective effect of selenium was confined to males (HR = 0.67, 95% CI = 0.50-0.89) and was most pronounced in former smokers. Participants with baseline plasma selenium concentrations in the lowest two tertiles (<121.6 ng/ml) experienced reductions in total cancer incidence, whereas those in the highest tertile showed an elevated incidence (HR = 1.20, 95% CI = 0.77-1.86). The Nutritional Prevention of Cancer trial continues to show a protective effect of selenium on cancer incidence, although not all site-specific cancers exhibited a reduction in incidence. This treatment effect was restricted to males and to those with lower baseline plasma selenium concentrations.

557 citations

Journal ArticleDOI
01 May 2003-BJUI
TL;DR: The results (to January 1996, the end of blinded treatment) of the Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 µg daily) designed to test the hypothesis that seenium supplementation (SS) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA.
Abstract: OBJECTIVE To present the results (to January 1996, the end of blinded treatment) of the Nutritional Prevention of Cancer (NPC) Trial, a randomized trial of selenium (200 µg daily) designed to test the hypothesis that selenium supplementation (SS) could reduce the risk of recurrent nonmelanoma skin cancer among 1312 residents of the Eastern USA. MATERIALS AND METHODS Original secondary analyses of the NPC to 1993 showed striking inverse associations between SS and prostate cancer incidence. A subsequent report revealed that this effect was accentuated among men with the lowest baseline plasma selenium concentrations. The effects of treatment overall and within subgroups of baseline prostate-specific antigen (PSA) and plasma selenium concentrations were examined using incidence rate ratios and Cox proportional hazards models. RESULTS SS continued to significantly reduce the overall incidence (relative risk and 95% confidence interval) of prostate cancer (0.51, 0.29–0.87). The protective effect of SS appeared to be confined to those with a baseline PSA level of ≤ 4 ng/mL (0.35, 0.13–0.87), although the interaction of baseline PSA and treatment was not statistically significant. Participants with baseline plasma selenium concentrations only in the lowest two tertiles (< 123.2 ng/mL) had significant reductions in prostate cancer incidence. A significant interaction between baseline plasma selenium and treatment was detected. CONCLUSION To the end of the blinded treatment the NPC trial continued to show a significant protective effect of SS on the overall incidence of prostate cancer, although the effect was restricted to those with lower baseline PSA and plasma selenium concentrations.

489 citations

Journal ArticleDOI
TL;DR: Routine examination of disease occurrence with the cluster evaluation permutation procedure would allow state health officials to prioritize case investigations and to respond in a timely and efficient manner to inquiries of reported clusters.
Abstract: The authors propose a procedure for the detection of significant clusters of chronic diseases, with particular reference to cancer. The procedure allows for variations in population density and avoids the problem of "post hoc" formation of hypotheses or self-defined populations. This accounts for several of the principal problems of cluster evaluations. The techniques are practical but "computer-intensive." The procedure, termed the "cluster evaluation permutation procedure," is applied to leukemia incidence data for an Upstate New York region obtained from the New York State Cancer Registry and census files. Comparisons are made with two other recently proposed clustering methods, namely the U-statistic method of Whittemore et al. (Biometrika 1987;74:631-7) and the "geographical analysis machine" of Openshaw et al. (Lancet 1988;1:272-3). Routine examination of disease occurrence with the cluster evaluation permutation procedure would allow state health officials to prioritize case investigations and to respond in a timely and efficient manner to inquiries of reported clusters.

290 citations


Cited by
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Journal ArticleDOI
TL;DR: This review examines the evidence for involvement of the oxidative stress in the carcinogenesis process and the role of enzymatic and non-enzymatic antioxidants in the process of carcinogenesis as well as the antioxidant interactions with various regulatory factors.

5,937 citations

Journal ArticleDOI
TL;DR: Using the GLOBOCAN and Cancer Incidence in Five Continents databases, overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world are described.
Abstract: Efforts to reduce global cancer disparities begin with an understanding of geographic patterns in cancer incidence, mortality, and prevalence. Using the GLOBOCAN (2002) and Cancer Incidence in Five Continents databases, we describe overall cancer incidence, mortality, and prevalence, age-adjusted temporal trends, and age-specific incidence patterns in selected geographic regions of the world. For the eight most common malignancies-cancers of lung, breast, colon and rectum, stomach, prostate, liver, cervix, and esophagus-the most important risk factors, cancer prevention and control measures are briefly reviewed. In 2002, an estimated 11 million new cancer cases and 7 million cancer deaths were reported worldwide; nearly 25 million persons were living with cancer. Among the eight most common cancers, global disparities in cancer incidence, mortality, and prevalence are evident, likely due to complex interactions of nonmodifiable (ie, genetic susceptibility and aging) and modifiable risk factors (ie, tobacco, infectious agents, diet, and physical activity). Indeed, when risk factors among populations are intertwined with differences in individual behaviors, cultural beliefs and practices, socioeconomic conditions, and health care systems, global cancer disparities are inevitable. For the eight most common cancers, priorities for reducing cancer disparities are discussed.

3,433 citations

Journal ArticleDOI
TL;DR: Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.

3,359 citations

Journal ArticleDOI
TL;DR: In this article, a spatial scan statistic for the detection of clusters in a multi-dimensional point process is proposed, where the area of the scanning window is allowed to vary, and the baseline process may be any inhomogeneous Poisson process or Bernoulli process with intensity pro-portional to some known function.
Abstract: The scan statistic is commonly used to test if a one dimensional point process is purely random, or if any clusters can be detected. Here it is simultaneously extended in three directions:(i) a spatial scan statistic for the detection of clusters in a multi-dimensional point process is proposed, (ii) the area of the scanning window is allowed to vary, and (iii) the baseline process may be any inhomogeneous Poisson process or Bernoulli process with intensity pro-portional to some known function. The main interest is in detecting clusters not explained by the baseline process. These methods are illustrated on an epidemiological data set, but there are other potential areas of application as well.

3,314 citations

01 Jan 2001
TL;DR: The essential trace mineral, selenium, is of fundamental importance to human health as mentioned in this paper, and it is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS.
Abstract: The essential trace mineral, selenium, is of fundamental importance to human health. As a constituent of selenoproteins, selenium has structural and enzymic roles, in the latter context being best-known as an antioxidant and catalyst for the production of active thyroid hormone. Selenium is needed for the proper functioning of the immune system, and appears to be a key nutrient in counteracting the development of virulence and inhibiting HIV progression to AIDS. It is required for sperm motility and may reduce the risk of miscarriage. Deficiency has been linked to adverse mood states. Findings have been equivocal in linking selenium to cardiovascular disease risk although other conditions involving oxidative stress and inflammation have shown benefits of a higher selenium status. An elevated selenium intake may be associated with reduced cancer risk. Large clinical trials are now planned to confirm or refute this hypothesis. In the context of these health effects, low or diminishing selenium status in some parts of the world, notably in some European countries, is giving cause for concern.

3,068 citations