William F. Page

Acromegaly and gastrointestinal cancer

A cohort of 1041 men who were discharged from the hospital with a diagnosis of acromegaly were examined for subsequent cancer. With a mean follow‐up time of 8.3 years, an increased rate of cancers of the digestive organs was observed (27 cases; standard incidence ratio [SIR], 2.0; 95% confidence interval [CI], 1.3 to 2.9). Rates were elevated for cancers of the esophagus (7 cases; SIR, 3.1), stomach (4 cases; SIR, 2.5), and colon (13 cases; SIR, 3.1). The increased risk of colon cancer in acromegaly is consistent with previous clinical reports and suggests opportunities for etiologic research and early cancer detection. It would seem prudent to also evaluate this risk in current research on the use of growth hormone in older individuals to increase muscle mass and reduce body fat.

Multiple sclerosis in US veterans of the Vietnam era and later military service: race, sex, and geography.

We identified 5,345 cases of multiple sclerosis (MS) among US veterans who first entered military service between 1960 and 1994, and who were “service‐connected” for MS by the Department of Veterans Affairs (VA). Two controls per case were matched on age, date of service entry, and branch of service. Available for service and VA files were demographic and military data for 4,951 cases and 9,378 controls. Versus white men, relative risk of MS was significantly higher for all women, at 2.99 for whites, 2.86 for blacks, and 3.51 for those of other races. This was a significant increase from our prior series of veterans of World War II and the Korean Conflict, where white women had a relative risk of 1.79. Risk for black men was higher now (0.67 vs 0.44), while other men remained low (0.30 vs 0.22). Residence at service entry in the northern tier of states had a relative risk of 2.02 versus the southern tier, which was significantly less than the 2.64 for the earlier series. Residence by individual state at birth and service entry for white men further supported this decreasing geographic differential. Such marked changes in geography, sex, and race in such a short interval strongly imply a primary environmental factor in the cause or precipitation of this disease.

Heredity and prostate cancer: A study of World War II veteran twins

Increased risk of prostate cancer among men with a family history of the disease has been observed in several epidemiological studies, and family studies have identified hereditary prostate cancer characterized by early onset and autosomal dominant inheritance.

Intelligence and education as predictors of cognitive state in late life A 50-year follow-up

We evaluated the relation of education and intelligence in early adult life to cognitive function in a group of elderly male twins.The Army General Classification Test (AGCT) was administered to US armed forces inductees in the early 1940s. Fifty years later, as part of a study of dementia in twins, we tested the cognitive status of 930 of these men using the modified Telephone Interview for Cognitive Status (TICS-m). TICS-m scores obtained in later life were correlated with AGCT scores (r equals 0.457) and with years of education (r equals 0.408). Thus, in univariate analyses, the AGCT score accounted for 20.6% and education accounted for 16.7% of variance in cognitive status. However, these two effects were not fully independent. A multivariable model using AGCT score, education, and the interaction of the two variables as predictors of the TICS-m score explained 24.8% of the variance, a slightly but significantly greater proportion than was explained by either factor alone. In a separate analysis based on 604 pairs of twins who took the AGCT, heritability of intelligence (estimated by AGCT score) was 0.503. Although this study does not address the issue of education and premorbid IQ as risk factors for dementia, the findings suggest that basic cognitive abilities in late life are related to cognitive performance measures from early adult life (ie, education and IQ).

Epidemiology of Multiple Sclerosis in US Veterans

Previously, we studied the effect of population ancestry on the risk of multiple sclerosis (MS) in US veterans of World War II, comparing by state 1980 US census ancestry data with MS case/control rat

Vital status ascertainment through the files of the Department of Veterans Affairs and the Social Security Administration

Veterans of US military service are a valuable resource for epidemiologic studies, and the Department of Veterans Affairs (VA) files provide an effective way to gather mortality information on veterans, so long as these files provide reasonably complete death reporting. To determine the completeness of VA death reporting, we assembled an independent sample of known veteran deaths among males born between 1936 and 1955 and assessed the performance of VA death reporting in this sample. We also compared VA death ascertainment to Social Security Administration (SSA) ascertainment. Based on the more than 4300 deaths in our study, we found VA death reporting to be approximately 90% complete by itself and 96% complete when used in conjunction with SSA death reporting. In addition, we found no evidence that VA death reporting changed substantially after passage of the Omnibus Budget Reconciliation Act of 1981, which limited eligibility for VA death benefits. Because veterans make up a large segment of the US population, our findings have particular relevance for studies in which mortality is a primary end point.

Epidemiology of Multiple Sclerosis in US Veterans VII. Risk Factors for MS

In previous papers of this series, we explored the epidemiology of MS, examining the effects of race, sex, geography, latitude and climate, migration, age at onset, population ancestry, and individual ethnicity on the risk of MS, using an unusually large cohort of MS cases and pre-illness matched controls comprising US veterans of World War II (WWII) and the Korean Conflict (KC). In this paper, we examine primarily the effect of other factors on the risk of MS in this cohort and their relation to those previously studied. We found here that latitude tier of residence at entry into active duty (EAD), years of education, and socioeconomic class (coded from occupation) were similarly associated with MS risk among white men, black men, and white women. Higher levels of each factor showed increased MS risk. Multivariate analyses indicated that for white male WWII subjects an urban address, 9 or more years of education, uncorrected visual acuity less than 20/20 at EAD, a more northern latitude, and a higher proportion of the subjects EAD state population reporting Swedish ancestry each significantly increased the risk of MS. White male KC subjects showed roughly the same patterns, except that uncorrected visual acuity less than 20/20 was associated with lower MS risk (ancestry/ethnicity was not studied). For black male WWII and KC subjects combined, a similar analysis (omitting ancestry/ethnicity) showed that only latitude at EAD and 9 or more years of education were independently associated with a significantly higher MS risk, and for WWII plus KC white women (also without ancestry/ethnicity), only latitude was a significant risk factor in these multivariate analyses. The smaller number of subjects, especially in these last two groups, limited the power to detect statistically significant risks in these last analyses. Similarities to white men of WWII in univariate analyses for all other groups suggest that findings for the former would otherwise apply to the latter. Although the interpretations of these associations may be obscure, in addition to geography, age, sex, and race, per se, higher socioeconomic status is significantly associated with higher MS risk in black and white men and in white women in the United States. NEUROLOGY 1997;48: 204-213

Trauma exposure, resilience, social support, and PTSD construct validity among former prisoners of war.

Abstract  Background: The aim of this study was to investigate predictors of persistent symptoms of posttraumatic stress disorder (PTSD) and to examine the construct validity of PTSD in a national sample of 270 World War II and Korean Conflict prisoners of war (POWs). Method: POWs were interviewed at two points in time (1965 and 1990). Predictors included PTSD symptomatology measured in 1965 by items from the Cornell Medical Index (CMI), severity of captivity trauma, resilience factors, and post-trauma social support. The criterion, symptomatology in the early 1990s, was evaluated with the PTSD module of the Structured Clinical Interview for DSM (SCID). Results: The CMI provided only partial coverage of PTSD criteria and appeared to provide only a general index of distress. Clustering of SCID items in two-dimensional space via multidimensional scaling analysis offers some construct validation for the DSMs differentiation of PTSD symptoms into criterion groups, although there was not a perfect match. Trauma severity is best related to PTSD symptomatology experienced in 1990, mitigated in part by greater education level and age at the time of trauma exposure. Surprisingly, 1965 distress added only a modest amount to the prediction of current distress, while post-trauma social support added none. Conclusions: These findings support previous work showing the severe psychological sequelae of POW status 40–50 years after captivity, and indicate that trauma severity during captivity is the best predictor of current PTSD symptomatology. Results also add to our understanding of the conceptual differentiation of PTSD symptoms into separate and distinct symptom clusters.

Genetic component of lung cancer: cohort study of twins

Epidemiological and molecular epidemiological findings suggest that inherited predisposition may be a component of lung cancer risk and an important modulator of the carcinogenic effects of cigarette smoke. We have carried out a genetic analysis of lung cancer mortality on the National Academy of Sciences/National Research Council Twin Registry. The registry is composed of 15,924 male twin pairs who were born in the USA between 1917 and 1927 and who served in the armed forces during World War II. As evidence for a genetic effect on lung cancer, we required concordance for lung cancer death to be greater among monozygotic than among dizygotic twin pairs. No genetic effect on lung cancer mortality was observed. The ratio of observed to expected concordance among monozygotic twins did not exceed that among dizygotic twins (overall rate ratio 0.75 [95% CI 0.35-1.6]), even though monozygotic twin pairs are more likely to be concordant for smoking than dizygotic twin pairs in this population. A cohort analysis (accounting for age, sex, race, and smoking intensity) of lung cancer mortality found no lung cancer deaths during 300 person-years of follow-up (observed to expected ratio 0 [0-4.09]) among 47 monozygotic twin smokers whose smoking twins had died of lung cancer, even though smoking histories were very similar within twin pairs. In our study, there is little if any effect of inherited predisposition on development of lung cancer. Genetic factors are not likely to be strongly predictive of lung cancer risk in most male smokers older than 50, the age group in which the vast majority of cases occur.

Mortality in US Army Gulf War Veterans Exposed to 1991 Khamisiyah Chemical Munitions Destruction

OBJECTIVES We investigated whether US Army Gulf War veterans who were potentially exposed to nerve agents during the March 1991 weapons demolitions at Khamisiyah, Iraq, are at increased risk of cause-specific mortality. METHODS The cause-specific mortality of 100487 exposed US Army Gulf War veterans was compared with that of 224980 unexposed US Army Gulf War veterans. Exposure was determined with the Department of Defense 2000 plume model. Relative risk estimates were derived from Cox proportional hazards models. RESULTS The risks of most disease-related mortality were similar for exposed and unexposed veterans. However, exposed veterans had an increased risk of brain cancer deaths (relative risk [RR]=1.94; 95% confidence interval [CI]=1.12, 3.34). The risk of brain cancer death was larger among those exposed 2 or more days than those exposed 1 day when both were compared separately to all unexposed veterans (RR=3.26; 95% CI=1.33, 7.96; RR=1.72; 95% CI=0.95,3.10, respectively). CONCLUSIONS Exposure to chemical munitions at Khamisiyah may be associated with an increased risk of brain cancer death. Additional research is required to confirm this finding.