A cohort study of twins and cancer.

Given the current explosion of knowledge of the genetics and molecular biology of cancer, the possibility of widespread testing for inherited predisposition to cancer has been raised. The main objective of this study was to assess the effect of inherited predisposition on cancer mortality among the National Academy of Sciences-National Research Council Twin Registry. The twins were white male United States veterans of World War II, who were born during the period 1917-1927. The follow-up period was from 1946 to 1990, and some cause of death was determined with the use of death certificates. We compared concordance for death from cancer among 5690 monozygotic twin pairs to that among 7248 dizygotic pairs. A possible effect of inherited predisposition to death from cancer was considered present if concordance for cancer mortality among monozygotic twin pairs was greater than it was among dizygotic twin pairs. Among monozygotic and dizygotic twins, a total of 1918 cancer deaths was observed. Concordance for death from cancer at all sites among monozygotic twins was higher than it was among dizygotic twins (overall rate ratio, 1.4; 95% confidence interval, 1.0-2.0). For each zygosity group, two or fewer pairs were observed to be concordant for death from cancer of a specific site, with the exception of lung cancer.(ABSTRACT TRUNCATED AT 250 WORDS)

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 subject's 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.

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 = 0.457) and with years of education (r = 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).

A comparison of melanoma mortality among WWII veterans of the Pacific and European theaters.

PURPOSE: To determine whether cutaneous melanoma is associated with past military service in tropical locations, as a test of the 'critical period' sunlight exposure hypothesis. METHODS: Mortality data from a longitudinal follow-up study of 5524 former prisoners of war (POW) and 3713 non-POW veteran controls, all white male veterans of World War II (WWII), were examined to determine whether death attributed to melanoma was associated with history of military service in Pacific or European theaters during WWII or with POW status. Deaths from colon cancer were used as a comparison outcome. RESULTS: During 50 years of follow-up, there were 18 deaths from melanoma and 83 deaths from colon cancer among the cohort. Melanoma mortality varied with theater of war and POW status, whereas colon cancer mortality was similar for all subgroups. Pacific War POWs were at the highest risk overall (odds ratio (OR), 3.35; 95% confidence interval (CI), 0.39-28.76), whereas veterans of the Pacific War had nearly the same risk of melanoma (OR, 1.04; 95% CI, 0.09-11.94) compared with veterans of the European War. European theater POWs had a higher risk than non-POW veterans (OR, 2.76; 95% CI, 0.31-24.81). None of these differences, however, were statistically significant. CONCLUSIONS: To the extent that POW status is associated with higher sun exposure, these data are consistent with the hypothesis that exposure to high levels of solar radiation in young adulthood is associated with a higher risk of melanoma mortality.

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.

Malnutrition and subsequent ischemic heart disease in former prisoners of war of World War II and the Korean conflict.

The harsh treatment of former prisoners of war (POWs) of World War II and the Korean conflict resulted in severe malnutrition. Although rarely linked to specific long-term medical problems, a specific marker of malnutrition, self-reported lower limb edema (presumably due to a vitamin B deficiency) was associated with a three-fold increase in subsequent death attributed to ischemic heart disease (IHD) during the follow-up period from 1967 through 1975. Although there is at present no medical basis for linking edema, which is perhaps a marker for some unmeasured risk factor, to subsequent IHD, this finding may nonetheless have medical implications for the group of former POWs and other populations with severe dietary deficiency. It also suggests there may be a need to reexamine currently held theories on malnutrition and subsequent chronic disease.

Twenty-four year mortality in World War II US male veteran twins discordant for cigarette smoking.

BACKGROUND: This study was undertaken to test the constitutional hypothesis which attributes the association of tobacco smoking with morbidity and mortality to genetic predispositions to smoking and/or disease. METHODS: Subjects were World War II veterans, born in the US between 1917 and 1927, and surveyed at mean age 47 for present and past smoking habits. Twenty-four year mortality follow-up data were available for 1515 male twin pairs discordant for lifelong cigarette smoking. Using the first or only death of a smoking-discordant pair, 24-year relative risks of mortality were calculated by zygosity, cause of death, amount smoked, and age at death. RESULTS: We found that active smokers at baseline, regardless of zygosity, had a higher risk of death than their co-twins who had never smoked or quit smoking (monozygotic pairs: relative risk [RR] = 2.5; 95% confidence interval [CI] : 1.3-6.1 and RR = 1.7; 95% CI : 1.2-2.5; dizygotic pairs: RR = 2.4; 95% CI : 1.4-3.8 and RR = 2.0; 95% CI : 1.7-3.3). The elevated risk of death among smokers was due to deaths from lung cancer (monozygotic pairs: RR = 5.0; 95% CI: 2. 6-15.0; dizygotic pairs: RR = 11.0; 95% CI : 4.3-45.0) or deaths from cardiovascular diseases (monozygotic pairs: RR = 3.9; 95% CI : 1.9-115; dizygotic pairs: RR = 2.8; 95% CI : 1.7-4.9). Apart from these findings the relationship of smoking with all-cause mortality was stronger for earlier/younger deaths and for heavy to moderate smoking. CONCLUSIONS: The present results, from the largest and longest-studied series of smoking-discordant twins negate the constitutional hypothesis that genetic or early shared familial influences underlie the significant association between tobacco smoking and premature mortality.

Concordance rates for benign prostatic disease among twins suggest hereditary influence.

OBJECTIVES: The etiology of benign prostatic hyperplasia (BPH) is unknown. Evidence for a hereditary trait would provide new avenues for investigation. METHODS: We compared the concordance for benign prostate disease in monozygotic (MZ) and dizygotic (DZ) twins who served in the United States military in World War II and have been followed by the Medical Follow-up Agency, Institute of Medicine of the National Academy of Sciences. Questionnaires completed in 1985 by 10,000 twins were reviewed for evidence of prostatic disease. Key words indicating benign prostatic disease (prostate, prostatectomy, BPH, TURP, and prostatism) were identified in 533 (5.3%) of the questionnaires. RESULTS: The average age was 64 +/- 3 years (range 56 to 68 in 1985). After eliminating men with known prostate cancer, there were 256 twin pairs that were informative for benign prostatic disease: both twins were concordant in 25 instances and discordant in 231, with only one twin mentioning benign prostatic disease. The pairwise concordance for MZ twins was 14.7% (19 of 129) and for DZ pairs it was 4.5% (5 of 112). The relative risk for benign prostatic disease for MZ twins was thus 3.3 (p = 0.008). The probandwise concordance rates, which express the probability of BPH in a cotwin of an affected twin, were 25.7% for MZ twins and only 8.5% for DZ twins. A covariance analysis estimated that 49% of the observed variance between twins could be attributed to genetic effects. CONCLUSIONS: These data provide preliminary evidence for the heritability of benign prostatic disease.

Self-reported alcohol intake and cognition in aging twins.

OBJECTIVE: To determine the relationship between long-term alcohol intake and cognitive functioning in aging Caucasian men. METHOD: A retrospective cohort and co-twin-control study of self-reported alcohol intake and cognitive testing using the National Academy of Sciences-National Research Council (NAS-NRC) Twin Panel of U.S. veterans (born between 1917 and 1927). The study included 4,739 twins with two self-reported drinking histories (1970s and 1980s) and a telephone mental status interview (1990 and 1991) that also included 145 individuals with a diagnosis of alcoholism. RESULTS: Age and education adjusted cognitive scores were lower (p < .05) in diagnosed alcoholics than in the remainder of the subjects. To compare age and education adjusted cognitive scores in alcohol intake, the 4,739 twins were divided, based upon questionnaire data, into nondrinkers and 5 quintiles of drinkers by average reported drinks of alcohol weekly (< 1.0, 1-3.3, 3.4-8.1, 8.2-16.0, > 16.0). Past drinkers had scores lower (p < .05) than nondrinkers and all but quintiles 1 and 5 of the drinkers. The light drinkers in quintile 1 and the heavy drinkers in quintile 5 scored lower (p < .05) than the moderate drinkers in quintile 4. Monozygotic twins in quintile 4 scored higher (p < .05) than their co-twins in quintiles 1-3. CONCLUSIONS: No evidence was found to indicate an association between moderate long-term alcohol intake and lower cognitive scores in aging individuals. There was a suggestion of a small protective effect of past moderate alcohol intake on cognitive function with aging.

Mortality of veteran participants in the CROSSROADS nuclear test.

Operation CROSSROADS, conducted at Bikini Atoll in 1946, was the first post World War II test of nuclear weapons. Mortality experience of 40,000 military veteran participants in CROSSROADS was compared to that of a similar cohort of nonparticipating veterans. All-cause mortality of the participants was slightly increased over nonparticipants by 5% (p < .001). Smaller increases in participant mortality for all malignancies (1.4%, p = 0.26) or leukemia (2.0%, p = 0.9) were not statistically significant. These results do not support a hypothesis that radiation had increased participant cancer mortality over that of nonparticipants.

Cirrhosis mortality among former American prisoners of war of World War II and the Korean conflict: results of a 50-year follow-up.

In our earlier, 30-year follow-up of American prisoners of war (POWs) of World War II and the Korean conflict, we found evidence of increased cirrhosis mortality. Using federal records, we have now extended our follow-up to 50 years (42 years for Korean conflict veterans) and have used proportional hazards analysis to compare the mortality experience of POWs with that of controls. Compared with their controls, World War II POWs had a 32% higher risk of cirrhosis mortality (statistically significant), and mortality risk was higher in the first 30 years of follow-up and also among those aged 51 years and older. Korean POWs had roughly the same risk of cirrhosis mortality as their controls. Neither self-reported data on alcohol consumption nor supplemental morbidity data satisfactorily explained the differences in risk between POWs and controls, although there was evidence that POWs tended to have higher rates of hepatitis, helminthiasis, and nutritional deprivation.

Long-term heart disease and stroke mortality among former American prisoners of war of World War II and the Korean Conflict: results of a 50-year follow-up.

For the first 30 years after repatriation, former American prisoners of war (POWs) of World War II and the Korean Conflict had lower death rates for heart disease and stroke than non-POW veteran controls and the U.S. population, but subsequent morbidity data suggested that this survival advantage may have disappeared. We used U.S. federal records to obtain death data through 1996 and used proportional hazards analysis to compare the mortality experience of POWs and controls. POWs aged 75 years and older showed a significantly higher risk of heart disease deaths than controls (hazard ratio = 1.25; 95% confidence interval, 1.01-1.56), and their stroke mortality was also increased, although not significantly (hazard ratio = 1.13; 95% confidence interval, 0.66-1.91). These results suggest that circulatory disease sequelae of serious, acute malnutrition and the stresses associated with imprisonment may not appear until after many decades.

Ascertainment of mortality in the U.S. veteran population: World War II veteran twins.

Veterans now make up nearly two-thirds of U.S. males aged 65 and older, and thus medical research in the male geriatric population is largely concerned with veterans, whose mortality experience assumes greater importance as they age. Department of Veterans Affairs (VA) records provide an effective and efficient means of gathering information on mortality of veterans, but are useful only if they provide relatively complete ascertainment. We investigated the completeness of VA death reporting (via the Beneficiary Identification and Records Locator Subsystem [BIRLS]) in a large cohort of nearly 32,000 World War II veteran twins followed from 1946 through 1990, comparing VA and Social Security Administration (SSA) mortality ascertainment. The small number of additional deaths found using SSA records--roughly 3% of total deaths--provides evidence that VA death reporting was nearly complete. A further capture-recapture analysis, assuming independence of BIRLS and SSA mortality ascertainment, indicated that BIRLS ascertainment was 95.4% complete.

Self-esteem and internal versus external control among black youth in a summer aviation program.

Changes in self-esteem and belief in internal versus external control of reinforcement (skill versus chance) were investigated among 24 black male and female youngsters, aged 12 through 19, and from diverse backgrounds and geographical locations. Age, socioeconomic status, geographical location, and achievement in flight training were varied. Results showed significant gains in self-esteem by Ss under 16 years of age (p smaller than .05) and Ss from middle income families (p smaller than .005). There was no significant change in belief in internal versus external control among any of the subgroups.

Mortality and morbidity selection effects among US veterans.

Previous studies have documented a substantially lower mortality rate among US male veterans, a form of the "healthy worker" effect, but there have been no studies of morbidity selection effects among veterans. In this paper the evidence for mortality selection effects among US male veterans is reviewed, and data from two general health surveys are examined for evidence of a morbidity selection effect. Overall, there are no substantial differences in health characteristics between veterans and nonveterans, thus providing no evidence for a morbidity selection effect; the inclusion of military service-connected disabled veterans in this comparison, however, makes it somewhat problematic. Reconciliation of a clear mortality selection effect for veterans with the lack of evidence for a corresponding morbidity selection effect is attempted.

Migration biases in address tracing by commercial firms.

The results of a small experiment in address tracing have shown that subjects who were found by commercial tracing were less apt to have moved and were especially apt to have remained in the same state. The documented relation of migration and health status means that differential success in subject tracing can lead to subsequent study bias. Therefore, those who use commercial tracing of epidemiologic study subjects must carefully consider the possibility of a "missing migrant" effect, and that it may, in turn, produce a subsequent survey bias.