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Biomedical subjects

T M Mack

Publications and source records attributed to T M Mack.

At least 19 recordsLinked to original sources

DDT and related compounds and risk of pancreatic cancer.

BACKGROUND: A cohort mortality study among 5886 chemical manufacturing workers was completed in 1987 and showed increased mortality due to pancreatic cancer. PURPOSE: We conducted a nested case-control study of pancreatic cancer among these chemical manufacturing workers to identify risk factors for this disease. METHODS: Twenty-eight verified cases of pancreatic cancer and 112 matched controls were studied. Next of kin of each subject were interviewed to determine lifestyle factors, including tobacco, alcohol, and coffee consumption. Written work records and interviews with co-workers were used to determine chemical exposures at the plant under study. RESULTS: DDT was associated with pancreatic cancer (risk ratio [RR] for ever exposed compared with never exposed = 4.8; 95% confidence interval = 1.3-17.6). Among subjects who had a mean exposure to DDT of 47 months, the risk was 7.4 times that among subjects with no exposure. Two DDT derivatives, Ethylan and DDD, were additionally associated with pancreatic cancer (RR = 5.0 and 4.3, respectively); exposures to these two chemicals were correlated, and it was not possible to determine whether each acted independently of the other. Smoking was identified as an independent risk factor, but controlling for smoking (and other potential confounders) in the analyses did not appreciably alter the risks seen for DDT, DDD, or Ethylan. CONCLUSIONS: Exposure to DDT was associated with pancreatic cancer. The association was not explained by exposure to lifestyle factors or other chemicals, and risk increased with both duration of exposure and latency since first exposure. IMPLICATIONS: These results may indicate that DDT can cause pancreatic cancer in humans under circumstances of heavy and prolonged exposure.

Case-Control Studies

A revised estimate of twin concordance in systemic lupus erythematosus.

OBJECTIVE: Based on a small clinical series and previously published case reports, concordance for systemic lupus erythematosus (SLE) among monozygous (MZ) twins has been reported to be as high as 69%. Using a larger and less biased sample, we provide another estimate of this percentage. METHODS: We established a registry of twins with SLE, based upon self-reports and information provided by the patients' physicians. We used DNA fingerprinting to validate the reported zygosity in a sample of these twins. RESULTS: Of 107 twin pairs meeting the American College of Rheumatology 1982 revised criteria for the diagnosis of SLE, 24% of 45 MZ pairs and 2% of 62 dizygous (DZ) pairs were concordant. The frequency distributions of diagnostic criteria and disease symptoms in the SLE patients were similar to those in other published reports of SLE patients. Zygosity was confirmed by DNA fingerprinting in a subsample of 15 self-described MZ twins and 7 self-described DZ twins. All individuals had correctly predicted their zygosity. CONCLUSION: MZ concordance for SLE is similar to that for other autoimmune diseases and is much lower than previously believed.

Adolescent

Diet and colon cancer in Los Angeles County, California.

The diets of 746 colon cancer cases in Los Angeles County, California (USA) were compared with those of 746 controls matched on age, sex, race, and neighborhood. In both genders, total energy intake was associated with significantly increased risk, and calcium intake was associated with significantly decreased risk. These effects were reduced only slightly after adjustment for the nondietary risk factors (weight, physical activity, family history, and, if female, pregnancy history). In men, total fat and alcohol intakes were responsible for the calorie effect; in women, no individual source of calories was associated independently with risk. Neither saturated fat nor fat from animal sources was responsible for the fat effect. There were no additional independent significant effects for sucrose, fiber, cruciferous vegetables, beta-carotene, other vitamins, or any other nutrient or micronutrient. In univariate analyses, meats, poultry, breads, and sweets were associated with excess risk, and yogurt was protective. After adjustment for sources of calories, no individual food was associated with excess risk, but yogurt remained significantly protective. Total calories were associated with excess risk throughout the colon while the effects of calcium, fat, and alcohol appeared somewhat stronger in the distal colon. After adjustment, crude fiber was significantly protective in the ascending colon but not even weakly protective in the distal colon.

Adenocarcinoma

Malignant melanoma risk by nativity, place of residence at diagnosis, and age at migration.

Although geographic latitude is clearly linked to the risk of cutaneous malignant melanoma, the chronology of this link is unclear. Based on the 4,611 cases of melanoma with known place of nativity diagnosed in 1972-82 among the non-Latino White residents of Los Angeles County (California, United States) of known place of origin, migrants to Los Angeles from higher US latitudes enjoy relative safety from skin melanoma. This relative safety is largely unaffected by the interval since migration, even after decades of residence in Los Angeles. The same relative protection is enjoyed by native residents of more northerly US communities in comparison with co-resident migrants from the southwestern US. While the observed effect of latitude is consistent with the accepted importance of solar radiation as a determinant of melanoma risk, it suggests that early, rather than late or cumulative, exposure is of most importance. This finding does not affirm the belief that protection of adult skin from exposure to the sun will reduce the risk from melanoma. It does suggest that decades must pass before it will be possible to assess the impact on melanoma risk of any increase in ultraviolet radiation delivered to the earth as a result of the destruction of atmospheric ozone.

Adult

Cancers of the prostate and breast among Japanese and white immigrants in Los Angeles County.

Using age-adjusted incidence rates and proportional incidence ratios, the risks of prostate cancer and breast cancer in three racial/ethnic groups - Spanish-surnamed whites, other whites and Japanese - were studied in Los Angeles County native residents and compared with those in immigrants and representative 'homeland' populations. An algorithm based on social security numbers was developed and utilised to estimate age at immigration for non-US-born Los Angeles County cancer patients. For prostate cancer, the incidence rates in Los Angeles County were much higher than those in the homelands for each racial/ethnic group. However, prostate cancer rates of immigrants were similar to those of US-born patients in the Spanish-surnamed white and Japanese populations, regardless of age at immigration. For breast cancer, the incidence rates in Los Angeles County were also high compared with those in the homelands. However, the timing of immigration to the US was important in determining breast cancer risk. When social security numbers indicated that migration occurred later in life, rates for breast cancer were substantially lower than when migration occurred early, although they were still much higher than in the homeland populations. These findings suggest that environmental factors in early life rather than in later life are important in the etiology of breast cancer and that later life events can substantially impact the likelihood of developing clinically detectable prostate cancer.

Age Factors

Life-style, workplace, and stomach cancer by subsite in young men of Los Angeles County.

A case-control study involving interviews with 137 incident male cases of stomach cancer under the age of 55 yr and an equal number of age- (within 5 yr), race-, and sex-matched neighborhood controls in Los Angeles County was conducted. Cases were more likely to be foreign born and had less education compared with controls. Any use of tobacco products conferred a 2-fold increase risk for stomach cancer; the effect was present in all subsites: the cardia; fundus/body; and antrum/pylorus. Weekly use of alcoholic beverages was also a risk factor, but the effect was not observed in the antrum/pylorus. In comparison with controls, cases had a significantly higher intake of beef (cardia only) and barbecued/smoked foods, had a lower intake of fresh fruits/vegetables, and were more likely to prefer white than whole grain bread. Occupational exposure to metal dust was associated with a 70% increased risk of stomach cancer, with an increase in risk as the duration of exposure increased. This association was most pronounced for tumors in the antrum and pylorus. Subjects with a history of stomach or duodenal ulcer showed a 2-fold increased risk of stomach cancer. The effects of smoking, alcohol, intake of white bread, history of ulcer, and exposure to metal dust remained statistically significant when these variables were examined simultaneously in multivariate analyses and when the multivariate analyses were confined to directly interviewed subjects.

Adult

Reproductive factors and colon cancers.

In Los Angeles County, the age-adjusted incidence rate of colon cancer in men is almost 30% higher than that in women; however, in the descending and sigmoid colon, age-specific incidence rates for women are higher than those for men before age 55. Since menstrual and/or reproductive factors may be involved in producing this crossover in age-specific rates, they were examined in a population-based case-control study involving 327 white women with adenocarcinoma of the colon and age-, race- and neighbourhood-matched controls. After adjustment for other factors associated with colon cancer in this study (family history of large bowel cancer, total fat intake, calcium, weight and activity level), ever having been pregnant was protective (RR = 0.56, 95% CI = 0.33-0.97). For one to two pregnancies, the RR was 0.76 (CI = 0.42-1.37); for three or more pregnancies, the RR was 0.45 (CI = 0.25-0.81). However, the relationship between the number of pregnancies and colon cancer risk was actually U-shaped, with risk decreasing with successive pregnancies up to four and then increasing with additional pregnancies. The U-shaped relationship was present for incomplete as well as for full-term pregnancies and was more striking for cancers occurring in the distal (descending and sigmoid) than proximal (caecum to splenic flexure) colon. Risk was not related to age at menarche or use of exogenous oestrogens, but delayed natural menopause was weakly protective in the proximal but not distal colon. The crossover in incidence rates in the distal colon can be completely accounted for by the pregnancy effect. The U-shape of the pregnancy curve suggests the possibility of competing factors, some protective, especially after one or several pregnancies, and others conferring increasing risk with successive pregnancies, regardless of the pregnancy outcome.

Adenocarcinoma

Recall bias in subjective reports of familial cancer.

Both twins in a pair in which one had suffered breast cancer (115 pairs) were asked about the occurrence of cancer among first- and second-degree relatives. For all cancer sites together, there was agreement about 129 cases; another 48 cancers were mentioned only by the case twin and another 55 only by the co-twin. For breast cancer, there was agreement about 22 events; another 12 cases were provided by the cancer twin and four by the co-twin. The odds ratio for a family history of cancer was 1.14; for breast cancer the corresponding value was 1.48. The results are suggestive of some recall bias in subjective reports on familial cancer.

Adult

Risks and benefits of long-term treatment with estrogens.

The goal of contemporary hormone replacement is to minimize net predictable lifetime risk; success therefore depends upon quantitative assessments of the net quality of life, of net morbidity and of net mortality. Estrogens ameliorate menopausal symptoms, maintain bone integrity, and produce endometrial cancer; these facts and their quantitative aspects can be stimulated. Other links are gradually becoming clear: estrogens increase biliary disease, but prevent heart disease, and, it now seems, stroke. Conventional wisdom to the contrary notwithstanding, a critical review suggests that breast cancer is probably increased in frequency by long-term estrogen use; the increase is modest as a risk factor but because breast cancer is a common disease, it is substantial in absolute terms. The addition of progestin seems attractive as a method of opposing undesirable estrogenic effects on the endometrium. In fact, there is reason for concern about the effect of an added progestin upon the risks from breast cancer, heart disease, and stroke; even the magnitude of the expected reduction in endometrial cancer may not be great when the hormone is administered sequentially. Using a simple deterministic model of post-menopausal life with hormone replacement, we have inserted available estimates of the regimen-specific relative risk for each outcome, and translated each net impact into common denominators of morbidity and mortality. While estrogens probably increase net morbidity, as measured by either the number of hospitalizations to be anticipated or by the more arbitrary measure of expected days of disability, these negative changes are mostly due to gallbladder disease and endometrial cancer, both largely treatable conditions. Largely because of protection against heart disease, estrogen replacement in modest dose is likely to reduce substantially the number of deaths to be expected in women treated through age 75 and even into more advanced age. Hormone replacement which includes systemic progestin supplementation has not been empirically tested; it may be beneficial, but it is at least as likely to be harmful. Either a modest increment in the number of additional breast cancers produced by estrogens, a modest reduction in the number of cardiac events prevented by estrogens, or a simultaneous minor shift in the same direction for each condition, would have the effect of shifting the net reduction in cumulative deaths into an increase in the number of deaths as a result of treatment.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged

A case-control study of occupational and dietary factors in colorectal cancer in young men by subsite.

With the hope that exposures responsible for colorectal cancer might be especially obvious among those in whom it develops early, 147 men with colorectal carcinomas first diagnosed between the ages of 25 and 44 years were compared to neighborhood controls. Physical activity on the job was protective for tumors located in the transverse and descending portions of the colon. Rectal cancer and to a lesser extent sigmoid cancers were associated with jobs in which dusts or fumes were inhaled, especially if those jobs were held for long periods in young adulthood. While risk for rectal cancer did not seem to be limited to any particular type of dust or fume, the excess risk was strongest for wood and metal dusts. Consumption of fruits and vegetables and a preference for whole grain breads were protective for colon but not rectal cancers, while consumption of deep fried foods and barbecued/smoked meats increased risk at specific subsites. Beef intake, alcohol consumption, and cigarette smoking appeared to play little or no role at any subsite.

Adenocarcinoma

Cardiovascular benefits of estrogen replacement therapy.

Epidemiologic case-study and cohort-study data concerning effects of estrogen replacement therapy on the risk of cardiovascular disease in postmenopausal women are reviewed. Although there is conflicting literature, most research strongly suggests that estrogens, and estrogen replacement therapy in particular, reduce the risk of cardiovascular disease. Such reduced risk in estrogen users is most likely mediated in part by the beneficial effects of estrogen therapy on lipid metabolism. Risks associated with the use of estrogens and possible effects when progestational agents are added to an estrogen regimen are also discussed.

Breast Neoplasms

Tobacco, alcohol, diet, occupation, and carcinoma of the esophagus.

Information on occupation, smoking, food and beverage consumption, and medical history were compared between 275 incident cases of carcinoma of the esophagus and 275 neighborhood controls who were matched to the cases on age (within 5 years), race, and sex. Tobacco use, mainly cigarette smoking, was a significant risk factor for carcinoma of the esophagus. Ex-smokers of cigarettes showed a reduced risk relative to those who continued to smoke, and current smokers of two or more packs per day displayed a higher risk than those who smoked less. Alcohol consumption was another significant risk factor for carcinoma of the esophagus; there was a highly significant trend with average daily dose of ethanol. Relative to controls, cases also consumed significantly more fried bacon or ham, less fresh fruits and raw vegetables, and were more likely to prefer white than whole grain bread. Finally, there was a significant association between carcinoma of the esophagus and long-term occupational exposure to metal dust; this association was largely confined to the lower one-third section of the esophagus.

Alcohol Drinking

Adenocarcinoma of the stomach and exposure to occupational dust.

The authors studied 1,342 cases of adenocarcinoma of the stomach identified by a population-based cancer registry in Los Angeles County, California. The cases were males aged 20-64 years first diagnosed between 1972 and 1982. To determine whether exposure to occupational dust increased the risk of developing stomach cancer, occupational titles were rated for the likelihood of exposure to various kinds of dust. Men who worked in dusty jobs had a risk for developing stomach cancer 1.3 times that of unexposed men (95% confidence interval = 1.2-1.4). The association of exposure to dust with stomach cancer was stronger at higher levels of exposure. The risk was not uniform throughout the stomach: the highest risk (1.8 times that of unexposed men) was found for the antrum/pylorus. At that site, exposure to mineral dust carried the greatest risk for cancer (3.7 times the risk for unexposed men). The highest risks from dust exposure were observed in blacks. Risk was related to race, socioeconomic status, and immigrant status, but these factors did not entirely explain the association with dust exposure. The observed relation between dust exposure and stomach cancer is consistent with results of previous mortality and case-control studies of cancer in men who worked in dusty occupations. Ingested dust may be one factor in the etiology of adenocarcinoma of the stomach.

Adenocarcinoma

Re-evaluating the role of progestogen therapy after the menopause.

An estrogen-progestogen regimen of hormone replacement therapy has become widely used in recent years, primarily as a means to protect the endometrium from the carcinogenic effects of unopposed estrogen therapy (ERT). In this article, we evaluate the probable effects of this regimen on mortality from endometrial cancer as well as mortality from other chronic diseases. We conclude from this analysis that ERT is to be preferred to combination therapy for postmenopausal women without a uterus, primarily because it is predicted that ERT confers a significantly greater benefit on heart disease risk. In women with a uterus, if progestogens are to be prescribed, they should be given in the lowest possible dose needed to achieve the desired histologic changes in the endometrium, since the predicted loss in heart disease benefit from adding the progestogen is substantial.

Breast Neoplasms