Thomas M. Mack

Estrogens and endometrial cancer in a retirement community.

All cases of endometrial cancer occurring among the residents of an affluent retirement community were compared with controls chosen from a roster of all women in the same community. Evidence of estrogen and other drug use and of selected medical conditions was obtained from three sources: medical records of the principal care facility, interviews, and the records of the local pharmacy. The risk ratio for any estrogen use was estimated from all available evidence to be 8.0 (95 per cent confidence interval, 3.5 to 18.1). and the for conjugated estrogen use to be 5.6 (95 per cent confidence interval, 2.8 to 11.1). Increased risk from estrogens was shown for invasive as well as noninvasive cancer, and a dose-response effect was demonstrated. For an estrogen user, the risk from endometrial cancer appeared to exceed by far the base-line risk from any other single cancer.

Menopausal Estrogen Therapy and Hip Fractures

Abstract The association between menopausal estrogen therapy and hip fracture was studied in a retirement community. Ninety-one hip fracture cases during a 5-year period in female residents under a...

Diverticulitis in the United States: 1998-2005: changing patterns of disease and treatment.

Objectives:Diverticular disease imposes an impressive clinical burden to the United States population, with over 300,000 admissions and 1.5 million days of inpatient care annually. Consensus regarding the treatment of diverticulitis has evolved over time, with increasing advocacy of primary anastomosis for acute diverticulitis, and nonoperative treatment of recurrent mild/moderate diverticulitis. We analyzed whether these changes are reflected in patterns of practice in a nationally-representative patient cohort. Methods:We used the 1998 to 2005 nationwide inpatient sample to analyze the care received by 267,000 patients admitted with acute diverticulitis, and 33,500 patients operated electively for diverticulitis. Census data were used to calculate population-based incidence rates of disease and surgical treatment. Weighted logistic regression with cluster adjustment at the hospital level was used for hypothesis testing. Results:Overall annual age-adjusted admissions for acute diverticulitis increased from 120,500 in 1998 to 151,900 in 2005 (26% increase). Rates of admission increased more rapidly within patients aged 18 to 44 years (82%) and 45 to 74 years (36%). Elective operations for diverticulitis rose from 16,100 to 22,500 per year during the same time period (29%), also with a more rapid increase (73%) in rates of surgery for individuals aged 18 to 44 years. Multivariate analysis found no evidence that primary anastomosis is becoming more commonly used. Conclusions:We are the first to report dramatic changes in rates of treatment for diverticulitis in the United States. The causes of this emerging disease pattern are unknown, but certainly deserve further investigation. For patients undergoing surgery for acute diverticulitis, there was little change over time in the likelihood of a primary anastomosis.

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, β-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.

High constant incidence in twins and other relatives of women with breast cancer

The incidence of breast cancer rises steeply between ages 25 and 50, and more slowly thereafter. In contrast, the incidence in the unaffected (contralateral) breast of women who have had breast cancer remains constant at about 0.7% per year for at least the next 20 years after diagnosis, irrespective of age at first diagnosis. The incidence in relatives of the patients seems to show a similar pattern. The incidence in a prospective study of monozygotic twins of patients was approximately constant at 1.3% per year (77 cases), again about 0.7% per breast. At ages older than a patients age at diagnosis, her mother and sisters have an incidence of 0.3–0.4% per year. Above the index patients age at diagnosis, the rate in relatives shows no temporal trend and is independent of the patients age at diagnosis. A statistically simple explanation is that incidence in susceptible women increases to a high constant level by a predetermined age that varies between families, but this seems inconsistent with conventional models of carcinogenesis and susceptibility. The very high incidence in monozygotic twins of patients indicates that a high proportion, and perhaps the majority, of breast cancers arise in a susceptible minority of women.

Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease

BACKGROUND Relatives of young adults with Hodgkins disease are at increased risk of Hodgkins disease, and lines of evidence implicate both inheritance and environment. METHODS We have identified and followed 432 sets of twins affected by Hodgkins disease. The number of cases of Hodgkins disease observed before the age of 50 years in the healthy monozygotic and dizygotic twins of the patients with Hodgkins disease was compared with the number expected from national age-specific incidence rates. RESULTS None of the 187 pairs of dizygotic twins became concordant for Hodgkins disease, whereas 10 of the 179 pairs of monozygotic twins did; in 5 of these pairs, the second case appeared after the original ascertainment. During the observation period, 0.1 (monozygotic) and 0.1 (dizygotic) cases in the unaffected twins were expected. Monozygotic twins of patients with Hodgkins disease thus had a greatly increased risk (standardized incidence ratio, 99; 95 percent confidence interval, 48 to 182), whereas no increase in the risk for dizygotic twins of patients with Hodgkins was observed. CONCLUSIONS Genetic susceptibility underlies Hodgkins disease in young adulthood.

Childhood sun exposure influences risk of multiple sclerosis in monozygotic twins

Objective: To address the role of childhood sun exposure on the risk of multiple sclerosis (MS) after controlling for genetic susceptibility, we investigated the association between sun exposure and MS comparing disease-discordant monozygotic (MZ) twins. Method: Twins with MS were sought by yearly newspaper advertisements throughout North America from 1980 to 1992. Diagnosis was verified by updated medical documentation through 2005. This analysis was restricted to 79 disease- and exposure-discordant monozygotic twin pairs who had ranked themselves before 1993 in relation to each of nine childhood sun exposure activities. A sun exposure index (SI) was defined as the sum of those exposures for which one twin ranked higher than his or her co-twin. The SI difference within each twin pair was calculated by subtracting the SI value of the affected twin from the SI value of the unaffected twin (range −9 to +9). The results were then analyzed using conditional logistic models. Result: Each of the nine sun exposure–related activities during childhood seemed to convey a strong protection against MS within MZ twin pairs. Depending on the activity, the odds ratio (OR) ranged from 0.25 to 0.57. For example, the risk of subsequent MS was substantially lower (OR 0.40, 95% CI 0.19 to 0.83) for the twin who spent more time suntanning in comparison with the co-twin. For each unit increase in SI, the relative risk of MS decreased by 25%. Conclusion: Early sun avoidance seems to precede the diagnosis of multiple sclerosis (MS). This protective effect is independent of genetic susceptibility to MS.

Environmental epigenetics: prospects for studying epigenetic mediation of exposure–response relationships

Changes in epigenetic marks such as DNA methylation and histone acetylation are associated with a broad range of disease traits, including cancer, asthma, metabolic disorders, and various reproductive conditions. It seems plausible that changes in epigenetic state may be induced by environmental exposures such as malnutrition, tobacco smoke, air pollutants, metals, organic chemicals, other sources of oxidative stress, and the microbiome, particularly if the exposure occurs during key periods of development. Thus, epigenetic changes could represent an important pathway by which environmental factors influence disease risks, both within individuals and across generations. We discuss some of the challenges in studying epigenetic mediation of pathogenesis and describe some unique opportunities for exploring these phenomena.

Estrogen use and cardiovascular disease

In general, epidemiologic data from case-control and cohort studies have suggested that postmenopausal estrogen use confers a moderate degree of protection from coronary artery disease (CAD). Reductions have been found in all-cause mortality and mortality from acute myocardial infarction among estrogen replacement users as compared with never-users. Even a small decline in the death rate from CAD among estrogen users would have a major impact on the overall risk:benefit ratio associated with estrogen use.

Risk factors for penile cancer: results of a population-based case-control study in Los Angeles County (United States).

The etiology of penile cancer is poorly understood, with neonatal circumcision being one of the few recognized nondemographic risk factors. Multiple logistic regression was used to analyze interview data from 100 matched case–control pairs; cases of carcinoma in situ (CIS) and invasive carcinoma of the penis were analyzed separately as well as together. Phimosis was strongly associated with invasive carcinoma (adjusted odds ratio [OR] = 16; 95% confidence interval [CI] = 4.5–57) but not CIS (OR = 1.7; 95% CI = 0.32–7.8), and these associations persisted when the analyses were restricted to uncircumcised subjects. Neonatal circumcision was inversely associated with invasive carcinoma (OR = 0.41; 95% CI = 0.13–1.1) but not CIS, and the observed association with invasive carcinoma was weakened appreciably when the analysis was restricted to subjects with no history of phimosis (OR = 0.79; 95% CI = 0.29–2.6). Other factors positively associated with invasive carcinoma or CIS or both were injury to the penis, cigarette smoking, physical inactivity and, to a lesser extent, genital warts and other infections or inflammation of the penis. Conclusions: Although many effects were imprecisely estimated in this study, the protective effect of circumcision on invasive penile cancer appears to be mediated in large part by phimosis; furthermore, the effects of certain factors such as phimosis and circumcision appear to differ for CIS and invasive carcinoma.