The mRNA expression of 17beta-hydroxysteroid dehydrogenase (17HSD) types 1 and 2 enzymes catalyzing opposite reaction of estrogen metabolism was investigated in colon cancer. Further, the significance of the 17HSD type 2 enzyme as a possible marker of colorectal cancer (CRC) prognosis was studied. In the normal mucosa, 17HSD type 2 mRNA was predominantly expressed in the surface epithelium and in the upper parts of the crypts. In the lamina propria expression was seen in endothelial cells and mononuclear phagocytes. In colorectal tumors, 17HSD type 2 expression was in most cases downregulated. Female patients had significantly more cancers with high 17HSD type 2 mRNA expression (n=11/35; 31%) than male patients (n=3/39; 8%) (P=0.02). We observed a significant impact of 17HSD type 2 mRNA expression on survival in female patients with distal colorectal cancer (n=24), with an overall cumulative 5-year survival rate of 54% in those with low 17HSD type 2 mRNA expression. None of the female patients with high 17HSD type 2 mRNA expression survived (n=11; P=0.0068; log rank 7.32). In male patients, no significant association with survival was observed. Our data provide evidence suggesting that low 17HSD type 2 mRNA expression is an independent marker of favorable prognosis in females with distal colorectal cancer, supporting the presence of gender- and location-related differences in the pathogenesis of colon cancer.
AIMS: To evaluate the 10-year incidence of later infarction and subsequent mortality, as well as predictors of later infarction, in patients with suspected myocardial infarction and alive on day 15 after admission. METHODS AND RESULTS: 5993 patients admitted with suspected myocardial infarction and alive on day 15 after admission were registered in The First Danish Verapamil Infarction Trial database in 1979-81. 2586 had definite infarction, 402 probable infarction and 3005 no infarction as they fulfilled 3, 2 and 1 criteria for infarction. They were followed for 10 years with respect to later infarction and death, i.e., including death after later infarction. The 10 year infarction rate after index admission was 48.8% in definite, 47.3% in probable and 24.6% in no infarction patients (P 65 years with definite or probable infarction. CONCLUSION: The 10-year infarction rate in patients with suspected myocardial infarction in whom the diagnosis is ruled out is lower than in those with definite or probable infarction, but the mortality after a later infarction is similar in all three groups.
Comment In: Eur Heart J. 1998 Apr;19(4):534-59597397
OBJECTIVES: High tumor grade and lymph node positivity are associated with poor prognosis in breast carcinoma. Prognostic markers are used to define which patient groups benefit from different treatment modalities, some of which are potentially very toxic. Matrix metalloproteinases (MMPs) degrade the extracellular matrix, and type IV collagenases MMP-2 and -9 have been linked to invasive behavior of several malignancies. Tissue inhibitors of metalloproteinases (TIMPs) -1 and -2 inhibit their activity and are therefore considered to have an inhibitory effect on tumor progression. The role of TIMPs in progression of breast carcinoma is, however, still poorly known. Here the effect of TIMP-1 and -2 on survival was examined in lymph node-positive breast carcinoma patients. METHODS: TIMP-1 or -2 was evaluated with avidin-biotin immunohistochemical staining from paraffin-embedded sections of primary breast carcinoma of 132 cases. RESULTS: Positive staining for TIMP-1 and -2 was observed in 81 and 84% of the tumors respectively. TIMP-1 correlated to the grade of the tumor (p = 0.047). Absence of TIMP-1 protein correlated with favorable disease-specific survival of the patients with high-grade tumors. After 10 years of follow-up as high as 88% of patients with a grade 2-3, but TIMP-1-negative tumor were alive, when only 61% of the TIMP-1-positive cases in this group survived by that time (p = 0.03). CONCLUSION: Our results suggest that lack of TIMP-1 protein expression is associated with a favorable prognosis in patients with node-positive high-grade breast carcinoma.
BACKGROUND: In many biomedical disorders, early age at onset (AAO) is an index of high liability to illness which is manifest by an increased risk of illness in relatives. Most but not all prior studies report such a pattern for major depression (MD). METHOD: Lifetime MD and AAO were assessed at personal interview using modified DSM-III-R criteria in 13864 twin pairs, including 4229 onsets of MD, from the Swedish National Twin Registry. Analyses were conducted using Cox proportional hazards models. RESULTS: Controlling for year of birth, gender, zygosity, co-twin history of MD and the interaction of zygosity and co-twin history, the best-fit model showed a significant main effect and a quadratic effect of AAO of MD in the co-twin on the log hazard ratio for MD in the index twin. When examined together, these effects predicted that from the ages of 15 to approximately 35 years, AAO of MD is moderately negatively related to risk of illness in relatives. However, past age 35, the function flattens out, with little change of risk in relatives with further increases of AAO. Even when the co-twin had a late AAO, the risk in the index twin substantially exceeded that seen when the co-twin had no history of MD. CONCLUSION: In this large sample, AAO is a meaningful, albeit modest, index of familial liability to MD. The relationship is nonlinear and results largely from an increased liability in individuals with an early AAO. These results should be interpreted in the context of the limitations of long-term recall.
BACKGROUND: Alcohol intake has been reported to be positively associated with an increased risk of postmenopausal breast cancer; however, the association with the estrogen receptor (ER) and progesterone receptor (PR) status of the breast tumors remains unclear. METHODS: Self-reported data on alcohol consumption were collected in 1987 and 1997 from 51,847 postmenopausal women in the population-based Swedish Mammography Cohort. Through June 30, 2004, 1188 invasive breast cancer case patients with known ER and PR status were identified during an average 8.3-year follow-up. We used Cox proportional hazards models to estimate multivariable relative risks (RRs) of breast cancer, adjusting for age; family history of breast cancer; body mass index; height; parity; age at menarche, first birth, and menopause; education level; use of postmenopausal hormones; and diet. Heterogeneity among groups was evaluated using the Wald test. All statistical tests were two-sided. RESULTS: Alcohol consumption was associated with an increased risk for the development of ER-positive (+) tumors, irrespective of PR status (highest intake [> or = 10 g of alcohol per day] versus nondrinkers, multivariable RR = 1.35, 95% confidence interval [CI] = 1.02 to 1.80; Ptrend
Comment In: J Natl Cancer Inst. 2005 Nov 2;97(21):1563-416264173
Aging Research Center, Division of Geriatric Epidemiology and Medicine, Department of Neurotec, Karolinska Institutet and the Stockholm Gerontology Research Center, Olivecronas väg 4, Box 6401, S-113 82 Stockholm, Sweden.
To explore the relationship between light to moderate alcohol consumption and risk of dementia and Alzheimer's disease in very old people, a community-based dementia-free cohort (n = 402) was followed for almost 6 years to detect incident dementia using the Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition-Revised criteria. Data from the entire cohort and a subpopulation of those with baseline Mini-Mental State Examination score > or =24 (n = 317) were analyzed with Cox models. In the entire population, light to moderate drinking was significantly associated with a decreased risk of incident dementia and Alzheimer's disease compared with nondrinking (adjusted relative risk 0.5, 95% confidence interval 0.3 to 0.7). In the analysis of the subpopulation, however, the inverse association between light to moderate drinking and risk of incident dementia and Alzheimer's disease was less evident and no longer statistically significant. This study suggested that light to moderate alcohol drinking might protect against dementia and Alzheimer's disease among old people, although the possibility that such an association may be due to information bias cannot be totally ruled out.
BACKGROUND: Our aim was to examine the association between use of alcohol and subsequent incidence of primary infertility. METHODS: The study subjects were chosen from a population-based cohort of Danish women aged 20-29 years. Eligible women were nulliparous and not pregnant (n = 7760). Information on alcohol intake and potential confounders (age, education, marital status, diseases in the reproductive organs, and cigarette smoking) was assessed at enrollment. The incidence of fertility problems during follow-up was obtained by record linkage with the Danish Hospital Discharge Register and the Danish Infertility Cohort Register. Main outcome measures were hazard ratios of infertility according to alcohol intake at baseline estimated in a multivariate Cox proportional hazards model. RESULTS: During a mean follow-up of 4.9 years, 368 women had experienced infertility. Alcohol intake at baseline was unassociated with infertility among younger women, but was a significant predictor for infertility among women above age 30. In this age group, the adjusted hazard ratio for consuming seven or more drinks per week was 2.26 (95% confidence interval: 1.19-4.32) compared with women consuming less than one drink per week. CONCLUSIONS: These findings suggest that alcohol intake is a predictor for infertility problems among women in the later reproductive age group.
BACKGROUND: Male gender is an independent coronary risk factor. METHOD: Long-term follow-up of 989 Danish men who underwent legal castration between 1929 and 1968. RESULTS: The legally castrated men were unmarried and belonged to social class IV and V more often than were Danish men in general. During the follow-up until 2000, 835 of the 989 (85%) castrated men died, including 148 who died of myocardial infarction. In multiple Poisson regression analyses, the men had a standardized mortality rate (SMR) for all-cause mortality of 1.30 (95% CI: 1.26-1.36) and a SMR for mortality of myocardial infarction of 1.08 (95% CI: 1.04-1.16). Thus, the castrated men had a lower proportion of deaths of myocardial infarction (148/792, 18.7% (95% CI: 16.0-21.6%)) than was expected based on the mortality rates for the Danish male population (136/608, 22.4%). The castrated men had discordant changes for the SMR for all-cause mortality and mortality of myocardial infarction whereas subgroups of the Danish population previously has been found to have concordant changes for the two SMRs. CONCLUSION: The castrated men had fewer deaths of myocardial infarction than expected, so men may not have increased risk of coronary heart disease from unphysiologically low levels of endogenous androgens.
BACKGROUND: Two contradictory hypotheses have been proposed to explain the relationship between allergic conditions and malignancies, the immune surveillance hypothesis and the antigenic stimulation hypothesis. The former advocates that allergic conditions may be protective against development of cancer, whereas the latter proposes an increased risk. This relationship has been studied in several case-control studies, but only in a few cohort studies. METHODS: The association between allergic conditions and risk of developing leukemia, Hodgkin's disease, non-Hodgkin's lymphoma and myeloma was investigated in a cohort of 16,539 Swedish twins born 1886-1925. Prospectively collected, self-reported information about allergic conditions such as asthma, hay fever or eczema was obtained through questionnaires administered in 1967. The cohort was followed 1969-99 and cancer incidence was ascertained from the Swedish Cancer Registry. RESULTS: Hives and asthma tended to increase the risk of leukemia (relative risk [RR] = 2.1, 95% Confidence Interval [CI] 1.0-4.5 and RR = 1.6, 95% CI 0.8-3.5, respectively). There was also an indication of an increased risk of non-Hodgkin's lymphoma associated with eczema during childhood (RR = 2.3, 95% CI 1.0-5.3). CONCLUSION: In contrast to most previous studies, our results do not indicate a protective effect of allergic conditions on the risk of developing hematological malignancies. Rather, they suggest that allergic conditions might increase the risk of some hematological malignancies.