We investigated the associations between two CYP1A1 polymorphisms (Ile462Val and Thr461Asn) and one CYP1B1 polymorphism (Leu432Val) and breast cancer risk. The study population consisted of 483 breast cancer patients and 482 healthy population controls, all of homogenous Finnish origin. No statistically significant overall associations were found between the CYP1A1 and CYP1B1 genotypes and breast cancer risk. However, a significant increase in the breast cancer risk was seen for women who had smoked 1-9 cigarettes/day and carried the CYP1B1 432Val allele; the OR was 2.6 (95% CI 1.07-6.46) for women carrying the Leu/Val genotype and 5.1 (95% CI 1.30-19.89, P for trend 0.005) for women with the Val/Val genotype compared to similarly smoking women homozygous for the 432Leu allele. Furthermore, when CYP1B1 genotypes were combined with the previously analyzed N-acetyl transferase (NAT2) genotypes, a significant increase in breast cancer risk was found among women who had at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype (OR 1.52; 95% CI 1.03-2.24) compared to women carrying a combination of CYP1B1 Leu/Leu and NAT2 rapid acetylator genotypes. This risk was seen to be confined to ever smokers; the OR was 2.46 (95% CI 1.11-5.45) for ever smokers carrying at least one CYP1B1 432Val allele together with the NAT2 slow acetylator genotype compared to ever smokers with the CYP1B1 Leu/Leu and NAT2 rapid acetylator genotype combination. Our results suggest that the CYP1B1 polymorphism may be an important modifier of breast cancer risk in Finnish Caucasian women who have been exposed to tobacco smoke and/or carry the NAT2 slow acetylator genotype.
OBJECTIVE: We present results from a large, population-based cohort study in Sweden, where we assessed ovarian cancer risk among patients hospitalized for diabetes mellitus. METHODS: The cohort was composed of patients identified in the Swedish In-Patient Register as having a hospital discharge diagnosis of diabetes mellitus in 1965-1994. The follow-up was done by linkages with the national cancer register and other population-based registers. Standardized incidence ratios (SIR) were used as a measure of relative risk. RESULTS: After exclusion of the first year of follow-up (to avoid selection bias), 141,627 women remained in the cohort, contributing 865,746 years of follow-up to the study. The overall SIR for ovarian cancer was 0.97 (95% confidence interval (CI) 0.87-1.08). We found no difference in the risk estimates among women who had been hospitalized for classic complications of diabetes and for those who had not, or according to the duration of follow-up. Women above 40 years of age at first hospitalization presented a SIR of 0.96 (95% CI 0.85-1.07). CONCLUSIONS: Our study provides evidence of lack of an association between diabetes mellitus and ovarian cancer.
The incidence of endometrial cancer varies up to 10-fold between high- and low-incidence regions, suggesting the importance of environmental factors, including diet, in the etiology of this disease. However, few studies have examined the role of diet in the etiology of endometrial cancer. Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we analyzed data from a large, case-control study of Swedish-born postmenopausal women aged 50-74 yr (709 cases and 2,887 controls) residing in Sweden between 1994 and 1995. We found no clear association between foods or food groups and endometrial cancer risk, although high consumption of certain foods, such as Brassica vegetables, coffee, and legumes, might be associated with small-to-moderate reduced risks of endometrial cancer, while red meat consumption might be associated with a small-to-moderate increased risk. Daily use of calcium supplements appeared to lower endometrial cancer risk (OR = 0.5, 95% CI = 0.3-0.9, P for trend = 0.04), especially among women with low calcium intake from dairy products. On the other hand, the use of iron supplements appeared to increase the risk (OR = 1.7, 95% CI = 0.9-3.3, P for trend = 0.03). The findings are discussed with respect to previous studies and the possible underlying mechanisms.
Xenobiotic metabolizing enzymes (XMEs) are important detoxifiers of hazardous environmental agents, and their polymorphisms may therefore modify the risk of environmentally induced cancers. Consequently, the XME polymorphisms have been extensively studied in this context during recent years. Particular attention has been given to the polymorphisms of glutathione S-transferase (GST) M1, P1 and T1 genes. Previous studies have provided abundant data indicating these polymorphisms as important modifiers of individual susceptibility to cancers of environmental origin. It can be postulated that if the at-risk genotypes of these genes were real risk factors for the environmental cancers, their prevalence would presumably decrease with age in cancer-free part of the population.
We tested the hypothesis in a population based group of 2105 Finns (1,051 men, 1,054 women) in five age strata (27, 37, 47, 57 and 67 years of age), all without clinically diagnosed cancer.
For GSTM1 genotype, a significant interaction was seen between gender and age among never smokers (p=0.003). Currently smoking men tended to be less likely (OR 0.57, 95% CI 0.31-1.03), and currently smoking women more likely (OR 1.70, 95% CI 0.97-2.97) homozygotes for the GSTP1*B allele compared with never smokers. Moreover, the likelihood of being a concurrent carrier of the putatively protective genotypes of all of the three studied GSTs was almost three-fold (OR 2.80, 95% CI 1.10-7.12) in heavy smokers in the two oldest age-groups compared with the other genotypes.
Our findings based on a novel study design provide support to the previous case-control studies suggesting that GST genotypes modify individual risk of environmentally-induced cancers.
We investigated the roles of EPHX1 Tyr113His and His139Arg polymorphisms in lung cancer susceptibility in a Finnish study population comprising of 230 lung cancer cases and a large control group (n=2105). The controls were distributed into five age strata, which enabled us to examine the potential age-related changes in the putative EPHX1 at-risk genotypes in the cancer free population. Although the exon 3 slow activity associated allele (His113) containing genotypes posed a decreased lung cancer risk compared with the homozygous wild-type Tyr113/Tyr113 genotype (OR, 0.68; 95% CI, 0.49-0.94), no association was seen for the EPHX1 phenotypes interpreted from the combined exons 3 and 4 genotype data. Neither was any difference seen in the prevalence of the EPHX1 Tyr113His genotypes or interpreted EPHX1 phenotypes in the different age groups.
The consumption of fatty fish, which contains large amounts of omega-3 fatty acids, may lower the risk of hormone-responsive cancers. Our aim was to study the association of fish consumption and endometrial cancer risk in Sweden, a country with a wide range of high fatty fish consumption. Using data from a large, nationwide case-control study (709 cases and 2888 controls), we analyzed consumption of both fatty (e.g., salmon and herring) and lean (e.g., cod and flounder) fish in relation to endometrial cancer risk, adjusting estimates for a wide range of potentially confounding variables. Odds ratios (ORs) and 95% confidence intervals (CIs) were computed from unconditional logistic regression models fit by maximum likelihood methods. Consumption of fatty fish was inversely associated with endometrial cancer risk. The multivariate OR for women in the highest quartile level (median, 2.0 servings per week), compared to women with in the lowest (median, 0.2 servings per week), was 0.6 (95% CI, 0.5-0.8; P for trend, 0.0002). The corresponding OR for women in the highest quartile level of lean fish (median, 2.5 servings per week), compared to women in the lowest (median, 0.6 servings per week), was 1.0 (95% CI, 0.8-1.3; P-value for trend, 0.72). Total fish consumption was inversely associated with risk, although weakly. Our results suggest that the consumption of fatty fish, but not other types of fish, may decrease the risk of endometrial cancer.
Statins (HMG-CoA-reductase inhibitors) are suggested to act as a predisposing factor for autoimmune diseases, have immunomodulatory effects, and possibly prevent some cancer types - the sum of these effects is unknown in cancers of viral aetiology, such as Merkel cell carcinoma (MCC). Aim of our study was to find out whether statin users in Finland have an increased incidence of MCC.
A cohort of 224715 male and 230220 female statin users during 1994-2007 was identified from the Prescription Register of the National Social Insurance Institution. This cohort was followed up through the Finnish Cancer Registry for MCC up to 2009.
There were altogether 50 cases of MCCs, while the expected number of cases, calculated on the basis of the MCC incidence in comparable Finnish population, was 39.9 (SIR 1.25, 95% CI 0.93-1.65). The standardized incidence ratio (SIR) for MCC in ages
N-acetyltransferase 2 (NAT2) is a polymorphic enzyme participating in the metabolism of numerous pharmaceutical drugs and carcinogens found in tobacco smoke and diet. The NAT2 gene is highly polymorphic and several different allelic variants exist that determine the acetylator phenotype. In the course of our case-control study, we developed a new method based on fluorogenic allele-specific probes for analyzing the C282T and T341C polymorphisms of the NAT2 gene in 483 Finnish breast cancer patients and 482 healthy population controls. The slow NAT2 acetylation capacity-associated genotypes posed a somewhat increased overall breast cancer risk (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.01-1.73). This association was found to be confined to the advanced (stage III or IV) breast cancer (OR, 2.60; 95% CI, 1.29-5.24). When stratified by smoking habits, women who had smoked
A cohort including all female workers born 1906 through 1945 (n = 413,877) in Finland was identified through the Population Census of Finland of 1970. Incident cases of cancers of the gastrointestinal tract were explored during 1971 to 1995. Job titles in census records were converted to exposures of 31 occupational agents through a job-exposure matrix. For each agent, the product of level and probability of exposures was calculated and subdivided in three categories: zero, low and medium/high. Poisson regression models estimated relative risks (RR) for each agent, standardized for birth cohort, follow-up period, and socioeconomic status. Adjustment at job title level was done for alcohol use for cancers of the esophagus and liver and smoking for pancreatic cancer. The results showing either statistically significant RR at the medium/high level of exposure (RRH) or statistically significant trend (P