Intra-uterine exposure to saccharine and risk of bladder cancer in man

Animal experiments show that rats fed saccharine are more likely to develop bladder tumours if they have been exposed to saccharine in utero through their mothers' food. The risk of bladder tumours in humans following in utero exposure to saccharine has not been evaluated previously. In Denmark the use of saccharine increased sharply during the second World War as a result of scarcity of sugar, and import and export figures indicate that saccharine consumption was on average 4-5 times higher during the war-time period than in the pre-war decade. The risk of bladder tumours at ages 20-34 was 1.0 (95% confidence interval 0.7-1.6) among men born in 1941-1945 compared with men born 1931-1940. Among women the risk was 0.3 (0.1-1.0). This study provides no evidence of an increased risk of human bladder cancer during the first 30-35 years of life associated with in utero saccharine exposure.     

Novel breast cancer risk alleles and endometrial cancer risk

Genome-wide association studies have identified several novel risk alleles for breast cancer. We hypothesized that genetic variants that are associated with breast cancer, a hormone-related disease, would also be associated with endometrial cancer, another hormone-related disease. We conducted a case-control study nested within the Nurses' Health Study and the Women's Health Study to investigate the associations between these 7 newly identified risk alleles for breast cancer and endometrial cancer risk using 692 invasive endometrial cancer cases and 1,723 matched controls. We used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) to assess the risk of endometrial cancer. In contrast to the breast cancer findings, we did not observe an increased risk of endometrial cancer. We observed an inverse association among rs2981582 (FGFR2) variant carriers [OR= 0.75 (95% CI: 0.60-0.95)]. We also observed a nonsignificant inverse association with rs889312 (MAP3K1) variant carriers [OR = 0.85 (95% CI: 0.68-1.05)] and rs1219648 (FGFR2) variant carriers [OR= 0.86 (95% CI: 0.69-1.06) and endometrial cancer risk. We did not observe associations with the other single nucleotide polymorphisms (SNPs) and endometrial cancer risk. Replication studies investigating these polymorphisms and endometrial cancer risk are warranted. However, our findings do suggest the potential importance of biological differences between endometrial and breast cancer with respect to the genes identified in the scans. The molecular mechanisms underlying these differences remain to be defined.     

Oral contraceptives and the risk of endometrial cancer

The relationship between the use of combbination oral contraceptives (OCs) and the risk of endometrial cancer was assessed in a case-control study conducted in the Swiss Canton of Vaud between 1 January 1988 and 31 July 1990. Subjects included 122 women aged 75 or less with histologically confirmed endometrial cancer, and 309 control women in hospital for acute conditions unrelated to OC use. Overall, 14 percent of cases and 27 percent of controls had ever used OCs, corresponding to a multivariate relative risk (RR) of 0.5 (95 percent confidence interval [CI]: 0.3. 0.8). The risk of endometrial cancer was found to be related inversely to duration of OC use: RR=1.0 for less than two years of OC use; 0.5 for two to five years; and 0.3 (95 percent CI: 0.1, 0.7) for more than five years. The protection appeared greater within 20 years since last use, and the RR rose to 0.8 after 20 or more years since last use; numbers are too small, however, for reliable inference from these subanalyses. No significant interaction or modifying effect was observed with other major factors related to endometrial cancer, including parity, body mass index, estrogen replacement therapy, and cigarette smoking. While this study provides further evidence for the protective effect of OCs against risk of endometrial cancer, the relationship requires continued evaluation to assess the long-term implications and public health impact of OC use.This work was supported in part by the Swiss National Science Foundation Grant No. 3.866-0.88.     

Cigarette smoking and the risk of endometrial cancer

Epidemiological studies have shown that cigarette smoking is associated with a reduced risk of endometrial cancer, in contrast to the increased risks observed with many other non-respiratory-tract cancers, including those of the bladder, pancreas, and cervix uteri. Some studies of endometrial cancer suggest that the inverse association with smoking is limited to certain groups of women, such as those who are postmenopausal or those taking hormone-replacement therapy. The biological mechanisms that might underlie this association remain unclear, although several have been proposed, including an antioestrogenic effect of cigarette smoking on circulating oestrogen concentrations, a reduction in relative bodyweight, and an earlier age at menopause. We have examined the evidence for an association between cigarette smoking and risk of endometrial cancer, including studies related to the proposed biological mechanisms.     

Family history and the risk of endometrial cancer

The association between a family history of endometrial, breast and ovarian cancer and the risk of endometrial cancer was analyzed on the basis of data from a case-control study conducted in northern Italy between 1983 and 1993. A total of 726 histologically confirmed endometrial-cancer patients (median age 61) admitted to a network of general and teaching hospitals in the Greater Milan area were interviewed. The controls were 2, 123 women (median age 59), admitted for acute, non-neoplastic, non-hormone-related diseases to the same network of hospitals were the cases had been identified, with admission diaagnoses unrelated to any of the known or suspected risk factors for endometrial cancer. Among cases, 37 (5.1%) reported a history of endometrial cancer in first-degree relatives. The corresponding figure among controls was 77 (3.6%). In comparison with women with no family history of endometrial cancer, the odds ration (OR) of endometrial cancer was 1.5 (95%CI[confidence interval], 1.0-2.3) in women with a history of endometrial cancer in first-degree relatives. NO relation emerged between endometrial cancer and a family history of breast or wvarian cace. These results suggest that a family history of endomertial cancer increases the risk of contracting the same disease. However, the proportion of cases attributable to this factor was small: less than 1%of endometrial cancers in this population were attributable to familial (and hence potentially genetic) factors. © 1994 Wiley-Liss, Inc.     

Tubal sterilization and the risk of endometrial cancer

Several animal and human studies suggest that tubal occlusion may curtail ovarian function, altering the production and balance of endogenous estrogens and progesterone, 2 hormones closely related to endometrial carcinogenesis. Despite this, and the increasing world-wide popularity of this method of contraception, little is known about its relationship with the risk of developing endometrial cancer. To assess whether tubal sterilization influences a woman's risk of developing epithelial endometrial carcinoma, data from a large multicenter population-based case-control study of endometrial cancer were analyzed. Cases were 437 women aged 20 to 54 years with histologically confirmed epithelial endometrial cancer ascertained through 6 population-based cancer registries in the United States. Controls were 3200 women selected at random from the populations of the areas from which the cases were detected. As compared with women who had never had tubal sterilization, women who had had this surgery had a crude odds ratio of 0.58 [95% confidence interval (CI), 0.43–0.78]. However, after adjusting for the combined confounding effects of age and parity, the magnitude of the protective association decreased to 0.87 (95% CI, 0.63–1.20). The magnitude of the protective effect did not significantly change with years since surgery or age at surgery. Although a modest, non-significant protective effect is suggested, these findings indicate that tubal sterilization does not substantially alter the risk of developing epithelial endometrial cancer in women 20 to 54 years of age. If there is an increase in risk, these data indicate that it is unlikely to be any greater than 20%. © 1996 Wiley-Liss, Inc.     

Genetic polymorphisms and endometrial cancer risk

For most sporadic cancers, genetic susceptibility results from the additive effect of multiple genetic variants, each of which contributes a modest risk individually. The study of genetic single nucleotide polymorphisms (SNPs) may help explain the differences in individual cancer susceptibility and may assist in identifying novel markers of risk that can be utilized to create more effective and tailored cancer prevention strategies. Genetic polymorphisms in functionally critical genes have been suggested as risk factors for the development of a variety of cancers, including endometrial cancer. Candidate SNPs may be involved in DNA damage repair, steroid metabolism, carcinogen metabolism, cell-cycle control, apoptosis and steroid receptor activation pathways. In this review, recent findings of genetic association studies exploring genetic polymorphisms and their association with endometrial cancer are reported. In addition, the challenges of genetic association studies, such as power and bias, and the need for validation of promising findings are explored.     

Organochlorines and endometrial cancer risk.

There is concern that persistent environmental pollutants such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) increase breast cancer risk, at least partially through estrogenic effects. Because the endometrium is more sensitive to estrogenic stimulation than the breast, such a carcinogenic effect should be more pronounced in the endometrium than the breast. In a population-based case-control study in Sweden, we measured serum concentrations of 10 chlorinated pesticides and 10 PCB congeners in 154 endometrial cancer cases and 205 population controls. Information on potential confounders was obtained by mailed questionnaires. We used logistic regression to calculate odds ratios (ORs) as measures of relative risk. We performed analyses for lipid-adjusted concentrations of each individual substance and after grouping substances according to putative hormonal effects. We found no significant associations of increasing levels of pesticide or PCB exposure with endometrial cancer risk. The multivariate OR was 1.0 (95% confidence interval, 0.6-2.0; P for trend, 0.78) for the highest compared with the lowest quartile of dichlorodiphenyldichloroethylene (DDE), the predominant dichlorodiphenyltrichloroethane metabolite. Corresponding ORs were 1.0 for hexachlorobenzene, 0.9 for beta-hexachlorocyclohexane, 1.4 for oxychlordane, and 1.2 for trans-nonachlor. Analyses of substances grouped by putative hormonal effect also showed no associations with endometrial cancer risk. For all estrogenic compounds, the OR for the highest compared with the lowest quartile was 1.1 (95% confidence interval, 0.6-2.2; P for trend, 0.90). Our data do not support the hypothesis that the organochlorine exposure studied increases the risk for endometrial cancer.     

Sleep duration and endometrial cancer risk

Purpose  

Recent data indicate that night shift work is associated with increased endometrial cancer risk, perhaps through a pathway involving lower melatonin production. Melatonin is an antiestrogenic hormone, with production in a circadian pattern that is dependent on presence of dark at night. Sleep duration is positively associated with melatonin production and may be an indicator of melatonin levels in epidemiologic studies.     

Metabolic syndrome and endometrial cancer risk

BackgroundVarious studies reported direct associations between endometrial cancer risk and individual components of the metabolic syndrome (MetS), i.e. obesity, diabetes, hypertension, and dyslipidemia, but only a few epidemiological studies considered the association with MetS overall.MethodsWe analyzed data from a case–control study including 454 women with incident endometrial cancer and 798 controls admitted to the same hospitals as cases for acute conditions. Different definitions of MetS were considered, including a combination of self-reported history of diabetes, drug-treated hypertension, drug-treated hyperlipidemia, and various measures of (central) obesity. Odds ratios (ORs) were computed from unconditional logistic regression models, adjusted for major confounding factors.ResultsThe multivariate ORs of endometrial cancer were 2.18 for type 2 diabetes, 1.77 for hypertension, 1.20 for hyperlipidemia, between 1.62 and 2.23 for various definitions of central obesity, and 3.83 for women with a body mass index (BMI) >30 kg/m². The risk of endometrial cancer was significantly increased for subjects with MetS, the ORs ranging between 1.67 and 2.77 when waist circumference was included in MetS definition, and 8.40 when BMI was considered instead.ConclusionsThis study indicates a direct association between various MetS components, besides overweight, with the risk of endometrial cancer.     

Genetic polymorphisms and endometrial cancer risk

For most sporadic cancers, genetic susceptibility results from the additive effect of multiple genetic variants, each of which contributes a modest risk individually. The study of genetic single nucleotide polymorphisms (SNPs) may help explain the differences in individual cancer susceptibility and may assist in identifying novel markers of risk that can be utilized to create more effective and tailored cancer prevention strategies. Genetic polymorphisms in functionally critical genes have been suggested as risk factors for the development of a variety of cancers, including endometrial cancer. Candidate SNPs may be involved in DNA damage repair, steroid metabolism, carcinogen metabolism, cell-cycle control, apoptosis and steroid receptor activation pathways. In this review, recent findings of genetic association studies exploring genetic polymorphisms and their association with endometrial cancer are reported. In addition, the challenges of genetic association studies, such as power and bias, and the need for validation of promising findings are explored.     

Circulating enterolactone and risk of endometrial cancer

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.     

Night shift work and the risk of endometrial cancer

Melatonin has several oncostatic properties, including possible anti-estrogenic and anti-aromatase activity, and seems to be linked with fat metabolism. Night workers have lower levels of melatonin, which may predispose them to develop cancer. Endometrial cancer risk is influenced significantly by hormonal and metabolic factors; therefore, we hypothesize that night workers may have an increased risk of endometrial cancer. Of the 121,701 women enrolled in a prospective cohort study, 53,487 women provided data on rotating night shift work in 1988 and were followed through on June 1, 2004. A total of 515 women developed medical record-confirmed invasive endometrial cancer. We used Cox regression models to calculate multivariate relative risks (MVRRs), controlling for endometrial cancer risk factors. Women who worked 20+ years of rotating night shifts had a significantly increased risk of endometrial cancer [MVRR, 1.47; 95% confidence interval (95% CI), 1.03-1.14]. In stratified analyses, obese women working rotating night shifts doubled their baseline risk of endometrial cancer (MVRR, 2.09; 95% CI, 1.24-3.52) compared with obese women who did no night work, whereas a nonsignificant increase was seen among non-obese women (MVRR, 1.07; 95% CI, 0.60-1.92). Women working rotating night shifts for a long duration have a significantly increased risk of endometrial cancer, particularly if they are obese. We speculate that this increased risk is attributable to the effects of melatonin on hormonal and metabolic factors. Our results add to growing literature that suggests women who work at night may benefit from cancer prevention strategies.     

Alcoholism and risk for endometrial cancer.

Endogenous estrogens increase the risk of endometrial cancer and are also elevated among women with high alcoholic intake. It is incompletely known, however, whether alcohol intake in general and alcohol abuse in particular increases risk for endometrial cancer. We thus analyzed prospectively the risk for endometrial cancer among 36,856 women hospitalized with alcoholism between 1965 and 1994 through linkages between several national Swedish registers. Compared with the general population, women who were alcoholics had an overall 24% lower risk of developing endometrial cancer, a finding challenging our a priori hypothesis. However, among women below the age of 50 years at follow-up, the mean age of menopause among Swedish women, the risk was 70% higher, whereas the risk among women aged 50 years or more at follow-up was 40% lower compared with the general population. Hence, the effect of alcoholism on endometrial cancer appears to be age dependent.     

Physical activity and risk of endometrial cancer: a report from the Shanghai endometrial cancer study.

We evaluated the type and amount of physical activity associated with risk of endometrial cancer. In this population-based case-control study, in-person interviews were completed among 832 incident endometrial cancer cases and 846 age-matched controls. Physical activity from exercise, household activities, and transportation was assessed in adolescence and adulthood, as was lifetime occupational activity. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence limits (95% CL). Women reporting exercise participation in both adolescence and adulthood were at nearly a 40% reduced risk (OR, 0.63; 95% CL, 0.42-0.95), compared with women reporting no exercise in either life period. Postmenopausal women who initiated exercise in adulthood were also at reduced risk (OR, 0.76; 95% CL, 0.56-1.02). Reductions in risk were also observed for common lifestyle activities, including household activity (both life periods) and walking for transportation (adulthood). Examination of the independent and combined effect of exercise and lifestyle activities revealed that women with less active lifestyles but who reported exercise were at 35% reduced risk (OR, 0.65; 95% CL, 0.41-1.02), whereas nonexercisers with more active lifestyles were at 40% to 45% reduced risk. These findings suggest that both lifestyle activities of lower intensity (e.g., walking and doing household chores) and intentional exercise can reduce endometrial cancer risk.     

Use of talcum powder and endometrial cancer risk

Purpose  

Use of talcum powder in the perineal area has been associated with an increased risk of ovarian cancer, and a recent cohort study found a positive association with endometrial cancer. We sought to confirm this association using data from the Australian National Endometrial Cancer Study (ANECS).