Infertility and incident endometrial cancer risk: a pooled analysis from the epidemiology of endometrial cancer consortium (E2C2).

BACKGROUND: Nulliparity is an endometrial cancer risk factor, but whether or not this association is due to infertility is unclear. Although there are many underlying infertility causes, few studies have assessed risk relations by specific causes. METHODS: We conducted a pooled analysis of 8153 cases and 11 713 controls from 2 cohort and 12 case-control studies. All studies provided self-reported infertility and its causes, except for one study that relied on data from national registries. Logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Nulliparous women had an elevated endometrial cancer risk compared with parous women, even after adjusting for infertility (OR=1.76; 95% CI: 1.59-1.94). Women who reported infertility had an increased risk compared with those without infertility concerns, even after adjusting for nulliparity (OR=1.22; 95% CI: 1.13-1.33). Among women who reported infertility, none of the individual infertility causes were substantially related to endometrial cancer. CONCLUSIONS: Based on mainly self-reported infertility data that used study-specific definitions of infertility, nulliparity and infertility appeared to independently contribute to endometrial cancer risk. Understanding residual endometrial cancer risk related to infertility, its causes and its treatments may benefit from large studies involving detailed data on various infertility parameters.

The etiology of uterine sarcomas: a pooled analysis of the epidemiology of endometrial cancer consortium.

BACKGROUND: Uterine sarcomas are characterised by early age at diagnosis, poor prognosis, and higher incidence among Black compared with White women, but their aetiology is poorly understood. Therefore, we performed a pooled analysis of data collected in the Epidemiology of Endometrial Cancer Consortium. We also examined risk factor associations for malignant mixed mullerian tumours (MMMTs) and endometrioid endometrial carcinomas (EECs) for comparison purposes. METHODS: We pooled data on 229 uterine sarcomas, 244 MMMTs, 7623 EEC cases, and 28,829 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for risk factors associated with uterine sarcoma, MMMT, and EEC were estimated with polytomous logistic regression. We also examined associations between epidemiological factors and histological subtypes of uterine sarcoma. RESULTS: Significant risk factors for uterine sarcoma included obesity (body mass index (BMI)≥30 vs BMI<25 kg m(-2) (OR: 1.73, 95% CI: 1.22-2.46), P-trend=0.008) and history of diabetes (OR: 2.33, 95% CI: 1.41-3.83). Older age at menarche was inversely associated with uterine sarcoma risk (≥15 years vs <11 years (OR: 0.70, 95% CI: 0.34-1.44), P-trend: 0.04). BMI was significantly, but less strongly related to uterine sarcomas compared with EECs (OR: 3.03, 95% CI: 2.82-3.26) or MMMTs (OR: 2.25, 95% CI: 1.60-3.15, P-heterogeneity=0.01). CONCLUSION: In the largest aetiological study of uterine sarcomas, associations between menstrual, hormonal, and anthropometric risk factors and uterine sarcoma were similar to those identified for EEC. Further exploration of factors that might explain patterns of age- and race-specific incidence rates for uterine sarcoma are needed.

Colorectal cancer following tamoxifen therapy for breast cancer (United States).

BACKGROUND: An analysis combining data from several clinical trials has raised concern that tamoxifen therapy may increase the risk of a subsequent colorectal malignancy. We conducted a nested case-control study to test this hypothesis. METHODS: A cohort of women diagnosed with breast cancer in 1978-1992 was identified from the western Washington population-based cancer registry. Cases included women who subsequently developed colorectal cancer prior to 1995. Controls were a random sample of the cohort who did not develop a second primary malignancy, matched to cases on age, stage, and year of initial cancer diagnosis. Tamoxifen use was ascertained by medical record abstraction and physician questionnaires. RESULTS: Thirty-six percent of the 122 cases for whom information could be obtained received tamoxifen versus 38% of 194 controls. Relative to non-users and adjusted for receipt of other therapies, there was no increased risk of colorectal cancer associated with tamoxifen use in general (matched odds ratio [mOR] = 0.9, 95% CI 0.6-1.6), longer durations of use (for > or =37 months, mOR = 0.8, 95% CI 0.4-1.9), higher cumulative doses of therapy (for > or =15 g, mOR = 0.8, 95% CI 0.4-1.6), or use that started at least 5 years prior to the end of study follow-up (mOR = 1.1, 95% CI 0.3-3.7). CONCLUSIONS: We found no overall increased risk for colorectal cancer among tamoxifen users.

Changes in the phospholipid composition of the arterial cell can result in severe atherosclerotic lesions.

The oxysterol concentration in the plasma and the phospholipid composition of vascular tissue obtained by coronary artery bypass grafting (CABG) were compared with plasma and vascular tissue from age and sex matched controls. The plasma from CABG patients had a higher concentration of oxysterols than was present in the controls. Human endothelial cells were cultured for 72 hours in a medium containing plasma obtained from CABG patients, from controls or from the same controls to which 5 oxysterols were added to make the total oxysterol level equivalent to that in the CABG plasma and then pulsed with calcium (45Ca(2+)) for one hr. A significantly higher influx of 45Ca(2+) was noted in the endothelial cells cultured in the plasma obtained from CABG patients and from the controls with 5 added oxysterols, but not in those cultured without added oxysterols indicating that oxysterols increased calcium influx into endothelial cells. A phospholipid analysis indicated that the arterial tissue from CABG patients had 48.2% sphingomyelin in its phospholipid fraction compared to 10% in arterial tissue from umbilical cords. The saphenous vein obtained during CABG surgery from the same patient had only 24% sphingomyelin in its phospholipid fraction and unlike the coronary arteries had no atherosclerotic lesions. The higher level of oxysterol in the plasma of patients suffering from severe atherosclerosis could increase the concentration of sphingomyelin in the arterial cell membrane and thereby increase calcium influx required for producing the calcific type VII lesions in the coronary arteries.

Adolescent addiction and delinquency in the family system.

Drug abuse and delinquent behavior in adolescents have been closely linked in the literature. It is possible that these links are not causal, but rather covariates of the common factor of family. This paper seeks to examine the behaviors of addiction and delinquency within the framework of family systems theory.

Multiple births and risk of epithelial ovarian cancer.

BACKGROUND AND METHODS: Prevailing hypotheses about the causes of ovarian carcinogenesis predict that women with a history of multiple births (twins, triplets, etc.) should be at increased risk of epithelial ovarian cancer. However, the scant available evidence suggests that they may actually be at lower risk. To resolve this issue, we pooled data from eight studies involving 2859 parous women with epithelial ovarian cancer (case patients) and 7434 parous women without ovarian cancer (control women). In addition to assessing their history of multiple births (and the sex of the children, where available), we obtained information on age, parity, oral contraceptive use, and other reproductive factors for each woman. Details of tumor histology were available for all case patients. We estimated the relative risks of various histologic types of ovarian cancers associated with multiple births by using multivariable logistic regression analysis, adjusting for matching and confounding variables. RESULTS: Among these parous women, 73 case patients (2. 6%) and 257 control women (3.5%) had a history of multiple births. The adjusted summary odds ratio (OR) for developing all types of epithelial ovarian cancer that are associated with multiple births was 0.81 (95% confidence interval [CI] = 0.61-1.08). We found no evidence that risks associated with multiple births differed among women with borderline or invasive tumors and among women with same-sex and opposite-sex offspring from multiple births. The risk reductions appeared specific for nonmucinous tumors (n = 2453; summary adjusted OR = 0.71 [95% CI = 0.52-0.98]); in contrast, associations with mucinous tumors (n = 406) were heterogeneous across studies. CONCLUSIONS: Parous women with nonmucinous ovarian cancer are no more likely to have a history of multiple births than other parous women, counter to the predictions of current hypotheses for causes of ovarian cancer.

Colorectal cancer incidence in Asian migrants to the United States and their descendants.

OBJECTIVES: To examine the incidence of colorectal cancer among Asian residents of the United States according to country of birth. METHODS: We determined the incidence of colorectal cancer during 1973-1986 among Asian residents in three areas of the western United States (Hawaii, San Francisco/Oakland SMSA, and western Washington state) in relation to country of birth. Numerators for the rates were obtained from the Surveillance, Epidemiology and End Results (SEER) program; a special tabulation of the 1980 US Census was used to estimate the size and composition of the population at risk. RESULTS: US-born Japanese men experienced incidence rates of colorectal cancer twice as high as foreign-born Japanese men and about 60% higher than those of US-born white men. Incidence among US-born Japanese women was about 40% higher than that among Japanese women born in Japan or US-born white women. Foreign-born Chinese men had about the same incidence of colorectal cancer as US-born white men, while US-born Chinese men experienced slightly reduced rates. Chinese women had rates that were generally 30-40% lower than that of US-born white women, regardless of place of birth. Incidence rates for both US-born and foreign-born Filipinos were 20-50% those of US-born whites. CONCLUSIONS: These findings suggest that one or more exposures or characteristics that differ between Japanese migrants and their descendants affect the development of colorectal cancer.

A simple case of anemia: pathophysiology of a common symptom.

Anemia is a common symptom associated with a variety of diseases, disorders, and dietary deficiencies. A review of hemoglobin and hematocrit levels may not be sufficient to determine the severity of the underlying problem. This article gives the reader an enhanced understanding of red cell morphology and reviews some of the common problems associated with anemia.

Reproductive risk factors for mucinous and non-mucinous epithelial ovarian cancer.

We evaluated reproductive risk factors for mucinous and non-mucinous tumors in a population-based case-control study of epithelial ovarian cancer among women ages 20-79 years. We observed a reduction in risk of tumors of both types in association with one or more full-term pregnancies and with use of oral contraceptives for 5 or more years. While findings of some previous studies support the hypothesis that certain aspects of a woman's reproductive life have a different impact on the risk of these subtypes of ovarian epithelial cancer, our data suggest that this issue is not yet resolved.

Incidence of testicular cancer in the United States: has the epidemic begun to abate?

In response to a report that testicular cancer incidence in non-Hispanic White males in Los Angeles county had fallen in the 1990s, particularly in young men, the authors analyzed data collected by the Surveillance, Epidemiology, and End Results (SEER) program from 1973 to 1995. While the incidence rate of testicular cancer in US White males ages 15-64 years did stabilize in the first half of the 1990s, after a number of years of a steady increase, there was no indication of an actual decline.

Logistic regression analysis for more than one characteristic of exposure.

When more than one characteristic of an exposure is under study, it is easy to misinterpret the results of a logistic regression analysis that incorporates terms for each characteristic. For example, in a study of the risk of endometrial cancer in relation to the duration and the recency of use of estrogen replacement therapy (ERT), simultaneously including terms for duration and recency of exposure to ERT in a logistic model may leave the mistaken impression that it is possible to adjust for recency when a given duration of ERT use is compared with no use. In this article, the authors show why such an adjusted comparison is impossible, and they discuss several pitfalls in the interpretation of logistic regression coefficients when two or more characteristics of exposure are under study. They also suggest a method for avoiding these pitfalls.

The incidence of gastric carcinoma in Asian migrants to the United States and their descendants.

OBJECTIVES: We examined the incidence of gastric carcinoma in Chinese, Japanese, and Filipino residents of the United States to obtain additional information about the etiology of this disease. METHODS: The age, race, and birthplace of residents of Hawaii, San Francisco/Oakland, and northwestern Washington who were diagnosed with gastric carcinoma during the period 1973-1986 were obtained from population-based registries, and a special tabulation from the 1980 Census was used to estimate the number of person-years at risk for each category of resident. RESULTS: The incidence of gastric carcinoma in Japanese-Americans was three to six times higher than that of US-born whites, with the highest rates occurring in those persons born in Japan. The rate in US-born Chinese and Chinese men who immigrated to the US was similar to that of whites, whereas the rate in Chinese female migrants was twice that of white American women. Filipino men, regardless of birthplace, were only at 60% the risk of US-born white men, while their female counterparts had a rate very similar to that of US-born white women. The high incidence observed among Japanese-Americans and Chinese female immigrants was largely restricted to sites other than the gastric cardia. CONCLUSIONS: Our findings suggest that dietary and other lifestyle differences between the different generations of Japanese-Americans, and between Japanese residents of the US and Japan may provide clues regarding the etiologies of stomach cancers that arise beyond the gastric cardia.

CYP2D6 genotype and the incidence of anal and vulvar cancer.

The risks of anal and vulvar cancer are strongly related to cigarette smoking. Smokers are exposed to a substantial quantity of tobacco-specific nitrosamines, including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK is present in the mucus of the female genital tract. The enzyme debrisoquine 4-hydroxylase (CYP2D6) activates NNK and is present in foreskin kerotinocytes and cervical epithelial cells. A polymorphism for the gene CYP2D6 exists, and persons who possess alleles that are associated with reduced levels of CYP2D6 activity might be expected to be at a relatively lower risk of cancers arising from NNK exposure. To test this hypothesis, we conducted a case-control study to examine the association of CYP2D6 genotype and the incidence of anal and vulvar cancer among cigarette smokers in western Washington State. We tested for 14 alleles (*1-*12, *14, and *17) among cases (25 men and 43 women with anal cancer, 64 women with vulvar cancer) and controls (30 men and 110 women). Contrary to the hypothesis, cases were not less likely than controls to have one (43.9 versus 40.7%) or two (6.8 versus 4.3%) inactivating alleles (*3, *4, *5, *6, *7, *8, *11, or *12). There was a suggestion that, if anything, the combined anal and vulvar cancer risk increased (rather than decreased) with an increasing number of CYP2D6 inactivation alleles: odds ratio = 1.2, 95% confidence interval = 0.7-2.0 with one inactivating allele; odds ratio = 1.8, 95% confidence interval = 0.6-5.4 with two inactivating alleles. These results provide no support for the hypothesis that cigarette smokers who carry the CYP2D6 alleles that result in a low activity phenotype have a decreased risk of anogenital cancer.

Incidence of adenocarcinoma of the prostate in Asian immigrants to the United States and their descendants.

PURPOSE: We characterize the incidence of adenocarcinoma of the prostate among Chinese, Japanese and Filipino immigrants to the United States and their descendants. MATERIALS AND METHODS: Subjects included 1,511 Asian and 16,000 white residents of Hawaii, San Francisco/Oakland and western Washington diagnosed with primary adenocarcinoma of the prostate during 1973 through 1986, and identified from the Surveillance, Epidemiology and End Results program. The size and composition of the population at risk were provided by a special tabulation of the 1980 United States Census. RESULTS: Among Asian-Americans 45 to 69 years old the annual rate per 100,000 for Chinese (24.0), Japanese (29.6) and Filipino (56.8) men born in China, Japan and the Philippines, respectively, was approximately half that of United States born Chinese, Japanese and Filipino men (44.4, 42.2 and 111.3, respectively). For Japanese Americans 70 to 84 years old at diagnosis differences in incidence persisted between those born in Japan (238.0) and the United States (446.4), while for older Chinese Americans incidence rates were nearly the same for those born in China (428.3) and the United States (425.0). In contrast, older Filipino men born in the Philippines had a higher rate (400.1) than their United States born counterparts (264.9) but the latter rate was based on a small number of men. Among United States residents the annual incidence for all generations of Asian-Americans was roughly half that of white men born in the United States (215.9). CONCLUSIONS: These results suggest that, irrespective of birthplace or age, Asian-American men retain 1 or more genetic or lifestyle characteristics that make their risk of prostate cancer less than that of white residents of the United States.

Hair product use and the risk of breast cancer in young women.

OBJECTIVES: The reported mutagenic and carcinogenic effects of some chemicals present in hair dyes have raised concern that hair dye use could increase breast cancer risk. This case-control study evaluated how detailed aspects of hair coloring and hair spray application by reproductive-age women may affect breast cancer risk. METHODS: Cases were white female residents of three counties of western Washington state 45 years of age or less, who were diagnosed with breast cancer between 1983 and 1990 (n = 844). A sample of similarly aged women residing in the same counties served as controls (n = 960). Information on hair coloring and hair spray use, as well as other exposures, was ascertained during in-person interviews. RESULTS: Breast cancer cases were slightly more likely than controls to report ever having used some type of hair coloring application, including use of rinses, semi-permanent or permanent dyes, as well as bleaching then dyeing or frosting their hair (relative risk [RR] = 1.3, 95% CI = 1.0-1.6, adjusted for age, fullterm pregnancies, family history of breast cancer, and weight). In subgroup analyses, women with exclusive use of just one of these methods of hair coloring application had no elevation in risk (similarly adjusted RR = 1.1, 95% CI = 0.9-1.3), whereas women who used two or more of these methods did have an elevated risk (RR = 1.9, 95% CI = 1.4-2.5). Hair spray use was not related to the risk of breast cancer (ever versus never users: RR = 1.0, 95% CI = 0.8- 1.3). CONCLUSION: The lack of an association between exclusive use of a single type of hair coloring application and breast cancer risk argues that hair coloring application does not influence breast cancer risk among reproductive-age women. Thus, the results of the present study, as well as negative ones from most (but not all) prior studies, are most consistent with the conclusion that neither hair coloring application nor hair spray application influences breast cancer risk.

1-Methoxy-agroclavine from Penicillium sp. WC75209, a novel inhibitor of the Lck tyrosine kinase.

A high-throughput screen was developed and implemented to identify inhibitors of the Lck tyrosine kinase. This report describes the identification of a specific inhibitor of this enzyme from the solid fermentation culture of the Penicillium sp., WC75209. The active compound was isolated and structurally characterized as 1-methoxy-5R, 10S-agroclavine, a new member of the ergot alkaloid family.

Characteristics of women with and without breast augmentation.

OBJECTIVE: To compare selected characteristics of women with and without augmentation mammaplasty to identify differences between these 2 groups of women. DESIGN AND STUDY PARTICIPANTS: White women identified as controls in previously conducted population-based, case-control studies formed the study population for the present cross-sectional analysis (N=3570). MAIN OUTCOME MEASURE: Interview information on selected characteristics was compared between women who had received augmentation mammaplasty (n=80) and other women (n=3490) using the prevalence odds ratio (pOR) as the measure of association. RESULTS: Women with breast implants were more likely to drink a greater average number of alcoholic drinks per week (for > or =7 drinks vs 0 drinks: pOR=2.9, 95% confidence interval [CI]=1.5-5.5), be younger at first pregnancy (for age <20 years vs age 20-29 years: pOR=1.6, 95% CI=1.0-2.7), be younger at first birth (for age <20 years vs age 20-29 years: pOR=1.9, 95% C1=1.1-3.3), have a history of terminated pregnancies (for > or =1 termination vs 0 terminations: pOR=2.0, 95% CI=1.2-3.4), have ever used oral contraceptives (pOR=2.2, 95% CI=1.0-4.7), have ever used hair dyes (pOR=4.5, 95% CI=1.3-15.4), and have had a greater lifetime number of sexual partners (for > or =14 partners vs < or =4 partners: pOR=8.9, 95% CI=3.1-25.5) than other women. A history of smoking, lactation, high blood pressure, or thyroid disorders, as well as the number of pregnancies, full-term births, or miscarriages, differed little between women with and without implants. Women with breast augmentation were much less likely to be heavy than other women (for > or =74 kg vs <56 kg: pOR=0.1, 95% CI=0.03-0.3). CONCLUSION: The differences we found between women with and without breast implants suggest that consideration and evaluation of confounding factors in future studies will help to clarify some of the long-term health consequences of having breast implants.