Alcohol consumption and endometrial cancer risk: the multiethnic cohort

The role of alcohol intake in the etiology of endometrial cancer is unclear. We examined the impact of alcohol intake on endometrial cancer risk among 41,574 postmenopausal African-American, Japanese-American, Latina, Native-Hawaiian and White women recruited to the prospective Multiethnic Cohort Study in 1993-1996. During an average of 8.3 years of follow-up, 324 incident invasive endometrial cancer cases were identified among these women. Data on alcohol intake and endometrial cancer risk factors were obtained from the baseline questionnaire. Relative risks (RRs) and 95% confidence intervals (CIs) for endometrial cancer associated with alcohol intake were estimated using log-linear (Cox) proportional hazard models stratified by age, year of recruitment, ethnicity and study center, and adjusted for several confounding factors. Increased alcohol consumption was associated with increased risk (p trend = 0.013). Compared to nondrinkers, women consuming >or=2 drinks/day had a multivariate RR of 2.01 (95% CI: 1.30, 3.11). There was no increase in risk associated with <1 drink/day (RR = 1.01; 95% CI: 0.77, 1.33) and 1 to <2 drinks/day (RR = 1.09; 95% CI: 0.62, 1.93). There was no clear effect modification by body mass index, postmenopausal hormone use, parity, oral contraceptive use or smoking status, though our power to detect such interactions was limited. Our results suggest that only alcohol consumption equivalent to 2 or more drinks per day increases risk of endometrial cancer in postmenopausal women.     

Haplotypes of the estrogen receptor beta gene and breast cancer risk

Exposure to exogenous (oral contraceptives, postmenopausal hormone therapy) and endogenous (number of ovulatory cycles, adiposity) steroid hormones is associated with breast cancer risk. Breast cancer risk associated with these exposures could hypothetically be modified by genes in the steroid hormone synthesis, metabolism and signaling pathways. Estrogen receptors are the first step along the path of signaling cell growth and development upon stimulation with estrogens. The National Cancer Institute Breast and Prostate Cancer Cohort Consortium has systematically selected haplotype tagging SNPs in genes along the steroid hormone synthesis, metabolism and binding pathways, including the estrogen receptor beta (ESR2) gene. Four htSNPs tag the 6 major (>5% frequency) haplotypes of the ESR2 gene. These polymorphisms have been genotyped in 5,789 breast cancer cases and 7,761 controls nested within the American Cancer Society Cancer Prevention Study II, European Prospective Investigation into Cancer and Nutrition, Multiethnic Cohort, Nurses' Health Study and Women's Health Study cohorts. None of the SNPs were independently associated with breast cancer risk. One haplotype of the ESR2 gene was associated with breast cancer risk before correction for multiple testing (OR 1.17, 95% CI 1.07-1.28, p = 0.0007). This haplotype remained associated with breast cancer risk after adjustment for multiple testing using a permutation procedure. There was no statistically significant heterogeneity in SNP or haplotype odds ratios across cohorts. These data suggest that inherited variants in ESR2 (while possibly conferring a small increased risk of breast cancer) are not associated with appreciable (OR > 1.2) changes in breast cancer risk among Caucasian women.     

Lifestyle determinants of 5alpha-reductase metabolites in older African-American, white, and Asian-American men.

Men with higher endogenous 5alpha-reductase activity may have higher prostate cancer risk. This hypothesis raises two questions: (a) Could racial differences in 5alpha-reductase activity explain the observed racial differences in prostate cancer risk? and (b) Could a man reduce his activity level by modifying his lifestyle? To address these questions, we measured two hormonal indices of 5alpha-reductase activity [serum levels of androstane-3alpha-17beta-diol glucuronide (3alpha-diol G) and androsterone glucuronide (AG)] in healthy, older African-American, white, and Asian-American men, who are at high, intermediate, and low prostate cancer risk, respectively. We also examined associations between these metabolite levels and such lifestyle characteristics as body size and physical activity as well as select aspects of medical history and family history of prostate cancer. Men included in this cross-sectional analysis (n = 1054) had served as control subjects in a population-based case-control study of prostate cancer we conducted in California, Hawaii, and Vancouver, Canada and provided information on certain personal attributes and donated blood between March 1990 and March 1992. In this study, concentrations of 3alpha-diol G declined significantly with age and increased significantly with body mass index. Mean levels of 3alpha-diol G, adjusted for age and body mass index, were 6.1 ng/ml in African-Americans, 6.9 ng/ml in whites and 4.8 ng/ml in Asian-Americans. These differences were statistically significant (African-Americans versus whites: P < 0.01; whites versus Asian-Americans: P < 0.001). Concentrations of AG decreased significantly with age, but only in whites, and were unrelated to any of the reported personal attributes. Mean levels of AG, adjusted for age, were 44.1 ng/ml in African-Americans, 44.9 ng/ml in whites, and 37.5 ng/ml in Asian-Americans (Asian-Americans versus whites, P < 0.001). In conclusion, older African-American and white men have similar levels of these two indices of 5alpha-reductase activity, and these levels are higher than those of older Asian-American men. This difference may be related to the lower prostate cancer risk in Asian-Americans.     

Association of vegetable, fruit, and grain intakes with colorectal cancer: the Multiethnic Cohort Study

BACKGROUND: It is uncertain whether or not vegetables, fruit, or grains protect against colorectal cancer. OBJECTIVE: In a large prospective study, we investigated the association of vegetable, fruit, and grain intakes with colorectal cancer risk. DESIGN: Between 1993 and 1996, 85 903 men and 105 108 women completed a quantitative food-frequency questionnaire that included approximately 180 foods and beverages in the Multiethnic Cohort Study. A diagnosis of colorectal cancer was made in 1138 men and 972 women after an average follow-up of 7.3 y. Cox proportional hazards models were used to calculate multivariate-adjusted relative risks and 95% CIs for colorectal cancer. RESULTS: In men, multivariate adjustment for energy intake, dietary, and nondietary variables resulted in relative risks in the highest quintile group of 0.74 (95% CI: 0.59, 0.93; P for trend = 0.02) for vegetables and fruit combined, 0.80 (95% CI: 0.64, 0.99; P for trend = 0.09) for fruit alone, and 0.85 (95% CI: 0.69, 1.05; P for trend = 0.05) for vegetables alone. When colon and rectal cases were separated among men, the inverse associations were stronger for colon than for rectal cancer. In women, none of the associations with vegetables, fruit, or vegetables and fruit combined were significant. Grain intake was not associated with colorectal cancer for either men or women. CONCLUSION: The intake of vegetables and fruit was inversely related to colorectal cancer risk among men but not among women. The association appears stronger for colon than for rectal cancer.     

A pooled analysis of case-control studies of thyroid cancer¶ I. Methods

Objective: Because the etiology of thyroid cancer is not well described, we conducted a pooled analysis of all published case- control studies, as well as two identified unpublished studies. This paper describes the major characteristics of the 14 studies included in the analysis, as well as the statistical methods employed. Four studies were conducted in the United States (1 each in Washington State, California, Connecticut and Hawaii), 8 in Europe (3 in Sweden, 2 in Norway, 1 in Switzerland, 1 in Italy and 1 in Greece), and 2 in Asia (1 in China and 1 in Japan).Methods: The original datasets were obtained and restructured in a uniform format. Data on socio-demographic characteristics, anthropometric measures, smoking and alcohol consumption, history of benign thyroid diseases and of other selected medical conditions and treatments, family history of cancer and of benign thyroid conditions, occupation, residence in endemic goitre areas, and dietary habits were analyzed. For women, we also analyzed menstrual and reproductive factors and use of female hormones. Radiotherapy and, in Japan, exposure to the A-bombs were considered as potential confounding factors.Results: A total of 2,725 cases (2,247 females and 478 males) and 4,776 controls (3,699 females and 1,077 males) were included in this study. Of the cases, 79% were classified as papillary thyroid carcinomas, 14% as follicular, 2% medullary, 1% anaplastic, 1% other histologies, and 3% histological type unknown. Each of the datasets was checked for outliers and consistency. Data were analysed separately by study center, gender, and the two major histologic types (papillary, follicular). Frequency tables and simple statistics were computed for each variable under study. Conditional logistic regression was used to compute odds ratios. For matched studies, the original matching was preserved, whereas, for unmatched ones, five-year age groups were used for matching. Study-specific analyses were computed, and then the data from all the studies were pooled conditioning on study. Heterogeneity between studies, geographic areas and study designs was assessed, and the modifying effect of age was also evaluated.     

Association between breast cancer susceptibility loci and mammographic density: the Multiethnic Cohort

Introduction  

Mammographic density is a strong risk factor for breast cancer. Our objective was to examine its association with polymorphisms identifying breast cancer susceptibility loci that were ascertained in recent genome-wide association studies.     

Trends in birth defects for a Hawaiian population exposed to heptachlor and for the United States

The 1980-1982 milk supply contamination on the island of Oahu, Hawaii, by the insecticide heptachlor offered an opportunity to investigate the possible human teratogenicity of this organochlorine. An analysis of incidence rates for 23 major congenital malformations, derived from hospital-generated data collected by the Birth Defects Monitoring Program of the Centers for Disease Control, failed to show any remarkable rate increase on Oahu in 1981-1983, based on comparisons with the rates for previous time periods on this island and with the rates for two unexposed populations (the other Hawaiian islands and the total U.S.). A rise in the rates of cardiovascular malformations and hip dislocation was apparent but antedated the exposure. These results suggest that no major rate increase for malformations recognized at birth resulted from the heptachlor contamination on Oahu. However, misclassification of exposure status in this study may have obscured a more moderate effect.     

Breast cancer survival among Hawaii Japanese and Caucasian women. Ten-year rates and survival by place of birth

Unlike past breast cancer survival comparisons between Japan and the United States, a recent study in Hawaii showed that Japanese women did not retain their survival advantage over Caucasian women after adjustment was made for stage at diagnosis. To test whether this finding in Hawaii was due to the limited duration of the follow-up (five years) or to the effects of migration, the survival experience of 1,357 Caucasian and 1,029 Japanese women with invasive breast carcinoma diagnosed in Hawaii between 1960 and 1979 was examined over a 10-year period as well as by place of birth. Multivariate adjustment by the proportional hazards regression model confirmed that the survival advantage of Japanese women in Hawaii is fully explained by their earlier stage of disease at diagnosis and suggested that, after recognition, the disease progresses at a similar pace in the two races. The survival comparison by place of birth revealed that second generation Hawaii Japanese women had better breast cancer survival rates than Japanese migrants from Japan, even after adjusting for stage, and that for Caucasian women, nativity was not associated with survival. These findings suggest that westernization, genetic constitution, or early life exposures cannot explain the overall or stage-adjusted breast cancer survival patterns observed among Caucasian and Japanese women in Hawaii.