Measures of body fatness and height in early and mid-to-late adulthood and prostate cancer: risk and mortality in The Pooling Project of Prospective Studies of Diet and Cancer.

BACKGROUND: Advanced prostate cancer etiology is poorly understood. Few studies have examined associations of anthropometric factors (e.g. early adulthood obesity) with advanced prostate cancer risk. PATIENTS AND METHODS: We carried out pooled analyses to examine associations between body fatness, height, and prostate cancer risk. Among 830 772 men, 51 734 incident prostate cancer cases were identified, including 4762 advanced (T4/N1/M1 or prostate cancer deaths) cases, 2915 advanced restricted (same as advanced, but excluding localized cancers that resulted in death) cases, 9489 high-grade cases, and 3027 prostate cancer deaths. Cox proportional hazards models were used to calculate study-specific hazard ratios (HR) and 95% confidence intervals (CI); results were pooled using random effects models. RESULTS: No statistically significant associations were observed for body mass index (BMI) in early adulthood for advanced, advanced restricted, and high-grade prostate cancer, and prostate cancer mortality. Positive associations were shown for BMI at baseline with advanced prostate cancer (HR = 1.30, 95% CI = 0.95-1.78) and prostate cancer mortality (HR = 1.52, 95% CI = 1.12-2.07) comparing BMI ≥35.0 kg/m2 with 21-22.9 kg/m2. When considering early adulthood and baseline BMI together, a 27% higher prostate cancer mortality risk (95% CI = 9% to 49%) was observed for men with BMI <25.0 kg/m2 in early adulthood and BMI ≥30.0 kg/m2 at baseline compared with BMI <25.0 kg/m2 in early adulthood and BMI <30.0 kg/m2 at baseline. Baseline waist circumference, comparing ≥110 cm with <90 cm, and waist-to-hip ratio, comparing ≥1.00 with <0.90, were associated with significant 14%-16% increases in high-grade prostate cancer risk and suggestive or significant 20%-39% increases in prostate cancer mortality risk. Height was associated with suggestive or significant 33%-56% risks of advanced or advanced restricted prostate cancer and prostate cancer mortality, comparing ≥1.90 m with <1.65 m. CONCLUSION: Our findings suggest that height and total and central adiposity in mid-to-later adulthood, but not early adulthood adiposity, are associated with risk of advanced forms of prostate cancer. Thus, maintenance of healthy weight may help prevent advanced prostate cancer.

Cancer deaths and cases attributable to lifestyle factors and infections in China, 2013.

BACKGROUND: The burden of cancer in China is high, and it is expected to further increase. Information on cancers attributable to potentially modifiable risk factors is essential in planning preventive measures against cancer. We estimated the number and proportion of cancer deaths and cases attributable to ever-smoking, second-hand smoking, alcohol drinking, low fruit/vegetable intake, excess body weight, physical inactivity, and infections in China, using contemporary data from nationally representative surveys and cancer registries. METHODS: The number of cancer deaths and cases in 2013 were obtained from the National Central Cancer Registry of China and data on most exposures were obtained from the China National Nutrition and Health Survey 2002 or 2006 and Global Adult Tobacco Smoking 2010. We used a bootstrap simulation method to calculate the number and proportion of cancer deaths and cases attributable to risk factors and their corresponding 95% confidence intervals (CIs), allowing for uncertainty in data. RESULTS: Approximately 718 000 (95% CI 702 100-732 200) cancer deaths in men and 283 100 (278 800-288 800) cancer deaths in women were attributable to the studied risk factors, accounting for 52% of all cancer deaths in men and 35% in women. The numbers for incident cancer cases were 952 500 (95% CI 934 200-971 400) in men and 442 700 (437 200-447 900) in women, accounting for 47% of all incident cases in men and 28% in women. The greatest proportions of cancer deaths attributable to risk factors were for smoking (26%), HBV infection (12%), and low fruit/vegetable intake (7%) in men and HBV infection (7%), low fruit/vegetable intake (6%), and second-hand smoking (5%) in women. CONCLUSIONS: Effective public health interventions to eliminate or reduce exposure from these risk factors, notably tobacco control and vaccinations against carcinogenic infections, can have considerable impact on reducing the cancer burden in China.

Central adiposity, obesity during early adulthood, and pancreatic cancer mortality in a pooled analysis of cohort studies.

BACKGROUND: Body mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk. DESIGN: We conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18-21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. RESULTS: Higher waist-to-hip ratio (HR = 1.09, 95% CI 1.02-1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00-1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11-1.25 per 5 kg/m(2)), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m(2), HR = 1.36, 95% CI 1.20-1.55 for BMI 25.0 < 27.5 kg/m(2), HR = 1.48, 95% CI 1.20-1.84 for BMI 27.5 to <30 kg/m(2), HR = 1.43, 95% CI 1.11-1.85 for BMI ≥30 kg/m(2)). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01-1.10 per 5 kg/m(2)). CONCLUSIONS: Our results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.

Reproductive factors, exogenous hormone use and risk of hepatocellular carcinoma among US women: results from the Liver Cancer Pooling Project.

BACKGROUND: Hepatocellular carcinoma (HCC) occurs less commonly among women than men in almost all regions of the world. The disparity in risk is particularly notable prior to menopause suggesting that hormonal exposures during reproductive life may be protective. Exogenous oestrogenic exposures such as oral contraceptives (OCs), however, have been reported to increase risk, suggesting that estrogens may be hepatocarcinogenic. To examine the effects of reproductive factors and exogenous hormones on risk, we conducted a prospective analysis among a large group of US women. METHODS: In the Liver Cancer Pooling Project, a consortium of US-based cohort studies, data from 799,500 women in 11 cohorts were pooled and harmonised. Cox proportional hazards regression models were used to generate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations of reproductive factors and exogenous hormones with HCC (n=248). RESULTS: Bilateral oophorectomy was associated with a significantly increased risk of HCC (HR=2.67, 95% CI=1.22-5.85), which did not appear to be related to a shorter duration of exposure to endogenous hormones or to menopausal hormone therapy use. There was no association between OC use and HCC (HR=1.12, 95% CI=0.82-1.55). Nor were there associations with parity, age at first birth, age at natural menopause, or duration of fertility. CONCLUSIONS: The current study suggests that bilateral oophorectomy increases the risk of HCC but the explanation for the association is unclear. There was no association between OC use and HCC risk. Examination of endogenous hormone levels in relation to HCC may help to clarify the findings of the current study.

Steroid hormone measurements from different types of assays in relation to body mass index and breast cancer risk in postmenopausal women: Reanalysis of eighteen prospective studies.

Epidemiological studies have examined breast cancer risk in relation to sex hormone concentrations measured by different methods: "extraction" immunoassays (with prior purification by organic solvent extraction, with or without column chromatography), "direct" immunoassays (no prior extraction or column chromatography), and more recently with mass spectrometry-based assays. We describe the associations of estradiol, estrone and testosterone with both body mass index and breast cancer risk in postmenopausal women according to assay method, using data from a collaborative pooled analysis of 18 prospective studies. In general, hormone concentrations were highest in studies that used direct assays and lowest in studies that used mass spectrometry-based assays. Estradiol and estrone were strongly positively associated with body mass index, regardless of the assay method; testosterone was positively associated with body mass index for direct assays, but less clearly for extraction assays, and there were few data for mass spectrometry assays. The correlations of estradiol with body mass index, estrone and testosterone were lower for direct assays than for extraction and mass spectrometry assays, suggesting that the estimates from the direct assays were less precise. For breast cancer risk, all three hormones were strongly positively associated with risk regardless of assay method (except for testosterone by mass spectrometry where there were few data), with no statistically significant differences in the trends, but differences may emerge as new data accumulate. Future epidemiological and clinical research studies should continue to use the most accurate assays that are feasible within the design characteristics of each study.

Dairy products and pancreatic cancer risk: a pooled analysis of 14 cohort studies.

Pancreatic cancer has few early symptoms, is usually diagnosed at late stages, and has a high case-fatality rate. Identifying modifiable risk factors is crucial to reducing pancreatic cancer morbidity and mortality. Prior studies have suggested that specific foods and nutrients, such as dairy products and constituents, may play a role in pancreatic carcinogenesis. In this pooled analysis of the primary data from 14 prospective cohort studies, 2212 incident pancreatic cancer cases were identified during follow-up among 862 680 individuals. Adjusting for smoking habits, personal history of diabetes, alcohol intake, body mass index (BMI), and energy intake, multivariable study-specific hazard ratios (MVHR) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazards models and then pooled using a random effects model. There was no association between total milk intake and pancreatic cancer risk (MVHR = 0.98, 95% CI = 0.82-1.18 comparing ≥500 with 1-69.9 g/day). Similarly, intakes of low-fat milk, whole milk, cheese, cottage cheese, yogurt, and ice-cream were not associated with pancreatic cancer risk. No statistically significant association was observed between dietary (MVHR = 0.96, 95% CI = 0.77-1.19) and total calcium (MVHR = 0.89, 95% CI = 0.71-1.12) intake and pancreatic cancer risk overall when comparing intakes ≥1300 with <500 mg/day. In addition, null associations were observed for dietary and total vitamin D intake and pancreatic cancer risk. Findings were consistent within sex, smoking status, and BMI strata or when the case definition was limited to pancreatic adenocarcinoma. Overall, these findings do not support the hypothesis that consumption of dairy foods, calcium, or vitamin D during adulthood is associated with pancreatic cancer risk.

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.

Association of baseline sex hormone levels with baseline and longitudinal changes in waist-to-hip ratio: Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: Waist-to-hip ratio (WHR) is strongly associated with prevalent atherosclerosis. We analyzed the associations of baseline serum levels of testosterone (T), estradiol (E2), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone (DHEA) with WHR in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. SUBJECTS: Baseline data was available for 3144 men and 2038 postmenopausal women, who were non-users of hormone therapy, who were 45-84 years of age, and of White, Chinese, Black or Hispanic racial/ethnic groups. Of these, 2708 men and 1678 women also had longitudinal measurements of WHR measured at the second and/or the third study visits (median follow-up 578 days and 1135 days, respectively). RESULTS: In cross-sectional analyses adjusted for age, race and cardiovascular disease risk factors, T was negatively associated with baseline WHR in men, whereas in both sexes, E2 was positively associated and SHBG was negatively associated with WHR (all P<0.001). In longitudinal analyses, further adjusted for follow-up time and baseline WHR, baseline T was negatively associated with WHR at follow-up (P=0.001) in men, whereas in both sexes, E2 was positively associated (P=0.004) and SHBG was negatively associated with WHR (P<0.001). The longitudinal association of E2, but not T, was independent of SHBG. In cross-sectional or longitudinal analyses, there were no associations between DHEA and WHR in either men or women. CONCLUSION: Sex hormones are associated with WHR at baseline and also during follow-up above and beyond their baseline association. Future research is needed to determine if manipulation of hormones is associated with changes in central obesity.

Changes in BMI modulate age-associated changes in sex hormone binding globulin and total testosterone, but not bioavailable testosterone in young adult men: the CARDIA Male Hormone Study.

OBJECTIVES: To compare age-associated 8-year changes in total testosterone, calculated bioavailable testosterone and sex hormone binding globulin (SHBG) across five groups of men stratified according to change in body mass index (BMI) (i.e., BMI stable (+/-0.69 kg/m(2)), decreased (-0.7 kg/m(2)), increased minimally (0.7-1.74 kg/m(2)), increased moderately (1.75-3.19 kg/m(2)) and increased most (> or =3.20 kg/m(2))). DESIGN: Eight-year longitudinal cohort study. SUBJECTS: Four hundred and seventy-four black and 695 white men, aged 24-31 years at the time of the first hormone measurement. MEASUREMENTS: Aging-related changes in serum SHBG, total testosterone and bioavailable testosterone. RESULTS: SHBG significantly increased with age for men whose BMI decreased, and there were progressively smaller increases for men whose BMI was stable, or whose BMI increased minimally or moderately (range 1.1-0.3 nM per year, P< or =0.03, respectively). There was no age relationship with SHBG among men whose BMI increased most. Total testosterone did not change with age for men whose BMI decreased, was stable or increased minimally, but for men whose BMI increased moderately and most there was a graded decrease in total testosterone with age (beta=-0.2 and -0.4 nM per year, respectively, P< or =0.005). However, bioavailable testosterone decreased with age to a similar extent across all groups. CONCLUSIONS: These results suggest that changes in BMI during young adulthood modulate age-related changes in SHBG and total testosterone, but not bioavailable testosterone.

Body mass index, physical activity, and risk of renal cell carcinoma.

OBJECTIVE: To investigate the association between obesity and risk of renal cell carcinoma and to examine whether the association is modified by physical activity. SUBJECTS: A population-based case-control study of 406 patients with renal cell carcinoma and 2434 controls conducted in Iowa. METHODS: Information was collected on weight at the ages 20-29, 40-49, and 60-69 years, height, nonoccupational physical activity, diet, and other lifestyle factors. Renal cell carcinoma risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, total energy intake, and other confounding factors. RESULTS: Height and total energy intake were not associated with risk in either sex. In men, neither physical activity nor level of obesity in any period of life was significantly associated with risk. In women, lower physical activity was associated with higher risk (OR=2.5; 95% CI=1.2-5.2 comparing exercise <1 time/month to >1 time/day). Compared with women in the lowest quartile for BMI, the risks of renal cell carcinoma for women in the highest 10% of BMI in their 20s, 40s, and 60s were 1.4 (CI=0.6-3.1), 1.9 (CI=0.9-4.2), and 2.3 (CI=0.9-6.0), respectively. When analyses were limited to self-respondent data, the corresponding ORs were 2.9 (CI=1.2-7.4), 3.2 (CI=1.3-7.5), and 2.1 (CI=0.7-6.4), respectively. There was little evidence that physical activity modifies the association of BMI with renal cell carcinoma. CONCLUSION: Nonoccupational physical activity was inversely associated and obesity was positively associated with risk of renal cell carcinoma among women. The risk appeared to be greater for women in the highest 10% of BMI in their 40s. Our finding of little evidence of an interaction between physical activity and BMI requires confirmation.

Alcohol and breast cancer: review of epidemiologic and experimental evidence and potential mechanisms.

The association of alcohol consumption with increased risk for breast cancer has been a consistent finding in a majority of epidemiologic studies during the past 2 decades. Herein, we summarize information on this association from human and animal investigations, with particular reference to epidemiologic data published since 1995. increased estrogen and androgen levels in women consuming alcohol appear to be important mechanisms underlying the association. Other plausible mechanisms include enhanced mammary gland susceptibility to carcinogenesis, increased mammary carcinogen dna damage, and greater metastatic potential of breast cancer cells, processes for which the magnitude likely depends on the amount of alcohol consumed. Susceptibility to the breast cancer-enhancing effect of alcohol may also be affected by other dietary factors (such as low folate intake), lifestyle habits (such as use of hormone replacement therapy), or biological characteristics (such as tumor hormone receptor status). Additional progress in understanding alcohol's enhancing effect on breast cancer will depend on a better understanding of the interactions between alcohol and other risk factors and on additional insights into the multiple biological mechanisms involved.

Postload plasma glucose concentration and 27-year prostate cancer mortality (United States).

OBJECTIVE: Findings from epidemiologic studies on the association between diabetes and prostate cancer risk are inconsistent. However, data from at least three studies suggest that the direction and strength of this association differs according to duration of diabetes. To determine the potential effects of early-stage abnormal glucose metabolism on risk, we assessed the relationship of postload glycemia in the absence of self-reported diabetes with risk of prostate cancer mortality. METHODS: Data from the Chicago Heart Association Detection Project in Industry were used to examine this relationship. Between 1967 and 1973 some employees of 84 Chicago area organizations underwent a health screening examination. Blood was drawn for measurement of plasma glucose concentration approximately 1 h after a 50-g oral glucose load among 20,433 men. After a mean length of follow-up of 27 years, 176 men died of prostate cancer. Cox regression was used to compute adjusted relative risks (RRs) and 95% confidence intervals (CIs). RESULTS: After controlling for age, body mass index, heart rate, education, and race, the RRs of prostate cancer mortality for postload plasma glucose levels of 6.7-8.8, 8.9-11, and > or = 11.1 mmol/L compared to < or = 6.6 mmol/L were 1.64, 1.37, and 1.64. respectively (p for trend=0.19). The RR (95% CI) associated with a 2.2 mmol/L (1 standard deviation) higher glucose concentration was 1.1 (0.95-1.2). CONCLUSIONS: These results provide weak evidence of an association between hyperglycemia and prostate cancer mortality.

Dietary folate intake, alcohol, and risk of breast cancer in a prospective study of postmenopausal women.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels: <10th, 11th-30th, 31st-50th, and >50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (>50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers of < or = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of > 4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.

Lack of association between the -308 polymorphism of the tumor necrosis factor-alpha gene and the insulin resistance syndrome.

BACKGROUND: Previous studies have demonstrated a role for tumor necrosis factor-alpha (TNF-alpha) in insulin resistance. A polymorphic variant of the TNF-alpha gene, the TNF2 allele, which is a guanine to adenine polymorphism at position -308 in the TNF-alpha promoter, is associated with higher basal and inducible promoter activity. The present study examined whether the TNF2 allele was associated with altered levels of different components of the insulin resistance syndrome, clustering of these components, or the 10-year change in the level of these components. METHODS: Components of the insulin resistance syndrome included insulin resistance, as determined by fasting insulin levels, body mass index, systolic blood pressure, triglycerides, uric acid, and high density lipoprotein-cholesterol. The study population was a subsample of participants from the Coronary Artery Risk Development in (Young) Adults (CARDIA) study, which included African American and white men and women aged 18-30. The sample included 243 black women, 142 black men, 392 white women, and 386 white men. Subjects were typed at the TNF-alpha locus. RESULTS: The frequency of the TNF2 allele was 12% in blacks and 16% in whites. Age-adjusted levels of the different components examined were not different at either baseline or year 10 in carriers of the TNF2 allele versus homozygotes for the wild-type allele, and the 10-year change in the level of different components was not different between the two genotype groups. There also was no evidence of increased clustering of components of the insulin resistance syndrome in carriers of the TNF2 allele. Moreover, there was no evidence of an association between the TNF2 allele and clustering across quartiles of BMI or quartiles of dietary fat intake (i.e., Key's score). CONCLUSIONS: In African Americans and whites, neither the TNF2 allele nor another polymorphism in the TNF-alpha gene or a neighboring gene with which the TNF2 allele is in linkage disequilibrium is associated with differences in the level of or increased clustering of components of the insulin resistance syndrome.

Abnormal glucose metabolism and pancreatic cancer mortality.

CONTEXT: Previous studies reported an increased risk of pancreatic cancer among persons with diabetes. Few data exist, however, on the association of postload plasma glucose concentration with pancreatic cancer, which could provide insight into the role of abnormal glucose metabolism in the etiology of pancreatic cancer. OBJECTIVE: To determine the independent association between postload plasma glucose concentration and risk of pancreatic cancer mortality among persons without self-reported diabetes. DESIGN: Prospective cohort study. SETTING AND PARTICIPANTS: Employees of 84 Chicago-area organizations, with an average age of 40 years at baseline, were screened from 1963 to 1973 and followed up for an average of 25 years. A total of 96 men and 43 women died of pancreatic cancer among 20,475 men and 15,183 women, respectively. MAIN OUTCOME MEASURES: Relationship of pancreatic cancer mortality with postload plasma glucose levels. RESULTS: Compared with a postload plasma glucose level of 6.6 mmol/L (119 mg/dL) or less and after adjusting for age, race, cigarette smoking, and body mass index, the relative risks (95% confidence intervals) of pancreatic cancer mortality were 1.65 (1.05-2.60) for postload plasma glucose levels between 6.7 (120) and 8.8 (159) mmol/L (mg/dL); 1.60 (0.95-2.70) for levels between 8.9 (160) and 11.0 (199); and 2.15 (1.22-3.80) for levels of 11.1 (200) or more; P for trend=.01. An association appeared to be stronger for men than women. Estimates were only slightly lower after excluding 11 men and 2 women who died of pancreatic cancer during the first 5 years of follow-up. In men only, higher body mass index and serum uric acid concentration also were independently associated with an elevated risk of pancreatic cancer mortality. CONCLUSION: These results suggest that factors associated with abnormal glucose metabolism may play an important role in the etiology of pancreatic cancer. JAMA. 2000;283:2552-2558

Factors associated with axillary lymph node metastasis from breast carcinoma: descriptive and predictive analyses.

BACKGROUND: Although axillary lymph node metastasis is one of the most important prognostic determinants of breast carcinoma prognoses, the reasons why tumors vary in their capability to produce for axillary metastases remain unclear. METHODS: The authors used data from the nationwide Patient Care Evaluation (PCE) survey of the American College of Surgeons to evaluate the correlations between patient/tumor characteristics and lymph node status, and to explore the use of these factors, which are all known prior to axillary dissection, in predicting lymph node status. The PCE data set contained 18,025 breast carcinoma cases diagnosed in 1990 after exclusion of women older than 79 years or with fewer than 6 lymph nodes examined. RESULTS: In a multivariate logistic regression model, larger tumor size, young age, African American or Hispanic race, outer half tumor location, poor or moderate differentiation, aneuploidy, and infiltrating ductal histology were independently associated with a higher likelihood of one or more positive lymph nodes. Contrary to expectation, cases negative for estrogen receptor (ER) and progesterone receptor (PR) had a lower risk of positive lymph nodes when adjusted for other factors (odds ratio = 0.82; 95% confidence interval: 0.74-0.91) compared with cases positive for both receptors. This model accurately predicted lymph node status in 2 validation data sets (a 50% random sample of 1990 PCE data and 1992 data from the National Cancer Data Base), but was less accurate in a third, older data set (1983 PCE data). However, the percentage of cases (1990 validation set) with predicted probabilities less than 0.05 or greater than 0.95 were only 4.6% and <0.1%, respectively. CONCLUSIONS: The authors concluded that 1) most variation in axillary lymph node metastatic status can be explained by routinely available data, 2) ER and PR status may be involved in the mechanism of this behavior, and 3) the difficulty of using prediction models to avert axillary dissection should not be underestimated.

Alcohol consumption and non-Hodgkin lymphoma in a cohort of older women.

We investigated the relation of alcohol consumption to risk of non-Hodgkin's lymphoma (NHL) in a cohort of 35 156 Iowa women aged 55-69 years who participated in the Iowa Women's Health Study in 1986. Alcohol consumption at baseline was obtained using a mailed questionnaire. During the 9-year follow-up period, 143 incident cases of NHL were identified. Higher alcohol consumption was significantly associated with a decreased risk of NHL (P-trend = 0.03). Compared to non-drinkers, multivariate-adjusted relative risks (RRs) were decreased for women with intake of < or = 3.4 g day(-1) (RR = 0.78; 95% confidence interval (CI) 0.51-1.21) and > 3.4 g day(-1) (RR = 0.59; 0.36-0.97). The inverse association could not be attributed to one particular type of alcoholic beverage, although red wine (RR = 0.21 for > 2 glasses per month vs non-drinker; 0.05-0.86; P-trend = 0.02) has the most distinct effect. The apparent protective effect was universal regardless of specific NHL grade or Working Formulation subtype, but was most pronounced for nodal NHL (RR = 0.48; 0.26-0.90; P-trend = 0.01) and low-grade NHL (RR = 0.52; 0.21-1.26; P-trend = 0.05). These data suggest that moderate alcohol consumption is inversely associated with the risk of NHL in older women and the amount of alcohol consumed, rather than the type of alcoholic beverages, appears to be the main effect determinant.

Hormone replacement therapy and risk of breast cancer with a favorable histology: results of the Iowa Women's Health Study.

CONTEXT: Long-term, postmenopausal use of hormone replacement therapy (HRT) appears to increase breast cancer risk. Whether the effect of HRT use on risk of breast cancer varies among histological types of invasive carcinoma is unknown. OBJECTIVE: To determine associations between HRT use and risk of ductal carcinoma in situ (DCIS), invasive carcinoma with favorable histology, and invasive ductal or lobular carcinoma. DESIGN: Prospective cohort study whose participants were followed up continuously for 11 years from January 1986 to December 1996. SETTING AND PARTICIPANTS: Iowa Women's Health Study, a population-based random sample of postmenopausal women aged 55 to 69 years in 1986. A total of 1520 incident breast cancer cases occurred in the at-risk cohort of 37 105 women. MAIN OUTCOME MEASURES: Multivariate-adjusted relative risk (RR) of tumor-specific breast cancers associated with duration of ever, current, or past HRT use. RESULTS: Duration of ever HRT use was associated with risk of invasive carcinoma with a favorable histology, with an RR of 1.81 (95% confidence interval [CI], 1.07-3.07) for those who used HRT 5 or fewer years vs an RR of 2.65 (95% CI, 1.34-5.23) for those who used HRT for more than 5 years (P for trend = .005) after adjustment for age and other breast cancer risk factors. There was no association between ever HRT use and the incidence of DCIS or invasive ductal or lobular carcinoma. Among current hormone users, after adjusting for age and other breast cancer risk factors, the RRs (95% CIs) of invasive carcinoma with a favorable histology were 4.42 (2.00-9.76) and 2.63 (1.18-5.89) for 5 or fewer years of use and for more than 5 years of use, respectively. Risk of invasive ductal or lobular carcinoma was associated with current use (< or =5 years) of HRT with an RR of 1.38 (95% CI, 1.03-1.85). CONCLUSIONS: Exposure to HRT was associated most strongly with an increased risk of invasive breast cancer with a favorable prognosis. These data add important clinical information for assessing the risks and benefits of HRT use.