Mammographic density and breast cancer risk: the multiethnic cohort study

In a nested case-control study (2001-2004), the authors investigated the association between mammographic density and breast cancer risk among women of Caucasian, Japanese, and Native Hawaiian ancestry in the Hawaii component of the Multiethnic Cohort Study. The authors retrieved several prediagnostic mammograms for breast cancer cases and for controls frequency-matched to cases by age and ethnicity. A reader who was blinded to case status and year of mammogram performed computer-assisted density assessment. Suitable mammographic readings were obtained for 607 cases and 667 controls. The authors used unconditional logistic regression to estimate odds ratios and 95% confidence intervals while adjusting for confounders. Mean percent density and mean dense area were significantly greater for cases than for controls: 39.6% vs. 29.7% and 37.3 cm2 vs. 28.4 cm2, respectively. For the earliest mammogram taken, the overall odds ratio for a 10% increase in breast density was 1.22 (95% confidence interval: 1.14, 1.30), and the overall odds ratio for a 10-cm2 increase in dense area was 1.17 (95% confidence interval: 1.11, 1.24). The similar sizes of the areas under the receiver operating characteristic curve (0.66) confirmed that percent density and dense area predicted breast cancer equally well. Because the risk estimates appeared higher for Caucasians and Native Hawaiians than for Japanese women, ethnicity-specific models may be necessary to predict risk from breast density in different ethnic groups.     

Nonsteroidal antiinflammatory drugs and bladder cancer: a pooled analysis

Case-control studies have shown that regular use of nonsteroidal antiinflammatory drugs (NSAIDs) decreases bladder cancer risk, but few cohort studies have evaluated this association. The authors investigated NSAID use and bladder cancer in 3 large prospective studies (NIH-AARP Diet and Health Study; Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; and U.S. Radiologic Technologists Study). Frequency of aspirin and nonaspirin NSAID use 1 year prior to baseline was ascertained using self-administered questionnaires. Study-specific hazard ratios and 95% confidence intervals were estimated using Cox regression models and were combined using a fixed-effects meta-analytic model. Data from all studies were aggregated, and aggregated hazard ratios were estimated. The analysis included 508,842 individuals, with 2,489 incident cases of bladder cancer. A reduction in risk was observed for individuals who reported regular use (>2 times/week) of nonaspirin NSAIDs compared with those who reported no use (hazard ratio (HR) = 0.92, 95% confidence interval (CI): 0.81, 1.04). The risk reduction was limited to nonsmokers (HR = 0.58, 95% CI: 0.41, 0.83) (P(trend) = 0.008) (P(interaction) = 0.02). No association was observed between regular aspirin use and bladder cancer risk (HR = 1.04, 95% CI: 0.94, 1.15). Results suggest that nonaspirin NSAIDs, but not aspirin, are associated with a reduction in risk of bladder cancer, particularly for nonsmokers.     

Nonsteroidal antiinflammatory drugs and decreased risk of advanced prostate cancer: modification by lymphotoxin alpha

The potentially protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) on prostate cancer may only exist among certain subgroups of men, such as those with particular variants in inflammatory response genes. To investigate this, the authors undertook a case-control study (n = 1,012) of the association between NSAIDs and more advanced prostate cancer in Ohio men recruited between 2001 and 2004 and evaluated whether this association was modified by a functional polymorphism in the lymphotoxin alpha (LTA) gene (LTA C+80A, where the CC genotype results in higher LTA production). The authors observed an inverse association between aspirin or ibuprofen use and disease (odds ratio = 0.67, 95% confidence interval: 0.52, 0.87). This was modified by the LTA C+80A variant (p for interaction = 0.03): Among men with the CC genotype, the inverse association between NSAIDs and prostate cancer was substantially stronger (odds ratio = 0.43, 95% confidence interval: 0.28, 0.67). For men without the CC genotype, NSAID use was not associated with disease (p = 0.30). The authors observed similar associations when examining dose/duration of NSAID use. This suggests that any potential chemoprevention of prostate cancer by NSAIDs may be most appropriate for men with the LTA +80CC genotype.     

Flavonols and pancreatic cancer risk: the multiethnic cohort study

Only a few prospective studies have investigated flavonols as risk factors for cancer, none of which has included pancreatic cancer. The latter is usually fatal, rendering knowledge about prevention particularly important. The authors estimated intakes of three flavonols-quercetin, kaempferol, and myricetin-for 183,518 participants in the Multiethnic Cohort Study and examined associations with incidence of pancreatic cancer. Baseline data were collected in Hawaii and California in 1993-1996. Diet was assessed by using a quantitative food frequency questionnaire. During 8 years of follow-up, 529 cases of exocrine pancreatic cancer occurred. Multivariate Cox regression models were calculated to estimate relative risks. Intake of total flavonols was associated with a reduced pancreatic cancer risk (relative risk for the highest vs. lowest quintile = 0.77, 95% confidence interval: 0.58, 1.03; p trend = 0.046). Of the three individual flavonols, kaempferol was associated with the largest risk reduction (relative risk = 0.78, 95% confidence interval: 0.58, 1.05; p trend = 0.017). Total flavonols, quercetin, kaempferol, and myricetin were all associated with a significant inverse trend among current smokers (relative risks for the highest vs. lowest quartile = 0.41, 0.55, 0.27, 0.55, respectively) but not never or former smokers. This study provides evidence for a preventive effect of flavonols on pancreatic cancer, particularly for current smokers.     

Vegetable intake and pancreatic cancer risk: the multiethnic cohort study

Investigators studying associations between vegetable intake and pancreatic cancer risk have reported inconsistent findings to date. To further explore these associations, the authors analyzed data on 183,522 participants enrolled in the Hawaii-Los Angeles Multiethnic Cohort Study in 1993-1996. Intakes of total vegetables, light green, dark green, yellow-orange, and cruciferous vegetables, tomato products, and legumes were estimated from a quantitative food frequency questionnaire. After an average of 8.3 years of follow-up, 529 pancreatic cancer cases were identified. Multivariate-adjusted Cox proportional hazards models were created. All statistical tests were two-sided. Overall, total vegetable intake was not associated with pancreatic cancer risk, nor was intake of vegetable subgroups. Current smokers, who were at increased risk of pancreatic cancer (relative risk = 1.78, 95% confidence interval: 1.40, 2.27), had a decreased risk with higher intake of dark green vegetables (for comparison of extreme quartiles, relative risk = 0.50, 95% confidence interval: 0.27, 0.92; p-trend = 0.029). The inverse association for dark green vegetables was also seen in African Americans (p-trend = 0.043). In stratified analyses, inverse associations with total vegetables, light green vegetables, and legumes were significant in overweight/obese subjects. In conclusion, the authors found no evidence for an inverse association between vegetable intake and pancreatic cancer overall, but inverse associations in high-risk persons suggest the need for further investigation.     

Use of nonsteroidal antiinflammatory drugs and risk of breast cancer: the Case-Control Surveillance Study revisited

Several studies have suggested that use of nonsteroidal antiinflammatory drugs (NSAIDs) may reduce the risk of breast cancer. Reductions in risk may vary according to the hormone receptor status of the tumor or the type of NSAID used. The authors extended a previous US hospital-based case-control study (the Case-Control Surveillance Study) to include 444 additional cases, for a total of 7,006 incident breast cancer cases (1976-2002). They examined the relation between regular NSAID use and breast cancer risk using logistic regression to adjust for confounding. The odds ratio for regular use of NSAIDs was 0.78 (95% confidence interval: 0.63, 0.97), and a trend of decreasing risk with increasing duration of use was statistically significant (p for trend = 0.02). The inverse association with regular use of NSAIDs was stronger among premenopausal women (odds ratio = 0.62). The overall odds ratios for regular use of aspirin and ibuprofen were 0.86 and 0.85, respectively. The effect of NSAID use on breast cancer risk did not vary according to the hormone receptor status of the tumor. In conclusion, long-term regular use of NSAIDs was associated with decreased risk of breast cancer. The type of NSAID used or the hormone receptor status of the tumor did not modify the effect.     

Multivitamin use and the risk of mortality and cancer incidence: the multiethnic cohort study

Although multivitamin/mineral supplements are commonly used in the United States, the efficacy of these supplements in preventing chronic disease or premature death is unclear. To assess the relation of multivitamin use with mortality and cancer, the authors prospectively examined these associations among 182,099 participants enrolled in the Multiethnic Cohort Study between 1993 and 1996 in Hawaii and California. During an average 11 years of follow-up, 28,851 deaths were identified. In Cox proportional hazards models controlling for tobacco use and other potential confounders, no associations were found between multivitamin use and mortality from all causes (for users vs. nonusers: hazard ratio = 1.07, 95% confidence interval: 0.96, 1.19 for men; hazard ratio = 0.96, 95% confidence interval: 0.85, 1.09 for women), cardiovascular diseases, or cancer. The findings did not vary across subgroups by ethnicity, age, body mass index, preexisting illness, single vitamin/mineral supplement use, hormone replacement therapy use, and smoking status. There also was no evidence indicating that multivitamin use was associated with risk of cancer, overall or at major sites, such as lung, colorectum, prostate, and breast. In conclusion, there was no clear decrease or increase in mortality from all causes, cardiovascular disease, or cancer and in morbidity from overall or major cancers among multivitamin supplement users.     

Racial/ethnic differences in endometrial cancer risk: the multiethnic cohort study

Few studies have examined differences in endometrial cancer risk among ethnic groups in the United States. The authors assessed the extent to which known risk factors for endometrial cancer explain the racial/ethnic differences in risk among 46,933 postmenopausal African-American, Native-Hawaiian, Japanese-American, Latina, and White women recruited to the prospective Multiethnic Cohort Study in 1993-1996. During a 7.3-year follow up period, 321 incident endometrial cancer cases were identified among these women. Data on known/suspected risk factors were obtained from baseline questionnaires, and comparisons of endometrial cancer incidence across racial/ethnic groups were estimated using log-linear proportional hazard models. Later age at menopause, unopposed estrogen therapy use, and obesity were associated with increased risk, while increasing parity and increasing duration of oral contraceptive use were associated with decreased risk. The relative risks for endometrial cancer (vs. Whites) were 0.76 (95% confidence interval (CI): 0.53, 1.08) for African Americans, 0.92 (95% CI: 0.58, 1.46) for Native Hawaiians, 0.61 (95% CI: 0.46, 0.83) for Japanese Americans, and 0.63 (95% CI: 0.46, 0.87) for Latinas. After adjustment for the risk factors, the relative risks were 0.68 (95% CI: 0.47, 0.98) for African Americans, 0.91 (95% CI: 0.56, 1.46) for Native Hawaiians, 0.74 (95% CI: 0.54, 1.01) for Japanese Americans, and 0.65 (95% CI: 0.47, 0.92) for Latinas. Results from this study show that the interethnic differences in endometrial cancer risk do not appear to be explained by differences in the distribution of known risk factors among women of different races/ethnicities.     

Vitamin D insufficiency in a multiethnic cohort of breast cancer survivors

BACKGROUND: Little is known about vitamin D status in breast cancer survivors. This issue is important because vitamin D influences pathways related to carcinogenesis. OBJECTIVE: The objective of this report was to describe and understand vitamin D status in a breast cancer survivor cohort. DESIGN: Data are from the Health, Eating, Activity, and Lifestyle study. With the use of a cross-sectional design, we examined serum concentrations of 25-hydroxyvitamin D [25(OH)D] in 790 breast cancer survivors from western Washington state, New Mexico, and Los Angeles County. Cancer treatment data were obtained from Surveillance, Epidemiology, and End Results registries and medical records. Fasting blood, anthropometry, and lifestyle habits were collected after diagnosis and treatment. We examined distributions of 25(OH)D by race-ethnicity, season, geography, and clinical characteristics. Multivariate regression tested associations between 25(OH)D and stage of disease. RESULTS: Five hundred ninety-seven (75.6%) of the women had low serum 25(OH)D, suggesting vitamin D insufficiency or frank deficiency. The overall mean (+/-SD) was 24.8 +/- 10.4 ng/mL, but it was lower for African Americans (18.1 +/- 8.7 ng/mL) and Hispanics (22.1 +/- 9.2 ng/mL). Women with localized (n = 424) or regional (n = 182) breast cancer had lower serum 25(OH)D than did women with in situ disease (n = 184) (P = 0.05 and P = 0.03, respectively). Multivariate regression models controlled for age, body mass index (in kg/m(2)), race-ethnicity, geography, season, physical activity, diet, and cancer treatments showed that stage of disease independently predicted serum 25(OH)D (P = 0.02). CONCLUSIONS: In these breast cancer survivors, the prevalence of vitamin D insufficiency was high. Clinicians might consider monitoring vitamin D status in breast cancer patients, together with appropriate treatments, if necessary.     

Risk factors for renal cell cancer: the multiethnic cohort

The association of body size, lifestyle, and medical conditions with renal cell cancer risk was examined among 161,126 Hawaii-Los Angeles Multiethnic Cohort participants (1993-2002). After 8.3 years of follow-up, 347 renal cell cancer cases (220 men, 127 women) were identified. Renal cell cancer risk increased with increasing body mass index in men (multivariate relative risk (RR) = 1.06 per unit of body mass index, p = 0.001) and women (RR = 1.07, p < 0.0001). The relative risks associated with being obese compared with being lean were 1.76 (95% confidence interval (CI): 1.20, 2.58) for men and 2.27 (95% CI: 1.37, 3.74) for women. Hypertension was associated with renal cell cancer (RR-men = 1.42, 95% CI: 1.07, 1.87; RR-women = 1.58, 95% CI: 1.09, 2.28). Smoking was confirmed to be a risk factor for both sexes. Among women, diuretic use was associated with increased risk (RR = 1.63, 95% CI: 1.04, 2.57), whereas physical activity was associated with reduced risk (ptrend = 0.027). Alcohol consumption was inversely associated with risk for men (ptrend = 0.045). Compared with nondrinkers, men who drank >or=1 drinks/day had a 31% lower risk (95% CI: 0.49, 0.96). Results show that body mass index, smoking, and hypertension are risk factors for renal cell cancer in both sexes.     

Residential magnetic field exposure and breast cancer risk: a nested case-control study from a multiethnic cohort in Los Angeles County, California

Some experimental and epidemiologic evidence suggests that residential exposure to power-frequency magnetic fields can increase breast cancer risk. This association was investigated in a nested case-control study of female breast cancer within a cohort of African Americans, Latinas, and Caucasians in Los Angeles County, California. Incident breast cancer was ascertained from 1993 to 1999 by linkage to county and state tumor registries. Controls were selected from a random sample of cohort members without breast cancer at baseline. Exposure was assessed in 1995-2001 by means of wiring configuration coding (an indirect measure of magnetic field exposure that has been associated with increased risk of childhood leukemia in Los Angeles and elsewhere in North America) in all homes occupied over the previous 10 years for 743 cases and 699 controls and by measurement of magnetic fields in the bedroom over a 7-day period for 347 cases and 286 controls. The estimated risk of breast cancer was not higher among women with wiring configuration codes associated with the highest magnetic fields (for a very high current configuration relative to very low, the adjusted odds ratio was 0.76 (95% confidence interval: 0.49, 1.18)). Stronger measured fields were not significantly associated with increased risk. These data suggest that residential magnetic field exposures commonly experienced by US women do not influence risk of breast cancer.     

Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study

Research on the relation between phytoestrogens and breast cancer risk has been limited in scope. Most epidemiologic studies have involved Asian women and have examined the effects of traditional soy foods (e.g., tofu), soy protein, or urinary excretion of phytoestrogens. The present study extends this research by examining the effects of a spectrum of phytoestrogenic compounds on breast cancer risk in non-Asian US women. African-American, Latina, and White women aged 35-79 years, who were diagnosed with breast cancer between 1995 and 1998, were compared with women selected from the general population via random digit dialing. Interviews were conducted with 1,326 cases and 1,657 controls. Usual intake of specific phytoestrogenic compounds was assessed via a food frequency questionnaire and a newly developed nutrient database. Phytoestrogen intake was not associated with breast cancer risk (odds ratio = 1.0, 95% confidence interval: 0.80, 1.3 for the highest vs. lowest quartile). Results were similar for pre- and postmenopausal women, for women in each ethnic group, and for all seven phytoestrogenic compounds studied. Phytoestrogens appear to have little effect on breast cancer risk at the levels commonly consumed by non-Asian US women: an average intake equivalent to less than one serving of tofu per week.     

Dietary fat, cooking fat, and breast cancer risk in a multiethnic population

Our objective was to examine the association between dietary fat intake, cooking fat usage, and breast cancer risk in a population-based, multiethnic, case-control study conducted in the San Francisco Bay area. Intake of total fat and types of fat were assessed with a food frequency questionnaire among 1,703 breast cancer cases diagnosed between 1995 and 1999 and 2,045 controls. In addition, preferred use of fat for cooking was assessed. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). High fat intake was associated with increased risk of breast cancer (highest vs. lowest quartile, adjusted OR = 1.35, 95% CI = 1.10-1.65, P(trend) < 0.01). A positive association was found for oleic acid (OR = 1.55, 95% CI = 1.14-2.10, P(trend) < 0.01) but not for linoleic acid or saturated fat. Risk was increased for women cooking with hydrogenated fats (OR = 1.58, 95% CI = 1.20-2.10) or vegetable/corn oil (rich in linoleic acid; OR = 1.30, 95% CI = 1.06-1.58) compared to women using olive/canola oil (rich in oleic acid). Our results suggest that a low-fat diet may play a role in breast cancer prevention. We speculate that monounsaturated trans fats may have driven the discrepant associations between types of fat and breast cancer.     

Reduced risk of colorectal cancer among long-term users of aspirin and nonaspirin nonsteroidal antiinflammatory drugs

Use of nonsteroidal antiinflammatory drugs (NSAIDs) has been associated with a reduced risk of colorectal cancer, but limited information is available on the effect of individual nonaspirin NSAIDs. In addition, the dose-response relation of aspirin in reducing the risk of colorectal cancer has not been described. We carried out a population-based cohort study with secondary case-control analysis to determine the association between the risk of colorectal cancer and use of aspirin and individual NSAIDs, including the role of dose and duration. The General Practice Research Database in the U.K. was the source population. We traced 943,903 persons 40-79 years of age and free of cancer and colorectal adenoma between January 1994 and September 1997. A total of 2,002 incident cases of colorectal cancer were ascertained. The incidence rate of colorectal cancer per 10,000 person-years was 7.3. The risk of colorectal cancer was reduced in users of nonaspirin NSAIDs and became evident after 6 months of continuous treatment. The adjusted relative risk was 0.5 (95% confidence interval = 0.4-0.7). The reduction in risk disappeared completely 1 year after stopping NSAID treatment. The risk of developing colorectal cancer was reduced in long-term users of aspirin at doses of 300 mg daily (relative risk = 0.6; 95% confidence interval = 0.4-0.9). Daily doses of 75 and 150 mg aspirin were not associated with a reduced risk of colorectal cancer. Our data support the existence of an important protective effect of nonaspirin NSAID continuous intake against colorectal cancer and point to a similar reduction in risk for aspirin at doses of at least 300 mg daily. One-year treatment with NSAIDs would prevent one case of colorectal cancer in a population of 1,000 persons 70-79 years of age.