Multivariate Relative Risk Research Articles

No association between fruit, vegetables, antioxidant nutrients and risk of renal cell carcinoma

Previous epidemiologic studies that have examined the relationship between renal cell carcinoma (RCC) risk and intakes of plant foods and antioxidant nutrients have yielded inconsistent results. We therefore examined the associations between intakes of fruit, vegetables, carotenoids, flavonoids, vitamin E and vitamin C and RCC risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study cohort. At baseline, 27,062 male Finnish smokers aged 50-69 years completed a 276-item dietary questionnaire that included questions on frequency of consumption and portion size. During up to 19 years of follow-up, 255 men developed RCC. Cox proportional hazards models were utilized to estimate relative risks (RR) and 95% confidence intervals (CI). Despite a large range in intake, no association was observed between fruit, vegetables or antioxidant nutrients and RCC risk. For example, multivariate RRs and 95% CIs for the highest versus the lowest quartile of intake were 0.79 (0.55-1.14), 1.23 (0.85-1.79), 1.09 (0.74-1.60), 0.83 (0.57-1.21), 1.09 (0.73-1.64) and 0.99 (0.67-1.46) for fruit, vegetables, total carotenoids, total flavonoids, total vitamin E and vitamin C, respectively (all p values for trend > 0.05). Our results indicate that diet may not play a large role in the etiology of RCC in male smokers, although further examination of these associations in nonsmokers, women and diverse racial populations is warranted.

Abstract B100: Alcohol consumption and risk of renal cell cancer: The NIH-AARP Diet and Health study

Abstract Introduction: There is substantial epidemiologic evidence that alcohol consumption is positively associated with the development of several cancers, notably in the breast, mouth, pharynx and laryngeal. Epidemiologic studies have reported inconsistent findings on the relationship between alcohol consumption and risk of renal cell cancer (RCC), prospective cohort studies have reported statistically non-significant inverse association between alcohol consumption and the risk of RCC. Therefore, we investigated the association between alcohol consumption and RCC in the NIH-AARP Diet and Health study. Methods: We analyzed 490,159 eligible men (n=292,101) and women (n=198,058) in the prospective NIH-AARP Diet and Health study. At baseline, we assessed alcohol and other nutrient intakes with a food frequency questionnaire, and collected data on demographics, lifestyle, and medical history. We used Cox proportional hazards models to calculate relative risks (RR) and 95% confidence intervals (CI), adjusting for age, race, height, body mass index (BMI), marriage status, physical activity, smoking history, history of diabetes and hypertension, and intakes of protein and energy. Results: During an average of 7 years of follow-up, we identified 1,106 cases of RCC: 811 were men, 295 were women. 21% of the men and 30% of the women did not drink alcohol. The percentage of current smokers increased with amount of alcohol consumed for both sexes. Alcohol was inversely associated with risk of RCC. Per 10g/day increment, RR was 0.96 (95% CI:0.93–0.99). There was a significant interaction by sex. Alcohol showed a null association with RCC in men: the multivariate RR (95%CI) was 0.96 (0.93–1.00) for every 10g increase in alcohol consumption per day. The findings were similar for different alcoholic beverage types. The multivariate RR (95%CI) was 0.95 (0.90–1.00) for every 1 serving of beer per day, 1.05 (0.94–1.16) for every 1 serving of wine per day, and 0.96 (0.92–1.01) for every 1 serving of liquor per day. However, alcohol showed an inverse association with RCC in women: the multivariate RR (95%) was 0.60 (0.45–0.80) for every 10g increase in alcohol consumption per day. The multivariate RR (95%CI) was 0.85 (0.53–1.38) for every 1 serving of beer per day, 0.40 (0.22–0.74) for every 1 serving of wine per day, and 0.68 (0.45–1.01) for every 1 serving of liquor per day. There was no significant alcohol-renal cell cancer interactions observed with BMI, smoking or oral contraceptives. Conclusion: Alcohol consumption is inversely associated with the risk of renal cell cancer only in women. Citation Information: Cancer Prev Res 2010;3(1 Suppl):B100.

Abstract A116: Carotenoid intakes and risk of breast cancer by estrogen receptor status: A pooled analysis of 16 prospective cohort studies

Abstract Associations between dietary carotenoid intakes and breast cancer risk by estrogen receptor (ER) status remain unclear. We prospectively investigated these associations using a pooled analysis of the primary data from 16 cohort studies. During follow-up of 996,735 women ranging from 6 to 22 years, 34,524 breast cancer cases (4,552 ER-/19,722 ER+) were identified. We used Cox proportional hazards models to estimate study-specific relative risks (RRs) and 95% confidence intervals (CIs) and pooled the estimates using a random-effects model. In the preliminary analyses, comparing the highest and lowest quintiles of intake, beta-carotene intake was associated with a 10% lower risk of ER- breast cancer (pooled multivariate RR = 0.89 (95% CI: 0.81–0.99), Ptrend = 0.07) but not with risk of ER+ breast cancer (pooled multivariate RR = 1.02 (95% CI: 0.97–1.08), Ptrend = 0.76, Ptest for common effects by ER status = 0.02). Similarly, lutein/zeaxanthin intake was associated with a 13% reduced risk of ER- breast cancer (pooled multivariate RR = 0.87 (95%CI: 0.79–0.96), P trend = 0.04) but not with risk of ER+ breast cancer (pooled multivariate RR = 0.99 (95%CI: 0.93–1.06), Ptrend = 0.33, Ptest for common effects by ER status = 0.03). Alpha-carotene, beta-cryptoxanthin and lycopene intakes were not associated with breast cancer risk regardless of ER status. We observed similar associations when we categorized carotenoid consumption using identical absolute intake cutpoints or modeled intakes as continuous variables. The associations between carotenoid intake and risk of ER- and ER+ breast cancer did not differ by alcohol consumption, smoking habits, or menopausal status (Ptest for interaction > 0.05). Beta-carotene and lutein/zeaxanthin intakes appeared to be associated with a lower risk of ER-breast cancer but not with risk of ER+ breast cancer. Citation Information: Cancer Prev Res 2010;3(1 Suppl):A116.

Choline and betaine intake and risk of breast cancer among post-menopausal women

Background:Choline and betaine, similar to folate, are nutrients involved in one-carbon metabolism and hypothesised to reduce breast cancer risk. No prospective study among post-menopausal women has examined choline and betaine intakes in relation to breast cancer risk.Methods:We examined the intake of choline and betaine and breast cancer risk among 74 584 post-menopausal women in the Nurses’ Health Study. Nutrient intake was assessed using a validated food-frequency questionnaire six times since 1984. During 20 years of follow-up from 1984 until 2004, we documented 3990 incident cases of invasive breast cancer.Results:Overall, choline (mean±s.d.; 326±61 mg per day) and betaine (104±33 mg per day) intake was not associated with a reduced risk of post-menopausal breast cancer. Participants in the highest quintile of intakes had multivariate relative risks of 1.10 (95% confidence interval (95% CI): 0.99–1.22; P-value, test for trend=0.14) for choline and 0.98 (95% CI: 0.89–1.09; P-value, test for trend=0.96) for betaine, compared with those in the lowest quintiles of intakes. The results were similar in breast cancer stratified by hormone receptor (oestrogen receptor/progesterone receptor) status. The association between choline intake and breast cancer risk did not differ appreciably by alcohol intake (non-drinker, <15 or 15+ g per day) or several other breast cancer risk factors, including family history of breast cancer, history of benign breast disease, body mass index, post-menopausal hormone use, and folate intake.Conclusion:We found no evidence that higher intakes of choline and betaine reduce risk of breast cancer among post-menopausal women.

Lack of association between dietary protein intake and risk of stroke among middle-aged men

Prospective cohort studies in Japanese populations have shown an inverse association between dietary protein and stroke risk. However, this association has not been examined among any study populations of US men. Our objective was to examine the relation between dietary protein and risk of stroke in men who participated in the Health Professionals Follow-Up Study. A total of 43,960 men who were free of cardiovascular disease and cancer at baseline were included in the analysis. Dietary protein (total, animal, and vegetable) was assessed with the use of a food-frequency questionnaire at 5 time points during the follow-up period of 1986-2004. Cox proportional hazards models were used to calculate multivariate relative risks and 95% CIs, which represented the effect of the substitution of protein for an equal percentage of energy from carbohydrate. During 18 y of follow-up there were 1057 incident stroke events (638 ischemic, 171 hemorrhagic, and 248 of unknown type). For total stroke, the relative risk for the top quintile of percentage energy from protein compared with the bottom was 1.14 (95% CI: 0.90, 1.43; P for linear trend: 0.43) for total protein, 1.11 (95% CI: 0.87, 1.41; P for linear trend: 0.52) for animal protein, and 0.82 (95% CI: 0.60, 1.12; P for linear trend: 0.17) for vegetable protein. The results were similar when ischemic and hemorrhagic stroke subtypes were considered separately. In contrast to studies in Japanese populations, this study did not show a statistically significant association between total, animal, or vegetable protein and risk of stroke in this population of US men.

Smoking Interaction with Clopidogrel; Another Smoker's Paradox?

The American Heart Association estimates that one in five deaths from cardiovascular disease are directly linked to cigarette smoking. Individuals who smoke are two to six times more likely to develop coronary artery disease than nonsmokers. However, individuals who quit smoking will reduce their risk to levels equivalent to those of a nonsmoker within three years. Refer to the page 119-124 Exposure to cigarette smoke is an established risk factor for coronary heart disease in both Western and Asian countries. The multivariate relative risk of coronary heart disease mortality for current smokers was 1.8-3.7 compared to nonsmokers.1) Poor prognosis in smokers results from: 1) induction of hypercoagulability due to increased platelet activation, dyslipidemia, and endothelial dysfunction; 2) increased catecholamine release leading to increased heart rate, blood pressure, coronary vasoconstriction, and even arrhythmogenic effect; and 3) reduction in oxygen delivery due to increased carbon monoxide levels.2) The term of smoker's paradox has been coined by Barbash et al.3) who reported better outcomes among the smokers receiving thrombolytic therapy for acute myocardial infarction. Similarly, Cohen et al.4) reported that cigarette smoking was associated with a lower rate of subsequent target lesion revascularization in patients undergoing percutaneous coronary intervention (PCI). Hasdai et al.5) reported that current smokers during an index percutaneous intervention had fewer adverse events in the univariable analysis than the nonsmokers and former smokers. This improved can be explained in part by better covariables such as younger age or a more favorable clinical and angiographic profile. Therefore, this term may be misleading.6) Clopidogrel, an inhibitor of the platelet P2Y12 adenosine diphosphate receptor, improves prognosis in patients with acute coronary syndrome (ACS). However, there is significant response variability and a diminished clopidogrel response is associated with an increased risk of ischemic events.7) Smoking induces cytochrome P450 1A2 (CYP1A2), a hepatic enzyme involved in the metabolism of clopidogrel. Clopidogrel shows better inhibition of platelet aggregation in smokers than nonsmokers,8) and smokers are less likely to be hyporesponders than nonsmokers.9) In this issue of the Journal, Cho et al.10) investigated the association between smoking status and post-clopidogrel platelet reactivity in patients with acute myocardial infarction. Differences in the clinical situation and timing of the platelet test could explain the differences with the Bliden study.8) The decreases in CYP1A2 activity induced by smoking may also disappear after three days. The CHARISMA (Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance) trial compared long-term clopidogrel 75 mg/day vs. placebo in patients at high risk for cardiovascular events, and clopidogrel significantly reduced mortality in smokers but not in former or never-smokers.11) In addition to CYP1A2 activation by smoking, smokers may simply be a higher-risk group because of enhanced platelet activity and therefore benefit more from antithrombotic intervention. The Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis In Myocardial Infarction 28 (CLARITY-TIMI 28) trial compared the effect of clopidogrel on angiographic and clinical outcomes in 3,429 ST elevation myocardial infarction patients by smoking intensity: not current smokers (n=1,732), and smokers of 1 to 9 (n=206), 10 to 19 (n=354), 20 to 29 (n=715), and ≥30 cigarettes/day (n=422). Clopidogrel reduced the primary end point of a closed infarct-related artery or death/myocardial infarction, particularly among those who smoked ≥10 cigarettes/day.12) The CURRENT-OASIS 7 (Clopidogrel Optimal Loading Dose Usage to Reduce Recurrent Events/Optimal Antiplatelet Strategy for Interventions) trial, which tested high-dose vs. usual-dose clopidogrel in ACS patients undergoing PCI, showed that smokers (vs. nonsmokers) had significant benefit with the higher clopidogrel dose. Smoking increases the risk for cardiovascular events and mortality in patients with established cardiovascular disease, but clopidogrel treatment may be more effective in smokers. Therefore, the interaction of smoking with acute myocardial infarction deserves further study in more patients using designs that show fewer time limitations.

Age-Modification of Lipoprotein, Lipid, and Lipoprotein Ratio-Associated Risk for Coronary Artery Calcium (from the Multi-Ethnic Study of Atherosclerosis [MESA

Although abnormal lipoproteins and lipoprotein ratios are powerful risk factors for clinical cardiovascular events, these associations are stronger in younger than in older subjects. Whether age modifies the relation of lipoproteins and lipoprotein ratios to the relative risk of subclinical cardiovascular disease (CVD), as assessed by coronary artery calcium (CAC) scores, has not been examined in a contemporary, multiethnic cohort. We performed multivariate relative risk regression analyses to determine the relative risks for associations of lipoproteins and lipoprotein ratios with prevalent CAC in participants in Multi-Ethnic Study of Atherosclerosis (MESA). The participants were community-dwelling adults aged 45 to 84 years without clinically apparent CVD at baseline. We excluded those taking lipid-lowering therapy (15%) and stratified the results by decades of age. A total of 5,092 participants met the inclusion criteria. In the fully adjusted models, per SD of low-density lipoprotein, the age-stratified, adjusted relative risk for CAC was 1.17 (95% confidence interval [CI] 1.07 to 1.28) for those aged 45 to 84 years but was 1.05 (95% CI 1.01 to 1.10) for those aged 75 to 84 years (p-interaction = 0.12). The relative risk per SD of total/high-density lipoprotein cholesterol ratio was 1.20 (95% CI 1.12 to 1.29) for those aged 45 to 54 years but only 1.04 (95% CI 1.00 to 1.09) for those aged 75 to 84 years (p-interaction <0.001). The lipoproteins levels and lipoprotein ratios were associated with increased relative risks for CAC across all age categories. However, these associations were markedly attenuated by age. In conclusion, abnormal lipoprotein levels in middle age are a powerful risk factor for early atherosclerosis, as manifested by prevalent CAC.

Body size and risk of MS in two cohorts of US women

To examine whether obesity during childhood, adolescence, or adulthood is associated with an increased risk of multiple sclerosis (MS). Women in the Nurses' Health Study (n = 121,700) and Nurses' Health Study II (n = 116,671) provided information on weight at age 18 and weight and height at baseline, from which body mass index was derived. Women also selected silhouettes representing their body size at ages 5, 10, and 20. Over the total 40 years of follow-up in both cohorts combined, we confirmed 593 cases of MS. Cox proportional hazards models, adjusting for age, latitude of residence, ethnicity, and cigarette smoking, were used to estimate the rate ratios and 95% confidence intervals (CI). Obesity at age 18 (body mass index > or =30 kg/m(2)) was associated with a greater than twofold increased risk of MS (multivariate relative risk(pooled) = 2.25, 95% CI: 1.50-3.37, p trend <0.001). After adjusting for body size at age 20, having a large body size at ages 5 or 10 was not associated with risk of MS, whereas a large body size at age 20 was associated with a 96% increased risk of MS (95% CI: 1.33-2.89, p trend = 0.009). No significant association was found between adult body mass and MS risk. Obese adolescents have an increased risk of developing multiple sclerosis (MS). Although the mechanisms of this association remain uncertain, this result suggests that prevention of adolescent obesity may contribute to reduced MS risk.

Energy Intake and Risk of Postmenopausal Breast Cancer: An Expanded Analysis in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) Cohort

Although animal experiments have consistently shown a positive relationship between breast cancer and energy intake, evidence from human studies remains inconclusive. In the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial cohort, 29,170 women, ages 55 to 75 years, who successfully completed a food frequency questionnaire (FFQ) at entry (1993-2001), were followed through 2007, and 1,319 incident breast cancers were ascertained (median time from FFQ completion to diagnosis, 4.4 years). Women in the highest quartile of energy intake, relative to the lowest, had modestly, but significantly, increased breast cancer risk [multivariate relative risk (RR), 1.21; 95% confidence interval (95% CI), 1.03-1.42; P(trend) = 0.03]. The inclusion of body mass index and physical activity in the model reduced risk slightly (RR, 1.18; 95% CI, 1.00-1.39; P(trend) = 0.07). However, in similar analyses using energy intake from a FFQ administered approximately five years after entry (27,428 women; 806 incident breast cancers; median time from FFQ completion to diagnosis, 2.7 years), women in the highest and lowest quartiles of energy intake had similar risk. When follow-up time after the first FFQ was divided into three 4-year periods, the multivariate RRs for high versus low energy intake increased from 1.21 to 1.37 to 1.55 with increasing time since dietary assessment. Although the divergent results for the two FFQs could be due to subtle questionnaire differences, our findings suggest a modest positive association between energy intake and postmenopausal breast cancer that strengthens with time since dietary assessment.

Long-Term and Recent Recreational Physical Activity and Survival After Breast Cancer: The California Teachers Study

Long-term physical activity is associated with lower breast cancer risk. Little information exists on its association with subsequent survival. California Teachers Study cohort members provided information in 1995-1996 on long-term (high school through age 54 years) and recent (past 3 years) participation in moderate and strenuous recreational physical activities. The 3,539 women diagnosed with invasive breast cancer after cohort entry and through December 31, 2004, were followed through December 31, 2005. Of these, 460 women died, 221 from breast cancer. Moderate and strenuous physical activities were combined into low (<or=0.50 h/wk/y of any activity), intermediate (0.51-3.0 h/wk/y of moderate or strenuous activity but no activity >3.0 h/wk/y), or high activity (>3.0 h/wk/y of either activity type). Multivariable relative risks (RR) and 95% confidence intervals (95% CI) for mortality were estimated using Cox proportional hazards methods, adjusting for race/ethnicity, estrogen receptor status, disease stage, and baseline information on comorbidities, body mass index, and caloric intake. Women with high or intermediate levels of long-term physical activity had lower risk of breast cancer death (RR, 0.53; 95% CI, 0.35-0.80; and RR, 0.65; 95% CI, 0.45-0.93, respectively) than women with low activity levels. These associations were consistent across estrogen receptor status and disease stage, but were confined to overweight women. Deaths due to causes other than breast cancer were related only to recent activity. Consistent long-term participation in physical activity before breast cancer diagnosis may lower risk of breast cancer death, providing further justification for public health strategies to increase physical activity throughout the lifespan.

Height, Body Mass Index, and Physical Activity in Relation to Glioma Risk

Whether energy balance during early life and/or adulthood is related to glioma risk is unknown. We therefore investigated height, body mass index (BMI), and physical activity in relation to glioma risk in the prospective NIH-AARP Diet and Health Study. Participants completed a baseline questionnaire (sent in 1995-1996) inquiring about height, weight, and potential confounders. A second questionnaire (sent in 1996) inquired about physical activity during ages 15 to 18, 19 to 29, and 35 to 39 years and the past 10 years and body weight at ages 18, 35, and 50 years. During follow-up from 1995/1996 to 2003, we documented 480 cases of glioma among 499,437 respondents to the baseline questionnaire and 257 cases among 305,681 respondents to the second questionnaire. Glioma risk among tall persons (>or=1.90 m) was twice that of short persons [<1.60 m; multivariate relative risk (RR), 2.12; 95% confidence interval (95% CI), 1.18-3.81; P(trend) = 0.006]. Risk among participants who were obese (BMI 30.0-34.9 kg/m(2)) at age 18 years was nearly four times that of persons of normal weight (BMI 18.5-24.9 kg/m(2)) at age 18 years (RR, 3.74; 95% CI, 2.03-6.90; P(trend) = 0.003); 11 cases were obese at age 18 years. Risk among participants who were active during ages 15 to 18 years was 36% lower than that of persons who were inactive during ages 15 to 18 years (RR, 0.64; 95% CI, 0.44-0.93; P(trend) = 0.02). BMI and physical activity after age 18 years were unrelated to glioma risk. Adult height, BMI during adolescence, and physical activity during adolescence were each associated with glioma risk, supporting a role for early-life energy balance in glioma carcinogenesis.

Prenatal acetaminophen exposure and risk of wheeze at age 5 years in an urban low-income cohort

BackgroundAcetaminophen has been associated with asthma and is in part metabolised via the glutathione pathway. Inner-city minority children have high asthma morbidity and a relatively high frequency of a minor...

Family history of melanoma and Parkinson disease risk

Co-occurrence of Parkinson disease (PD) and melanoma has been reported in numerous studies. If this was due to common genetic mechanisms, a positive family history of melanoma would be associated with an excessive PD risk, independent of environmental risk factors for PD. We prospectively examined associations between a family history of melanoma and PD among 157,036 men and women free of PD at baseline (1990 for men and 1982 for women) who participated in 2 ongoing US cohorts: the Health Professional Follow-up Study and the Nurses' Health Study. Information on family history of melanoma in parents or siblings was assessed via questionnaire. Relative risks and 95% confidence intervals were estimated using Cox proportional hazards models and pooled using a fixed-effects model. During 14-20 years follow-up, we identified 616 incident PD cases. A family history of melanoma in a first-degree relative was associated with a higher risk of PD (multivariate relative risk = 1.85; 95% confidence interval: 1.2, 2.8; p = 0.004), after adjusting for smoking, ethnicity, caffeine intake, and other covariates. In contrast, we did not observe significant associations between a family history of colorectal, lung, prostate, or breast cancer and PD risk. Interactions between melanoma family history and age, smoking, or caffeine intake were not significant and subgroup analyses according to these factors generated similar results. Our findings support the notion that melanoma and Parkinson disease (PD) share common genetic components. The genetic determinants of melanoma could therefore be explored as susceptibility candidate genes for PD.

Relationship between common carotid intima-media thickness and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis

BackgroundMean maximum carotid intima-media thickness (CIMT) is associated with both coronary artery disease and cerebral thromboembolism. Thoracic aortic calcification (TAC) detected by computed tomography (CT) is also highly associated with vascular disease and cardiovascular risk. No previous study has examined the relationship between CIMT and TAC in a large patient cohort. We performed a cross-sectional study to determine whether, at baseline, there is a relationship between CIMT and CT-determined TAC score. MethodsIn the Multi-Ethnic Study of Atherosclerosis, the study cohort included a population based sample of four ethnic groups (Chinese, White, Hispanic and African-American) of 6814 women and men ages 45–84 years. After exclusion of 198 persons due to incomplete information, we compared results of 6616 participants with both CIMT and TAC. TAC was measured from the lower edge of the pulmonary artery bifurcation to the cardiac apex. CIMT at the common carotid artery site was represented as the mean maximal CIMT of the right and left near and far walls, respectively. Multivariable relative risk regression analysis was used to evaluate relationships between TAC and CIMT. ResultsThe prevalence of TAC was 28% (n=1846) and the mean maximum (+SD) CIMT was 0.87±0.19mm. A higher prevalence of TAC was noted across increasing CIMT quartiles (1st: 12%, 2nd: 21%, 3rd: 30%, 4th: 49%, p<0.0001). One standard deviation increase in CIMT was associated with a 16% higher likelihood for presence of TAC after adjusting for demographics and cardiovascular disease (CVD) risk factors (95% CI: 1.12–1.26). In addition, individuals with CIMT in the highest quartile, as compared to those with CIMT in the first quartile, had a 76% higher likelihood for presence of TAC (prevalence ratio [PR]: 1.76, 95% CI: 1.37–2.26). In race-ethnic stratified analyses, similar associations were seen in all groups. Among those with TAC>0, a higher CIMT was significantly associated with continuous TAC scores (log transformed) in the overall population as well as among all ethnic-racial groups. ConclusionsOur study demonstrates that TAC is associated with increasing severity of carotid atherosclerotic burden as measured by CIMT. The combined utility of these two noninvasive measures of subclinical atherosclerosis for CVD risk assessment needs to be determined in future studies.

Conjugated linoleic acid intake and breast cancer risk in a prospective cohort of Swedish women

BackgroundStudies in animals and in vitro suggest that conjugated linoleic acids (CLAs), a group of fatty acids found mainly in dairy products and in the meat of ruminants, have protective effects against mammary carcinogenesis. However, findings from epidemiologic studies on CLA intake in relation to breast cancer risk are sparse and inconsistent. ObjectiveThe objective was to examine prospectively the association between CLA intake and the incidence of invasive breast cancer in the Swedish Mammography Cohort. DesignIn 1987–1990, 61,433 cancer-free women completed a food-frequency questionnaire from which we estimated each woman’s CLA intake. Cox proportional hazards models were used to estimate relative risks, adjusted for breast cancer risk factors. ResultsDuring a mean follow-up of 17.4 y, 2952 incident cases of breast cancer were ascertained. In multivariate analyses, no significant association was observed between dietary CLA intake and risk of breast cancer, overall or by estrogen receptor (ER) and progesterone receptor (PR) status. The multivariate relative risks (95% CI) for the highest quintile of CLA intake (≥155.7 mg/d) compared with the lowest quintile (<78.1 mg/d) were 1.04 (0.92, 1.17) for overall breast cancer, 1.09 (0.90, 1.31) for ER+/PR+ tumors, 1.09 (0.78, 1.53) for ER+/PR– tumors, and 0.84 (0.57, 1.24) for ER–/PR– tumors. ConclusionThe results provide no evidence of a protective effect of CLA against breast cancer development in women.

Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabetes mellitus

BackgroundDiet is a key component of a healthy lifestyle in the prevention of type 2 diabetes mellitus (T2DM). The role of long-chain omega-3 (n–3) fatty acids (LCFAs) in the development of T2DM remains unresolved. ObjectiveWe examined the association between dietary LCFAs and incidence of T2DM in 3 prospective cohorts of women and men. DesignWe followed 195,204 US adults (152,700 women and 42,504 men) without preexisting chronic disease at baseline for 14 to 18 y. Fish and LCFA intakes were assessed at baseline and updated at 4-y intervals by using a validated food-frequency questionnaire. ResultsDuring nearly 3 million person-years of follow-up, 9380 new cases of T2DM were documented. After adjustment for other dietary and lifestyle risk factors, LCFA intake was positively related to incidence of T2DM. The pooled multivariate relative risks in 3 cohorts across increasing quintiles of LCFAs were as follows: 1 (reference), 1.00 (95% CI: 0.91, 1.09), 1.05 (95% CI: 0.97, 1.13), 1.17 (95% CI: 1.07, 1.28), and 1.24 (95% CI: 1.09, 1.40) (P for trend < 0.001). Compared with those who consumed fish less than once per month, the relative risk of T2DM was 1.22 (95% CI: 1.08, 1.39) for women who consumed ≥5 servings fish/wk (P for trend <0.001). ConclusionsWe found no evidence that higher consumption of LCFAs and fish reduces the risk of T2DM. Instead, higher intakes may modestly increase the incidence of this disease. Given the beneficial effects of LCFA intake on many cardiovascular disease risk factors, the clinical relevance of this relation and its possible mechanisms require further investigation.

DASH-Style Diet Associates with Reduced Risk for Kidney Stones

The impact of the Dietary Approaches to Stop Hypertension (DASH) diet on kidney stone formation is unknown. We prospectively examined the relation between a DASH-style diet and incident kidney stones in the Health Professionals Follow-up Study (n = 45,821 men; 18 yr of follow-up), Nurses' Health Study I (n = 94,108 older women; 18 yr of follow-up), and Nurses' Health Study II (n = 101,837 younger women; 14 yr of follow-up). We constructed a DASH score based on eight components: high intake of fruits, vegetables, nuts and legumes, low-fat dairy products, and whole grains and low intake of sodium, sweetened beverages, and red and processed meats. We used Cox hazards regression to adjust for factors that included age, BMI, and fluid intake. Over a combined 50 yr of follow-up, we documented 5645 incident kidney stones. Participants with higher DASH scores had higher intakes of calcium, potassium, magnesium, oxalate, and vitamin C and had lower intakes of sodium. For participants in the highest compared with the lowest quintile of DASH score, the multivariate relative risks for kidney stones were 0.55 (95% CI, 0.46 to 0.65) for men, 0.58 (95% CI, 0.49 to 0.68) for older women, and 0.60 (95% CI, 0.52 to 0.70) for younger women. Higher DASH scores were associated with reduced risk even in participants with lower calcium intake. Exclusion of participants with hypertension did not change the results. In conclusion, consumption of a DASH-style diet is associated with a marked decrease in kidney stone risk.

Antioxidant Supplementation and Risk of Incident Melanomas

To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants. Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort). Western Washington State. A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry. Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk.

Coffee and black tea consumption and risk of breast cancer by estrogen and progesterone receptor status in a Swedish cohort

Coffee and tea consumption has been inconsistently associated with the risk of breast cancer. We examined the associations of caffeinated coffee and black tea consumption with the incidence of breast cancer, overall and by estrogen receptor (ER) and progesterone receptor (PR) status of the tumor, in the Swedish Mammography Cohort. We prospectively followed up 61,433 women who were cancer free at baseline in 1987-1990. Coffee and tea consumption was assessed with a food-frequency questionnaire administered at baseline and in 1997. Incident invasive breast cancer cases were ascertained by linkage with Swedish Cancer registers. Over a mean follow-up of 17.4 years, through December 2007, there were 2,952 incident cases of invasive breast cancer identified. Coffee consumption was not associated with risk of overall breast cancer (multivariate relative risk (RR) for ≥ 4 cups/day versus <1 cup/day = 1.02; 95% CI, 0.87-1.20) or with any subtype defined by ER and PR status. Black tea consumption was significantly positively associated with risk of overall breast cancer and ER+/PR+ tumors. The multivariate RRs comparing ≥ 2 cups/day of tea with no consumption were 1.22 (95% CI, 1.05-1.42) for overall breast cancer and 1.36 (95% CI, 1.09-1.69) for ER+/PR+ tumors. Findings from this prospective study do not support a role of coffee consumption in the development of breast cancer but suggest that black tea consumption may be positively associated with risk of ER+/PR+ tumors.

Alcohol and Risk of Breast Cancer by Histologic Type and Hormone Receptor Status in Postmenopausal Women: The NIH-AARP Diet and Health Study

Little is known about the association between alcohol and breast cancer by different tumor characteristics. The study consisted of 184,418 postmenopausal women aged 50-71 years in the National Institutes of Health-AARP Diet and Health Study (1995-2003). Alcohol use, diet, and potential risk factors for cancer were assessed with a mailed questionnaire at baseline. The relative risks and 95% confidence intervals were estimated by using Cox proportional hazards regression. Breast cancer cases and estrogen receptor and progesterone receptor status were identified through linkage to state cancer registries. During an average of 7 years of follow-up, 5,461 breast cancer cases were identified. Alcohol was significantly positively associated with total breast cancer: Even a moderate amount of alcohol (>10 g/day) significantly increased breast cancer risk. In a comparison of >35 g versus 0 g/day, the multivariate relative risks were 1.35 (95% confidence interval (CI): 1.17, 1.56) for total breast cancer, 1.46 (95% CI: 1.22, 1.75) for ductal tumors, and 1.52 (95% CI: 0.95, 2.44) for lobular tumors. The multivariate relative risks for estrogen receptor-positive/progesterone receptor-positive, estrogen receptor-positive/progesterone receptor-negative, and estrogen receptor-negative/progesterone receptor-negative tumors were 1.46 (95% CI: 1.12, 1.91) for >35 g versus 0 g/day, 1.13 (95% CI: 0.73, 1.77) for >20 g versus 0 g/day, and 1.21 (95% CI: 0.79, 1.84) for >20 g versus 0 g/day, respectively. Moderate consumption of alcohol was associated with breast cancer, specifically hormone receptor-positive tumors.