American Journal of Epidemiology

The timeliness of survival monitoring is particularly important in a field such as transplantation medicine, where progress occurs rapidly. Period analysis, a method successfully applied for improving the timeliness of survival monitoring in population-based cancer survival analysis, could potentially be useful in the field of transplantation as well. Using data from the Collaborative Transplant Study, the authors compared the ability of traditional, cohort-based analysis methods and the period analysis method to provide timely 5-year graft and patient survival estimates for kidney, heart, and liver transplants in 6 age groups (0–17, 18–29, 30–39, 40–49, 50–59, ≥60 years) on 378 occasions between 1990–1992 and 2000–2002. Overall, period estimates provided superior predictions for the survival of most recent transplants on 344 of 378 occasions (91%); in the organ-specific analysis, this proportion ranged between 83% for heart and 100% for kidney graft survival. This evaluation provides evidence that the period analysis method can improve the timeliness of survival monitoring in solid organ transplantation. The method appears useful for providing more up-to-date long-term survival estimates than traditional methods, and its use in pertinent studies is encouraged.

Changes in the rates of condom use and number of sexual partners were evaluated among 140 female sex workers in Kibera, Kenya, participating in a 6-month study of diaphragm safety and acceptability for prevention of sexually transmitted infections conducted in 2004&ndash;2005. Analyses were stratified by partner type. Multivariable Tobit regression modeling was used to assess the association between study visit and proportion of acts protected. Participants completed 140 baseline visits and 390 bimonthly follow-up visits. The mean percentage of coital acts reported as protected by a condom increased from 56% at baseline to 68% at the 6-month visit (P < 0.01). Similar increases were observed for condom use by all partner types. Additionally, the mean number of sexual partners decreased over the study. Furthermore, consistent (i.e., 100%) diaphragm use during follow-up was associated with a higher proportion of coital acts protected by a condom in analyses adjusted for study visit and coital frequency. These findings suggest that, despite concerns that introduction of the diaphragm would result in more risky sexual behaviors, reported condom use increased and number of partners decreased.

Use of smokeless tobacco in the United States has been relatively constant in recent years, as tobacco companies continue aggressive marketing campaigns. The health effects of smokeless tobacco use need further documentation. Thus, the authors examined whether current use of smokeless tobacco was associated with increased incidence of cardiovascular disease (CVD) in 14,498 men and women aged 45&ndash;64 years at baseline (1987&ndash;1989) in the Atherosclerosis Risk in Communities (ARIC) Study. There were 2,572 incident CVD events (myocardial infarction, coronary revascularization, coronary death, or stroke) during a median of 16.7 years of follow-up (maximum = 19.1 years). Current use of smokeless tobacco at baseline was associated with 1.27-fold greater CVD incidence (95% confidence interval: 1.06, 1.52) than was nonuse, independently of demographic, socioeconomic, and lifestyle and other tobacco-related variables. Past use of smokeless tobacco was not associated with CVD incidence. In conclusion, current use of smokeless tobacco was associated with increased risk of CVD incidence in ARIC cigarette nonsmokers. Current users of smokeless tobacco should be informed of its harm and advised to quit the practice. Current cigarette smokers should also be given sufficient information on safe, therapeutic methods of quitting which do not include switching to smokeless tobacco.

Recent interest has focused on the role that inflammation may play in the development of prostate cancer and whether use of aspirin or other nonsteroidal antiinflammatory drugs (NSAIDs) affects risk. In a population-based case-control study designed to investigate the relation between these medications and prostate cancer risk, detailed exposure data were analyzed from 1,001 cases diagnosed with prostate cancer between January 1, 2002, and December 31, 2005, and 942 age-matched controls from King County, Washington. A significant 21% reduction in the risk of prostate cancer was observed among current users of aspirin compared with nonusers (95% confidence interval (CI): 0.65, 0.96). Long-term use of aspirin (>5 years: odds ratio = 0.76, 95% CI: 0.61, 0.96) and daily use of low-dose aspirin (odds ratio = 0.71, 95% CI: 0.56, 0.90) were also associated with decreased risk. There was no evidence that the association with aspirin use varied by disease aggressiveness, but there was effect modification (Pinteraction = 0.02) with a genetic variant in prostaglandin-endoperoxide synthase 2 (PTGS2) (rs12042763). Prostate cancer risk was not related to use of either nonaspirin NSAIDs or acetaminophen. These results contribute further evidence that aspirin may have chemopreventive activity against prostate cancer and highlight the need for additional research.

In numerous studies, investigators have examined the association of active smoking with risk of invasive breast cancer, but to the authors&rsquo; knowledge, no cohort study has assessed smoking in relation to the risk of in situ breast cancer, the postulated penultimate stage preceding invasive breast cancer. The authors examined the latter association using data collected at baseline from 63,393 women in the Women's Health Initiative Clinical Trial. A total of 486 cases of ductal carcinoma in situ (DCIS) of the breast were identified during 8 years of follow-up between 1993 and 2005. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. For the primary analysis, invasive breast cancer was treated as a competing risk. After adjustment for covariates, associations with smoking status, smoking intensity, duration, pack-years, and age at quitting were all close to the null value and showed few meaningful trends. Sensitivity analyses performed to address different possibilities with respect to the natural history of breast cancer also did not provide consistent evidence of an association of smoking with DCIS. The results of this large cohort study provide little support for an association of cigarette smoking with risk of DCIS in postmenopausal women.

The authors examined nutritional risk factors for prostate cancer among 9,559 participants in the Prostate Cancer Prevention Trial (United States and Canada, 1994&ndash;2003). The presence or absence of cancer was determined by prostate biopsy, which was recommended during the trial because of an elevated prostate-specific antigen level or an abnormal digital rectal examination and was offered to all men at the trial's end. Nutrient intake was assessed using a food frequency questionnaire and a structured supplement-use questionnaire. Cancer was detected in 1,703 men; 127 cancers were high-grade (Gleason score 8&ndash;10). There were no associations of any nutrient or supplement with prostate cancer risk overall. Risk of high-grade cancer was associated with high intake of polyunsaturated fats (quartile 4 vs. quartile 1: odds ratio = 2.41, 95% confidence interval (CI): 1.33, 4.38). Dietary calcium was positively associated with low-grade cancer but inversely associated with high-grade cancer (for quartile 4 vs. quartile 1, odds ratios were 1.27 (95% CI: 1.02, 1.57) and 0.43 (95% CI: 0.21, 0.89), respectively). Neither dietary nor supplemental intakes of nutrients often suggested for prostate cancer prevention, including lycopene, long-chain n-3 fatty acids, vitamin D, vitamin E, and selenium, were significantly associated with cancer risk. High intake of n-6 fatty acids, through their effects on inflammation and oxidative stress, may increase prostate cancer risk.

The purpose of this analysis was to characterize the natural history of weight change in the years prior to death among older persons and to examine how this pattern varies according to longevity and cause of death. Weight trajectories were analyzed by using data from 800 male decedents from the Baltimore Longitudinal Study of Aging (Maryland, 1958&ndash;2005) observed beginning an average of 19 years before death. A model including 3 distinct periods of weight change (weight stability/gain, mild weight loss, and accelerated weight loss before death) provided the best fit for all age-at-death groups. Approximately 9 years before death, the rate of weight loss increased to an average of 0.39 kg/year (P < 0.001) for all-cause mortality. For cancer deaths, weight loss accelerated significantly 3 years before death, regardless of age group. For cardiovascular deaths, the best-fitting inflection point increased with age, from 5 years for participants aged 60&ndash;69 years to 9&ndash;10 years before death for those aged 80 years or older. Results suggest that weight loss in older persons may begin earlier than previously believed. The duration of weight loss for noncancer deaths suggests that even distal changes in energy balance may be linked to risk of death.

Sibling and twin study designs provide control for confounding factors that are typically unmeasured in traditional cohort studies. Using nationally representative data from the National Longitudinal Study of Adolescent Health collected at 3 visits during 1994&ndash;2002, the authors evaluated the longitudinal association between birth weight and later obesity in a traditional cohort study (n = 13,763; ages 11&ndash;21 years at baseline), controlling for sex, age, race/ethnicity, and parental education. Among persons with a nonobese mother, high birth weight (>4 kg) participants were more likely than normal birth weight (&ge;2.5&ndash;&le;4 kg) participants to become obese later in life (incidence rate ratio = 1.46, 95% confidence interval: 1.28, 1.67). In a matched sibling pair sample (full siblings: n = 513; monozygotic twins: n = 207; dizygotic twins: n = 189), the authors examined longitudinal within-pair differences. Birth weight difference was positively associated with body mass index difference later in life for female monozygotic pairs only (&beta; = 2.67, 95% confidence interval: 0.99, 4.35). Given the null associations observed in the sibling sample, the commonly observed positive association between birth weight and later obesity from cohort analyses may be attributed to confounding by maternal characteristics. Further research is needed to identify specific factors that contribute to the birth weight&ndash;obesity relation.

The health consequences of obesity and overweight have been well documented, but less research has examined their social and economic consequences. This paper examines the long-term consequences of early adult overweight for midlife health and socioeconomic attainment using prospective nationally representative panel data from American adults in the Monitoring the Future Study (1986&ndash;2008). Growth mixture models identified 2 distinct latent classes of trajectories of body mass index (BMI) from age 19 to 35 years: a persistently overweight class (BMI >25 kg/m2) and a second class exhibiting more moderate growth in BMI to age 35 years. Women (odds ratio (OR) = 2.16, 95% confidence interval (CI): 1.39, 3.36) and those from a lower childhood socioeconomic position (OR = 1.71, 95% CI: 1.30, 2.24) were more likely to be in the persistently overweight class. Compared with those in the moderately increasing BMI class, those in the persistently overweight class were more likely to have a chronic health problem at age 40 years (OR = 2.74, 95% CI: 2.20, 3.43), to have no further education beyond high school (OR = 1.33, 95% CI: 1.04, 1.69), and to have a higher odds of receiving welfare or unemployment compensation at age 40 years (OR = 1.76, 95% CI: 1.49, 2.04). These findings highlight the importance of addressing persistent obesity and overweight early in the life course.

The authors aimed to determine the relation between birth-weight variations within the normal range and intelligence in young adulthood. A historical birth cohort study was conducted. Data from the Medical Birth Register of Norway were linked with register data from the Norwegian National Conscript Service. The sample comprised 52,408 sibships of full brothers who were born singletons at 37&ndash;41 completed weeks&rsquo; gestation during 1967&ndash;1984 in Norway and were intelligence-tested at the time of mandatory military conscription. Generalized estimating equations were used to fit population-averaged panel data models. The analyses showed that in men with birth weights within the 10th&ndash;90th percentile range, a within-family difference of 1 standard deviation in birth weight standardized to gestational age was associated with a within-family difference of 0.07 standard deviation (99% confidence interval: 0.03, 0.09) in intelligence score, after adjustment for a range of background factors. There was no significant between-family association after adjustment for background factors. In Norwegian males, normal variations in intrauterine growth are associated with differences in intelligence in young adulthood. This association is probably not due to confounding by familial and parental characteristics.

The authors discuss how the sibship design can be used to detect and control for familial confounding. Family-level confounding is especially problematic when estimating modest individual-level effects in the presence of familial confounders with large effects. This circumstance arises frequently in studies which relate indicators of fetal growth, such as birth weight, to outcomes that are strongly associated with parental socioeconomic status and genes. The study by Eriksen et al. in this issue of the Journal (Am J Epidemiol. 2010;172(5):530&ndash;536) uses the sibship design to capture the relation between birth weight, gestational age, and intelligence score among Norwegian males born as singletons at 37&ndash;41 completed weeks&rsquo; gestation during 1967&ndash;1984. Their study illustrates how valuable the design can be in this kind of scenario. It also illustrates the potential complexity of sibship studies and the challenges they present for appropriate interpretation.

Epidemiology is at the center of translational science. Uniquely among biomedical disciplines, the methods and perspective of epidemiology span research from discovery to effective interventions and ultimately to their dissemination and implementation. However, shorthand designations for various phases of translational science, such as "T1, T2, T3, and T4," may be proliferating past the level of their usefulness. It is worthwhile to reflect on the actual nature of the science undertaken by epidemiologists along the continuum of discovery to application. The new challenge for epidemiology is the integration of knowledge and effective interventions into various societal settings working with allied disciplines not necessarily in the biomedical domain to ensure that these interventions have their intended effects on individual and public health.

Recent emphasis on translational research (TR) is highlighting the role of epidemiology in translating scientific discoveries into population health impact. The authors present applications of epidemiology in TR through 4 phases designated T1&ndash;T4, illustrated by examples from human genomics. In T1, epidemiology explores the role of a basic scientific discovery (e.g., a disease risk factor or biomarker) in developing a "candidate application" for use in practice (e.g., a test used to guide interventions). In T2, epidemiology can help to evaluate the efficacy of a candidate application by using observational studies and randomized controlled trials. In T3, epidemiology can help to assess facilitators and barriers for uptake and implementation of candidate applications in practice. In T4, epidemiology can help to assess the impact of using candidate applications on population health outcomes. Epidemiology also has a leading role in knowledge synthesis, especially using quantitative methods (e.g., meta-analysis). To explore the emergence of TR in epidemiology, the authors compared articles published in selected issues of the Journal in 1999 and 2009. The proportion of articles identified as translational doubled from 16% (11/69) in 1999 to 33% (22/66) in 2009 (P = 0.02). Epidemiology is increasingly recognized as an important component of TR. By quantifying and integrating knowledge across disciplines, epidemiology provides crucial methods and tools for TR.

The authors examined the association between circulating 25-hydroxyvitamin D3 (25(OH)D3), the best indicator of total vitamin D exposure, and incident, sporadic colorectal adenoma risk in a pooled analysis of primary data from 3 colonoscopy-based case-control studies conducted in Minnesota, North Carolina, and South Carolina between 1991 and 2002. The pooled study included 616 colorectal adenoma cases and 770 polyp-free controls. Multivariable logistic regression was used to estimate the association between circulating 25(OH)D3 and colorectal adenoma risk. Stratified analyses and the likelihood ratio test were used to examine effect modification by various risk factors. In the pooled analysis, higher circulating 25(OH)D3 concentrations were statistically significantly associated with decreased colorectal adenoma risk (highest vs. lowest quartile odds ratio = 0.59, 95% confidence interval: 0.41, 0.84). The observed inverse association was stronger among participants who used nonsteroidal antiinflammatory drugs regularly (highest vs. lowest quartile odds ratio = 0.33, 95% confidence interval: 0.19, 0.56). Inverse associations between 25(OH)D3 and colorectal adenoma did not differ substantially by other risk factors or by adenoma characteristics. These findings support the hypothesis that greater vitamin D exposure may reduce the risk of colorectal adenoma and suggest that it may do so more strongly in combination with antiinflammatory agents.

In this systematic review, the authors aimed to assess the effectiveness of community programs for prevention of cardiovascular disease (CVD). They searched numerous electronic databases (CDSR, DARE, HTA, EED, and CENTRAL via the Cochrane Library, MEDLINE, MEDLINE In Process, EMBASE, CINAHL, PsycINFO, HMIC, and ASSIA) and relevant Web sites from January 1970 to mid-July 2008. Controlled studies of community programs for the primary prevention of CVD were included. Net changes in CVD risk factors were used to generate an overall index for net change in 10-year CVD risk. The authors identified 36 relevant community programs that took place between 1970 and 2008. These programs were multifaceted interventions employing combinations of media, screening, and counseling activities and environmental changes and were primarily evaluated using controlled before-after studies. In 7 studies, investigators reported changes in CVD/total mortality rates, and in 5 they reported net changes. In all cases, these net changes were positive but were largely nonsignificant. In 22 studies, investigators reported changes in physiologic CVD risk factors, and there was a positive trend in the calculated CVD risk score. The average net reduction in 10-year CVD risk was 0.65%. Community programs for CVD prevention appear to have generally achieved favorable changes in overall CVD risk and, with adaptation to current circumstances, deserve continued consideration as possible approaches to preventing CVD.

Multiple imputation is increasingly recommended in epidemiology to adjust for the bias and loss of information that may occur in analyses restricted to study participants with complete data ("complete-case analyses"). However, little guidance is available on applying the method, including which variables to include in the imputation model and the number of imputations needed. Here, the authors used multiple imputation to analyze the prevalence of wheeze among 81-month-old children in the Avon Longitudinal Study of Parents and Children (Avon, United Kingdom; 1991&ndash;1999) and the association of wheeze with gender, maternal asthma, and maternal smoking. The authors examined how inclusion of different types of variables in the imputation model affected point estimates and precision, and assessed the impact of number of imputations on Monte Carlo variability. Inclusion of variables associated with the outcome in the imputation model increased odds ratios and reduced standard errors. When only 5 or 10 imputations were used, variability due to the imputation procedure was substantial enough to affect conclusions. Careful preliminary analysis identified the scope for multiple imputation to reduce bias and improve efficiency and provided guidance for building the imputation model. When data are missing, such preliminary analyses should be routinely undertaken and reported, regardless of whether multiple imputation is used in the final analysis.

This paper describes a multistage process to improve the completeness and time-/cost-effectiveness of ascertaining deaths in large employee cohorts. The process uses the vital status data service of the Social Security Administration (SSA) to identify people who can be confirmed as living, in order to reduce the number of records submitted for a National Death Index (NDI) search. The accuracy of SSA results is verified by submitting a sample of known-living and known-deceased people. For the NDI search results, an algorithm based on a discrete combination of matching variables is applied to distinguish NDI records as true, false, or questionable matches to reduce the number of death certificate requests to state offices. Subsequent decision making is based on manual reviews at various stages. In a cohort of over 200,000 employees, an SSA vital status search reduced the size of the NDI death record search by 85%. The algorithm sorted thousands of NDI records into 15 distinct strata and reduced the number of death certificate requests by 76%. The authors believe that the matching process is enhanced by obtaining paper copies of death certificates from the states, because death certificates often provide additional information and aid in determining true matches to company employees.

Given the recent evolution of therapeutic trends, the frequency and determinants of multiclass-resistant HIV infection in the modern combination highly active antiretroviral therapy (HAART) era are less well understood. In this study, the authors characterize the epidemiology of antiretroviral multiclass resistance among HAART-na&iuml;ve patients enrolled in a province-wide HAART distribution program in British Columbia, Canada. HAART and resistance testing are free to eligible individuals in British Columbia. This study was based on patients who initiated na&iuml;ve on HAART and were followed during January 1, 2000&ndash;June 30, 2007. Explanatory logistic and survival models were built to identify those factors most influential in the emergence of multiclass resistance. Among the 1,820 individuals in our study, 833 (46%) were tested for antiretroviral resistance at least once during their follow-up. Multiclass resistance was observed in 142 individuals (n = 833; 17%) during a median follow-up of 14 months (interquartile range, 3&ndash;34 months) (incidence rate, 0.8 cases/1,000 person-months). The authors found that initial nonnucleoside reverse transcriptase inhibitor-based HAART was the main determinant of multiclass resistance. Given that these inhibitors are still widely used, priority should be given to make resistance testing and viral load monitoring a standard part of human immunodeficiency virus care to maximize the long-term efficacy and efficiency of HAART.

The authors assessed the relation between exposure to dampness and molds in dwellings and the development of allergic rhinitis in childhood in a 6-year, population-based prospective cohort study of 1,863 children aged 1&ndash;7 years at baseline in 1991 (follow-up rate, 77%) from Espoo, Finland. The studied exposures were history of water damage, presence of moisture and visible mold, and perceived mold odor in the home, based on parent-administered questionnaire. A total of 246 (13.2%) children developed physician-diagnosed allergic rhinitis during the study period, resulting in an incidence rate of 440 cases per 10,000 person-years (95% confidence interval (CI): 387, 499). In logistic regression adjusting for confounding, any mold or dampness exposure indicator at baseline (adjusted odds ratio = 1.55, 95% CI: 1.10, 2.18), at follow-up (adjusted odds ratio = 1.62, 95% CI: 1.21, 2.18), or both (adjusted odds ratio = 1.96, 95% CI: 1.29, 2.98) was an important independent determinant of the risk of allergic rhinitis. Of the individual indicators, water damage and moisture on the surfaces were consistent determinants of allergic rhinitis. The results of this cohort study, which assessed exposure before the onset of allergic rhinitis, strengthen considerably the evidence of the role of indoor dampness problems as determinants of allergic rhinitis in children.

Endogenous reproductive hormones and oxidative stress have been independently linked to risk of chronic disease but mostly in postmenopausal women. The interplay between endogenous reproductive hormones and oxidative stress among premenopausal women, however, has yet to be clearly elucidated. The objective of this study was to investigate the association between endogenous reproductive hormones and F2-isoprostanes in the BioCycle Study. Women aged 18&ndash;44 years from western New York State were followed prospectively for up to 2 menstrual cycles (n = 259) during 2005&ndash;2007. Estradiol, progesterone, luteinizing hormone, follicle-stimulating hormone, sex hormone-binding globulin, F2-isoprostanes, and thiobarbituric acid-reactive substances were measured up to 8 times per cycle at clinic visits timed by using fertility monitors. F2-Isoprostane levels had an independent positive association with estradiol (&beta; = 0.02, 95% confidence interval: 0.01, 0.03) and inverse associations with sex hormone-binding globulin and follicle-stimulating hormone (&beta; = &ndash;0.04, 95% confidence interval: &ndash;0.07, &ndash;0.003; &beta; = &ndash;0.02, 95% confidence interval: &ndash;0.03, &ndash;0.002, respectively) after adjustment for age, race, age at menarche, -tocopherol, beta-carotene, total cholesterol, and homocysteine by inverse probability weighting. Thiobarbituric acid-reactive substances, a less specific marker of oxidative stress, had similar associations. If F2-isoprostanes are specific markers of oxidative stress, these results call into question the commonly held hypothesis that endogenous estradiol reduces oxidative stress.

Experimental studies have implicated telomere dynamics in cardiomyocyte size and replication potential; shorter telomeres mark attenuated proliferation and increased apoptosis. The authors examined whether this translates into an impact of telomere length (TL) on left ventricular (LV) mass in the general population. In 334 randomly selected Flemish participants (mean age = 46.5 years; 52.5% women), they measured TL in circulating leukocytes using quantitative polymerase chain reaction, expressing it as telomere/genomic DNA ratio (T/S). After a median 7.4 years of follow-up (interquartile range, 6.2&ndash;8.5) during 1996&ndash;2007, they measured LV mass by echocardiography. In multivariable-adjusted analyses accounting for sex, age, body weight and height, systolic blood pressure, and antihypertensive drug use, LV mass and LV mass index significantly increased with mean leukocyte TL in the entire population and in the 198 normotensive subjects. For a 1-standard-deviation increment in T/S ratio, LV mass (mean = 170 g) and LV mass index (mean = 92 g/m2) increased by 5.20 g (P = 0.003) and 2.70 g/m2 (P = 0.004), respectively, in all subjects and by 8.03 g (P = 0.0001) and 3.74 g/m2 (P = 0.0007) in normotensive subjects. There were corresponding associations with LV wall thicknesses (P < 0.007) but not LV internal diameter (P = 0.26) in normotensive subjects. Longer mean leukocyte TL is associated with increased LV mass, particularly in normotensive subjects. This association could have a biologic basis related to the role of TL in determining cardiomyocyte size and replication potential.

The obesity epidemic is attributed in part to reduced physical activity. Evidence supports that reducing time spent sitting, regardless of activity, may improve the metabolic consequences of obesity. Analyses were conducted in a large prospective study of US adults enrolled by the American Cancer Society to examine leisure time spent sitting and physical activity in relation to mortality. Time spent sitting and physical activity were queried by questionnaire on 53,440 men and 69,776 women who were disease free at enrollment. The authors identified 11,307 deaths in men and 7,923 deaths in women during the 14-year follow-up. After adjustment for smoking, body mass index, and other factors, time spent sitting (&ge;6 vs. <3 hours/day) was associated with mortality in both women (relative risk = 1.34, 95% confidence interval (CI): 1.25, 1.44) and men (relative risk = 1.17, 95% CI: 1.11, 1.24). Relative risks for sitting (&ge;6 hours/day) and physical activity (<24.5 metabolic equivalent (MET)-hours/week) combined were 1.94 (95% CI: 1.70, 2.20) for women and 1.48 (95% CI: 1.33, 1.65) for men, compared with those with the least time sitting and most activity. Associations were strongest for cardiovascular disease mortality. The time spent sitting was independently associated with total mortality, regardless of physical activity level. Public health messages should include both being physically active and reducing time spent sitting.

The authors investigated associations between serum C-reactive protein (CRP) concentrations and colon and rectal cancer risk in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (1992&ndash;2003) among 1,096 incident cases and 1,096 controls selected using risk-set sampling and matched on study center, age, sex, time of blood collection, fasting status, menopausal status, menstrual cycle phase, and hormone replacement therapy. In conditional logistic regression with adjustment for education, smoking, nutritional factors, body mass index, and waist circumference, CRP showed a significant nonlinear association with colon cancer risk but not rectal cancer risk. Multivariable-adjusted relative risks for CRP concentrations of &ge;3.0 mg/L versus <1.0 mg/L were 1.36 (95% confidence interval (CI): 1.00, 1.85; P-trend = 0.01) for colon cancer and 1.02 (95% CI: 0.67, 1.57; P-trend = 0.65) for rectal cancer. Colon cancer risk was significantly increased in men (relative risk = 1.74, 95% CI: 1.11, 2.73; P-trend = 0.01) but not in women (relative risk = 1.06, 95% CI: 0.67, 1.68; P-trend = 0.13). Additional adjustment for C-peptide, glycated hemoglobin, and high density lipoprotein cholesterol did not attenuate these results. These data provide evidence that elevated CRP concentrations are related to a higher risk of colon cancer but not rectal cancer, predominantly among men and independently of obesity, insulin resistance, and dyslipidemia.

The authors examined the impact of a widower's preparedness before his wife's death from cancer on his risk of long-term morbidity. In a population-based study, 691 (76%) of 907 Swedish men who lost a wife to breast, ovarian, or colon cancer in 2000 or 2001 answered an anonymous questionnaire in 2004 or 2005 measuring preparedness at the time of the wife's death and psychological well-being at follow-up. Men aged 38&ndash;61 years with a low degree of preparedness at the time of their spouse's death had increased risk of psychological morbidity and other symptoms, such as anxiety (adjusted relative risk (aRR) = 2.1, 95% confidence interval (CI): 1.0, 4.3), a heightened startle response (aRR = 5.3, 95% CI: 1.2, 23.6), emotional numbness (aRR = 2.1, 95% CI: 1.2, 3.6), little or no grief resolution (aRR = 2.7, 95% CI: 1.3, 5.4), and sleep disorders (aRR = 2.3, 95% CI: 1.2, 4.3), 4&ndash;5 years after the loss. For older widowers (aged 62&ndash;80 years), a low degree of preparedness increased the risk of having repeated painful memories (aRR = 2.8, 95% CI: 1.5, 5.2) and a heightened startle response (aRR = 5.7, 95% CI: 1.5, 21.4) at follow-up. These results show that to improve the long-term psychological well-being of widowers, it may be fruitful to identify care-related facilitators and inhibitors of preparedness.

Results from case-control and cohort studies of the association between fruit and vegetable consumption and gastric cancer risk have been inconsistent. Cases for the current study consisted of incident distal gastric cancers identified between 1996 and 2007 among members of the Shanghai Women's Health Study (n = 206) and the Shanghai Men's Health Study (n = 132). Intakes of fruits, vegetables, and select micronutrients were assessed on the basis of validated food frequency questionnaires. Multivariate-adjusted hazards ratios and 95% confidence intervals were calculated by Cox proportional hazards regression. For women, no associations were found between gastric cancer risk and the highest intake of fruits (hazard ratio (HR) = 1.02, 95% confidence interval (CI): 0.68, 1.54; Ptrend = 0.87) or vegetables (HR = 0.89, 95% CI: 0.60, 1.31; Ptrend = 0.32). For men, increased fruit intake was associated with decreased risk of distal gastric cancer (for the highest quartile of intake, HR = 0.50, 95% CI: 0.29, 0.84; Ptrend = 0.004), but no association was seen with increased intake of vegetables (HR = 1.00, 95% CI: 0.59, 1.68; Ptrend = 0.87). The inverse association with fruit intake for men was more evident among ever smokers (Ptrend = 0.001) than never smokers (Ptrend = 0.67). No associations between dietary intakes of select antioxidant micronutrients were seen for men or women. Fruit intake is inversely associated with distal gastric cancer risk among men in Shanghai, China.

In this issue of the Journal, Nakaya et al. (Am J Epidemiol. 2010;172(4):377&ndash;385) report null findings from a large-scale prospective study of the prognostic value of 2 personality dimensions, neuroticism and extraversion, for cancer risk and mortality. The study stands out because of its exceptionally large sample size and its methodological strengths. The authors discuss the Nakaya et al. study in the context of persistent beliefs about the role of personality in cancer onset and survival despite a pattern of null findings in the literature, as well as the influence of extreme outlier findings from one investigator group that continue to be cited. They question whether it is time for the field to move on from considering a role for personality in cancer to more promising and modifiable factors.

Personality traits have been studied extensively as risk and prognostic factors for cancer; however, the association remains unclear. This prospective, population-based cohort study comprised 59,548 Swedish (1974&ndash;1999) and Finnish (1976&ndash;2004) participants who completed a questionnaire eliciting information for the Eysenck Personality Inventory and on health behavior at baseline. To analyze the association of personality traits extraversion and neuroticism with risk of cancer, the authors identified 4,631 cancer cases for a maximum 30 years of follow-up. To assess the association with cancer survival among the Finnish participants, they identified 2,733 cancer cases and, later, 1,548 deaths for a maximum 29 years of follow-up. Hazard ratios were estimated by treating the personality scales as continuous variables and are presented per one increase in score on each scale. In multivariate analyses, extraversion and neuroticism were not significantly associated with risk of cancers at all sites (extraversion: hazard ratio = 0.99, 95% confidence interval: 0.98, 1.01; neuroticism: hazard ratio = 1.00, 95% confidence interval: 0.99, 1.02). Results showed no significant association between these traits and the hazard ratio for death after cancers at all sites, and they do not support the hypothesis that extraversion and neuroticism are direct risk factors for cancer or survival after cancer.

This study examined the relation between immune response to cytomegalovirus (CMV) and all-cause and cardiovascular disease (CVD) mortality, and possible mediating mechanisms. Data were derived from the Sacramento Area Latino Study on Aging, a population-based study of older Latinos (aged 60&ndash;101 years) in California followed in 1998&ndash;2008. CMV immunoglobulin G (IgG), tumor necrosis factor, and interleukin-6 were assayed from baseline blood draws. Data on all-cause and CVD mortality were abstracted from death certificates. Analyses included 1,468 of 1,789 participants. For individuals with CMV IgG antibody titers in the highest quartile compared with lower quartiles, fully adjusted models showed that all-cause mortality was 1.43 times (95% confidence interval: 1.14, 1.79) higher over 9 years. In fully adjusted models, the hazard of CVD mortality was also elevated (hazard ratio = 1.35, 95% confidence interval: 1.01, 1.80). A composite measure of tumor necrosis factor and interleukin-6 mediated a substantial proportion of the association between CMV and all-cause (18.9%, P < 0.001) and CVD (29.0%, P = 0.02) mortality. This study is the first known to show that high CMV IgG antibody levels are significantly related to mortality and that the relation is largely mediated by interleukin-6 and tumor necrosis factor. Further studies investigating methods for reducing IgG antibody response to CMV are warranted.

Human cytomegalovirus (CMV) is a human herpesvirus, and infection is widespread in the human population. Prevalence of seropositivity for human CMV increases with age. CMV establishes persistent infection in vascular arterial and venous endothelial tissue. It has been associated with atherosclerosis and graft rejection in heart transplant recipients. The antiviral drug ganciclovir prevents CMV disease in heart transplant patients, and valganciclovir and CMV immune globulin reduce rejection rates and cardiovascular disease. Human CMV infection has been associated with proinflammatory cytokine increases and nonresponsiveness to antiinfluenza vaccine in the elderly. Enhanced expression of proinflammatory cytokines has also been associated with enhanced mortality in the elderly. In this issue of the Journal, Roberts et al. (Am J Epidemiol. 2010;000(00):000&ndash;000) report that, in a large population-based cohort of elderly Sacramento area Latino subjects in California followed from 1998 to 2008, more than 95% were seropositive for human CMV. In that study, Kaplan-Meier survival curves suggested worse cardiovascular disease survival for individuals in the highest quartile of human CMV immunoglobulin G antibody titers over 9 years of follow-up. Theirs is the first study known to report a relation between high human CMV antibody levels and mortality.