American Journal of Epidemiology

Although recent studies suggest that 13% of young adults, including at least one-fourth of African Americans, experience parental incarceration, little research has examined links between parental incarceration and physical health. Using data from the National Longitudinal Study of Adolescent Health (1994&ndash;2008) and gender-based theories of stress, the authors examined whether parental incarceration is associated with increased body mass index among women but not men. Panel analysis spanning adolescence and adulthood, controlling for stressful life events, internalizing behaviors, and a range of individual, familial, and neighborhood characteristics, reveals that body mass index for women who have experienced parental incarceration is 0.49 units (P < 0.004) higher than that for women whose parents have never been incarcerated. This association is not evident among men. Similarly, in change score models between waves II and IV, women experiencing parental incarceration have a 0.92-unit increase in body mass index (P < 0.026) relative to women who did not have a parent undergo incarceration. In supplemental analysis examining if gender differences in incarceration stress response (externalizing vs. internalizing) explain these findings, the authors found that obesity status moderates the relation between depression and parental incarceration. Results suggest a stress internalization process that, for the first time, links parental incarceration with obesity among women.

Experimental evidence and case-control studies suggest that dihydropyridine calcium channel blockers (DiCCBs) may protect against Parkinson&rsquo;s disease. The authors conducted a historical cohort study in Denmark to investigate the association between DiCCB use and risk of Parkinson&rsquo;s disease (1998&ndash;2006). Individual-level data on filled drug prescriptions, diagnostic information, and covariates were linked between nationwide registries. Among DiCCB users, 173 incident cases of Parkinson&rsquo;s disease were detected during 461,984 person-years of follow-up, compared with 5,538 cases during 17,343,641 person-years of follow-up among nonusers. After adjustment for age, sex, year, propensity score, and use of other antihypertensive drugs and statins, DiCCB use was associated with a reduced risk of Parkinson&rsquo;s disease (rate ratio (RR) = 0.71, 95% confidence interval (CI): 0.60, 0.82). This association was not present in patients who had previously used DiCCBs (RR = 1.04, 95% CI: 0.87, 1.24). DiCCB users aged &ge;65 years were at lower risk of Parkinson&rsquo;s disease than DiCCB users aged <65 years (RR = 0.59, 95% CI: 0.40, 0.85). Among patients with Parkinson&rsquo;s disease, DiCCB use was associated with reduced risk of death (adjusted RR = 0.66, 95% CI: 0.47, 0.91) but not dementia (adjusted RR = 0.97, 95% CI: 0.60, 1.56). In conclusion, DiCCB exposure was associated with a reduced risk of incident Parkinson&rsquo;s disease, particularly in older patients, and with reduced mortality among patients with Parkinson&rsquo;s disease.

A high level of influence on core aspects of life in general and at the workplace in particular is believed to reduce the risk of ill health. In this issue of the Journal, Joensuu et al. (Am J Epidemiol. 2012;175(7):609&ndash;619) shake this belief by presenting prospective associations between high decision authority at work and increased all-cause, cardiovascular, and alcohol-related mortality among Finnish forest company employees followed through 2005. In this invited commentary, the author welcomes these findings as a much needed inspiration for reflections on the current state of psychosocial epidemiology and how it can be advanced in the future. Although it is important to investigate possible harmful effects of too high decision authority, the author argues that it is even more important to be aware that psychosocial factors originate from societal structures and social contexts. Understanding these structures and contexts, their changes over time, and their relation to psychosocial factors is key for understanding the effect of psychosocial factors on health and illness. Joensuu et al. have presented thought-provoking findings. It is the hope of the author that this will push the research community to emphasize the "social" in "psychosocial epidemiology."

Inconsistent evidence of the hypothesized favorable effects of high job control on health may have resulted from a failure to treat job control as a multifactor concept. The authors studied whether the 2 components of job control, decision authority and skill discretion, were differentially associated with cause-specific mortality in 13,510 Finnish forest company employees with no history of severe illness. Surveys on work characteristics were carried out in 1986 and 1996, and the respondents were followed up until the end of 2005 by use of the Statistics Finland National Death Registry. During a mean follow-up of 15.5 years, 981 participants died. In the analyses adjusted for confounders, employees with high and intermediate levels of skill discretion had a lower all-cause mortality risk than those with low skill discretion, with hazard ratios of 0.84 (95% confidence interval (CI): 0.69, 1.02) and 0.81 (95% CI: 0.69, 0.96), respectively. In contrast, high decision authority was associated with elevated risks of all-cause, cardiovascular, and alcohol-related mortality, with hazard ratios of 1.28 (95% CI: 1.06, 1.54), 1.49 (95% CI: 1.11, 2.02), and 2.03 (95% CI: 1.03, 4.00), respectively. The results suggest that job control is not an unequivocal concept in relation to mortality; decision authority and skill discretion show different and to some extent opposite associations.

The study of disease variability in populations is a goal of modern epidemiology. Because most common diseases arise out of a combination of factors and events (exposures, heritability, comorbidities, and chance), developing simple models of characterizing joint events is a daunting task. Dr. Weinberg argues successfully in this issue of the Journal (Am J Epidemiol. 2012;175(7):602&ndash;605) that additive null models can capture pure forms of independent causal effects in studies of rare conditions. Moreover, the concept of exposure modification, which characterizes most gene-environment interactions reported to date, is introduced. More cross-talk between biologists and epidemiologists is needed to tackle key issues in chronic disease etiology, and the argument for the use of parsimonious joint models in epidemiology is convincing.

Most diseases arise not purely through genetic abnormalities nor purely through environmental causes, but as "complex" conditions brought about by the combined effects of genetic susceptibility factors, nongenetic experiences and exposures, and bad luck. Finding simple models capable of both characterizing such joint effects and providing new insight into pathogenesis remains an ongoing challenge in etiologic epidemiology. Additive null models can capture certain pure forms of independent etiologic effects in studies of rare conditions and can be useful for predicting possible effects of interventions. The concept of exposure modification is here proposed as useful, particularly in thinking about biologic interactions between exposures and genetic variants. Openness to parsimonious joint models and the insights they can provide is key to advancing our understanding of etiology.

Over the past 60 years, revolutionary discoveries made by epidemiologists have contributed to marked declines in cardiovascular disease morbidity and mortality. Now, in an era of increasingly constrained resources, researchers in cardiovascular epidemiology face a number of challenges that call for novel, paradigm-shifting approaches. In this paper, the authors pose to the community 4 critical questions: 1) How can we avoid wasting resources on studies that provide little incremental knowledge? 2) How can we assure that we direct our resources as economically as possible towards innovative science? 3) How can we be nimble, responding quickly to new opportunities? 4) How can we identify prospectively the most meritorious research questions? Senior program staff at the National Heart, Lung, and Blood Institute invite the epidemiology community to join them in an ongoing Web-based blog conversation so that together we might develop novel approaches that will facilitate the next generation of high-impact discoveries.

No prediction rule is currently available for advanced colorectal neoplasms, defined as invasive cancer, an adenoma of 10 mm or more, a villous adenoma, or an adenoma with high-grade dysplasia, in average-risk Chinese. In this study between 2006 and 2008, a total of 7,541 average-risk Chinese persons aged 40 years or older who had complete colonoscopy were included. The derivation and validation cohorts consisted of 5,229 and 2,312 persons, respectively. A prediction rule was developed from a logistic regression model and then internally and externally validated. The prediction rule comprised 8 variables (age, sex, smoking, diabetes mellitus, green vegetables, pickled food, fried food, and white meat), with scores ranging from 0 to 14. Among the participants with low-risk (&le;3) or high-risk (>3) scores in the validation cohort, the risks of advanced neoplasms were 2.6% and 10.0% (P < 0.001), respectively. If colonoscopy was used only for persons with high risk, 80.3% of persons with advanced neoplasms would be detected while the number of colonoscopies would be reduced by 49.2%. The prediction rule had good discrimination (area under the receiver operating characteristic curve = 0.74, 95% confidence interval: 0.70, 0.78) and calibration (P = 0.77) and, thus, provides accurate risk stratification for advanced neoplasms in average-risk Chinese.

Although previous studies have found a protective association between attendance at religious services and depression, the extent to which this association is driven by depressed persons&rsquo; dropping out of religious activities is not clear. The authors examined whether early onset of a major depressive episode (MDE) predicted a subsequent decrease in religious service attendance. Data came from 3 follow-up studies of the National Collaborative Perinatal Project birth cohort (mean age = 37 years at last follow-up; n = 2,097; 1959&ndash;2001). The generalized estimating equations method was used to calculate the impact of an early MDE diagnosis (before age 18 years) on the likelihood of change in level of religious service attendance from childhood to adulthood. Twenty-seven percent of study participants met the criteria for lifetime MDE (n = 567), of whom 31% had their first onset prior to age 18 years. Women with early MDE onset were 1.42 times more likely (95% confidence interval: 1.19, 1.70) than women with adult-onset MDE or no lifetime MDE to stop attending religious services by the time of the first adult follow-up wave. No significant associations were observed among men. These findings suggest that women are more likely to stop attending religious services after onset of depression. Selection out of religious activities could be a significant contributor to previously observed inverse correlations between religious service attendance and psychopathology during adulthood.

It has been noted that there is ambiguity in the expression "attributable fraction," and epidemiologic literature has drawn a distinction between "excess fraction" and "etiologic fraction." These quantities do not necessarily approximate one another, and the etiologic fraction is not generally estimable without strong biologic assumptions. In previous studies, researchers have explained the relations between excess and etiologic fractions in the potential-outcome framework, and few authors have explained the relations between these concepts by showing the correspondence between the potential-outcome model and the sufficient-cause model. In this article, the authors thoroughly clarify the conceptual relations between excess, attributable, and etiologic fractions by explicating the correspondence between these 2 models. In so doing, the authors take into account the potential completion time of each sufficient cause, which contributes to further insight to clarify the 2 types of etiologic fraction, i.e., accelerating etiologic proportion and total etiologic proportion. These 2 measures cannot be distinguished in epidemiologic data, and the differences might be subtle. However, they are closely related to a very fundamental issue of causal inference, that is, how researchers define etiology. Further, the authors clarify the relation between 3 distinct assumptions&mdash;positive monotonicity, no preventive action (or sufficient-cause positive monotonicity), and no preventive sequence.

The authors conducted a time-series analysis to examine seasonal variation of mortality risk in association with particulate matter less than 2.5 &mu;m in aerodynamic diameter (PM2.5) and chemical species in Xi&rsquo;an, China, using daily air pollution and all-cause and cause-specific mortality data (2004&ndash;2008). Poisson regression incorporating natural splines was used to estimate mortality risks of PM2.5 and its chemical components, adjusting for day of the week, time trend, and meteorologic effects. Increases of 2.29% (95% confidence interval: 0.83, 3.76) for all-cause mortality and 3.08% (95% confidence interval: 0.94, 5.26) for cardiovascular mortality were associated with an interquartile range increase of 103.0 &mu;g/m3 in lagged 1&ndash;2 day PM2.5 exposure. Stronger effects were observed for the elderly (&ge;65 years), males, and cardiovascular diseases groups. Secondary components (sulfate and ammonium), combustion species (elemental carbon, sulfur, chlorine), and transition metals (chromium, lead, nickel, and zinc) appeared most responsible for increased risk, particularly in the cold months. The authors concluded that differential association patterns observed across species and seasons indicated that PM2.5-related effects might not be sufficiently explained by PM2.5 mass alone. Future research is needed to examine spatial and temporal varying factors that might play important roles in modifying the PM2.5&ndash;mortality association.

Low birth weight is associated with increased risk of cardiovascular disease and type 2 diabetes in later life. The fetal insulin hypothesis suggests that shared genetic factors partly explain this association. If fetal genes predispose to both low birth weight and cardiovascular disease in adulthood, fathers of offspring with low birth weight should display an unfavorable profile of cardiovascular risk factors. To study this, the authors linked data on more than 14,000 parents, collected from the second Health Study of Nord Tr&oslash;ndelag County, Norway (HUNT 2, 1995&ndash;1997), to offspring data from the Norwegian Medical Birth Registry (1967&ndash;2005). Linear regression was used to study associations of offspring birth weight for gestational age with the parents&rsquo; body mass index, waist circumference, blood pressure, glucose, and serum lipids. All analyses were adjusted for shared environment by means of the socioeconomic measures, lifestyle, and cardiovascular risk factors of the partner. The authors found that low offspring birth weight for gestational age was associated with increased paternal blood pressure, body mass index, waist circumference, and unfavorable levels of glucose and lipids. For mothers, associations similar to those for fathers were found for blood pressure, whereas associations in the opposite direction were found for glucose, lipids, and body mass index. The paternal findings strengthen the genetic hypothesis.

Menstrual bleeding patterns are considered relevant indicators of reproductive health, though few studies have evaluated patterns among regularly menstruating premenopausal women. The authors evaluated self-reported bleeding patterns, incidence of spotting, and associations with reproductive hormones among 201 women in the BioCycle Study (2005&ndash;2007) with 2 consecutive cycles. Bleeding patterns were assessed by using daily questionnaires and pictograms. Marginal structural models were used to evaluate associations between endogenous hormone concentrations and subsequent total reported blood loss and bleeding length by weighted linear mixed-effects models and weighted parametric survival analysis models. Women bled for a median of 5 days (standard deviation: 1.5) during menstruation, with heavier bleeding during the first 3 days. Only 4.8% of women experienced midcycle bleeding. Increased levels of follicle-stimulating hormone (&beta; = 0.20, 95% confidence interval: 0.13, 0.27) and progesterone (&beta; = 0.06, 95% confidence interval: 0.03, 0.09) throughout the cycle were associated with heavier menstrual bleeding, and higher follicle-stimulating hormone levels were associated with longer menses. Bleeding duration and volume were reduced after anovulatory compared with ovulatory cycles (geometric mean blood loss: 29.6 vs. 47.2 mL; P = 0.07). Study findings suggest that detailed characterizations of bleeding patterns may provide more insight than previously thought as noninvasive markers for endocrine status in a given cycle.

Extant analyses of the relation between economic conditions and population health were often based on annualized data and were susceptible to confounding by nonlinear time trends. In the present study, the authors used generalized additive models with nonparametric smoothing splines to examine the association between economic conditions, including levels of economic activity in New York State and the degree of volatility in the New York Stock Exchange, and monthly rates of death by suicide in New York City. The rate of suicide declined linearly from 8.1 per 100,000 people in 1990 to 4.8 per 100,000 people in 1999 and then remained stable from 1999 to 2006. In a generalized additive model in which the authors accounted for long-term and seasonal time trends, there was a negative association between monthly levels of economic activity and rates of suicide; the predicted rate of suicide was 0.12 per 100,000 persons lower when economic activity was at its peak compared with when it was at its nadir. The relation between economic activity and suicide differed by race/ethnicity and sex. Stock market volatility was not associated with suicide rates. Further work is needed to elucidate pathways that link economic conditions and suicide.

The authors assessed the risks of drug-related death, suicide, and homicide after release from New York City jails in 155,272 people who were incarcerated anytime from 2001 through 2005 and examined whether the mortality rate was associated with homelessness. Using jail records matched with death and single-adult homeless registries in New York City, they calculated standardized mortality ratios (SMRs) and relative risks. After adjustment for age, sex, race, and neighborhood, the risks of drug-related death and homicide in formerly incarcerated persons were 2 times higher than those of New York City residents who had not been incarcerated in New York City jails during the study period. These relative risks were greatly elevated during the first 2 weeks after release (for drug-related causes, SMR = 8.0, 95% confidence interval (CI): 5.2, 11.8; for homicide, SMR = 5.1, 95% CI: 3.2, 7.8). Formerly incarcerated people with histories of homelessness had higher rates of drug-related death (RR = 3.4, 95% CI: 2.1, 5.5) and suicide (RR = 2.1, 95% CI: 1.2, 3.4) than did persons without such histories. For individuals who died of drug-related causes, longer jail stays were associated with a shorter time until death after release. These results suggest that jail- and community-based interventions are needed to reduce the excess mortality risk among formerly incarcerated people.

The apolipoprotein E gene (APOE) has been found to be associated with age-related macular degeneration (AMD). Reported associations have been questioned, as they are opposite those for Alzheimer&rsquo;s disease and cardiovascular disease. The authors examined associations between APOE genotype and AMD using a case-control study (2,287 cases and 2,287 controls individually matched on age, sex, and country of origin) nested within Melbourne Collaborative Cohort Study participants aged 48&ndash;86 years at AMD detection. The odds ratio for early AMD among participants with 2-containing genotypes (22/23/24) was 1.32 (95% confidence interval (CI): 1.11, 1.58; P = 0.002) versus persons with genotype 33. Associations with early AMD varied by smoking status; 2-containing genotypes were positively associated with early AMD for never and previous smokers (never smokers: odds ratio (OR) = 1.40, 95% CI: 1.12, 1.76 (P = 0.003); previous smokers: OR = 1.39, 95% CI: 1.00, 1.93 (P = 0.05)) but not for current smokers (OR = 0.66, 95% CI: 0.34, 1.30 (P = 0.2; interaction P = 0.05). The 4-containing genotype group (34/44) had an inverse association with early AMD among current smokers only (OR = 0.41, 95% CI: 0.22, 0.77 (P = 0.005)). These results highlight the importance of stratifying by smoking status in elderly populations. Smokers who survive to old age may be more likely to possess unknown genotypes which modify exposure-disease associations.

The authors examined the association between white blood cell (WBC) count and the development of gastric cancer in a 19-year follow-up study of 2,558 Japanese subjects aged &ge;40 years (1988&ndash;2007). The subjects were stratified into 4 groups according to baseline WBC quartile (&le;4.4, 4.5&ndash;5.2, 5.3&ndash;6.3, or &ge;6.4 x 103 cells/&mu;L). During follow-up, 128 subjects developed gastric cancer. The age- and sex-adjusted incidence of gastric cancer increased linearly with higher WBC level: 1.7, 2.6, 3.9, and 5.4 per 1,000 person-years, respectively, for the 4 quartile groups (P for trend < 0.01). The risk of gastric cancer was 2.22-fold (95% confidence interval: 1.19, 4.14) higher in the highest WBC quartile group than in the lowest group after adjustment for confounding factors. With respect to Helicobacter pylori infection status, H. pylori-seropositive subjects in the highest WBC quartile group showed a significantly greater risk of gastric cancer than those in the lower 3 quartile groups, whereas such an association was not observed in H. pylori-seronegative subjects. There was no evidence of heterogeneity in the association (P for heterogeneity = 0.65). The study findings suggest that higher WBC levels are a risk factor for gastric cancer, especially in subjects with H. pylori infection.

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ER&beta; rs1256049, ER&beta; rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for &ge;30 days vs. <30 days, OR = 0.50, 95% CI: 0.32, 0.80) were inversely associated with lung cancer in never smokers, while age at first birth (for ages 21&ndash;25, 26&ndash;30, and &ge;31 years vs. &le;20 years, ORs were 1.54, 2.17, and 1.30, respectively), age at menopause (for ages 49&ndash;51 and &ge;52 years vs. &le;48 years, ORs were 1.37 and 1.59; Ptrend = 0.003), and reproductive period (for 31&ndash;33, 34&ndash;36, 37&ndash;39, and &ge;40 years vs. &le;30 years, ORs were 1.06, 1.25, 1.45, and 1.47; Ptrend = 0.026) were positively associated. Among smokers, parity was inversely associated with lung cancer, but there was no association with other reproductive factors. The COMT rs4680 A allele was positively associated with lung cancer in never smokers (for G/A or A/A vs. G/G, OR = 1.46, 95% CI: 1.12, 1.90) but not in ever smokers. No associations were seen with other polymorphisms. These results support a risk-enhancing role of estrogens in lung carcinogenesis among never smokers.

Pleiotropy across the 8q24 region is perhaps the most intriguing of the genome-wide association findings relating to cancer. This region of chromosome 8 is a gene desert, far from any recognized genes. Guarrera et al., whose work is reported in this issue (Am J Epidemiol. 2012;175(6):479&ndash;487), took an epidemiologic approach to learn more about the 8q24 region. They capitalized on their ascertainment of other endpoints in members of the cohort at the Turin site of the European Prospective Investigation Into Cancer and Nutrition to investigate multiple outcomes for additional pleiotropic effects in the 8q24 region. Alternative design options might involve genotyping of more variants, incorporation of more cases, or use of a single control group close to the size of the most common case group. Their analytic methods reflect the uncertainty of the underlying biology. The findings sharpen the scientific question about how variation in the 8q24 region affects pathogenesis. The genome-wide association effort is possible because of the economy of scale afforded by extremely dense genotyping. Strict adherence to the hypothesis-driven approach would ignore information that is obtainable at a trivial cost. The genome-wide association strategy tests whether agnostic data-mining methods can advance knowledge alongside or even in place of the standard hypothesis-driven approach, which is the conventional scientific method children learn in kindergarten and onward, even through graduate school and beyond.

The 8q24 region is a gene desert, although chromosomal aberrations and somatic amplification involving this region, including translocations involving the protooncogene c-MYC, have been frequently reported in people with cancer. To investigate the role of variants in 8q24 region, the authors analyzed data from a prospective study (n = 10,372 participants who were followed for 11 years) in which a large number of health events (>1,500) occurred (1993&ndash;1998). They genotyped all subjects for 5 candidate single nucleotide polymorphisms (rs672888, rs1447295, rs9642880, rs16901979, and rs6983267) that were identified in previous genome-wide scans. Although significant associations with individual single nucleotide polymorphisms were small in magnitude, the authors observed higher increases in the risks of different types of cancer with specific haplotypes, particularly when subjects were homozygous for the haplotype: for breast cancer and homozygotes for haplotype CAGCT, hazard ratio = 3.40, 95% confidence interval: 1.24, 9.21; for prostate cancer and grouped rare haplotypes, hazard ratio = 7.43, 95% confidence interval: 3.00, 18.37; and for brain cancer and homozygotes for haplotype CGGCT, hazard ratio = 13.48, 95% confidence interval: 3.00, 59.53. Significant associations were also observed between haplotypes and deaths from cardiovascular diseases and cerebrovascular diseases; the most stable association was between homozygotes for haplotypes CGTCG and CAGCT and total deaths in men (hazard ratio = 3.5, 95% confidence interval: 1.8, 6.9, and hazard ratio = 2.8, 95% confidence interval: 1.3, 6.4, respectively). In conclusion, the authors have observed a strong pleiotropic effect of the 8q24 region in a large prospective study. This observation can shed light on the mechanisms underlying reported associations between 8q24 variants and disparate chronic diseases.

Prospective epidemiologic studies have characterized major risk factors for incident diabetes by a variety of diabetes case definitions. Whether different definitions alter the association of diabetes with risk factors is largely unknown. Using 1987&ndash;1998 data from the ongoing Atherosclerosis Risk in Communities (ARIC) Study, the authors assessed the relation of traditional risk factors with 3 different diabetes case definitions and 4 fasting glucose categories. They compared the study protocol case definition with 2 nested case definitions, self-reported diabetes and a multiple-evidence definition. Significant differences in risk factor associations by case definition and by screening cutpoints were observed. Specifically, the magnitude of the association between the risk factors (baseline metabolic syndrome, fasting glucose, blood pressure, body mass index, and serum insulin) and incident diabetes differed by case definition. Associations with these risk factors were weaker with a case definition based on self-report compared with other definitions. These results illustrate the potential limitations of case definitions that rely solely on self-report or those that incorporate measured glucose values to ascertain undiagnosed cases. Although the ability to identify risk factors of diabetes was consistent for the case definitions studied, tests of novel risk factors may result in different estimates of effect sizes depending on the definition used.

Vulnerability of the central nervous system to mercury is increased during early development. This study aimed to evaluate whether cord blood total mercury levels may have a negative effect on both mental and psychomotor development in a maternal-birth cohort from moderate-high fish consumption areas. Study subjects were 1,683 child participants in the INMA (Environment and Childhood) Project from 4 areas of Spain between 2003 and 2010. Cord blood total mercury levels were analyzed by atomic absorption spectrometry. Infant neurodevelopment was assessed around age 14 months by the Bayley Scales of Infant Development. Sociodemographic, lifestyle, and dietary information was obtained by questionnaire during pregnancy. The geometric mean of total mercury levels was 8.4 &mu;g/L (95% confidence interval (CI): 8.1, 8.7). In multivariate analysis, a doubling in total mercury levels did not show an association with mental (&beta; = 0.1, 95% CI: &ndash;0.68, 0.88) or psychomotor (&beta; = &ndash;0.05, 95% CI: &ndash;0.79, 0.68) developmental delay; however, stratified findings by sex suggest a negative association between prenatal exposure to total mercury and psychomotor development among female infants (&beta; = &ndash;1.09, 95% CI: &ndash;2.21, 0.03), although follow-up is required to confirm these results.

Evidence concerning the role of Helicobacter pylori infection in the development of colorectal cancer remains controversial. The authors assessed the association of H. pylori seroprevalence with risk of colorectal cancer in a large population-based case-control study from Germany in 2003&ndash;2007. Serum antibodies to H. pylori in general and the cytotoxin-associated gene A protein (CagA) were measured in 1,712 incident colorectal cancer cases and 1,669 controls. The association between H. pylori seroprevalence and colorectal cancer risk was estimated by logistic regression, with adjustment for potential confounders and stratification by age group, sex, anatomic subsites, and cancer stage. Overall, H. pylori seroprevalence was higher in cases (46.1%) than in controls (40.1%), resulting in an age- and sex-adjusted odds ratio of 1.30 (95% confidence interval (CI): 1.14, 1.50). Adjustment for established colorectal cancer risk factors decreased the odds ratio to 1.26 (95% CI: 1.09, 1.47), with a further reduction to 1.18 (95% CI: 1.01, 1.38) after additional adjustment for previous colorectal endoscopy. Stratified analyses showed risk elevation to be essentially confined to left-sided colorectal cancer, with an odds ratio of 1.22 (95% CI: 1.02, 1.45), suggesting that H. pylori infection may be associated with a small yet relevant risk increase in the left colorectum.