Lisa Gallicchio

Sleep duration and mortality: a systematic review and meta-analysis

Epidemiologic studies have shown that sleep duration is associated with overall mortality. We conducted a systematic review of the associations between sleep duration and all‐cause and cause‐specific mortality. PubMed was systematically searched up to January, 2008 to identify studies examining the association between sleep duration and mortality (both all‐cause and cause‐specific) among adults. Data were abstracted serially in a standardized manner by two reviewers and analyzed using random‐effects meta‐analysis. Twenty‐three studies assessing the associations between sleep duration and mortality were identified. All examined sleep duration measured using participant self‐report. Among the 16 studies which had similar reference categories and reported sufficient data on short sleep and mortality for meta‐analyses, the pooled relative risk (RR) for all‐cause mortality for short sleep duration was 1.10 [95% confidence interval (CI): 1.06, 1.15]. For cardiovascular‐related and cancer‐related mortality, the RRs associated with short sleep were 1.06 (95% CI: 0.94, 1.18) and 0.99 (95% CI: 0.88, 1.13), respectively. Similarly, among the 17 studies reporting data on long sleep duration and mortality, the pooled RRs comparing the long sleepers with medium sleepers were 1.23 (95% CI: 1.17, 1.30) for all‐cause mortality, 1.38 (95% CI: 1.13, 1.69) for cardiovascular‐related mortality, and 1.21 (95% CI: 1.11, 1.32) for cancer‐related mortality. Our findings indicate that both short sleepers and long sleepers are at increased risk of all‐cause mortality. Further research using objective measures of sleep duration is needed to fully characterize these associations.

Genome-wide association study of circulating vitamin D levels

The primary circulating form of vitamin D, 25-hydroxy-vitamin D [25(OH)D], is associated with multiple medical outcomes, including rickets, osteoporosis, multiple sclerosis and cancer. In a genome-wide association study (GWAS) of 4501 persons of European ancestry drawn from five cohorts, we identified single-nucleotide polymorphisms (SNPs) in the gene encoding group-specific component (vitamin D binding) protein, GC, on chromosome 4q12-13 that were associated with 25(OH)D concentrations: rs2282679 (P = 2.0 × 10−30), in linkage disequilibrium (LD) with rs7041, a non-synonymous SNP (D432E; P = 4.1 × 10−22) and rs1155563 (P = 3.8 × 10−25). Suggestive signals for association with 25(OH)D were also observed for SNPs in or near three other genes involved in vitamin D synthesis or activation: rs3829251 on chromosome 11q13.4 in NADSYN1 [encoding nicotinamide adenine dinucleotide (NAD) synthetase; P = 8.8 × 10−7], which was in high LD with rs1790349, located in DHCR7, the gene encoding 7-dehydrocholesterol reductase that synthesizes cholesterol from 7-dehydrocholesterol; rs6599638 in the region harboring the open-reading frame 88 (C10orf88) on chromosome 10q26.13 in the vicinity of ACADSB (acyl-Coenzyme A dehydrogenase), involved in cholesterol and vitamin D synthesis (P = 3.3 × 10−7); and rs2060793 on chromosome 11p15.2 in CYP2R1 (cytochrome P450, family 2, subfamily R, polypeptide 1, encoding a key C-25 hydroxylase that converts vitamin D3 to an active vitamin D receptor ligand; P = 1.4 × 10−5). We genotyped SNPs in these four regions in 2221 additional samples and confirmed strong genome-wide significant associations with 25(OH)D through meta-analysis with the GWAS data for GC (P = 1.8 × 10−49), NADSYN1/DHCR7 (P = 3.4 × 10−9) and CYP2R1 (P = 2.9 × 10−17), but not C10orf88 (P = 2.4 × 10−5).

Arsenic in drinking water and lung cancer: A systematic review

Exposure to inorganic arsenic via drinking water is a growing public health concern. We conducted a systematic review of the literature examining the association between arsenic in drinking water and the risk of lung cancer in humans. Towards this aim, we searched electronic databases for articles published through April 2006. Nine ecological studies, two case-control studies, and six cohort studies were identified. The majority of the studies were conducted in areas of high arsenic exposure (100 microg/L) such as southwestern Taiwan, the Niigata Prefecture, Japan, and Northern Chile. Most of the studies reported markedly higher risks of lung cancer mortality or incidence in high arsenic areas compared to the general population or a low arsenic exposed reference group. The quality assessment showed that, among the studies identified, only four assessed arsenic exposure at the individual level. Further, only one of the ecological studies presented results adjusted for potential confounders other than age; of the cohort and case-control studies, only one-half adjusted for cigarette smoking status in the analysis. Despite these methodologic limitations, the consistent observation of strong, statistically significant associations from different study designs carried out in different regions provide support for a causal association between ingesting drinking water with high concentrations of arsenic and lung cancer. The lung cancer risk at lower exposure concentrations remains uncertain.

Cruciferous vegetable consumption and lung cancer risk: a systematic review.

Background: Cruciferous vegetables, rich in isothiocyanates, may protect against lung cancer. Glutathione S-transferases are important in metabolizing isothiocyanates; hence, variants in GST genes may modify the association between cruciferous vegetable intake and lung cancer. We carried out a systematic review to characterize the association between cruciferous vegetable intake and lung cancer risk, with an emphasis on the potential interaction between cruciferous vegetables and GSTM1 and GSTT1 gene variants. Methods: A search of the epidemiologic literature through December 2007 was conducted using 15 bibliographic databases without language restrictions. Thirty studies on the association between lung cancer and either total cruciferous vegetable consumption (6 cohort and 12 case-control studies) or specific cruciferous vegetables (1 cohort and 11 case-control studies) were included. Results: The risk for lung cancer among those in the highest category of total cruciferous vegetable intake was 22% lower in case-control studies [random-effects pooled odds ratio, 0.78; 95% confidence interval (95% CI), 0.70-0.88] and 17% lower in cohort studies (pooled relative risk, 0.83; 95% CI, 0.62-1.08) compared with those in the lowest category of intake. The strongest inverse association of total cruciferous vegetable intake with lung cancer risk was seen among individuals with GSTM1 and GSTT1 double null genotypes (odds ratio, 0.41; 95% CI, 0.26-0.65; P for interaction = 0.01). Conclusions: Epidemiologic evidence suggests that cruciferous vegetable intake may be weakly and inversely associated with lung cancer risk. Because of a gene-diet interaction, the strongest inverse association was among those with homozygous deletion for GSTM1 and GSTT1. (Cancer Epidemiol Biomarkers Prev 2009;18(1):184–95)

Correlates of circulating 25-hydroxyvitamin D: Cohort Consortium Vitamin D Pooling Project of Rarer Cancers

Low vitamin D status is common globally and is associated with multiple disease outcomes. Understanding the correlates of vitamin D status will help guide clinical practice, research, and interpretation of studies. Correlates of circulating 25-hydroxyvitamin D (25(OH)D) concentrations measured in a single laboratory were examined in 4,723 cancer-free men and women from 10 cohorts participating in the Cohort Consortium Vitamin D Pooling Project of Rarer Cancers, which covers a worldwide geographic area. Demographic and lifestyle characteristics were examined in relation to 25(OH)D using stepwise linear regression and polytomous logistic regression. The prevalence of 25(OH)D concentrations less than 25 nmol/L ranged from 3% to 36% across cohorts, and the prevalence of 25(OH)D concentrations less than 50 nmol/L ranged from 29% to 82%. Seasonal differences in circulating 25(OH)D were most marked among whites from northern latitudes. Statistically significant positive correlates of 25(OH)D included male sex, summer blood draw, vigorous physical activity, vitamin D intake, fish intake, multivitamin use, and calcium supplement use. Significant inverse correlates were body mass index, winter and spring blood draw, history of diabetes, sedentary behavior, smoking, and black race/ethnicity. Correlates varied somewhat within season, race/ethnicity, and sex. These findings help identify persons at risk for low vitamin D status for both clinical and research purposes.

Relations among Menopausal Symptoms, Sleep Disturbance and Depressive Symptoms in Midlife

OBJECTIVES To investigate the relations among hot flashes, other menopausal symptoms, sleep quality and depressive symptoms in midlife women. METHODS A large population-based cross-sectional study of 639 women (ages 45-54 years) consisting of a questionnaire including the Center for Epidemiologic Studies-Depression (CES-D) Scale, demographics, health behaviors, menstrual history, and menopausal symptoms. RESULTS After controlling for menopausal status, physical activity level, smoking status and current self-reported health status elevated CES-D score is associated with frequent nocturnal hot flashes, frequent trouble sleeping, experiencing hot flashes, nausea, headaches, weakness, visual problems, vaginal discharge, irritability, muscle stiffness, and incontinence. CONCLUSIONS The present study found significant links between depressive symptoms and several menopausal symptoms including hot flashes, sleep disturbance, irritability, muscle stiffness, and incontinence after controlling for covariates. These findings suggest that a potential mechanism in which bothersome menopausal symptoms may influence depressed mood during the midlife is through sleep disturbance.

Adulthood consumption of preserved and nonpreserved vegetables and the risk of nasopharyngeal carcinoma: a systematic review.

The incidence rates of nasopharyngeal carcinoma (NPC) are dramatically higher in certain regions of Asia compared to the rest of the world. Few risk factors for NPC are known; however, in contrast to the hypothesized health benefits of nonpreserved vegetables, it is thought that preserved vegetable intake may play a role in contributing to the higher incidence of NPC in high‐risk regions. Therefore, the purpose of this study was to systematically review the epidemiologic evidence on the associations between adulthood intake of preserved and nonpreserved vegetables and NPC risk. A search of the epidemiological literature from 1966 to 2004 was performed using several bibliographic databases, including PubMed and the Chinese Biomedical Literature Database System. There were no language restrictions. Meta‐analysis was conducted to obtain pooled odds ratios (ORs) for the highest‐versus‐lowest categories of preserved and nonpreserved vegetable intake. A total of 16 case‐control studies were identified in the search. Results showed that highest‐versus‐lowest preserved vegetable intake was associated with a 2‐fold increase in the risk of NPC (Random Effects Odds Ratio (RE OR) 2.04; 95% Confidence Limits (CL) 1.43, 2.92). Conversely, high nonpreserved vegetable intake was associated with 36% decrease in the risk of NPC (RE OR 0.64; 95% CL 0.48, 0.85). Findings for both preserved and nonpreserved vegetables were consistent across vegetable type and by country of study. Further research in high‐risk areas to gain insight into the risk associated with preserved vegetables and protection associated with nonpreserved vegetables may advance understanding of NPC and yield clues for prevention.

Circulating 25-hydroxyvitamin D and the risk of rarer cancers: design and methods of the Cohort Consortium Vitamin D Pooling Project of rarer cancers

The Cohort Consortium Vitamin D Pooling Project of Rarer Cancers (VDPP), a consortium of 10 prospective cohort studies from the United States, Finland, and China, was formed to examine the associations between circulating 25-hydroxyvitamin D (25(OH)D) concentrations and the risk of rarer cancers. Cases (total n = 5,491) included incident primary endometrial (n = 830), kidney (n = 775), ovarian (n = 516), pancreatic (n = 952), and upper gastrointestinal tract (n = 1,065) cancers and non-Hodgkin lymphoma (n = 1,353) diagnosed in the participating cohorts. At least 1 control was matched to each case on age, date of blood collection (1974–2006), sex, and race/ethnicity (n = 6,714). Covariate data were obtained from each cohort in a standardized manner. The majority of the serum or plasma samples were assayed in a central laboratory using a direct, competitive chemiluminescence immunoassay on the DiaSorin LIAISON platform (DiaSorin, Inc., Stillwater, Minnesota). Masked quality control samples included serum standards from the US National Institute of Standards and Technology. Conditional logistic regression analyses were conducted using clinically defined cutpoints, with 50–<75 nmol/L as the reference category. Meta-analyses were also conducted using inverse-variance weights in random-effects models. This consortium approach permits estimation of the association between 25(OH)D and several rarer cancers with high accuracy and precision across a wide range of 25(OH)D concentrations.

Correlates of sexual functioning among mid-life women

Objective Studies have reported a decline in sexual functioning among women undergoing the menopausal transition. Few studies, however, have examined the associations between hormones and sexual dysfunction during this time period. Therefore, the purpose of this study was to examine the associations between participant characteristics and endogenous hormones with sexual functioning in mid-life women. Methods Data were analyzed from a community-based sample of 441 women aged 45–54 years who stated that they were sexually active at the time of the study. Each participant completed a survey that included questions pertaining to sexual functioning and provided a blood sample that was used to measure estrogen and androgen concentrations. Results Among women who reported being sexually active, poorer self-reported health and the experiencing of depressive symptoms were significantly associated with not being satisfied with sexual relations after adjustment for other covariates. None of the hormones examined were significantly associated with overall sexual satisfaction. However, statistically significant associations between both total testosterone levels and the free testosterone index with satisfaction with the frequency of sexual relations were observed. Conclusions Our findings indicate that the experiencing of depressive symptoms and the reporting of poor overall health are important correlates of sexual dysfunction. Further, our results suggest that higher total and free testosterone levels are significantly associated with a desire for increased frequency of sexual relations among mid-life women.

Cytochrome gene polymorphisms, serum estrogens, and hot flushes in midlife women

OBJECTIVE: The purpose of this study was to evaluate whether genetic polymorphisms in selected cytochrome P450 enzymes (CYPc17α, CYP1A1, and CYP1B1), estradiol (E2) levels, and estrone levels were associated with hot flushes. METHODS: Women with hot flushes were those aged 45–54 years who reported ever experiencing hot flushes (n = 354). Women without hot flushes were those aged 45–54 years who reported never experiencing hot flushes (n = 258). Each participant completed a questionnaire and provided a blood sample for determination of genotypes, E2 levels, and estrone levels. RESULTS: Carriers of the CYP1B1 (Val432Leu) polymorphism were more likely to report having any hot flushes (risk ratio [RR] 1.16, 95% confidence interval (CI) 0.98–1.37) and at least weekly hot flushes (RR 1.29, 95% CI 0.98–1.70) than women without the polymorphism, although these associations were of borderline statistical significance. In addition, carriers of the CYP1B1 polymorphism were likely to have a statistically significant 30% increased risk of reporting moderate to severe hot flushes (RR 1.30, 95% CI 1.02–1.67) and a statistically significant 27% increased risk of reporting hot flushes lasting a year or more (RR 1.27, 95% CI 1.00–1.61) compared with women without the polymorphism. There were no associations between CYP1A1 or CYPc17α polymorphisms and hot flushes. Low E2 and estrone levels were associated with hot flushes, but they did not alter the association between the CYP1B1 polymorphism and hot flushes. CONCLUSION: These data suggest that a CYP1B1 polymorphism may be associated with severe and persistent hot flushes, independent of E2 and estrone levels. LEVEL OF EVIDENCE: III