Exposure to particulate matter air pollution and risk of multiple sclerosis in two large cohorts of US nurses.

BACKGROUND: Air pollution is thought to raise the risk of neurological disease by promoting neuroinflammation, oxidative stress, glial activation and cerebrovascular damage. Multiple Sclerosis is a common auto-immune disorder, primarily affecting young women. We conducted, to a large prospective study of particulate matter (PM) exposure and multiple sclerosis (MS) risk in two prospective cohorts of women: the Nurses Health Study (NHS) and the Nurses Health Study II (NHS II). METHODS: Cumulative average exposure to different size fractions of PM up to the onset of MS was estimated using spatio-temporal models. We used multivariable Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of MS associated with each size fraction of PM independently. Participants were followed from 1998 through 2004 in NHS and from 1988 through 2007 for NHS II. We conducted additional sensitivity analyses stratified by smoking, region of the US, and age, as well as analyses restricted to women who did not move during the study. Analyses were adjusted for age, ancestry, smoking, body mass index at age 18, region, tract level population density, latitude at age 15, and UV index. RESULTS: We did not observe significant associations between air pollution and MS risk in our cohorts. Among women in the NHS II, the HRs comparing the top vs. bottom quintiles of PM was 1.11 (95% Confidence Intervals (CI): 0.74, 1.66), 1.04 (95% CI: 0.73, 1.50) and 1.09 (95% CI: 0.73, 1.62) for PM10 (≤10µm in diameter), PM2.5 (≤2.5µm in diameter), and PM2.5-10 (2.5 to 10µm in diameter) respectively, and tests for linear trends were not statistically significant. No association between exposure to PM and risk of MS was observed in the NHS. CONCLUSIONS: In this study, exposure to PM air pollution was not related to MS risk.

No association between vitamin D levels around time of birth and later risk of developing oligo- and polyarticular juvenile idiopathic arthritis: a Danish case-cohort study.

OBJECTIVES: Basic and epidemiological studies on rheumatic autoimmune diseases have suggested an association between vitamin D levels around time of birth and disease risk. The literature on vitamin D and juvenile idiopathic arthritis (JIA) is scarce. We hypothesized that low levels of 25-hydroxyvitamin D [25(OH)D] around time of birth would be associated with increased risk of oligo- or polyarticular JIA. METHOD: We conducted a case-cohort study of validated cases diagnosed with oligo- and polyarticular JIA (1993-2012) and controls matched on date of birth. Cases and controls were born in the period 1983-2010. Cases were diagnosed using international criteria. The concentration of 25(OH)D was assessed from neonatal dried blood spot (DBS) samples using high-sensitivity liquid chromatography tandem mass spectrometry (LC-MS/MS). Odds ratios (ORs) were calculated using conditional logistic regression and a two-way analysis of variance (ANOVA) was used to test for season and birth year 25(OH)D variations. A total of 300 matched pairs were included in the statistical analyses. RESULTS: No significant association was found between levels of 25(OH)D and JIA risk in the adjusted model [OR (per 25 nmol/L increase) 1.2, 95% confidence interval (CI) 0.9-1.6, p = 0.2]. 25(OH)D levels were found to fluctuate significantly with season (p < 0.0001) and year (p < 0.0001). The median level of 25(OH)D was 34.4 nmol/L in cases and 31.5 nmol/L in controls. CONCLUSIONS: Our study does not support the hypothesis that a window of vulnerability exists around time of birth with regard to 25(OH)D levels and later JIA risk. Further studies should explore whether 25(OH)D levels during early pregnancy or infancy may influence JIA risk.

Risk factors for multiple sclerosis, neuromyelitis optica and transverse myelitis.

BACKGROUND: Little is known about risk factors for neuromyelitis optica (NMO) or transverse myelitis (TM). OBJECTIVE: The objective of this paper is to evaluate whether established multiple sclerosis (MS) risk factors, including smoking history, a history of infectious mononucleosis (IM), anti-EBNA1 Ab titers and HLA-DR15 are associated with NMO or TM. METHODS: We conducted a case-control study among participants in the Accelerated Cure Project for Multiple Sclerosis (ACP) Repository, which includes patients with MS, NMO and TM. Controls include related and unrelated individuals without evidence of demyelinating disease. Analyses included 1237 cases of MS, 98 cases of NMO, 133 cases of TM and 488 healthy controls. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to assess the association between smoking, HLA-DR15, anti-EBNA1 Ab titers and a history of IM adjusting for gender, study site and ethnicity. RESULTS: Overall, the association between smoking, IM, HLA-DR15 and anti-EBNA1 Ab titers and odds of MS were as expected and no significant interactions were observed. However, there was little evidence of association between these MS risk factors and odds of NMO or TM. CONCLUSIONS: Established MS risk factors do not appear to be associated with susceptibility to TM or NMO and, among MS patients, these risk factors appear to act independently.

Caffeine and alcohol intakes have no association with risk of multiple sclerosis.

BACKGROUND: The association between alcohol and caffeine intakes and risk of multiple sclerosis (MS) is unclear; no prospective studies have examined this relationship. OBJECTIVE: We examined intakes of alcohol and caffeine in relation to risk of multiple sclerosis. METHODS: Intakes of alcohol and caffeine were examined in relation to the risk of MS in two large cohorts of women, the Nurses' Health Study (NHS; 92,275 women followed from 1980 to 2004) and Nurses' Health Study II (NHS II; 95,051 women followed from 1991 to 2005). Their diet was assessed at baseline and every four years thereafter. During the follow-up, 282 cases of MS were confirmed with onset of symptoms after baseline. Twenty-four cases were missing information on alcohol intake, leaving a total of 258 cases for the alcohol analyses. RESULTS: Neither total alcohol consumption, nor consumption of beer, wine, or liquor was related to MS risk. The multivariable-adjusted pooled relative risk (RR) found by comparing categories of alcohol intake to 0 gm/day was 1.07 (95% CI: 0.32-1.99) for 0.1-4.9 gm/day, 1.01 (0.32-1.99) for 5.0-14.9 gm/day, 1.21 (0.69-2.15) for 15.0-29.9 gm/day, and 0.80 (0.32-1.99) for 30+ gm/day; (p for trend=0.89). Caffeine intake was also not significantly associated with MS risk. The multivariable adjusted pooled RR comparing highest to lowest quintile of caffeine intake was 1.14; 95% CI: 0.79-1.66; p for trend=0.71. Consideration of caffeinated and decaffeinated coffee separately also yielded null results. CONCLUSION: These results do not support an association between alcohol and caffeine intakes and MS risk.

Depression and the risk of psoriasis in US women.

BACKGROUND: Depression is a common mental health condition that has been associated with psoriasis. In the absence of prospective data, it remains unclear whether depression precedes psoriasis as a risk factor. OBJECTIVES: To examine the association between depression and the risk of new-onset psoriasis. METHODS: A prospective cohort of 86 880 US female nurses, The Nurses' Health Study II, was followed up from 1993 to 2005. Participants reported anti-depressant use and completed the Mental Health Index (MHI), a subscale of the Short-Form 36 in 1993. The MHI assessed for depression and scores was categorized into four strata: 0-52, 53-75, 76-85 and 86-100, with lower scores associated with increasing depressive symptoms. We excluded participants with a history of psoriasis prior to 1993. A self-report of incident physician-diagnosed psoriasis constituted the main outcome measure. For a sensitivity analysis, we had a subset of confirmed psoriasis cases. RESULTS: Depression was associated with an increased risk of incident psoriasis. Compared to women in the non-depressed group (MHI 86-100), women who reported either having high depressive symptomatology (MHI scores < 52) or who were on anti-depressants had a multivariate relative risk (RR) of 1.59 for developing subsequent psoriasis (95% confidence interval [CI], 1.21-2.08). These associations became stronger among confirmed psoriasis cases. CONCLUSIONS: We found that depression was independently associated with an increased risk of psoriasis in this population of US women.

Infectious mononucleosis and risk of breast cancer in a prospective study of women.

PURPOSE: The association between infectious mononucleosis (IM) and risk of breast cancer is unclear; no prospective studies have examined this relationship. We examined self-reported history and age at IM in relation to risk of invasive breast cancer. METHODS: Self-reported history and age at IM were examined in relation to risk of invasive breast cancer in a large cohort of women, the Nurses' Health Study II (81,807 women followed from 1989 to 2007). Through questionnaires, women were asked whether they ever had IM and if so, at what age. During follow-up, 2,349 cases of invasive breast cancer were documented. Cox proportional hazards regression was used to estimate relative risks (RR) and 95 % confidence intervals (CI) for the association of IM with breast cancer. RESULTS: The multivariable-adjusted RR for history of IM and risk of invasive breast cancer was 1.00 (95 % CI: 0.90-1.11). Similar null results were obtained when estrogen receptor/progesterone receptor positive and negative tumors were considered separately. There were no clear patterns of association between age at IM and risk of breast cancer: compared to women with no history of IM, those who were ≤15 years old when they had IM were at lower risk (RR: 0.77; 95 % CI: 0.60, 0.97), but there was no association for women who had IM at ages 16-19, 20-24, or 30+. However, an increased RR (1.45; 95 % CI: 1.02-2.04) was observed for women who had IM at ages 25-29. CONCLUSION: Results of this large prospective study do not support a clear association between history of clinical IM and risk of invasive breast cancer.

Association of multiple sclerosis with restless legs syndrome and other sleep disorders in women.

OBJECTIVE: To assess the association of multiple sclerosis (MS) with concurrent restless legs syndrome (RLS) and daytime sleepiness. We also prospectively examined whether women with MS had an increased risk of developing RLS during 4 years of follow-up. METHODS: The main analysis was based on a cross-sectional study of 65,544 women (aged 41-58 years) free of diabetes, arthritis, and pregnancy, who were participating in the Nurses' Health Study II cohort. Participants were considered to have RLS if they met 4 RLS diagnostic criteria recommended by the International Restless Leg Syndrome Study Group and had restless legs ≥ 5 times/month. MS was self-reported and confirmed by medical record review. RESULTS: Among women with MS, the prevalence of RLS and severe RLS (15+ times/month) were 15.5% and 9.9% in 2005, respectively, relative to 6.4% and 2.6% among women without MS. After adjustment for potential confounders and the presence of other sleep disorders, women with MS had a higher likelihood of having RLS (odds ratio [OR] = 2.72, 95% confidence interval [CI] 1.89-3.93), severe RLS (OR = 4.12, 95% CI 2.65-6.42), and daily daytime sleepiness (OR = 2.11, 95% CI 1.31-3.42) compared with women without MS. Among the 172 women who had MS and were free of RLS in 2005, 9 developed RLS (5.2%) during a 4-year period and all had severe RLS. The adjusted relative risk of severe RLS was 3.58 (95% CI 1.53-8.35), comparing women with MS at baseline with those without MS. CONCLUSION: Women with MS had a significantly higher prevalence of RLS and daytime sleepiness and an increased risk of developing RLS in the future.

Habitual intake of dietary flavonoids and risk of Parkinson disease.

OBJECTIVE: To prospectively examine whether higher intakes of total flavonoids and their subclasses (flavanones, anthocyanins, flavan-3-ols, flavonols, flavones, and polymers) were associated with a lower risk of developing Parkinson disease (PD). METHODS: In the current analysis, we included 49,281 men in the Health Professional Follow-up Study and 80,336 women from the Nurses' Health Study. Five major sources of flavonoid-rich foods (tea, berry fruits, apples, red wine, and orange/orange juice) were also examined. Flavonoid intake was assessed using an updated food composition database and a validated food frequency questionnaire. RESULTS: We identified 805 participants (438 men and 367 women) who developed PD during 20-22 years of follow-up. In men, after adjusting for multiple confounders, participants in the highest quintile of total flavonoids had a 40%lower PD risk than those in the lowest quintile (hazard ratio [HR] = 0.60; 95% confidence interval 0.43, 0.83; p trend = 0.001). No significant relationship was observed in women (p trend = 0.62) or in pooled analyses (p trend = 0.23). In the pooled analyses for the subclasses, intakes of anthocyanins and a rich dietary source, berries, were significantly associated with a lower PD risk (HR comparing 2 extreme intake quintiles were 0.76 for anthocyanins and 0.77 for berries, respectively; p trend < 0.02 for both). CONCLUSIONS: Our findings suggest that intake of some flavonoids may reduce PD risk, particularly in men, but a protective effect of other constituents of plant foods cannot be excluded.

Bidirectional association between depression and obesity in middle-aged and older women.

OBJECTIVE: Although it has been hypothesized that the depression-obesity relation is bidirectional, few studies have addressed this hypothesis in a prospective setting. We aimed to examine the bidirectional relationship in middle-aged and elderly women. SUBJECTS: A total of 65 955 women aged 54-79 years in the Nurses' Health Study were prospectively followed from 1996 to 2006 with updated information on body weight, depression status and various covariates every 2 years. Depression was defined as self-report of physician-diagnosed depression and/or antidepressant use. Obesity was defined as a BMI ≥30.0 kg m(-2). The first three waves (1996-2000) were used as the baseline period and the last three waves (2002-2006) were used as the follow-up period. RESULTS: After adjusting for baseline age, physical activity, comorbidities, BMI and other covariates, depression at the baseline period was associated with an increased risk of obesity at the follow-up period in all women (multivariate-adjusted odds ratio (OR), 1.38; 95% confidence interval (95% CI), 1.24-1.53) and baseline non-obese women (OR, 1.51; 95% CI, 1.36-1.67). In the opposite direction, after adjusting for baseline age, physical activity, comorbidities, depression status and other covariates, obese women at baseline had a moderately increased risk of depression at the follow-up period compared with normal-weight women (OR, 1.11; 95% CI, 1.03-1.18), and this association was similar for new onset of depression (OR for obese versus normal weight women, 1.10; 95% CI, 1.02-1.20). CONCLUSIONS: Our results suggest a bidirectional association between depression and obesity in middle-aged and elderly women. Future studies are needed to confirm our findings in different populations, and investigate the potential mechanisms underlying this association. Our results underscore the importance of early detection and proper behavioral modifications to lower the burden of both conditions.

Stress and the risk of multiple sclerosis.

OBJECTIVE: Several studies have shown that stressful life events are associated with a subsequent significant increase in risk of multiple sclerosis (MS) exacerbations. We wanted to study prospectively whether stress can increase the risk of developing the disease itself. METHODS: We studied 2 cohorts of female nurses: the Nurses' Health Study (NHS) (n = 121,700) followed from 1976 and the Nurses' Health Study II (NHS II) (n = 116,671) followed from 1989. The risk of MS after self-report on general stress at home and at work in the NHS in 1982 was studied prospectively using Cox regression. Logistic regression was used to retrospectively estimate the effects of physical and sexual abuse in childhood and adolescence collected in the NHS II 2001. We identified 77 cases of MS in the NHS by 2005 and 292 in the NHS II by 2004. All analyses were adjusted for age, ethnicity, latitude of birth, body mass index at age 18, and smoking. RESULTS: We found no increased risk of MS associated with severe stress at home in the NHS (hazard ratio 0.85 [95% confidence interval (CI)] 0.32-2.26). No significantly increased risk of MS was found among those who reported severe physical abuse during childhood (odds ratio [OR] 0.68, 95% CI 0.41-1.14) or adolescence (OR 0.77, 95% CI 0.46-1.28) or those having been repeatedly forced into sexual activity in childhood (OR 1.47, 95% CI 0.87-2.48) or adolescence (OR 1.21, 95% CI 0.68-2.17). CONCLUSIONS: These results do not support a major role of stress in the development of the disease, but repeated and more focused measures of stress are needed to firmly exclude stress as a potential risk factor for MS.

Anti-Epstein-Barr virus antibodies as serological markers of multiple sclerosis: a prospective study among United States military personnel.

BACKGROUND: Elevated Epstein-Barr virus (EBV) antibody titers are risk factors for multiple sclerosis (MS), but the strength and consistency of this association are not well characterized. OBJECTIVES: The objectives of this study were to determine whether this association is confounded by vitamin D or modified by gender or race, and the usefulness of EBV nuclear antigen (EBNA) antibodies as a marker for MS. METHODS: We conducted a prospective study among US military personnel. Antibody titers against EBV antigens were measured in serum samples from 222 individuals who developed MS and 444 age, sex, and race/ethnicity matched controls. Conditional logistic regression was used to estimate relative risks. RESULTS: MS risk increased with increasing titers of anti-EBNA complex (p < 10(-9)) and anti-EBNA-1 (p = 5.8 × 10(-9)) titers. MS risk was 36-fold higher among individuals with anti-EBNA complex IgG titers ≥320 than among those with titers <20 (95% confidence interval [CI] 9.6-136), and 8-fold higher among those with anti-EBNA-1 ≥320 than among those with anti-EBNA-1 <20 (95% CI 2.6-23). These associations were consistent across gender and race/ethnicity groups and independent from 25-hydroxyvitamin D levels. Areas under the receiver operating characteristic (ROC) curves were 0.67 for EBNA complex and 0.65 for EBNA-1. CONCLUSIONS: Serum titers of pre-onset anti-EBNA antibodies are strong, robust markers of MS risk and could be useful in an MS risk score.

Genetic predictors of 25-hydroxyvitamin D levels and risk of multiple sclerosis.

Risk of multiple sclerosis (MS) decreases with increasing plasma levels of 25-hydroxyvitamin D [25(OH)D]. If this association reflected a protective effect of vitamin D, MS risk should be lower among individuals carrying genetic variants that predict high 25(OH)D levels. The aim of the study was to determine whether individuals with genotypes predicting higher 25(OH)D levels have decreased MS risk. Logistic regression was used to assess the association between single nucleotide polymorphisms (SNPs) associated with 25(OH)D levels and MS risk in 1,655 cases and 6,349 controls. Analyses were further stratified by HLA-DR15 status, assessed by genotyping a single SNP strongly correlated with the HLA DRB1 1501 risk haplotype, and complemented by considering a SNP near CYP27B1. SNPs in GC were predictors of 25(OH)D levels, but not MS risk, in either HLA-DR15 negative or HLA-DR15 positive individuals. In contrast, there was a suggestion of a difference in the effect of a CYP2R1 allele dependent on HLA-DR15 genotype. The 'A' allele of CYP2R1 rs10741657 was associated with increased 25(OH)D levels and a non-significant reduced MS risk among HLA-DR15 negative (OR = 0.89, 95% CI: 0.79, 1.01) that was not apparent in HLA-DR15 positive individuals. The 'C' allele of CYP27B1 rs703842 was inversely associated with MS risk; this association appeared stronger among HLA-DR15 negative (OR = 0.79, 95% CI: 0.69, 0.90) compared to HLA-DR15 positive individuals (OR = 0.91, 95% CI: 0.80, 1.04). This preliminary finding suggests the possibility that the putative beneficial effect of vitamin D on MS risk maybe attenuated in individuals carrying the HLA-DR15 MS risk allele.

EBNA1 and LMP1 variants in multiple sclerosis cases and controls.

BACKGROUND: Prior infection with Epstein-Barr virus (EBV) is an established risk factor for multiple sclerosis (MS). Some findings from observational studies, including possible epidemics and differences in prevalence, may be explained if different strains of EBV conferred different MS risk. METHODS: DNA was extracted from peripheral lymphocytes obtained from 66 MS cases and 66 age- and cohort-matched controls. Nested polymerase chain reaction (PCR) was performed to amplify the N- and C-terminus regions of EBNA1 and the hyper-variable region of the LMP1 gene. For EBNA1, we compared the presence of the prototype B95.8 vs variant sequence and the presence of multiple strains in MS cases and controls. For LMP1, we considered differences in the proportions of mutations between cases and controls. RESULTS: Comparing the proportion of mutant sequence between MS cases and controls in the EBNA1 N-terminal (0/28 vs 1/27) and C-terminal regions (3/40 vs 8/36) revealed no significant differences (P > 0.05). No individual variants in LMP1 were associated with risk of MS (all P > 0.05). Neither EBNA1 nor LMP1 variation was associated with anti-EBNA1 IgG antibody titers. CONCLUSIONS: These findings do not support a strong role for variation in EBNA1 N-terminus, EBNA1 C-terminus or LMP1 contributing to MS risk.

99th Dahlem conference on infection, inflammation and chronic inflammatory disorders: Epstein-Barr virus and multiple sclerosis: epidemiological evidence.

While the causes of multiple sclerosis (MS) are unknown, there is strong evidence that infection with Epstein-Barr virus (EBV) is an important factor. In this review, we discuss the epidemiological evidence and argue for a causal role of EBV in MS aetiology. One of the most striking and consistent observations is that MS is extremely rare among EBV-negative individuals. Further, the timing of EBV infection appears to be critical, with individuals who are infected during adolescence and young adulthood, when the infection is more likely to manifest as mononucleosis, having a two- to threefold greater risk of MS compared to individuals infected in early life. These observations challenge the hygiene hypothesis which states that being in a high hygiene environment in early life increases future risk of MS - if this general formulation were true, EBV-negative individuals would be expected to have an increased risk of MS. Additional support for the causal role of EBV comes from longitudinal, prospective studies which show remarkable consistency, in that antibodies against EBV are elevated prior to MS onset. However, while infection with EBV is consistent with many observations of MS epidemiology, there are some that remain unexplained, suggesting that other factors are also involved in determining risk.

Combined effects of smoking, anti-EBNA antibodies, and HLA-DRB1*1501 on multiple sclerosis risk.

OBJECTIVE: To examine the interplay between smoking, serum antibody titers to the Epstein-Barr virus nuclear antigens (anti-EBNA), and HLA-DR15 on multiple sclerosis (MS) risk. METHODS: Individual and pooled analyses were conducted among 442 cases and 865 controls from 3 MS case-control studies-a nested case-control study in the Nurses' Health Study/Nurses' Health Study II, the Tasmanian MS Study, and a Swedish MS Study. Conditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for the association between smoking, anti-EBNA titers, HLA-DR15, and MS risk. Study estimates were pooled using inverse variance weights to determine a combined effect and p value. RESULTS: Among MS cases, anti-EBNA titers were significantly higher in ever smokers compared to never smokers. The increased risk of MS associated with high anti-EBNA Ab titers was stronger among ever smokers (OR = 3.9, 95% CI = 2.7-5.7) compared to never smokers (OR = 1.8, 95% CI = 1.4-2.3; p for interaction = 0.001). The increased risk of MS associated with a history of smoking was no longer evident after adjustment for anti-EBNA Ab titers. No modification or confounding by HLA-DR15 was observed. The increased risk of MS associated with ever smoking was only observed among those who had high anti-EBNA titers (OR = 1.7, 95% CI = 1.1-2.6). CONCLUSIONS: Smoking appears to enhance the association between high anti-EBNA titer and increased multiple sclerosis (MS) risk. The association between HLA-DR15 and MS risk is independent of smoking. Further work is necessary to elucidate possible biologic mechanisms to explain this finding.

Polymorphisms of caffeine metabolism and estrogen receptor genes and risk of Parkinson's disease in men and women.

Caffeine intake has been associated with a decreased risk of Parkinson's disease (PD) in men but the effect in women is less clear, and appears to be modified by use of post-menopausal estrogens. In a nested case-control study within the Nurses Health Study (NHS) and the Health Professionals Follow-up Study (HPFS), we examined associations between single nucleotide polymorphisms (SNPs) of caffeine metabolizing genes (CYP1A2 and NAT2) and estrogen receptors (ESR1 and ESR2), their interaction with caffeine intake and hormone replacement therapy (PMH) use (collected prospectively) and risk of PD. We matched 159 female cases to 724 controls and 139 male cases to 561 controls on birth year, source of DNA (blood or buccal smear), age and sex. The CYP1A2 rs762551 polymorphism (lower enzyme inducibility) was marginally associated with an increased risk of PD (RR, for increasing number of minor alleles=1.34; 95% CI 1.02, 1.78 in women, but not in men. None of the NAT2 (classified as slow vs. fast acetylator), ESR1 or ESR2 polymorphisms were significantly associated with an altered risk of PD. Marginally significant interactions were observed between caffeine intake and the ESR1 polymorphism rs3798577 (p=0.07) and ESR2 polymorphism rs1255998 (p=0.07). The observed increased risk of PD among female but not male carriers of the rs762551 polymorphism of CYP1A2 and the interactions of caffeine with ESR1 rs3798577 and ESR2 rs1255998 may provide clues to explain the relationship between gender, caffeine intake, estrogen status and risk of PD and need to be replicated.

Persistent organochlorine pesticides in serum and risk of Parkinson disease.

BACKGROUND: Pesticides have been implicated as likely environmental risk factors for Parkinson disease (PD), but assessment of past exposure to pesticides can be difficult. No prior studies of pesticide exposure and PD used biomarkers of exposure collected before the onset of PD. Our investigation examined the association between prospective serum biomarkers of organochlorine pesticides and PD. METHODS: We conducted a nested case-control study within the Finnish Mobile Clinic Health Examination Survey, with serum samples collected during 1968-1972, and analyzed in 2005-2007 for organochlorine pesticides. Incident PD cases were identified through the Social Insurance Institution's nationwide registry and were confirmed by review of medical records (n = 101). Controls (n = 349) were matched for age, sex, municipality, and vital status. Adjusted odds ratios (ORs) of PD were estimated using logistic regression. RESULTS: Little association emerged with a summary score of the 5 organochlorine pesticides found at high levels, and only increasing dieldrin concentrations trended toward a higher risk of PD (OR per interquartile range [IQR] 1.28, 95% confidence interval [CI] 0.97-1.69, p = 0.08). Because of possible strong confounding by cigarette smoking among smokers, we ran additional analyses restricted to never smokers (n = 68 cases, 183 controls). In these analyses, increasing dieldrin concentrations were associated with increased odds of PD (OR per IQR 1.95, 95% CI 1.26-3.02, p = 0.003). None of the other organochlorine pesticides were associated with PD in these analyses. CONCLUSIONS: These results provide some support for an increased risk of Parkinson disease with exposure to dieldrin, but chance or exposure correlation with other less persistent pesticides could contribute to our findings.

Family history of melanoma and Parkinson disease risk.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.