Interaction between arsenic exposure from drinking water and genetic susceptibility in carotid intima–media thickness in Bangladesh

Epidemiologic studies that evaluated genetic susceptibility for the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima–media thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI = 14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β = − 5.1 μm, 95% CI = − 31.6, 21.3) or arsenic exposure alone (β = 7.2 μm, 95% CI = − 3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to the proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.     

miR-3940-5p associated with genetic damage in workers exposed to hexavalent chromium

To understand the regulation of genetic damage by epigenetics at the early stage of carcinogenesis after hexavalent chromium (Cr(VI)) and assessed genetic damage to explore their association with DNA repair genes mediated by differently expressed miRNA. Genetic damages were evaluated using cytokinesis-block micronucleus assay (CBMN) and serum 8-hydroxyguanine (8-OHdG) ELISA assay. Blood Cr level showed significant association with plasma miR-3940-5p level (r = −0.33, P = 0.001) and non-linear relationship with micronuclei frequency in CBMN and serum 8-OHdG level (β_std = 0.29, P = 0.039; β_std = 0.35, P = 0.001), with micronuclei frequency not increasing apparently under high Cr exposure. In contrast, no significant association was found between plasma miR-3940-5p level and the two genetic indicators. However, plasma miR-3940-5p level was linked to micronuclei frequency under high blood Cr level (β_std = 0.18, P = 0.015). To explore the effect of miR-3940-5p on genetic damage under high Cr exposure, the protein expression levels of miR-3940-5p-mediated DNA repair genes in leukocytes were quantified using enzyme-linked immunosorbent assay for subjects with high blood Cr level. The results showed that XRCC2 and BRCC3 protein levels were statistically associated with miR-3940-5p level respectively (β_std = −0.31, P = 0.010; β_std = −0.24, P = 0.037). Meanwhile, a weak but statistically negative association between XRCC2 level and micronuclei frequency was found (β_std = −0.15, P = 0.027). These data suggests that high Cr(VI) does not always aggravate genetic damage after reaching a high Cr(VI) exposure in real situation, which may be due to the regulation of miRNA on DNA repair genes responsive to high Cr(VI) exposure.     

OGG1 Ser326Cys polymorphism interacts with cigarette smoking to increase oxidative DNA damage in human sperm and the risk of male infertility

8-Oxoguanine DNA glycosylase 1 (OGG1) plays an important role in repairing oxidative DNA damage induced by chemical agents, such as tobacco. This study examined the effects of OGG1 Ser326Cys polymorphism and cigarette smoking, alone or combined, on sperm oxidative DNA damage and the risk of male infertility. A total of 620 idiopathic infertile subjects and 480 fertile controls were recruited in this study. Sperm 8-hydroxydeoxyguanine (8-OHdG) was measured by immunofluorescent assay using flow cytometry and genotypes were determined by OpenArray platform with a chip-based Taq-Man genotyping technology. Our results demonstrated that both cigarette smoking and OGG1 polymorphism can affect the sperm 8-OHdG levels. Individuals with variant Cys/Cys homozygote showed higher levels of sperm 8-OHdG than wide-type homozygote carriers (Ser/Ser). Stratified analysis found that the association between OGG1 polymorphism and sperm 8-OHdG levels was only observed among smokers with pack-years ≥5 but not among those subjects with pack-years < 5 (pack-years = packs smoked per day × years as a smoker). Further analysis based on the case–control study revealed that variant allele (Cys) of OGG1 was significantly associated with male infertility risk in a dominant model (OR = 1.35, 95% CI: 1.01–1.82; trend P < 0.001). Furthermore, we found a significant gene–environment interaction between OGG1 Ser326Cys polymorphism and cigarette smoking in relation to male infertility risk (P_interation = 0.0003). These findings provided the first evidence about potential interactive effects of OGG1 polymorphism and cigarette smoking on male infertility risk.     

A case-control study of polymorphisms in xenobiotic and arsenic metabolism genes and arsenic-related bladder cancer in New Hampshire

Arsenic is associated with bladder cancer risk even at low exposure levels. Genetic variation in enzymes involved in xenobiotic and arsenic metabolism may modulate individual susceptibility to arsenic-related bladder cancer. Through a population-based case-control study in NH (832 cases and 1191 controls), we investigated gene-environment interactions between arsenic metabolic gene polymorphisms and arsenic exposure in relation to bladder cancer risk. Toenail arsenic concentrations were used to classify subjects into low and high exposure groups. Single nucleotide polymorphisms (SNPs) in GSTP1, GSTO2, GSTZ1, AQP3, AS3MT and the deletion status of GSTM1 and GSTT1 were determined. We found evidence of genotype-arsenic interactions in the high exposure group; GSTP1 Ile105Val homozygous individuals had an odds ratio (OR) of 5.4 [95% confidence interval (CI): 1.5–20.2; P for interaction = 0.03] and AQP3 Phe130Phe carriers had an OR = 2.2 (95% CI: 0.8–6.1; P for interaction = 0.10). Bladder cancer risk overall was associated with GSTO2 Asn142Asp (homozygous; OR = 1.4; 95% CI: 1.0–1.9; P for trend = 0.06) and GSTZ1 Glu32Lys (homozygous; OR = 1.3; 95% CI: 0.9–1.8; P for trend = 0.06). Our findings suggest that susceptibility to bladder cancer may relate to variation in genes involved in arsenic metabolism and oxidative stress response and potential gene-environment interactions requiring confirmation in other populations.     

Influence of GSTs, CYP2E1 and mEH polymorphisms on 1, 3-butadiene-induced micronucleus frequency in Chinese workers

1,3-butadiene (BD) has been classified as a human carcinogen, however, the relationship between chromosomal damage and its metabolic polymorphisms is not clear. The present study used the CBMN assay to detect chromosomal damage in the peripheral lymphocytes of 166 exposed workers and 41 non-exposed healthy individuals. PCR and PCR-RFLP were applied to detect GSTT1, GSTM1, CYP2E1 c1c2 and mEH Tyr113His, His139Arg polymorphisms. The results demonstrated that the micronucleus (MN) frequency of the exposed workers was significantly higher than controls (P < 0.01). Among the exposed workers, the individuals with high BD exposures are more susceptible to chromosomal damage than those with low exposures (FR = 1.30, 95% CI 1.14-1.53; P < 0.05). Gender-difference was also found in our study: males got lower micronucleus frequency than females. Workers who carried the genotypes of GSTM1 (+), CYP2E1 (c1c2/c2c2) and mEH intermediate (I) group had significantly higher MN frequency than those carrying the genotypes of GSTM1 (−) (FR = 1.29, 95% CI 1.05-1.59; P < 0.05), CYP2E1 (c1c1) (FR = 1.55, 95% CI 1.24-1.93; P < 0.01) or mEH high (H) group (FR = 1.57, 95% CI 1.08-2.34; P < 0.05), respectively. Our data indicated that the current BD exposure level could cause significantly higher MN frequency in workers than controls. Polymorphisms of GSTM1, CYP2E1 and mEH are susceptible to altered chromosome damage.     

Predictors of cessation in African American light smokers enrolled in a bupropion clinical trial

Background

This is the first study to examine predictors of successful cessation in African American (AA) light smokers treated within a placebo-controlled trial of bupropion.

Methods

We analyzed data from a randomized, double-blind, placebo-controlled trial of bupropion and health education for 540 African American light smokers. African American light smokers (≤ 10 cigarettes per day, cpd) were randomly assigned to receive 150 mg bid bupropion SR (n = 270) or placebo (n = 270) for 7 weeks. All participants received health education counseling at weeks 0, 1, 3, 5 and 7. Using chi-square tests, two sample t-tests, and multiple logistic regression analyses, we examined baseline psychosocial and smoking characteristics as predictors of cotinine-verified 7-day point prevalence smoking abstinence among study participants at the end treatment (Week 7) and at the end of follow-up (Week 26).

Results

Participants who received bupropion were significantly more likely to quit smoking compared to those who received placebo (OR = 2.72, 95% CI = 1.60–4.62, P = 0.0002). Greater study session attendance (OR = 2.47, 95% CI = 1.76–3.46, P = 0.0001), and smoking non-menthol cigarettes increased the likelihood of quitting (OR = 1.84, 95% CI = 1.01–3.36, P = 0.05); while longer years of smoking (OR = 0.98, 95% CI = 0.96–1.00, P = 0.05) and higher baseline cotinine (OR = 0.97, 95% CI = 0.95–0.99, P = 0.002) significantly reduced the odds of quitting at Week 7. Conversely, at the end of follow-up (Week 26), treatment with bupropion vs. placebo (OR = 1.14, 95% CI = 0.65–2.02, P = 0.64) was not significantly associated with quitting and type of cigarette smoked (menthol vs. non-menthol) did not appear in the final logistic regression model. Greater study session attendance (OR = 1.96, 95% CI = 1.44–2.66, P = 0.0001); BMI (OR = 1.03, 95% CI = 1.00–1.07, P = 0.04); and weight efficacy (OR = 1.03, 95% CI = 1.01–1.05, P = 0.01) increased the likelihood of quitting at Week 26. Similar to our findings at Week 7, longer years of smoking (OR = 0.96, 95% CI = 0.94–0.99, P = 0.01) and higher baseline cotinine (OR = 0.97, 95% CI = 0.95–0.99, P = 0.02) significantly reduced the odds of quitting at Week 26.

Conclusions

Baseline cotinine levels, number of years smoked and study session attendance are associated with both short- and long-term smoking cessation, while bupropion and the type of cigarette smoked were associated with quitting on short term only.     

Genetic variations of CYP2B6 gene were associated with plasma BPDE-Alb adducts and DNA damage levels in coke oven workers

Polycyclic aromatic hydrocarbons (PAHs), the main components of coke oven emissions, can induce activation of cytochrome P450 (CYP) enzymes, which metabolize PAHs and result in DNA damage by forming adducts. This study was designed to know whether genetic variants of CYP genes are associated with plasma benzo[a]pyrene-7,8-diol-9,10-epoxide-albumin (BPDE-Alb) adducts and DNA damage in coke oven workers. In this study, 298 workers were divided into four groups according to the environmental PAHs exposure levels. The concentrations of plasma BPDE-Alb adducts were detected by reverse-phase high-performance liquid chromatography and the DNA damage levels were measured using comet assay. Twelve tag single nucleotide polymorphisms (tagSNPs) of 4 CYP genes were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In the top group, workers with CYP2B6 rs3760657GA genotype have lower BPDE-Alb adducts and DNA damage levels than those with rs3760657GG genotype (P < 0.05). In the control group, the DNA damage levels of subjects with CYP1A1 rs4646421AA or GA + AA genotypes were lower than those with GG genotype (P < 0.05). However, no such effects were shown for the other tagSNPs. These results suggested that genetic variations of CYP2B6 might be associated with low BPDE-Alb adducts and DNA damage levels in worker with high exposure to PAHs.     

Mutagenic and genotoxic effects of carbosulfan in freshwater fish Channa punctatus (Bloch) using micronucleus assay and alkaline single-cell gel electrophoresis

Carbosulfan insecticide is widely used in agriculture and was recently proposed for treatment against pyrethroid-resistant mosquitoes. The mutagenic and genotoxic effect of carbosulfan was carried out in fish Channa punctatus using micronucleus (MN) test and comet assay. The 96 h LC₅₀, estimated by probit analysis in a semi-static bioassay experiment, was 0.268 mg l⁻¹. Based on the LC₅₀ value, three sub-lethal concentrations of carbosulfan (1/4th LC₅₀ = ∼67 μg l⁻¹, 1/2nd LC₅₀ = ∼134 μg l⁻¹ and 3/4th LC₅₀ = ∼201 μg l⁻¹) were selected and fishes were exposed to the said concentrations for 96 h and the samplings were done at regular intervals of 24 h for assessment of the MN frequencies and DNA damage. In general, significant effects (P < 0.01) from both concentrations and time of exposure were observed in exposed fishes. The MN induction was highest on 96 h at all the concentrations in the peripheral blood. Similar trend was observed for the DNA damage measured in terms of the percentage of tail DNA in the erythrocyte and gill cells. This study confirmed that the comet and micronucleus assays are useful tools in determining potential genotoxicity of water pollutants and might be appropriate as a part of monitoring program.     

Effectiveness of school-based smoking intervention in middle school students of Linzhi Tibetan and Guangzhou Han ethnicity in China

Purpose

The purpose of this paper is to assess the effectiveness of school-based intervention aimed to increase knowledge, to change attitudes and to reduce smoking-related behavior in both Linzhi Tibetan and Guangzhou Han middle school students in China.

Design

A concurrent intervention study was conducted in both Linzhi and Guangzhou. Two schools were randomly chosen and one was randomly assigned to the intervention group and the other to the control group in both settings.

Setting/participants

Participants were grade one and grade two middle school students drawn from two schools in Linzhi, Tibet Autonomous Region (southwest China) and two schools in Guangzhou, Guangdong Province (south China).

Intervention

The intervention program lasted for one year and covered three aspects: health policies in school, health environment in school and personal health skills.

Main outcome measures

Primary outcomes were smoking-related knowledge, attitudes and behavior (including ever smoking, daily smoking, weekly smoking and current smoking) and were measured by a self-administered questionnaire before and after the intervention.

Results

This intervention increased smoking-related knowledge in both Tibetan (β = 1.32, 95% CI (0.87–1.77)) and Han ethnic groups (β = 0.47, 95% CI (0.11–0.83)). It changed attitudes toward smoking in Tibetan (β = 1.47, 95% CI (0.06–2.87)) but not so in Han (β = − 0.33, 95% CI (− 1.68–1.01)). The intervention changed the prevalence of smoking in neither ethnic groups (P > 0.05).

Conclusions

The impact of school-based smoking intervention is different among Tibetan and Han students. This intervention was more effective for Tibetans when compared with the Han ethnic group. More research is needed on how intervention can be adapted to address ethnic and cultural differences.     

Methods of “fake ID” obtainment and use in underage college students

Fake IDs are highly prevalent among underage college students, and are strongly associated with heavy drinking. However it is not currently known how exactly fake IDs are most commonly obtained and used, and how often individuals are caught. Such information could aid law enforcement and school personnel in their enforcement responsibilities, and might further elucidate the extent and means by which students “make ethical compromises” to gain illegal access to alcohol. A cross-sectional online survey of 1098 underage students at a large Midwestern university indicated that comparable to previous findings, 21.0% reported possessing a fake ID (which was strongly associated with past-month frequent heavy drinking; OR = 4.84, 95% CI = 3.41–6.86). Of those with fake IDs, 93.5% reported having used them, and 29.1% reported having been caught. Greek (i.e., fraternity/sorority) members were more likely than others to obtain them through a Greek organization (OR = 8.02, 95% CI = 1.81–35.54). Also, men were more likely than women to buy (OR = 2.74, 95% CI = 1.57–4.77), yet less likely to be given them (OR = 0.53, 95% CI = 0.31–0.90). Future studies might examine whether and how fake ID capture reduces (or exacerbates) drinking over time.     

Genetic polymorphisms in hMTH1, hOGG1 and hMYH and risk of chronic benzene poisoning in a Chinese occupational population

Oxidative damage to DNA induced by benzene is an important mechanism of its genotoxicity, which leads to chronic benzene poisoning (CBP). Therefore, genetic variation in DNA repair genes may contribute to susceptibility to CBP in the exposed population. We hypothesized that single nucleotide polymorphisms (SNPs) in hMTH1, hOGG1 and hMYH genes are associated with risk of CBP. We genotyped SNPs at codon 83 of hMTH1, codon 326 of hOGG1, and codon 324 of hMYH in 152 CBP patients and 152 healthy workers occupationally exposed to benzene without poisoning manifestations. The genotypes were determined by polymerase chain reaction-restrained fragment length polymorphism (PCR-RFLP) technique. There were 2.51-fold [adjusted odds ratio (OR_adj), 2.51; 95% CI, 1.14-5.49; P = 0.02] and 2.49-fold (OR_adj, 2.49; 95% CI: 1.52-4.07; P < 0.01) increased risk of CBP for individuals carrying genotypes of hMTH1 83Val/Met + Met/Met and hOGG1 326Cys/Cys, respectively. Compared with individuals carrying genotypes of hOGG1 326Cys/Cys and hMYH 324His/His at the same time, there was a 0.33-fold (OR_adj, 0.33; 95% CI: 0.15-0.72; P < 0.05) decreased risk of CBP for those with genotypes of hOGG1 326Ser/Cys + Ser/Ser and hMYH 324His/Gln + Gln/Gln. In the smoking group, there was a 0.15-fold (OR_adj, 0.15; 95% CI, 0.03-0.68; P = 0.01) decreased risk of CBP for subjects carrying genotypes of hMYH 324His/Gln + Gln/Gln compared with those of genotype of hMYH 324His/His. Therefore, our results suggested that polymorphisms at codons 83 of hMTH1 and codon 326 of hOGG1 might contribute to CBP in a Chinese occupational population.     

Early temperament,propensity for risk-taking and adolescent substance-related problems: A prospective multi-method investigation

One hundred thirty seven adolescents (M = 15.3 yrs, SD = 1.0 yr, n = 72 girls) were recruited into temperament groups when they were 4 months of age based on reactivity to novel auditory/visual stimuli (Fox, Henderson, Rubin, Calkins, & Schmidt, 2001). Behavioral inhibition was observed across infancy (14 and 24 months). Additionally, self-reported substance-related problems and behavioral risk-taking was assessed during adolescence. High behavioral inhibition increased risk for substance-related problems among boys, whereas high behavioral inhibition protected against substance-related problems among girls, B = − 1.18, SE = .48, 95% CI = − 2.13 to −.24; p < .05. Additionally, high behavioral inhibition protected lower risk-taking children from adolescent substance-related problems whereas high behavioral inhibition increased risk for substance-related problems among higher risk-taking children, B = .04, SE = .02, 95% CI = .00 to .08. Findings from this prospective, multi-informant, longitudinal study suggest that risk-taking and gender may interact with temperamental traits to place adolescents at differential risk for substance-related related behavior problems.     

Initial insight into why physical activity may help prevent adolescent smoking uptake

Introduction

Whereas research supports the importance of regular physical activity to decrease the likelihood of smoking uptake, the mechanisms accounting for this relationship are poorly understood. We sought to determine whether the enjoyment or reward derived from physical activity is one mechanism underlying the relationship between smoking and physical activity.

Methods

The sample was composed of 1374 adolescents participating in a prospective longitudinal survey study of health behaviors. Variables were measured via self-report every six months for eight waves of data spanning four years.

Results

An associative processes latent growth curve model revealed a significant and negative indirect effect of baseline physical activity on baseline smoking through baseline physical activity reward (b_indirect = −.18, z = −3.11, p = .002; 95% CI = −.29, −.07). Similarly, there was a significant and negative indirect effect of physical activity trend on smoking trend through physical activity reward trend (b_indirect = −.16, z = −2.09, p = .04; 95% CI = −.30, −.01). The effect of physical activity on smoking at baseline and across time was completely mediated by physical activity reward. There was less support for the idea that smoking progression was associated with reduced physical activity reward and subsequent declines in physical activity.

Conclusions

This study provides the first evidence implicating physical activity reward as one mechanism by which physical activity reduces the likelihood of adolescent smoking uptake. Smoking prevention interventions that promote physical activity and target physical activity enjoyment may have an important impact on adolescent smoking initiation and progression.     

Short-term efficacy of nicotine replacement therapy for smoking cessation in adolescents: A randomized controlled trial

The aim of this randomized, double-blind placebo-controlled clinical trial is to test the efficacy and safety of nicotine replacement therapy (NRT) in promoting end-of-treatment abstinence among adolescents and whether this relation is moderated by medication compliance. Participants (N = 257, age: 16.7 ± 1.13 years) attended an information meeting followed by a 6- or 9-week treatment. Self-reported smoking cessation, compliance, and side effects were measured by means of online questionnaires. Intent-to-treat analyses showed that independent of compliance, NRT is effective in promoting abstinence rates after 2 weeks (OR = 2.02, 95% CI = 1.11–3.69), but not end-of-treatment abstinence. However, end-of-treatment abstinence rates significantly increased in high-compliant (OR = 1.09, 95% CI = 1.01–1.17) and not in low-compliant participants. No serious adverse events were found. Future research is warranted to disentangle the process involving the decrease in abstinence rates and compliance rates from the third week after the quit date onwards.     

Relationship between miRNAs polymorphisms and peripheral blood leukocyte DNA telomere length in coke oven workers: A cross-sectional study

ObjectiveThe purpose of this study was to investigate the factors affecting telomere length (TL) in coke oven workers by analyzing the interaction between miRNAs polymorphisms and coke oven emissions (COEs) exposure.MethodsA total of 544 coke oven workers and 238 healthy controls were recruited. Peripheral blood was collected from the subjects, genomic DNA was extracted, leukocyte TL was detected by real-time quantitative polymerase chain reaction, and fifteen polymorphisms of eight miRNAs were genotyped by flight mass spectrometry.ResultsStatistical analysis showed that the peripheral blood DNA TL in the exposure group was shorter than that in the control group (P < 0.001). Generalized linear model found that COEs-exposure [β (95%CI) = -0.427 (−0.556, −0.299), P < 0.001], genotype CC+CT for miR-612 rs1144925 [β (95%CI) = −0.367 (−0.630, −0.104), P = 0.006], and the interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure [β (95% CI) = 0.564 (0.108, 1.020), P = 0.015] were associated with the shortened TL.ConclusionCOEs-exposure and miR-612 rs1144925 TT could promote telomere shortening in coke oven workers. The interaction of miR-181B1 rs12039395 TT genotype and COEs-exposure could protect telomere. This provides clues for further mechanistic studies between miRNA and telomere damage.     

Contingency management voucher redemption as an indicator of delayed gratification

This prospective analysis tested whether frequency of voucher redemptions during a contingency management (CM) substance use intervention was significantly associated with participants' ongoing substance use. Homeless, substance-dependent men who have sex with men (N = 131) were randomized into either a “full” or “lite” voucher-based CM intervention. All participants earned vouchers for attendance and participation; participants in the CM-full condition also received vouchers for substance abstinence and enactment of prosocial and/or health-promoting behaviors. Multivariate longitudinal negative binomial regression analyses (n = 118) assessed the association between substance use during the intervention and frequency of voucher redemptions. Participants who used methamphetamine (IRR = 0.66; 95% CI = 0.44–0.99) and/or opiates (IRR = 0.60; 95% CI = 0.40–0.99) during the intervention exhibited less time between voucher redemptions than individuals who achieved abstinence from these substances. Voucher redemption logs can be cost-effective and unobtrusive tools for measuring study participants' tendency to delay gratification.     

Breast cancer risk,dietary intake,and methylenetetrahydrofolate reductase (MTHFR) single nucleotide polymorphisms

Diet plays an important role in DNA methylation, synthesis, and repair; intake has been associated with breast cancer. The folate-metabolizing enzyme, methylenetetrahydrofolate reductase (MTHFR) is polymorphic at nucleotides 677 (C → T), resulting in allozymes with altered activity and is thus believed to cause interindividual differences in cancer risk susceptibility. I evaluated this polymorphism and its effect on the food intake and breast cancer risk association in a population-based case-control study of 100 breast cancer cases and 100 controls using a real-time PCR based assay. All subjects completed in-person interviews, which included a food-frequency questionnaire. Unconditional logistic regression models were used to calculate odds ratios and their 95% confidence intervals, after adjusting for potential confounding factors. Cases and controls were similar in the distribution of MTHFR polymorphisms at codon 677 (41.4% cases and 41.8% controls carried the T allele). An inverse association of breast cancer risk with food intake was observed in all genotype groups, particularly among subjects with the 677TT genotype. Compared with those with the 677CC genotype and high food intake frequency, the adjusted odds ratios (95% confidence intervals) associated with low food intake were 1.94 (1.15–3.26), 2.17 (1.34–3.51), and 2.51 (1.37–4.60) for subjects who had CC, CT, and TT genotypes (P for interaction, 0.05). Results of this study suggest that the MTHFR C677T polymorphism may modify the association between dietary intake and breast cancer risk.     

Hemoglobin adducts as biomarkers of estrogen homeostasis: Elevation of estrogenquinones as a risk factor for developing breast cancer in Taiwanese Women

The aim of this study was to establish a methodology to analyze estrogen quinone-derived adducts, including 17β-estradiol-2,3-quinone (E₂-2,3-Q) and 17β-estradiol-3,4-quinone (E₂-3,4-Q), in human hemoglobin (Hb). The methodology was then used to measure the levels of these adducts in Hb derived from female breast cancer patients (n = 143) as well as controls (n = 147) in Taiwan. Our result confirmed that both E₂-2,3-Q- and E₂-3,4-Q-derived adducts, including E₂-2,3-Q-4-S-Hb and E₂-3,4-Q-2-S-Hb, were detected in all breast cancer patients with median levels at 434 (215–1472) and 913 (559–2384) (pmol/g), respectively. Levels of E₂-2,3-Q-4-S-Hb correlated significantly with those of E₂-3,4-Q-2-S-Hb (r = 0.622–0.628, p < 0.001). By contrast, median levels of these same estrogen quinone-derived adducts in healthy controls were 71.8 (35.7–292) and 139 (69.1–453) (pmol/g). This translated to ∼6-fold increase in mean values of E₂-2,3-Q-4-S-Hb and E₂-3,4-Q-2-S-Hb in breast cancer patients compared to those in the controls (p < 0.001). Our findings add further support to the theme that cumulative body burden of estrogen quinones is an important indicator of breast cancer risk. We hypothesize that combination of genetic events and environmental factors may modulate estrogen homeostasis and enhance the production of estrogen quinones which lead to subsequent generation of pro-mutagenic DNA lesions in breast cancer patients.     

eNOS gene polymorphisms modify the association of PM10 with oxidative stress

Previous studies have suggested that air pollution increases various health outcomes through oxidative stress and oxidative stress-related genes modify the relationship between air pollution and health outcomes. Therefore, we evaluated the effect of PM₁₀ on the levels of malondialdehyde (MDA), oxidative stress biomarker, and the effect modification by genetic polymorphisms of eNOS, oxidative stress-related gene, in the 560 Korean elderly. We obtained urine samples repeatedly from participants during five medical examinations between 2008 and 2010 and all ambient air pollutant concentration data from the Korea National Institute of Environmental Research air quality monitoring system. We measured urinary levels of MDA to assess oxidative stress and genotyped eNOS (rs1799983, rs2853796, and rs7830). Mixed-effect model was used to estimate the effect of PM₁₀ on the level of oxidative stress biomarker and their modification by genotypes. PM₁₀ showed apparent positive effect on MDA level after adjusting for age, sex, BMI, cotinine level, temperature, dew point, levels of SO₂, O₃, NO₂, and CO, and season (p = 0.0133). Moreover, the association of PM₁₀ with MDA was found only in participants with eNOS GG genotype for rs1799983 (p = 0.0107), TT genotype for rs2853796 (p = 0.0289), or GT genotype for rs7830 (p = 0.0158) and in participants with a set of risky haplotypes (GTT, GTG, GGT, and TGT) (p = 0.0093). Our results suggest that PM₁₀ affect oxidative stress in the elderly and eNOS genotype affect the oxidative stress level in regard of exposure to PM₁₀.     

The association between CHRN genetic variants and dizziness at first inhalation of cigarette smoke

Numerous single nucleotide polymorphisms (SNPs) in multiple nicotinic receptor genes (CHRN) are associated with smoking. However few studies have examined the association between CHRN SNPs and subjective responses to smoking in adolescents which may relate to sustained smoking, such as dizziness at first inhalation. The objective of this study was to investigate the association between 61 SNPs in eight CHRN genes (CHRNA3, CHRNA4, CHRNA5, CHRNA6, CHRNA7, CHRNB2, CHRNB3, CHRNB4) and dizziness at first inhalation. Data were available from a longitudinal cohort investigation of 1293 students 12–13 year-old at baseline. Students completed self-report questionnaires at school every 3 months for 5 years during secondary school, and a mailed questionnaire three years later. DNA extracted from blood or saliva was genotyped for 61 CHRN SNPs selected using a gene tagging approach. Associations were modeled using logistic regression controlling for sex, race and age at first cigarette. Complete data were available for 356 of 475 participants (75%) who initiated smoking. The minor alleles of three SNPs in CHRNA6 (rs7812298, rs2304297, rs7828365) were associated with a decreased probability of dizziness (OR(95% CI) = 0.54 (0.36, 0.81), 0.59 (0.40, 0.86) and 0.58 (0.36, 0.95), respectively), while one SNP in each of three other genes (rs3743077 (CHRNA3), rs755204 (CHRNA4), rs7178176 (CHRNA7)) was associated with an increased probability of dizziness (OR(95% CI) = 1.40 (1.02, 1.90), 1.85 (1.05, 3.27) and 1.51 (1.06, 2.15), respectively). Thus, several SNPs located in CHRN genes are associated with dizziness at first inhalation, a smoking initiation phenotype that may relate to sustained smoking.