The Association of Aging-Related Polymorphisms with Susceptibility to Lung Cancer: A Case-Control Study in a Japanese Population.

BACKGROUND: Telomere length is associated with cancer as well as aging.  Telomerase reverse transcriptase (TERT), telomere RNA component (TERC) and oligonucleotide/oligosaccharide-binding fold containing 1 (OBFC1) are known to be involved in telomere length regulation. The tumor suppressor p53 (TP53), which has been shown to interact with tumor protein p53-binding protein 1 (TP53BP1), is implicated in the response to telomere shortening and aging.  Polymorphisms in the TP53 and TP53BP1 genes are associated with various types of cancer. The aim of this study is to evaluate the impact of aging-related polymorphisms on lung cancer risk. MATERIALS AND METHODS: This case-control study consists of 462 lung cancer cases and 379 controls from Japan.  We examined the effect of TERT rs2736100, TERC rs1881984, OBFC1 rs11191865, TP53 rs1042522 and TP53BP1 rs560191 on the risk of lung cancer using a Taq-Man real-time PCR assay. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: None of the main effects of any of the telomere-related polymorphisms were related to the risk of lung cancer.  Similarly, none of the interactive effects of any of the telomere-related polymorphisms with smoking were associated with lung cancer risk. The significant multiplicative interaction between TERT rs2736100 and TP53BP1 rs560191 was statistically significant (OR for interaction = 0.34, 95% CI = 0.14-0.84). The multiplicative interaction between OBFC1 rs11191865 and TP53BP1 rs560191 was also statistically significant (OR for interaction = 2.44, 95% CI = 1.02-5.87) but the OR for interaction was in the opposite direction. CONCLUSIONS: Our findings indicate that TP53BP1 rs560191 may predispose to lung cancer risk depending on the genotypes of telomere-related polymorphisms. Additional studies are warranted to confirm the findings suggested in the present study.
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Association between Telomere-Related Polymorphisms and the Risk of IPF and COPD as a Precursor Lesion of Lung Cancer: Findings from the Fukuoka Tobacco-Related Lung Disease (FOLD) Registry.

BACKGROUND: Lung cancer coexisting with idiopathic pulmonary fibrosis (IPF) or chronic obstructive pulmonary disease (COPD) can lead to poor prognosis.  Telomere-related polymorphisms may be implicated in the pathogenesis of these three lung diseases.  As to elucidate the mechanism of lung cancer via IPF or COPD may enable early detection and early treatment of the disease, we firstly examined the association between telomere-related polymorphisms and the risk of IPF and COPD in a case-control study. MATERIALS AND METHODS: A total of 572 patients with IPF (n = 155) or COPD (n = 417), who were derived from our on-going cohort study, and controls (n = 379), who were derived from our previous case-control study, were included in this study.  Telomerase reverse transcriptase (TERT) rs2736100, telomere RNA component (TERC) rs1881984, and oligonucleotide/oligosaccharide-binding fold containing1 (OBFC1) rs11191865 were genotyped with real-time PCR using TaqMan fluorescent probes. Unconditional logistic regression was used to assess the adjusted odds ratios and 95% confidence intervals. RESULTS: TERT rs2736100 was significantly associated with the risk of IPF; increases in the number of this risk allele increased the risk of IPF (Ptrend = 0.008).  Similarly, TERT rs2736100 was associated with the risk of COPD.  In regard to the combined action of the three loci, increasing numbers of "at-risk" genotypes increased the risk of IPF in a dose-dependent manner (P trend=0.003). CONCLUSIONS: TERT rs2736100 was associated with the risks of both IPF and COPD in a Japanese population. A combination of the "at-risk" genotypes might be important to identify the population at risk for IPF more clearly.

Prediction of hemodynamic fluctuations after induction of general anesthesia using propofol in non-cardiac surgery: a retrospective cohort study.

BACKGROUND: Although propofol is a common anesthetic agent for the induction of general anesthesia, hemodynamic fluctuations are occasionally prominent during induction/intubation. The aims of this study were to determine the influential factors on enhanced hemodynamic fluctuation and to establish a prediction formula to quickly determine the dose of propofol to protect against hemodynamic fluctuations. METHODS: This retrospective cohort study patients (n = 2097) were 18 years or older. They underwent general anesthesia induction using propofol and orotracheal intubation for non-cardiac surgery at Kyushu University Hospital during April 2015 to March 2016. Preoperative patient clinical information was collected from anesthesia preoperative evaluation records. Intraoperative data were obtained from computerized anesthesia records. If patients' post-induction mean arterial blood pressure (MAP) decreased or increased 30% or more from their pre-induction MAP, they were determined to have enhanced hemodynamic fluctuations. Unconditional logistic regression was used to assess the adjusted odds ratios (ORs) and 95% confidence intervals (CIs). Structural equation modeling (SEM) was conducted to simultaneously examine the direct and indirect effect (path coefficient = r) of potential variables. RESULTS: In the SEM analysis, age was significantly associated with enhanced hemodynamic fluctuations (adjusted odds ratio = 1.008, 95% CI = 1.001-1.015, P = 0.03). Age (path coefficient (r) = - 0.0113, 95% CI = - 0.0126-0.010, P < 0.001), American Society of Anesthesiologists physical status (ASA-PS) (r = - 0.0788, 95% CI = - 0.1431-0.0145, P = 0.02), sex (r = 0.057, 95% CI = 0.0149-0.9906, P = 0.01), and fentanyl dose (r = 0.1087, 95% CI = 0.0707-0.1467, P < 0.001) influenced the dose of propofol in induction. The prediction formula of "Propofol dose (mg) = [2.374 - 0.0113 × age (year) - 0.0788 (if ASA-PS 3 or 4) + 0.057 (if female) + 0.1087 × fentanyl dose (µg/kg)] × body weight (kg)" was derived. CONCLUSIONS: Age was associated with hemodynamic fluctuations in induction. Although the prediction formula is considered to be acceptable, future studies validating whether it can decrease patients' risk of enhanced hemodynamic fluctuations in clinical situations are necessary.

Dietary inflammatory index and risk of upper aerodigestive tract cancer in Japanese adults.

BACKGROUND: The inflammatory potential of diet that has been shown to be associated with cancer risk. We examined the association between dietary inflammatory potential as measured by the dietary inflammatory index (DII®) and risk of upper aerodigestive tract cancers in a Japanese case-control study. RESULTS: A positive association was observed between increasing DII scores and overall upper aerodigestive tract cancers, and across anatomic subsites. For upper aerodigestive tract cancers, the ORQ4vsQ1 = 1.73 (95% CI: 1.37-2.20); head and neck cancer, the ORQ4vsQ1 was 1.92 (95% CI: 1.42-2.59); and for esophageal cancer, the ORQ4vsQ1 was1.71 (95% CI: 1.54-1.90). Risks for hypopharyngeal and nasopharyngeal cancers were greatly elevated: (ORQ4vsQ1 = 4.05 (95% CI: 1.24-13.25) for hypopharyngeal cancer and ORQ4vsQ1 = 4.99 (95% CI: 1.14-21.79) for nasopharyngeal cancer. CONCLUSION: A more pro-inflammatory diet was associated with an elevated risk of upper aerodigestive tract cancers after accounting for important confounders. All anatomic subsites, except larynx, showed the consistently elevated risk with increasing DII score. Those subsites with known etiological associations with persistent infection showed the largest elevation in risk. These results warrant further evaluation in future studies. MATERIALS AND METHODS: This is a case-control study of 1,028 cases and 3,081 age- and sex-matched non-cancer controls recruited at Aichi Cancer Center. DII scores were computed based on estimates of macro- and micro-nutrients from a self-administered food frequency questionnaire. Scores were further categorized into quartiles (based on the distribution in controls). Conditional logistic regression models were fit to estimate odds ratio (OR) and 95% confidence intervals (CIs) adjusted for smoking, ethanol consumption, alcohol flushing, number of teeth, and occupation group.

Effects of tumor necrosis factor inhibitors and tocilizumab on the glycosylated hemoglobin levels in patients with rheumatoid arthritis; an observational study.

Rheumatoid arthritis (RA) and diabetes mellitus (DM) are associated with inflammation. We tried to investigate the influence of tumor necrosis factor inhibitors (TNFi) and tocilizumab (TCZ) on the glucose metabolism of RA patients. RA patients in whom treatment with TNFi or TCZ was initiated from 2008 to 2015 were studied based on their medical records. We analyzed patients whose glycosylated hemoglobin (HbA1c) levels were measured both before and 3 months after the initiation of these biologic agents. The association between HbA1c reduction and the treatment was evaluated. From 971 cases treated with these biologic agents, 221 cases whose medical records of HbA1c were available, were included (TNFi, n = 154; TCZ, n = 67). Both the TNFi and TCZ groups had significantly lower HbA1c values at 1 month and 3 months after the initiation of treatment (TNFi, p<0.001; TCZ, p<0.001). Although the pretreatment HbA1c values did not differ (TNFi, 6.2%; TCZ, 6.2%; p = 0.532), the 3-month treatment HbA1c values were lower (TNFi, 6.1%; TCZ, 5.8%; p = 0.010) and the changes in HbA1c (ΔHbA1c) were greater (TNFi, 0.1%; TCZ, 0.4%; p<0.001) in the TCZ group. The reduction of HbA1c-defined by the achievement of a ΔHbA1c of ≥0.5%-was associated with baseline diagnosis of diabetes mellitus, baseline diabetes treatment, hospitalization, medical change during the observation period, and TCZ. In the multivariate logistic regression analysis, TCZ was associated with the reduction of HbA1c in comparison to TNFi (adjusted OR = 5.59, 95% CI = 2.56-12.2; p<0.001). The HbA1c levels in RA patients were significantly lower after the initiation of TNFi or TCZ. Our study suggests that TCZ decreases the HbA1c levels in RA patients to a greater extent than TNFi.

Biological interaction of cigarette smoking on the association between genetic polymorphisms involved in inflammation and the risk of lung cancer: A case-control study in Japan.

Chronic inflammation serves an important role in lung carcinogenesis, thus genetic polymorphisms involved in this pathway may affect the risk of lung cancer. The present case-control study focused on the association between lung cancer risk and genetic polymorphisms involved in inflammatory pathways. The study comprised 462 lung cancer cases and 379 controls from Japan. The roles of interleukin 8 (IL8) rs4073, nuclear factor kappa B (NFκB) rs28362491, cytochrome b-245, alpha polypeptide (CYBA) rs4673, NAD(P) H dehydrogenase, quinone 1 (NQO1) rs1800566, nitric oxide synthase 2 and inducible (NOS2) rs2297518 polymorphisms in lung carcinogenesis were investigated. An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between the genetic polymorphisms and lung cancer risk. The multiplicative and additive [relative excess risk due to interaction, attributable proportion due to interaction (AP) and synergy index (SI)] interactions with cigarette smoking were also determined. A significant association was revealed between the TT genotype of NQO1 rs1800566 and an increased risk of lung cancer (OR=1.78; 95% CI=1.14-2.79). The additive interaction evaluations between CYBA rs4673 (AP=0.50, 95% CI=0.15-0.85; SI=2.66, 95% CI=1.01-6.99) and smoking were also statistically significant. NQO1 rs1800566 was significantly associated with lung cancer risk and smoking may influence the association between CYBA rs4673 and the risk of lung cancer. Additional studies with larger control and case populations are warranted in order to confirm the CYBA rs4673-smoking association suggested by the present study.

Vitamin D receptor gene polymorphisms, smoking, and risk of sporadic Parkinson's disease in Japan.

Epidemiological evidence on the relationships between the vitamin D receptor (VDR) single nucleotide polymorphisms (SNPs) rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), and rs2228570 (FokI) and Parkinson's disease (PD) is inconsistent. We investigated these relationships in 229 sporadic PD patients within six years of onset in Japan. Controls were 357 patients without neurodegenerative disease. Adjustment was made for sex, age, region of residence, and smoking. A significant inverse association was found between SNP rs2228570 and the risk of sporadic PD under the additive but not the co-dominant or dominant model (P=0.048); however, this fell below significance after adjustment for multiple comparisons (adjusted P=0.46). No significant relationships were found between SNPs rs731236, rs7975232, or rs1544410 and the risk of sporadic PD in any genetic model. VDR haplotypes inferred in the current study were not associated with sporadic PD. Compared with subjects with the GA or AA genotype of SNP rs2228570 who had ever smoked, those with the GG genotype who had never smoked had a 3.78-fold increased risk of sporadic PD; however, no significant interaction was observed. VDR SNP rs2228570 may be associated with sporadic PD in Japan. Smoking did not significantly modify the relationship between SNP rs2228570 and sporadic PD.

Association between genetic polymorphisms involved in the hypoxia-inducible factor pathway and lung cancer risk: a case-control study in Japan.

AIM: Hypoxia-inducible factor (HIF) contributes to the adaptation of tumor cells to hypoxic conditions, so genetic polymorphisms involved in this pathway may affect cellular response to hypoxia and be associated with cancer risk. Thus, we examined the association between the lung cancer risk and genetic polymorphisms involved in the HIF pathway. METHODS: This case-control study consists of 462 lung cancer cases and 379 controls from Japan. We examined the effect of HIF1A rs11549467, HIF1A rs11549465, HIF1A rs2057482, HIF2A rs13419896 and vascular endothelial growth factor A (VEGFA) rs833061 on the risk of lung cancer using TaqMan real-time PCR assay. Logistic regression was used to estimate the odds ratio (OR) and its 95% confidence interval (CI) of lung cancer risk. The multiplicative and additive interactions with cigarette smoking were also examined. RESULTS: The AA genotype of HIF2A rs13419896 (OR = 0.54, 95% CI = 0.30-0.99) and the CC genotype of VEGFA rs833061 (OR = 0.42, 95% CI = 0.24-0.75) were significantly associated with a decreased risk of lung cancer after adjustment of potential covariates. Additive interactions between these two polymorphisms and cigarette smoking were also significant. CONCLUSION: HIF2A rs13419896 and VEGFA rs833061 were significantly related to lung cancer risk, with possible interaction between polymorphisms and cigarette smoking. Further studies are needed to confirm these results.

Risk factors for development of systemic lupus erythematosus among Japanese females: medical history and reproductive factors.

AIM: The aim of the present study was to examine the influence of medical history and reproductive factors on the development of systemic lupus erythematosus (SLE) among Japanese females. METHODS: One hundred and sixty female SLE patients and 660 female volunteers were studied in a case-control study. Unconditional logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CIs). RESULTS: The present study demonstrated that medical histories of operations without blood transfusion (OR = 1.64, 95% CI = 1.10-2.44) and operations with blood transfusion (OR = 4.44, 95% CI = 1.93-10.23) increased the risk of SLE with adjustment for age, region, smoking and alcohol drinking. Among 91 SLE patients and 284 control subjects who had the experience of married life, nulliparity (OR = 2.29, 95% CI = 1.05-5.17), increased the risk of SLE, while the risk decreased according to the number of children (one to two vs. none, OR = 0.27, 95% CI = 0.10-0.73; three or more vs. none, OR = 0.14, 95% CI = 0.04-0.51; P for trend < 0.01). CONCLUSIONS: Several factors are suggested to be associated with the development of SLE among Japanese females.

CYP2E1 rs2031920, COMT rs4680 Polymorphisms, Cigarette Smoking, Alcohol Use and Lung Cancer Risk in a Japanese Population.

BACKGROUND: Cytochrome P450 2E1 (CYP2E1) and catechol-O-methyltransferase (COMT) genes may contribute to susceptibility to lung cancer because of their critical involvement in mechanisms of carcinogenesis. MATERIALS AND METHODS: We evaluated the role of CYP2E1 rs2031920 and COMT rs4680 in a case-control study involving 462 lung cancer cases and 379 controls in Japanese. Logistic regression was used to assess adjusted odds ratios (OR) and 95% confidence intervals (CI). Multiplicative and additive interactions with cigarette smoking or alcohol use were also examined. RESULTS: Neither CYP2E1 rs2031920 nor COMT rs4680 was associated with lung cancer risk overall. However, smokers with the CC genotype of CYP2E1 rs2031920 (OR = 3.57, 95% CI = 2.26-5.63) presented a higher risk of lung cancer than those with at least one T allele (OR = 2.91, 95% CI = 1.70-4.98) as compared to never-smokers with at least one T allele (reference). Subjects with excessive drinking and the CC genotype of CYP2E1 rs2031920 had a significantly higher risk (OR=2.22, 95% CI =1.39-3.56) than appropriate drinkers with at least one T allele. A similar tendency was observed between COMT rs4680 and either smoking or drinking habits. There were no multiplicative or additive interactions between the polymorphisms and either smoking or alcohol use. CONCLUSIONS: Our findings indicate that CYP2E1 rs2031920 and COMT rs4680 are not major contributors to lung cancer risk in our Japanese population. Future studies on the genetics of lung cancer in Japanese and their environment interactions are required.

High-Sensitivity C-Reactive Protein and Risks of All-Cause and Cause-Specific Mortality in a Japanese Population.

BACKGROUND: High-sensitivity C-reactive protein (hsCRP) levels are lower in Japanese compared with Western subjects. Since it is uncertain whether hsCRP is a potent predictor of mortality at low CRP concentrations, the present study examined associations with all-cause and cause-specific mortality in a large population of Japanese. MATERIALS AND METHODS: Subjects were 4,737 men and 6,343 women aged 49-76 years participating in the baseline survey of an ongoing cohort study of lifestyle-related diseases between February 2004 and July 2006. Hazard ratios for all-cause and cause-specific mortality associated with hsCRP levels were estimated using Cox proportional hazards regression. RESULTS: A total of 436 all-cause deaths occurred during a median follow- up of 8 years. The main cause of death was cancer. In men, hsCRP levels were positively associated with the risk of all-cause mortality as well as deaths from cancer and cardiovascular disease (CVD). All-cause mortality hazards for the 2nd (0.34-0.84 mg/L) and the 3rd (≥ 0.85 mg/L) tertiles of hsCRP were 1.27 (95% confidence interval [CI], 0.93-1.73) and 1.75 (1.30-2.37), respectively (p for trend=0.001). In women, increased risk of all- cause and cause-specific mortality associated with elevated hsCRP levels was observed, but the associations were not statistically significant. CONCLUSIONS: HsCRP may be an independent predictor of all-cause, cancer and CVD mortality in apparently healthy Japanese men, but not women. The differential effect of hsCRP in predicting mortality risk by sex warrants further investigation.

PARK16 polymorphisms, interaction with smoking, and sporadic Parkinson's disease in Japan.

Epidemiological evidence on the relationships between PARK16 single nucleotide polymorphisms (SNPs) and Parkinson's disease (PD) is inconsistent. We examined this issue in Japan. Included were 229 cases within six years of PD onset. Controls were 356 patients without neurodegenerative disease. Compared with subjects with the AA genotype of SNP rs823128, those with the AG genotype, but not the GG genotype, had a significantly reduced risk of sporadic PD. Compared with the AA genotype of SNP rs947211, both the AG genotype and the GG genotype were significantly related to an increased risk of sporadic PD. Using subjects with the AA genotype of SNP rs823156 as a reference group, there were significant inverse relationships under the additive and dominant models. No significant relationships were found between SNPs rs16856139 or rs11240572 and sporadic PD. The CAAAC, the TGAGA, and the CAGAC haplotypes were significantly related to sporadic PD. The additive interaction between SNP rs823128 and smoking affecting sporadic PD was significant, although the multiplicative interaction was not significant. The PARK16 SNPs rs823128, rs947211, and rs823156 and the CAAAC, TGAGA, and CAGAC haplotypes may be significantly associated with sporadic PD in Japan. New evidence of an additive interaction between SNP rs823156 and smoking is suggested.

CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians.

The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.

Characteristics of MPO-ANCA-positive granulomatosis with polyangiitis: a retrospective multi-center study in Japan.

We studied the clinico-pathological differences among PR3-ANCA-positive granulomatosis with polyangiitis (PR3-GPA), MPO-ANCA-positive GPA (MPO-GPA) and microscopic polyangiitis (MPA). ANCA-associated vasculitis (AAV) was classified using the European Medicines Agency classification. We retrospectively analyzed 38 patients with GPA and 41 with MPA treated in eight hospitals in Japan. Of the patients with GPA, 17 were positive for MPO-ANCA, and 15 for PR3-ANCA. All patients with MPA were MPO-ANCA positive. The mean ages of those with MPO-GPA were 69.6 years old, 10 years older than those with PR3-GPA. The majority (82 %) of patients with MPO-GPA were woman, a significantly greater proportion than for PR3-GPA. We also found that ear, nose and throat (ENT), nervous system involvement were significantly more common in MPO-GPA, but renal function was less impaired than those with MPA. Both PR3-GPA and MPO-GPA relapsed more frequently than MPA, but overall survival was significantly better (P < 0.01 and P < 0.05, respectively). Univariate analysis identified the following factors as predictors of a poor prognosis: MPA (P < 0.01), pulmonary UIP pattern (P < 0.005) Cr ≥ 1.7 mg/dl (P < 0.01) and absence of ENT involvement (P < 0.05), which were characteristics of MPA. In our cohort, MPO-GPA was most likely to affect older women and was associated with otitis media, nervous system involvement, mild renal impairment and more favorable outcome. It is clinically useful to differentiate MPO-GPA from MPA and PR3-GPA in patients with AAV.

Linking lifestyle factors and insulin resistance, based on fasting plasma insulin and HOMA-IR in middle-aged Japanese men: a cross-sectional study.

OBJECTIVE: Insulin resistance (IR) is regarded as one of the earliest features of many metabolic diseases, and major efforts are aimed at improving insulin function to confront this issue. The aim of this study was to investigate the relationship of body mass index (BMI), cigarette smoking, alcohol intake, physical activity, green tea and coffee consumption to IR. METHODS: We performed a cross-sectional study of 1542 male self defense officials. IR was defined as the highest quartile of the fasting plasma insulin (≥ 50 pmol/L) or the homeostasis model assessment-estimated IR (HOMA-IR ≥ 1.81). An unconditional logistic model was used to estimate the odds ratio (OR) and 95% confidence interval (CI) for the association between IR and influential factors. Stratified analysis by obesity status (BMI < 25 kg/m(2), non-obese; ≥ 25 kg/m(2), obese) was performed. RESULTS: IR was significantly positively related to BMI and glucose tolerance, negatively related to alcohol use. Independent of obesity status, significant trends were observed between IR and alcohol use. Drinking 30 mL or more of ethanol per day reduced IR by less than 40%. Strong physical activity was associated with decreased risk of IR based on fasting plasma insulin only in the obese. Coffee consumption was inversely associated with the risk of IR based on HOMA-IR in the non-obese group. CONCLUSION: Higher coffee consumption may be protective against IR among only the non-obese. Further studies are warranted to examine the effect modification of the obesity status on the coffee-IR association.

Exposure to secondhand tobacco smoke and lung cancer by histological type: a pooled analysis of the International Lung Cancer Consortium (ILCCO).

While the association between exposure to secondhand smoke and lung cancer risk is well established, few studies with sufficient power have examined the association by histological type. In this study, we evaluated the secondhand smoke-lung cancer relationship by histological type based on pooled data from 18 case-control studies in the International Lung Cancer Consortium (ILCCO), including 2,504 cases and 7,276 control who were never smokers and 10,184 cases and 7,176 controls who were ever smokers. We used multivariable logistic regression, adjusting for age, sex, race/ethnicity, smoking status, pack-years of smoking, and study. Among never smokers, the odds ratios (OR) comparing those ever exposed to secondhand smoke with those never exposed were 1.31 (95% CI: 1.17-1.45) for all histological types combined, 1.26 (95% CI: 1.10-1.44) for adenocarcinoma, 1.41 (95% CI: 0.99-1.99) for squamous cell carcinoma, 1.48 (95% CI: 0.89-2.45) for large cell lung cancer, and 3.09 (95% CI: 1.62-5.89) for small cell lung cancer. The estimated association with secondhand smoke exposure was greater for small cell lung cancer than for nonsmall cell lung cancers (OR=2.11, 95% CI: 1.11-4.04). This analysis is the largest to date investigating the relation between exposure to secondhand smoke and lung cancer. Our study provides more precise estimates of the impact of secondhand smoke on the major histological types of lung cancer, indicates the association with secondhand smoke is stronger for small cell lung cancer than for the other histological types, and suggests the importance of intervention against exposure to secondhand smoke in lung cancer prevention.

Modifying effect of N-acetyltransferase 2 genotype on the association between systemic lupus erythematosus and consumption of alcohol and caffeine-rich beverages.

OBJECTIVE: N-acetyltransferase 2 (NAT2) is involved in the metabolism of various environmental substances, both with and without carcinogenic potential. Alcoholic and nonalcoholic caffeine-rich beverages may be associated with markers of inflammation. Systemic lupus erythematosus (SLE) is a chronic, multifaceted inflammatory disease. We investigated the effects of alcoholic and nonalcoholic caffeine-rich beverages on risk of SLE and determined whether the effects were modified by NAT2 status. METHODS: The NAT2 polymorphism was genotyped in 152 SLE cases and 427 healthy controls, all women and Japanese. We assessed effect modification by testing an interaction term for the NAT2 polymorphism and consumption of beverages. RESULTS: Consumption of black tea (odds ratio [OR] 1.88, 95% confidence interval [95% CI] 1.03-3.41) and coffee (OR 1.57, 95% CI 0.95-2.61), but not green tea, was associated with an increased risk of SLE, while alcohol use (OR 0.33, 95% CI 0.20-0.55) was associated with a decreased risk of SLE. There were significant interactions between the NAT2 polymorphism and either alcohol use (Pinteraction = 0.026) or consumption of black tea (Pinteraction = 0.048). CONCLUSION: The NAT2 polymorphism significantly modified the effects of alcohol use and black tea consumption on SLE, emphasizing the importance of incorporating genetic and metabolic information in studies on management of SLE. Additional studies are warranted to confirm the findings suggested in this study.

Psychological stress in a Japanese population with systemic lupus erythematosus: finding from KYSS study.

OBJECTIVES: Daily psychological stress has been proposed as a risk factor for systemic lupus erythematosus (SLE) in Western countries. However, there is little information about the relationship between daily psychological stress and the risk of SLE in a Japanese population. We examined the association between SLE and daily psychological stress. METHODS: A case-control study was conducted to examine the relationship between daily psychological stress and SLE in Japanese females. The participants were 160 female SLE patients and 660 female volunteers. Unconditional logistic regression was used to compute OR and 95% confidence interval (CI), with adjustment for several covariates. RESULTS: Smoking (OR = 2.59; 95% CI, 1.74-3.86), walking (OR = 1.75; 95% CI, 1.81-2.56) and daily psychological stress (OR = 1.88; 95% CI, 1.14-3.10) were increased in patients with SLE after adjusting for age, region and all factors. Smokers with daily psychological stress (OR = 4.70; 95% CI = 2.53-8.77) were more prevalent than nonsmokers without daily psychological stress in SLE. The multiplicative interaction measures between smoking status and daily psychological stress did not reach statistical significance. CONCLUSIONS: The present study suggests the possibility that daily psychological stress as well as smoking might be associated with an increased risk of SLE.

Genetic polymorphisms involved in the inflammatory response and lung cancer risk: a case-control study in Japan.

Evidence is accumulating that chronic inflammation may have an important mechanism for the development and progression of lung cancer. Therefore, genetic polymorphisms in genes that involved in the inflammatory response may be associated with lung cancer risk. We evaluated the role of tumor necrosis factor α (TNFA) rs1799724, interleukin 1ß (IL1B) rs16944, IL6 rs1800796, myeloperoxidase (MPO) rs2333227 and C-reactive protein (CRP) rs2794520 in a case-control study comprised of 462 lung cancer cases and 379 controls in a Japanese population. Unconditional logistic regression was used to assess the adjusted odds ratios (OR) and 95% confidence intervals (95% CI). CRP rs2794520 (OR=1.64, 95% CI=1.19-2.26) and IL6 rs1800796 (OR=1.41, 95% CI=1.02-1.96) were associated with lung cancer risk. In addition, we assessed interactions between the polymorphisms and smoking. The polymorphisms did not significantly modify the association between smoking and lung cancer. As TNFA triggers a cytokine cascade, the modifying effect of the TNFA rs1799724 genotypes on the association of any of the remaining polymorphisms with lung cancer risk was also examined. There was a significant interaction between TNFA rs1799724 and MPO rs2333227 (Pinteraction=0.058). Future studies involving larger control and case populations will undoubtedly lead to a more thorough understanding of the role of the polymorphisms involved in the inflammation pathway in lung cancer.

MDR1 C3435T polymorphism and interaction with environmental factors in risk of Parkinson's disease: a case-control study in Japan.

It has been suggested that P-glycoprotein (P-gp), the product of multidrug resistance 1 (MDR1) gene, regulates the brain entry of various xenobiotics. Impaired function of P-gp may be associated with an increased risk of Parkinson's disease (PD). The aim of this study was to investigate the impact of a MDR1 C3435T polymorphism on PD risk alone or in combination with environmental factors. A total of 238 patients with PD and 368 controls were genotyped for the MDR1 C3435T polymorphism. Subjects with the TT genotype of the C3435T polymorphism showed a nonsignificantly increased risk of PD [odds ratio (OR)=1.49, 95% confidence interval (CI)=0.85-2.25] compared with those with the CC genotype. A gene-environment interaction was suggested, with a combination of at least one T allele and ever drinking conferring significantly higher risk (OR=1.83, 95% CI=1.07-3.15, p=0.029), compared with the CC genotype and never drinking. No significant interaction of smoking or occupational pesticide use with the C3435T polymorphism was observed. Our results suggest that the C3435T polymorphism may not play an important role in PD susceptibility in Japanese. Evidence of an interaction between the C3435T polymorphism and alcohol consumption was suggested.