DNA修复基因XRCC3多态性与肺癌易感性的关系

目的 研究DNA修复基因XRCC3多态性与肺癌易感性的关系。方法采用病例一对照研究，于2006年9月至2007年1月收集上海肺科医院原发性肺癌患者291例及同期住院的非肿瘤患者273例，应用Taqman探针结合实时荧光PCR方法分析病例组和对照组XRCC3基因Thr241Met的多态性分布，比较不同基因型与肺癌易感性的关系以及基因多态性与吸烟对肺癌的交互作用。对照组与病例组的比较用X。检验，以调整比值比及95％可信区间表示相对危险度，所有统计检验均为双侧概率检验，所有资料均用SPSS软件进行统计。结果与携带XRCC3密码子241野生纯合基因型（Thr／Thr）且不吸烟者相比，携带同样基因型且吸烟者患肺癌的风险会增加，其调整比值比（OR值）为2．47[95％可信区间（CI）为1．49-4，08，P〈0．01]；携带有杂合基因型（Thr／Met）且吸烟者患肺癌的风险也会增加，其调整OR值为2．28（95％CI为1．21-6．60，P=0，017）。野生纯合基因型（Thr／Thr）且吸烟量少于30包年可能对肺腺癌有较弱的保护作用（OR=0．49，95％CI为0．26-0．93，P=0，03）。携带有XRCC3密码子241Met等位基因且吸烟者患肺鳞癌的风险明显增加（调整OR=9．69，95％CI为3．27-28．72，P〈0．01）。携带241Met等位基因且吸烟剂量〈30包年和≥30包年的患者患肺鳞癌的风险也不同，OR值分别为8，00（95％CI为1．97-32．52，P〈0．01）和11．67（95％CI为2．98～45．73，P〈0．01）。结论DNA修复基因XRCC3多态性可能对肺癌易感性产生影响，并可能与吸烟有一定的协同作用。     

XRCC2 and XRCC3 gene polymorphism and risk of pancreatic cancer

OBJECTIVES: XRCC2 and XRCC3 are key components of the homologous recombination (HR) machinery that repairs DNA double-strand breaks. We hypothesized that the altered HR repair capacity conferred by single nucleotide polymorphisms (SNPs) would modify individual susceptibility to sporadic pancreatic cancer. METHODS: In a hospital-based case-control study, genomic DNA and exposure information was obtained from 468 patients with pathologically confirmed pancreatic adenocarcinoma and 498 frequency-matched healthy controls at M.D. Anderson Cancer Center during January 2000 to September 2006. Genotypes of XRCC2 31479 G>A (Arg188His) and XRCC3 17893 A>G and 18067 C>T (Thr241Met) were determined using the Masscode technology. Unconditional logistic regression models were used to estimate the odds ratio (OR) and its 95% confidence interval (CI) in non-Hispanic whites (408 cases and 449 controls). RESULTS: The distribution of genotype frequencies was not different between cases and controls. We observed a significant effect modification between XRCC2 polymorphism and smoking status and pack-year of smoking in modifying pancreatic cancer risk (P value for interaction 0.02 and 0.05, respectively). Compared with never-smokers carrying the XRCC2 Arg188Arg genotype, the OR (95% CI) for individuals carrying the (188)His allele was 2.32 (1.25-4.31) among ever-smokers, 1.43 (0.59-3.48) among light smokers (< or = 22 pack-years), and 3.42 (1.47-7.96) among heavy smokers (> or =22 pack-years). The two XRCC3 SNPs are in strong linkage disequilibrium, but there was no suggestive association between XRCC3 genotype and the risk of pancreatic cancer. CONCLUSION: XRCC2 Arg188His polymorphism may be one of the genetic modifiers for smoking-related pancreatic cancer.     

Hepatitis B or C viral infection and risk of pancreatic cancer: A meta-analysis of observational studies

AIM: To investigate if there is an association between hepatitis B virus (HBV) or hepatitis C virus (HCV) infection and the risk of pancreatic cancer. METHODS: All relevant studies published before 11 October, 2012 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and the Cochrane Library databases and with cross-referencing. The observational studies that reported RR or OR estimates with 95%CIs for the association between HBV or HCV and pancreatic cancer were included. A random-effects model was used to summarize meta-analytic estimates. The Newcastle-Ottawa quality assessment scale was applied to assess the quality of the methodology in the included studies. RESULTS: A total of 8 eligible studies were selected for meta-analysis. Overall, chronic hepatitis B and inactive hepatitis B surface antigen (HBsAg) carrier state (HBsAg positive) had a significantly increased risk of pancreatic cancer with OR of 1.20 (95%CI: 1.01-1.39), especially in the Chinese population (OR = 1.30, 95%CI: 1.05-1.56). Past exposure to HBV (possible occult HBV infection) had an increased OR of pancreatic cancer risk (OR = 1.24, 95%CI: 1.05-1.42), especially among those patients without natural immunity [anti hepatitis B core (HBc) positive/hepatitis B surface antibody (anti HBs) negative], with OR of 1.67 (95%CI: 1.13-2.22). However, past exposure to HBV with natural immunity (anti-HBc positive/anti-HBs positive) had no association with pancreatic cancer development, with OR 0.98 (95%CI: 0.80-1.16), nor did the HBV active replication (hepatitis B e antigen positive status), with OR 0.98 (95%CI: 0.27-1.68). The risk of pancreatic cancer among anti-HBs positive patients was significantly lower than among anti-HBs negative patients (OR = 0.54, 95%CI: 0.46-0.62). Past exposure to HCV also resulted in an increased risk of pancreatic cancer (OR = 1.26, 95%CI: 1.03-1.50). Significant between-study heterogeneity was observed. Evidence of publication bias for HBV/HCV infection-pancreatic cancer association was not found.     

Lung cancer risk among nonsmoking women in relation to diet and physical activity

To investigate the relationship between diet, physical activity, and the risk of lung cancer among female nonsmokers, and to compare it with female smokers in the same population, we conducted a case-control study. Data collected by personal interviews from 419 cases and 1593 controls were analyzed using unconditional logistic regression. As expected, among 130 nonsmoking cases, adenocarcinoma was the predominant cell type (49.2%), followed by squamous cell (20.2%) and small cell cancers (10.5%). The corresponding figures for 289 smoking cases were 29.3%, 27.5%, and 28.2%, respectively. Excess lung cancer risk was associated with consumption of red meat among nonsmokers (OR=2.20, 95%CI 1.07--4.51). Protective effects were observed for vegetables (OR=0.61, 95%CI 0.39--0.96), apples (OR=0.67, 95%CI 0.48--0.95), milk/dairy products (OR=0.54, 95%CI 0.32--0.93), coffee (OR=0.56, 95%CI 0.34--0.91), and wine (OR=0.69, 95%CI 0.49--0.98) among smokers only, and for black tea (OR=0.67, 95%CI 0.46--0.99) among nonsmokers only. An inverse association with risk emerged for physical exercise (or sport, walking), among smokers only. Some items of diet and physical activity appear to be important factors contributing to variation in lung cancer risk among women in the Czech Republic, however, their effects in nonsmokers may differ from those in smokers.     

Prevalence of colorectal neoplasia in smokers

OBJECTIVES: Smoking has been linked with colorectal neoplasia. Previous colonoscopy screening studies have omitted smoking and have examined only gender, age, and family history. Our aim was to use a screening population to measure the prevalence of neoplasia in smokers, the anatomic location of these lesions, and the strength of this association relative to other risk factors. METHODS: Data collected from the charts of 1988 screening colonoscopy patients included colonic findings, histology, risk factors for colorectal neoplasia, and smoking pattern. Current smokers were defined as those who had smoked more than 10 pack-years and were currently smoking or who had quit within the past 10 yr. Our outcomes were any adenomatous lesion and significant colonic neoplasia, which included adenocarcinoma, high grade dysplasia, villous tissue, large (>1 cm) adenomas, and multiple (more than two) adenomas. RESULTS: Multivariate analysis revealed that current smokers were more likely to have any adenomatous lesion (odds ratio [OR] = 1.89; 95% CI = 1.42-2.51; p < 0.001) as well as significant neoplasia (OR = 2.26; 95% CI = 1.56-3.27; p < 0.001) than those who had never smoked. The increased risk for smokers was predominantly for left-sided neoplasia. The risk for significant neoplasia was greater for smokers than for patients with a family history of colorectal cancer (OR = 1.20; 95% CI = 0.75-1.92; p > 0.05). CONCLUSIONS: Smoking is a significant risk factor for colorectal neoplasia in a screening population, especially for significant left-sided lesions. In our sample population, smoking posed a greater risk than family history of colorectal cancer.     

Interactions between smoking and other exposures associated with lung cancer risk in women: diet and physical activity

The objective of the study is to estimate the differences in the impact of diet and physical exercise on lung cancer risk in female nonsmokers vs. smokers, and reveal interactions, if any. In a hospital based case-control study, data collected by in-person interviews from 569 female lung cancer cases and 2120 controls were analyzed using unconditional logistic regression stratifying by appropriate factors. Protective effects were observed for intake of milk/dairy products (OR=0.57, 95%CI 0.35-0.94), vegetables (OR=0.60, 95%CI 0.40-0.91), apples (OR=0.69), wine (OR=0.77), and physical exercise (OR=0.59, 95%CI 0.42-0.83) among smokers only, while no similar effects were found among nonsmokers. In contrast, the intake of black tea was associated with a protective effect (OR=0.66, 95%CI 0.47-0.94) among nonsmokers only. Comparing the effects of dietary items and physical activity on lung cancer risk among nonsmokers versus smokers, statistically significant effect modifications were found for black tea (P 0.005), and milk/dairy products (P 0.047). Borderline effect modifications emerged for physical exercise (P 0.077). CONCLUSIONS: These results indicate protective effects of some components of healthful diet and physical exercise among smokers, and of the intake of black tea among nonsmokers. The observed interactions of the impact of black tea, milk/dairy products and physical activity upon lung cancer risk in women at different levels of the smoking habit deserve further studies.     

Prognostic significance of neutrophil to lymphocyte ratio in pancreatic cancer: A meta-analysis

AIM: To conduct a meta-analysis evaluating the association between the peripheral blood neutrophil to lymphocyte ratio (NLR) and the outcome of patients with pancreatic cancer.METHODS: Studies evaluating the relationship between the peripheral blood NLR and outcome of patients with pancreatic cancer published up to May 2014 were searched using electronic databases, including PubMed, Web of Science, Embase and Ovid. A meta-analysis was performed to pool the hazard ratios (HRs) or odds ratios (ORs) and their 95% confidence intervals (CIs) using either a fixed-effects model or a random-effects model to quantitatively assess the prognostic value of NLR and its association with clinicopathological parameters.RESULTS: Eleven studies containing a total of 1804 patients were eligible according to our selection criteria, and combined hazard ratios indicated that high NLR was a poor prognostic marker for pancreatic cancer patients because it had an unfavorable impact on the overall survival (OS) (HR = 2.61, 95%CI: 1.68-4.06, P = 0.000) and cancer specific survival (HR = 1.66, 95%CI: 1.08-2.57, P = 0.021). Subgroup analysis revealed that high NLR was associated with poor OS in patients with mixed treatment (HR = 4.36, 95%CI: 2.50-7.61, P = 0.000), chemotherapy (HR = 2.08, 95%CI: 1.49-2.9, P = 0.000), or surgical resection (HR = 1.2, 95%CI: 1.00-1.44, P = 0.048). Additionally, high NLR was significantly correlated with tumor metastasis (OR = 1.69, 95%CI: 1.10-2.59, P = 0.016), poor tumor differentiation (OR = 2.75, 95%CI: 1.19-6.36, P = 0.016), poor performance status (OR = 2.56, 95%CI: 1.63-4.03, P = 0.000), high cancer antigen 199 (OR = 2.62, 95%CI: 1.49-4.60, P = 0.000), high C-reactive protein (OR = 4.32, 95%CI: 2.71-6.87, P = 0.000), and low albumin (OR = 3.56, 95%CI: 1.37-9.27, P = 0.009).CONCLUSION: High peripheral blood NLR suggested a poor prognosis for patients with pancreatic cancer, and it could be a novel marker of survival evaluation and could help clinicians develop therapeutic strategies for pancreatic cancer patients.     

Genetic polymorphisms in methylenetetrahydrofolate reductase and thymidylate synthase and risk of pancreatic cancer.

BACKGROUND & AIMS: Human pancreatic cancer might be associated with folate deficiency and impaired metabolism. We tested this hypothesis by examining the contribution of functional polymorphisms in methylenetetrahydrofolate reductase (MTHFR) and thymidylate synthase (TS) to risk of cancer. METHODS: DNA from 163 pancreatic cancer patients and 337 control subjects was genotyped for MTHFR (677C > T and 1298A > C) and TS (5'-untranslated region tandem repeat and G/C). Association with risk of pancreatic cancer was estimated by logistic regression. All statistical tests were two-sided. RESULTS: We observed an increased risk of pancreatic cancer associated with the MTHFR 677CT (odds ratio [OR], 2.60; 95% confidence interval [CI], 1.61-4.29; P = .0005) or 677TT (OR, 5.12; 95% CI, 2.94-9.10; P < .0001) genotype compared with the MTHFR CC genotype. An increased risk of pancreatic cancer was also associated with the TS 3Rc/3Rc genotype (OR, 2.19, 95% CI, 1.13-4.31; P = .022) compared with the TS 3Rg/3Rg genotype. Joint effect between MTHFR C677T polymorphism and smoking or drinking increased risk of pancreatic cancer in a super-multiplicative manner. The ORs for smoking, the polymorphism, and both factors combined were 0.70 (95% CI, 0.30-1.63), 2.17 (95% CI, 1.17-4.21), and 3.10 (95% CI, 1.54-6.51), respectively. This joint effect was much stronger in heavy smokers (OR, 6.69; 95% CI, 3.39-13.63; P < .0001). The ORs for drinking, the polymorphism, and both factors combined were 0.98 (95% CI, 0.40-2.30), 2.81 (95% CI, 1.65-4.98), and 4.39 (95% CI, 2.25-8.78), respectively. CONCLUSION: The MTHFR and TS polymorphisms are genetic determinants for developing pancreatic cancer.     

TIM-3-574G>T基因多态性与中国汉族人群支气管哮喘的相关性分析

目的采用Meta分析评价T细胞免疫球蛋白黏蛋白域蛋白-3(TIM-3)-574 G>T(rs10515746)基因多态性与中国汉族人群支气管哮喘易感性的关系。 方法检索中外文献数据库中TIM-3-574 G>T基因多态性与中国汉族人群支气管哮喘易感性关系的病例对照研究，末次检索时间为2017年12月20日。采用RevMan 5.0对TIM-3-574 G>T基因多态性与哮喘易感的显性模型OR值进行合并、敏感性分析和亚组分析，以及采用Stata对纳入文献的发表偏倚情况进行评估。 结果共纳入5篇文献，其中病例组患者1 241例，对照组患者1 005例。Meta分析显示中国汉族人中TIM-3-574 G>T基因上突变型GT者的支气管哮喘发病风险较野生型纯合子GG者增加3.06倍(OR＝4.06，95%CI：2.34，7.05)，携带突变基因T者患支气管哮喘的风险比携带野生型G基因者增加3.31倍(OR＝4.31，95%CI：2.50，7.43)。亚组分析显示携带GT基因型的成人和儿童患病风险均较纯合子GG高(儿童组：OR＝4.07，95%CI：1.62，10.20；成人组：OR＝3.09，95%CI：1.40，6.85)。 结论T细胞免疫球蛋白黏蛋白域蛋白-3-574 G>T基因多态性与中国汉族人群支气管哮喘易感性有密切相关，突变T基因携带者患支气管哮喘的风险更高。     

代谢酶NAT2基因多态性与肺癌易感性关系的研究

目的 探讨代谢酶N-乙酰化转移酶2(NAT2)基因多态性与肺癌易感性的关系.方法 采用聚合酶链式反应-限制性片段长度多态性技术检测152名正常人和150例原发性肺癌患者的外周血NAT2基因型.应用病例对照研究分析NAT2基因多态性与肺癌易感性的关系.结果 ①NAT2等位基因型WT/WT、WT/Mx、Mx/Mx在对照组中分布频率分别为28.9%、52.0%和19.1%;在肺癌组中分布频率分别为22.0%、45.3%和32.7%,两组比较差异有统计学意义(P=0.023).②携带NAT2慢乙酰化基因型个体患肺癌的风险是携带NAT2快乙酰化基因型个体的1.84倍(95%CI为1.044～3.231,P=0.035).③携带慢乙酰化基因型个体患肺腺癌的风险进一步升高,是携带快乙酰化基因型个体的2.49倍(95%CJ为1.242～4.973,P=0.010).④携带NAT2慢乙酰化基因型吸烟者患肺癌的风险是携带快乙酰化基因型吸烟者的2.34倍(95%CI为1.007～5.424,P=0.048).结论 NAT2慢乙酰化基因型显著增加中国汉族人群尤其是吸烟者患肺癌的风险.     

Alcohol and Smoking as Risk Factors in Chronic Pancreatitis and Pancreatic Cancer

The aim of this study was to compare alcohol andsmoking as risk factors in the development of chronicpancreatitis and pancreatic cancer. We considered onlymale subjects: (1) 630 patients with chronic pancreatitis who developed 12 pancreatic and 47extrapancreatic cancers; (2) 69 patients withhistologically well documented pancreatic cancer and noclinical history of chronic pancreatitis; and (3) 700 random controls taken from the Verona pollinglist and submitted to a complete medical check-up.Chronic pancreatitis subjects drink more than controlsubjects and more than subjects with pancreatic cancer without chronic pancreatitis (P < 0.001).The percentage of smokers in the group with chronicpancreatitis is significantly higher than that in thecontrol group [odds ratio (OR) 17.3; 95% CI 12.6-23.8; P < 0.001] and in the group with pancreaticcarcinomas but with no history of chronic pancreatitis(OR 5.3; 95% CI 3.0-9.4; P < 0.001). In conclusion,our study shows that: (1) the risk of chronic pancreatitis correlates both with alcoholintake and with cigarette smoking with a trendindicating that the risk increases with increasedalcohol intake and cigarette consumption; (2) alcoholand smoking are statistically independent risk factors forchronic pancreatitis; and (3) the risk of pancreaticcancer correlates positively with cigarette smoking butnot with drinking.     

Predictive model for acute abdominal pain after transarterial chemoembolization for liver cancer

BACKGROUND Transarterial chemoembolization(TACE) is the first-line treatment for patients with unresectable liver cancer;however,TACE is associated with postembolization pain.AIM To analyze the risk factors for acute abdominal pain after TACE and establish a predictive model for postembolization pain.METHODS From January 2018 to September 2018,all patients with liver cancer who underwent TACE at our hospital were included.General characteristics;clinical,imaging,and procedural data;and postembolization pain were analyzed.Postembolization pain was defined as acute moderate-to-severe abdominal pain within 24 h after TACE.Logistic regression and a classification and regression tree were used to develop a predictive model.Receiver operating characteristic curve analysis was used to examine the efficacy of the predictive model.RESULTS We analyzed 522 patients who underwent a total of 582 TACE procedures.Ninety-seven(16.70%) episodes of severe pain occurred.A predictive model built based on the dataset from classification and regression tree analysis identified known invasion of blood vessels as the strongest predictor of subsequent performance,followed by history of TACE,method of TACE,and history of abdominal pain after TACE.The area under the receiver operating characteristic curve was 0.736 [95% confidence interval(CI):0.682-0.789],the sensitivity was 73.2%,the specificity was 65.6%,and the negative predictive value was 92.4%.Logistic regression produced similar results by identifying age [odds ratio(OR) = 0.971;95%CI:0.951-0.992;P = 0.007),history of TACE(OR = 0.378;95%CI:0.189-0.757;P = 0.007),history of abdominal pain after TACE(OR = 6.288;95%CI:2.963-13.342;P 0.001),tumor size(OR = 1.978;95%CI:1.175-3.330;P = 0.01),multiple tumors(OR = 2.164;95%CI:1.243-3.769;P = 0.006),invasion of blood vessels(OR = 1.756;95%CI:1.045-2.950;P = 0.034),and TACE with drug-eluting beads(DEBTACE)(OR = 2.05;95%CI:1.260-3.334;P = 0.004) as independent predictive factors for postembolization pain.CONCLUSION Blood vessel invasion,TACE history,TACE with drug-eluting beads,and history of abdominal pain after TACE are predictors of acute moderate-to-severe pain.The predictive model may help medical staff to manage pain.     

High risk of adult-onset asthma and work-related wheeze in farmers despite low prevalence of asthma in young farmers.

OBJECTIVE: To investigate risk factors for asthma in farmers. METHODS: A questionnaire was sent to all farms (n = 2499) and to 2900 controls aged 19-65 years from the general population in the county of Uppsala. Sixty per cent of the farms (1514 men and 248 women) and 64% of the controls (900 men, 943 women) responded. RESULTS: Only 13% of the male farmers had heredity for allergy compared to 24% of the controls, and fewer farmers were smokers. After adjusting for confounders, male farmers had a significantly lower prevalence of doctor-diagnosed asthma and nocturnal breathlessness than the controls (OR 0.75, 95%CI 0.57-0.98 and OR 0.61, 95%CI 0.44-0.84), but a significantly higher prevalence of work-related wheeze (OR 1.74, 95%CI 1.30-2.35). The risk for asthma increased with age in the farmers. Of male farmers with asthma, 70% had developed asthma after the age of 21, in contrast with only 30% of the asthmatic controls. The young female farmers had a high prevalence of asthma. CONCLUSION: Male farmers have an increased risk of work-related wheeze and adult-onset asthma increasing with age despite a lower prevalence of asthma during childhood and young age than in the general population.     

Secondhand Tobacco Smoke and COPD Risk in Smokers: A COPDGene Study Cohort Subgroup Analysis

Background: Exposure to secondhand tobacco smoke (SHS) can be a risk factor for chronic obstructive pulmonary disease (COPD), but its role among relatively heavy smokers with potential co-exposure to workplace vapors, gas, dust, and fumes (VGDF) has not been studied. Methods: To estimate the contribution of SHS exposure to COPD risk, taking into account smoking effects and work-related exposures to VGDF, we quantified SHS based on survey responses for 1400 ever-employed subjects enrolled in the COPDGene study, all current or former smokers with or without COPD. Occupational exposures to VGDF were quantified based on a job exposure matrix. The associations between SHS and COPD were tested in multivariate logistic regression analyses adjusted for age, sex, VGDF exposure, and cumulative smoking. Results and Discussion: Exposures to SHS at work and at home during adulthood were associated with increased COPD risk: odds ratio (OR) = 1.12 (95% confidence interval [CI]: 1.02–1.23; p = 0.01) and OR = 1.09 (95%CI: 1.00–1.18; p = 0.04) per 10 years of exposure adjusted for smoking and other covariates, respectively. In addition, subjects with employment histories likely to entail exposure to VGDF were more likely to have COPD: OR = 1.52 (95%CI: 1.16–1.98; p < 0.01) (adjusted for other covariates). While adult home SHS COPD risk was attenuated among the heaviest smokers within the cohort, workplace SHS and job VGDF risks persisted in that stratum. Conclusion: Among smokers all with at least 10 pack-years, adult home and work SHS exposures and occupational VGDF exposure are all associated with COPD.     

Effects of smoking, alcohol, exercise, education, and family history on the metabolic syndrome as defined by the ATP III

INTRODUCTION: Although several environmental factors are known to have diverse effects on the development of the metabolic syndrome, few studies have examined their relevance to Asians. METHODS: We gathered data from 4341 subjects on smoking, alcohol drinking, exercise, family history and education level by a self-administered questionnaire. The components of the metabolic syndrome as defined by the ATP III report were examined. RESULTS: The multivariate-adjusted odds ratio of hypertriglyceridemia was 1.4 (95% CI 1.0-1.8) and of low HDL-C was 1.9 (95% CI 1.3-2.6) in subjects who smoked more than 20 pack-years compared to nonsmokers. The relative risk of developing the metabolic syndrome in smokers (more than 20 pack-years) was 1.9 (95% CI 1.1-3.7) compared to nonsmokers. Alcohol consumption had a protective effect against low HDL-C (adjusted OR 0.6-0.2). The relative risk of the metabolic syndrome was 1.7 (95% CI 0.9-2.8) for lack of exercise, 1.5 (95% CI 1.1-2.1) for a positive family history and 2.0 (95% CI 1.2-3.4) in those with no or an elementary school education versus university graduation. CONCLUSION: Since subjects with a low education level and a family history had an elevated risk for the metabolic syndrome and thus for developing cardiovascular disease, particular attention should be paid to these subjects.     

A prospective study of cigarette smoking and the incidence of diabetes mellitus among US male physicians

PURPOSE: To determine the association between cigarette smoking and the incidence of type 2 diabetes mellitus. SUBJECTS AND METHODS: We studied 21,068 US male physicians aged 40 to 84 years in the Physicians' Health Study who were initially free of diagnosed diabetes mellitus, cardiovascular disease, and cancer. Information about cigarette smoking and other risk indicators was obtained at baseline. The primary outcome was reported diagnosis of type 2 diabetes mellitus. RESULTS: During 255,830 person-years of follow-up, 770 new cases of type 2 diabetes mellitus were identified. Smokers had a dose-dependent increased risk of developing type 2 diabetes mellitus: compared with never smokers, the age-adjusted relative risk was 2.1 (95% confidence interval [CI]: 1.7 to 2.6) for current smokers of > or = 20 cigarettes per day, 1.4 (95% CI: 1.0 to 2.0) for current smokers of <20 cigarettes per day, and 1.2 (95% CI: 1.0 to 1.4) for past smokers. After multivariate adjustment for body mass index, physical activity, and other risk factors, the relative risks were 1.7 (95% CI: 1.3 to 2.3) for current smokers of > or = 20 cigarettes per day, 1.5 (95% CI: 1.0 to 2.2) for current smokers of <20 cigarettes per day, and 1.1 (95% CI: 1.0 to 1.4) for past smokers. Total pack-years of cigarette smoking was also associated with the risk of type 2 diabetes mellitus (P for trend <0.001). CONCLUSIONS: These prospective data support the hypothesis that cigarette smoking is an independent and modifiable determinant of type 2 diabetes mellitus.     

Risk factors for the development of pancreatic cancer in familial pancreatic cancer kindreds

BACKGROUND & AIMS: Approximately 10% of pancreatic cancers are inherited, but the factors that affect tumorigenesis in familial pancreatic cancer are unknown. We sought to determine whether smoking or other factors could predict cancer risk in familial pancreatic cancer kindreds. METHODS: We conducted a nested case-control study including 251 members of 28 families. All families included 2 or more members with pancreatic cancer. We determined the effects of smoking, young age of onset within the family, diabetes mellitus, sex, and number/standing of affected relatives on the risk of pancreatic cancer. RESULTS: Smoking was an independent risk factor for familial pancreatic cancer (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.8-7.6), and the risk was greatest in males and subjects younger than 50 (OR, 5.2 and OR, 7.6, respectively). Smokers developed cancer 1 decade earlier than nonsmokers (59.6 vs. 69.1 years; P = 0.01), and the number of affected first-degree relatives also increased risk (OR, 1.4; 95% CI, 1.1-1.9 for each additional family member). Diabetes was not a risk factor for pancreatic cancer, although diabetes was associated with pancreatic dysplasia. One third of families demonstrated genetic anticipation, as the mean age of onset decreased by 2 decades between generations. CONCLUSIONS: Smoking is a strong risk factor in familial pancreatic cancer kindreds, particularly among males and those under age 50. Persons with multiple affected first-degree relatives are also at increased risk. These factors may be useful in selecting candidates for pancreatic cancer screening. Members of families with multiple pancreatic cancers should be counseled not to smoke.     

ABO blood type,long-standing diabetes,and the risk of pancreatic cancer

AIM: To retrospectively study pancreatic cancer patients with respect to their ABO blood type and diabetes. METHODS: Our analysis included a cohort of 1017 patients with pancreatic ductal cancer diagnosed at our hospital in Tokyo. They were divided into two groups: 114 patients with long-standing type 2 diabetes (DM group, defined as diabetes lasting for at least three years before the diagnosis of pancreatic cancer) and 903 patients without diabetes (non-DM group). Multivariate analysis was performed to identify factors that are associated with long-standing diabetes. The DM group was further divided into three subgroups according to the duration of diabetes (3-5 years, 5.1-14.9 years, and 15 years or more) and univariate analyses were performed. RESULTS: Of the 883 pancreatic cancer patients with serologically assessed ABO blood type, 217 (24.6%) had blood type O. Compared with the non-DM group, the DM group had a higher frequency of blood type B [odds ratio (OR) = 2.61, 95%CI: 1.24-5.47; reference group: blood type A]. Moreover, male (OR = 3.17, 95%CI: 1.67-6.06), older than 70 years of age (OR = 2.19, 95%CI: 1.20-3.98) and presence of a family history of diabetes (OR = 6.21, 95%CI: 3.38-11.36) were associated with long-standing type 2 diabetes. The mean ages were 64.8 ± 9.2 years, 67.1 ± 9.8 years, and 71.7 ± 7.0 years in the subgroups with the duration of diabetes, 3-5 years, 5.1-14.9 years, and 15 years or more, respectively (P = 0.007). A comparison of ABO blood type distribution among the subgroups also showed a significant difference (P = 0.03). CONCLUSION: The association of pancreatic cancer with blood type and duration of diabetes needs to be further examined in prospective studies.     

Smoking and timing of cessation: impact on pulmonary complications after thoracotomy

STUDY OBJECTIVE: The benefit of smoking cessation just prior to surgery in preventing postoperative pulmonary complications has not been proven. Some studies actually show a paradoxical increase in complications in those quitting smoking only a few weeks or days prior to surgery. We studied the effect of smoking and the timing of smoking cessation on postoperative pulmonary complications in patients undergoing thoracotomy. DESIGN AND SETTING: Prospective study conducted in a tertiary care cancer center in 300 consecutive patients with primary lung cancer or metastatic cancer to the lung who were undergoing anatomical lung resection. RESULTS: The groups studied were nonsmokers (21%), past quitters of > 2 months duration (62%), recent quitters of < 2 months duration (13%), and ongoing smokers (4%). Overall pulmonary complications occurred in 8%, 19%, 23%, and 23% of these groups, respectively, with a significant difference between nonsmokers and all smokers (p = 0.03) but no difference among the subgroups of smokers (p = 0.76). The risk of pneumonia was significantly lower in nonsmokers (3%) compared to all smokers (average, 11%; p < 0.05), with no difference detected among subgroups of smokers (p = 0.17). Comparing recent quitters and ongoing smokers, no differences in pulmonary complications or pneumonia were found (p = 0.67). Independent risk factors for pulmonary complications were a lower diffusing capacity of the lung for carbon monoxide (Dlco) [odds ratio [ OR] per 10% decrement, 1.41; 95% confidence interval [ CI], 1.17 to 1.70; p = 0.01) and primary lung cancer rather than metastatic disease (OR, 3.94; 95% CI, 1.34 to 11.59; p = 0.003). Among smokers, a lower Dlco percent predicted (OR per 10% decrement, 1.42; 95% CI, 1.16 to 1.75; p = 0.008) and a smoking history of > 60 pack-years (OR, 2.54; 95% CI, 1.28 to 5.04; p = 0.0008) were independently associated with overall pulmonary complications. CONCLUSIONS: In patients undergoing thoracotomy for primary or secondary lung tumors, there is no evidence of a paradoxical increase in pulmonary complications among those who quit smoking within 2 months of undergoing surgery. Smoking cessation can safely be encouraged prior to surgery.     

Cigarette smoking as a significant risk factor for digital vascular disease in patients with systemic sclerosis

OBJECTIVE: Patients with systemic sclerosis (SSc) are at high risk for digital vascular complications, including amputation and gangrene. Cigarette smoking is an important risk factor for vascular disease in the general population. We investigated the influence of cigarette smoking on digital ischemia in patients with SSc. METHODS: We studied 101 patients with SSc (87 women and 14 men, median age 53 years, median disease duration 13 years). Smoking history was defined in terms of current smoking status and total number of pack-years. Digital ischemic events were classified as debridement, hospital admission for intravenous (IV) administration of vasodilators, and digital amputation. The influence of smoking on digital ischemic events was examined using logistic regression, adjusting for age, sex, and disease duration. Results are expressed as the odds ratio (OR) and 95% confidence interval (95% CI). RESULTS: Of the 101 patients, 21 (21%) were current smokers, 37 (37%) were ex-smokers, and 43 (43%) had never smoked. After adjusting for age, sex, and disease duration, current smokers were significantly more likely than never-smokers to have had debridement (OR 4.5, 95% CI 1.1-18.3) or admission for IV vasodilators (OR 3.8, 95% CI 1.1-12.9). Patients smoking at higher intensity were more likely to require admission for IV vasodilators. CONCLUSION: Among patients with SSc, current smokers are 3-4 times more likely than never-smokers to incur digital vascular complications. Resources should be directed to supporting smoking cessation in patients with SSc.