Search

Urinary mutagenicity reflects systemic exposure to complex mixtures of genotoxic/carcinogenic agents and is linked to tumor development. Coal combustion emissions (CCE) and diesel engine exhaust (DEE) are associated with cancers of the lung and other sites, but their influence on urinary mutagenicity is unclear. We investigated associations between exposure to CCE or DEE and urinary mutagenicity. In two separate cross-sectional studies of nonsmokers, organic extracts of urine were evaluated for mutagenicity levels using strain YG1041 in the Salmonella (Ames) mutagenicity assay. First, we compared levels among 10 female bituminous (smoky) coal users from Laibin, Xuanwei, China, and 10 female anthracite (smokeless) coal users. We estimated exposure-response relationships using indoor air concentrations of two carcinogens in CCE relevant to lung cancer, 5-methylchrysene (5MC), and benzo[a]pyrene (B[a]P). Second, we compared levels among 20 highly exposed male diesel factory workers and 15 unexposed male controls; we evaluated exposure-response relationships using elemental carbon (EC) as a DEE-surrogate. Age-adjusted linear regression was used to estimate associations. Laibin smoky coal users had significantly higher average urinary mutagenicity levels compared to smokeless coal users (28.4 ± 14.0 SD vs. 0.9 ± 2.8 SD rev/ml-eq, p = 2 × 10 -5 ) and a significant exposure-response relationship with 5MC (p = 7 × 10 -4 ). DEE-exposed workers had significantly higher urinary mutagenicity levels compared to unexposed controls (13.0 ± 10.1 SD vs. 5.6 ± 4.4 SD rev/ml-eq, p = .02) and a significant exposure-response relationship with EC (p-trend = 2 × 10 -3 ). Exposure to CCE and DEE is associated with urinary mutagenicity, suggesting systemic exposure to mutagens, potentially contributing to cancer risk and development at various sites., (© 2021 Environmental Mutagen Society. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Twin studies suggest a familial aggregation of bladder cancer, but elements of this increased familial risk of bladder cancer are not well understood. To characterize familial risk of bladder cancer, we examined the relationship between family history of bladder and other types of cancer among first-degree relatives and risk of bladder cancer in 1193 bladder cancer cases and 1418 controls in a large population-based case-control study. Multivariate logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between family history of bladder cancer (defined as at least one first-degree family member with bladder cancer or a cancer of any other site). We also evaluated cancer aggregation of specific sites in family members. Participants with a first-degree relative with bladder cancer had nearly double the risk of bladder cancer (OR = 1.8, 95% CI 1.2-2.9) as those without a family history of bladder cancer. Risk was increased for having a sibling with bladder cancer (OR = 2.6, 95% CI 1.3-5.3) compared to no siblings with cancer. Bladder cancer risk was elevated when participants reported a first-degree relative with a history of female genital cancer (OR = 1.5, 95% CI 1.1-2.1), melanoma (OR = 1.9, 95% CI 1.02-3.6), and tobacco-associated cancer (OR = 1.3, 95% CI 1.06-1.6). These findings add to evidence of a familial predisposition to bladder cancer. Clarification of the aggregation of bladder cancer in families and with other cancer sites will be of interest as many loci and common polymorphisms related to bladder cancer have yet to be identified in large genomic studies., (© 2021 UICC.)

Germline variation and smoking are independently associated with pancreatic ductal adenocarcinoma (PDAC). We conducted genome-wide smoking interaction analysis of PDAC using genotype data from four previous genome-wide association studies in individuals of European ancestry (7,937 cases and 11,774 controls). Examination of expression quantitative trait loci data from the Genotype-Tissue Expression Project followed by colocalization analysis was conducted to determine whether there was support for common SNP(s) underlying the observed associations. Statistical tests were two sided and P < 5 × 10 -8 was considered statistically significant. Genome-wide significant evidence of qualitative interaction was identified on chr2q21.3 in intron 5 of the transmembrane protein 163 (TMEM163) and upstream of the cyclin T2 (CCNT2). The most significant SNP using the Empirical Bayes method, in this region that included 45 significantly associated SNPs, was rs1818613 [per allele OR in never smokers 0.87, 95% confidence interval (CI), 0.82-0.93; former smokers 1.00, 95% CI, 0.91-1.07; current smokers 1.25, 95% CI 1.12-1.40, P interaction = 3.08 × 10 -9 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention.r 2 = 0. 94) driving both the observed interaction and the expression quantitative trait loci signals. Future studies are needed to confirm and understand the differential biologic mechanisms by smoking status that contribute to our PDAC findings. SIGNIFICANCE: This large genome-wide interaction study identifies a susceptibility locus on 2q21.3 that significantly modified PDAC risk by smoking status, providing insight into smoking-associated PDAC, with implications for prevention., (©2021 American Association for Cancer Research.)

Populations exposed to arsenic in drinking water have an increased bladder cancer risk and evidence suggests that several factors may modify arsenic metabolism, influencing disease risk. We evaluated whether the association between cumulative lifetime arsenic exposure from drinking water and bladder cancer risk was modified by factors that may impact arsenic metabolism in a population-based case-control study of 1,213 cases and 1,418 controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between cumulative arsenic intake and bladder cancer stratified by age, sex, smoking status, body mass index (BMI), alcohol consumption and folate intake. P-values for interaction were computed using a likelihood ratio test. We observed no statistically significant multiplicative interactions although some variations in associations were notable across risk factors, particularly for smoking and BMI. Among former smokers and current smokers, those with the highest cumulative arsenic intake had elevated risks of bladder cancer (OR = 1.4, 95% CI: 0.96-2.0 and OR = 1.6, 95% CI: 0.91-3.0, respectively; while the OR among never smokers was 1.1, 95% CI: 0.6-1.9, p-interaction = 0.49). Among those classified as normal or overweight based on usual adult BMI, the highest level of cumulative arsenic intake was associated with elevated risks of bladder cancer (OR = 1.3, 95% CI: 0.89-2.0 and OR = 1.6, 95% CI: 1.1-2.4, respectively), while risk was not elevated among those who were obese (OR = 0.9, 95% CI: 0.4-1.8) (p-interaction = 0.14). Our study provides some limited evidence of modifying roles of age, sex, smoking, BMI, folate and alcohol on arsenic-related bladder cancer risk that requires confirmation in other, larger studies., (© 2018 UICC.)

Context: Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community., Objective: To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks., Evidence Acquisition: A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out., Evidence Synthesis: We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks., Conclusions: ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events., Patient Summary: While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear., (Copyright © 2017 European Association of Urology. All rights reserved.)

Background: Studies examining associations between circulating concentrations of C-peptide and total adiponectin, two biomarkers related to obesity and insulin secretion and sensitivity and pancreatic ductal adenocarcinoma (PDA) risk have shown inconsistent results and included limited numbers of smokers. Methods: We examined associations of these biomarkers and high molecular weight (HMW) adiponectin with PDA, overall, and by smoking status. We conducted a pooled nested case-control analysis in 3 cohorts (Prostate, Lung, Colorectal, and Ovarian Cancer Trial, Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, and Cancer Prevention Study-II), with 758 cases (435 current smokers) and 1,052 controls (531 smokers) matched by cohort, age, sex, race, blood draw date and follow-up time. We used conditional logistic regression adjusted for age, smoking, diabetes, and body mass index to calculate ORs and 95% confidence intervals (CI). Results: Circulating C-peptide concentration was not associated with PDA in never or former smokers, but was inversely associated with PDA in current smokers (per SD OR = 0.67; 95% CI, 0.54-0.84; P interaction = 0.005). HMW adiponectin was inversely associated with PDA in never smokers (OR = 0.43; 95% CI, 0.23-0.81), not associated in former smokers, and positively associated in smokers (OR = 1.23; 95% CI, 1.04-1.45; P Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance associations in nonsmokers. interaction Future studies of these biomarkers and PDA should examine results by smoking status. Conclusions: Associations of biomarkers of insulin secretion and sensitivity with PDA differ by smoking status. Smoking-induced pancreatic damage may explain the associations in smokers while mechanisms related to insulin resistance associations in nonsmokers. Impact: Future studies of these biomarkers and PDA should examine results by smoking status. Cancer Epidemiol Biomarkers Prev; 26(6); 914-22. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Purpose: Tobacco smoking and occupational exposures are the leading risk factors for developing urothelial bladder carcinoma (UBC), yet little is known about the contribution of these two factors to risk of UBC recurrence. We evaluated whether smoking status and usual adult occupation are associated with time to UBC recurrence for 406 patients with muscle-invasive bladder cancer submitted to The Cancer Genome Atlas (TCGA) project., Methods: Kaplan-Meier and Cox proportional hazard methods were used to assess the association between smoking status, employment in a high-risk occupation for bladder cancer, occupational diesel exhaust exposure, and 2010 Standard Occupational Classification group and time to UBC recurrence., Results: Data on time to recurrence were available for 358 patients over a median follow-up time of 15 months. Of these, 133 (37.2%) experienced a recurrence. Current smokers who smoked for more than 40 pack-years had an increased risk of recurrence compared to never smokers (HR 2.1, 95% CI 1.1, 4.1). Additionally, employment in a high-risk occupation was associated with a shorter time to recurrence (log-rank p = 0.005). We found an increased risk of recurrence for those employed in occupations with probable diesel exhaust exposure (HR 1.8, 95% CI 1.1, 3.0) and for those employed in production occupations (HR 2.0, 95% CI 1.1, 3.6)., Conclusions: These findings suggest smoking status impacts risk of UBC recurrence, although several previous studies provided equivocal evidence regarding this association. In addition to the known causal relationship between occupational exposure and bladder cancer risk, our study suggests that occupation may also be related to increased risk of recurrence., Competing Interests: The authors declare that they have no conflict of interest.

Selenium has been linked to a reduced risk of bladder cancer in some studies. Smoking, a well-established risk factor for bladder cancer, has been associated with lower selenium levels in the body. We investigated the selenium-bladder cancer association in subjects from Maine, New Hampshire, and Vermont in the New England Bladder Cancer Case-Control Study. At interview (2001-2005), participants provided information on a variety of factors, including a comprehensive smoking history, and submitted toenail samples, from which we measured selenium levels. We estimated odds ratios and 95% confidence intervals among 1,058 cases and 1,271 controls using logistic regression. After controlling for smoking, we saw no evidence of an association between selenium levels and bladder cancer (for fourth quartile vs. first quartile, odds ratio (OR) = 0.98, 95% confidence interval (CI): 0.77, 1.25). When results were restricted to regular smokers, there appeared to be an inverse association (OR = 0.76, 95% CI: 0.58, 0.99); however, when pack-years of smoking were considered, this association was attenuated (OR = 0.91, 95% CI: 0.68, 1.20), indicating potential confounding by smoking. Despite some reports of an inverse association between selenium and bladder cancer overall, our results, combined with an in-depth evaluation of other studies, suggested that confounding from smoking intensity or duration could explain this association. Our study highlights the need to carefully evaluate the confounding association of smoking in the selenium-bladder cancer association., (Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Bladder cancer is a complex disease with known environmental and genetic risk factors. We performed a genome-wide interaction study (GWAS) of smoking and bladder cancer risk based on primary scan data from 3002 cases and 4411 controls from the National Cancer Institute Bladder Cancer GWAS. Alternative methods were used to evaluate both additive and multiplicative interactions between individual single nucleotide polymorphisms (SNPs) and smoking exposure. SNPs with interaction P values < 5 × 10(-) (5) were evaluated further in an independent dataset of 2422 bladder cancer cases and 5751 controls. We identified 10 SNPs that showed association in a consistent manner with the initial dataset and in the combined dataset, providing evidence of interaction with tobacco use. Further, two of these novel SNPs showed strong evidence of association with bladder cancer in tobacco use subgroups that approached genome-wide significance. Specifically, rs1711973 (FOXF2) on 6p25.3 was a susceptibility SNP for never smokers [combined odds ratio (OR) = 1.34, 95% confidence interval (CI) = 1.20-1.50, P value = 5.18 × 10(-) (7)]; and rs12216499 (RSPH3-TAGAP-EZR) on 6q25.3 was a susceptibility SNP for ever smokers (combined OR = 0.75, 95% CI = 0.67-0.84, P value = 6.35 × 10(-) (7)). In our analysis of smoking and bladder cancer, the tests for multiplicative interaction seemed to more commonly identify susceptibility loci with associations in never smokers, whereas the additive interaction analysis identified more loci with associations among smokers-including the known smoking and NAT2 acetylation interaction. Our findings provide additional evidence of gene-environment interactions for tobacco and bladder cancer., (Published by Oxford University Press 2014.)

Objectives: Lung cancer rates in Xuanwei are the highest in China. In-home use of smoky coal has been associated with lung cancer risk, and the association of smoking and lung cancer risk strengthened after stove improvement. Here, we explored the differential association of tobacco use and lung cancer risk by the intensity, duration, and type of coal used., Materials and Methods: We conducted a population-based case-control study of 260 male lung cancer cases and 260 age-matched male controls. Odds ratios (OR) and 95% confidence interval (CI) for tobacco use was calculated by conditional logistic regression., Results: Use of smoky coal was significantly associated with an increased risk of lung cancer, and tobacco use was weakly and non-significantly associated with lung cancer risk. When the association was assessed by coal use, the cigarette-lung cancer risk association was null in hazardous coal users and elevated in less hazardous smoky coal users and non-smoky coal users. The risk of lung cancer per cigarette per day decreased as annual use of coal increased (>0-3 tons: OR: 1.09; 95% CI: 1.03-1.17; >3 tons: OR: 0.99; 95% CI: 0.95-1.03). Among more hazardous coal users, attenuation occurred at even low levels of usage (>0-3 tons: OR: 1.02; 95% CI: 0.91-1.14; >3 tons: OR: 0.94; 95% CI: 0.97-1.03)., Conclusion: We found evidence that smoky coal attenuated the tobacco and lung cancer risk association in males that lived in Xuanwei, particularly among users of hazardous coal where even low levels of smoky coal attenuated the association. Our results suggest that the adverse effects of tobacco may become more apparent as China's population continues to switch to cleaner fuels for the home, underscoring the urgent need for smoking cessation in China and elsewhere., (Published by Elsevier Ireland Ltd.)

The relationship between inflammation and cancer is well established in several tumor types, including bladder cancer. We performed an association study between 886 inflammatory-gene variants and bladder cancer risk in 1,047 cases and 988 controls from the Spanish Bladder Cancer (SBC)/EPICURO Study. A preliminary exploration with the widely used univariate logistic regression approach did not identify any significant SNP after correcting for multiple testing. We further applied two more comprehensive methods to capture the complexity of bladder cancer genetic susceptibility: Bayesian Threshold LASSO (BTL), a regularized regression method, and AUC-Random Forest, a machine-learning algorithm. Both approaches explore the joint effect of markers. BTL analysis identified a signature of 37 SNPs in 34 genes showing an association with bladder cancer. AUC-RF detected an optimal predictive subset of 56 SNPs. 13 SNPs were identified by both methods in the total population. Using resources from the Texas Bladder Cancer study we were able to replicate 30% of the SNPs assessed. The associations between inflammatory SNPs and bladder cancer were reexamined among non-smokers to eliminate the effect of tobacco, one of the strongest and most prevalent environmental risk factor for this tumor. A 9 SNP-signature was detected by BTL. Here we report, for the first time, a set of SNP in inflammatory genes jointly associated with bladder cancer risk. These results highlight the importance of the complex structure of genetic susceptibility associated with cancer risk.

In order to quantify the risk of pancreatic cancer associated with history of any allergy and specific allergies, to investigate differences in the association with risk according to age, gender, smoking status, or body mass index, and to study the influence of age at onset, we pooled data from 10 case-control studies. In total, there were 3,567 cases and 9,145 controls. Study-specific odds ratios and 95% confidence intervals were calculated by using unconditional logistic regression adjusted for age, gender, smoking status, and body mass index. Between-study heterogeneity was assessed by using the Cochran Q statistic. Study-specific odds ratios were pooled by using a random-effects model. The odds ratio for any allergy was 0.79 (95% confidence interval (CI): 0.62, 1.00) with heterogeneity among studies (P < 0.001). Heterogeneity was attributable to one study; with that study excluded, the pooled odds ratio was 0.73 (95% CI: 0.64, 0.84) (Pheterogeneity = 0.23). Hay fever (odds ratio = 0.74, 95% CI: 0.56, 0.96) and allergy to animals (odds ratio = 0.62, 95% CI: 0.41, 0.94) were related to lower risk, while there was no statistically significant association with other allergies or asthma. There were no major differences among subgroups defined by age, gender, smoking status, or body mass index. Older age at onset of allergies was slightly more protective than earlier age.

Bladder cancer results from the combined effects of environmental and genetic factors, smoking being the strongest risk factor. Evaluating absolute risks resulting from the joint effects of smoking and genetic factors is critical to assess the public health relevance of genetic information. Analyses included up to 3,942 cases and 5,680 controls of European background in seven studies. We tested for multiplicative and additive interactions between smoking and 12 susceptibility loci, individually and combined as a polygenic risk score (PRS). Thirty-year absolute risks and risk differences by levels of the PRS were estimated for U.S. males aged 50 years. Six of 12 variants showed significant additive gene-environment interactions, most notably NAT2 (P = 7 × 10(-4)) and UGT1A6 (P = 8 × 10(-4)). The 30-year absolute risk of bladder cancer in U.S. males was 6.2% for all current smokers. This risk ranged from 2.9% for current smokers in the lowest quartile of the PRS to 9.9% for current smokers in the upper quartile. Risk difference estimates indicated that 8,200 cases would be prevented if elimination of smoking occurred in 100,000 men in the upper PRS quartile compared with 2,000 cases prevented by a similar effort in the lowest PRS quartile (P(additive) = 1 × 10(-4)). Thus, the potential impact of eliminating smoking on the number of bladder cancer cases prevented is larger for individuals at higher than lower genetic risk. Our findings could have implications for targeted prevention strategies. However, other smoking-related diseases, as well as practical and ethical considerations, need to be considered before any recommendations could be made., (©2012 AACR.)

Background: To evaluate the dose-response relationship between cigarette smoking and pancreatic cancer and to examine the effects of temporal variables., Methods: We analyzed data from 12 case-control studies within the International Pancreatic Cancer Case-Control Consortium (PanC4), including 6507 pancreatic cases and 12 890 controls. We estimated summary odds ratios (ORs) by pooling study-specific ORs using random-effects models., Results: Compared with never smokers, the OR was 1.2 (95% confidence interval [CI] 1.0-1.3) for former smokers and 2.2 (95% CI 1.7-2.8) for current cigarette smokers, with a significant increasing trend in risk with increasing number of cigarettes among current smokers (OR=3.4 for ≥35 cigarettes per day, P for trend<0.0001). Risk increased in relation to duration of cigarette smoking up to 40 years of smoking (OR=2.4). No trend in risk was observed for age at starting cigarette smoking, whereas risk decreased with increasing time since cigarette cessation, the OR being 0.98 after 20 years., Conclusions: This uniquely large pooled analysis confirms that current cigarette smoking is associated with a twofold increased risk of pancreatic cancer and that the risk increases with the number of cigarettes smoked and duration of smoking. Risk of pancreatic cancer reaches the level of never smokers ∼20 years after quitting.

Context: Previous studies indicate that the population attributable risk (PAR) of bladder cancer for tobacco smoking is 50% to 65% in men and 20% to 30% in women and that current cigarette smoking triples bladder cancer risk relative to never smoking. During the last 30 years, incidence rates have remained stable in the United States in men (123.8 per 100,000 person-years to 142.2 per 100,000 person-years) and women (32.5 per 100,000 person-years to 33.2 per 100,000 person-years); however, changing smoking prevalence and cigarette composition warrant revisiting risk estimates for smoking and bladder cancer., Objective: To evaluate the association between tobacco smoking and bladder cancer., Design, Setting, and Participants: Men (n = 281,394) and women (n = 186,134) of the National Institutes of Health-AARP (NIH-AARP) Diet and Health Study cohort completed a lifestyle questionnaire and were followed up between October 25, 1995, and December 31, 2006. Previous prospective cohort studies of smoking and incident bladder cancer were identified by systematic review and relative risks were estimated from fixed-effects models with heterogeneity assessed by the I(2) statistic., Main Outcome Measures: Hazard ratios (HRs), PARs, and number needed to harm (NNH)., Results: During 4,518,941 person-years of follow-up, incident bladder cancer occurred in 3896 men (144.0 per 100,000 person-years) and 627 women (34.5 per 100,000 person-years). Former smokers (119.8 per 100,000 person-years; HR, 2.22; 95% confidence interval [CI], 2.03-2.44; NNH, 1250) and current smokers (177.3 per 100,000 person-years; HR, 4.06; 95% CI, 3.66-4.50; NNH, 727) had higher risks of bladder cancer than never smokers (39.8 per 100,000 person-years). In contrast, the summary risk estimate for current smoking in 7 previous studies (initiated between 1963 and 1987) was 2.94 (95% CI, 2.45-3.54; I(2) = 0.0%). The PAR for ever smoking in our study was 0.50 (95% CI, 0.45-0.54) in men and 0.52 (95% CI, 0.45-0.59) in women., Conclusion: Compared with a pooled estimate of US data from cohorts initiated between 1963 and 1987, relative risks for smoking in the more recent NIH-AARP Diet and Health Study cohort were higher, with PARs for women comparable with those for men.

Glucuronide conjugates of 4-aminobiphenyl and its N-hydroxy metabolite can be rapidly hydrolyzed in acidic urine to undergo further metabolic activation and form DNA adducts in the urothelium. We conducted a large multicenter case-control study in Spain to explore the etiology of bladder cancer and evaluated the association between urine pH and bladder cancer risk, alone and in combination with cigarette smoking. In total, 712 incident urothelial cell carcinoma cases and 611 hospital controls directly measured their urine pH with dipsticks twice a day (first void in the morning and early in the evening) during four consecutive days 2 weeks after hospital discharge. We found that a consistently acidic urine pH ≤6.0 was associated with an increased risk of bladder cancer [odds ratio (OR) = 1.5, 95% confidence interval (CI): 1.2-1.9] compared with all other subjects. Furthermore, risk estimates for smoking intensity and risk of bladder cancer among current smokers tended to be higher for those with a consistently acidic urine (OR = 8.8, 11.5 and 23.8) compared with those without (OR = 4.3, 7.7 and 5.8, respectively, for 1-19, 20-29 and 30+ cigarettes per day; P(interaction) for 30+ cigarettes per day = 0.024). These results suggest that urine pH, which is determined primarily by diet and body surface area, may be an important modifier of smoking and risk of bladder cancer.

Background: Cigarette smoking is the best-characterized risk factor for pancreatic cancer. However, data are limited for other tobacco smoking products and smokeless tobacco., Materials and Methods: We conducted a pooled analysis of cigar and pipe smoking and smokeless tobacco use and risk of pancreatic cancer using data from 11 case-control studies (6056 cases and 11,338 controls) within the International Pancreatic Cancer Case-Control Consortium (PanC4). Pooled odds ratios (OR) and the corresponding 95% confidence intervals (CI) were estimated by unconditional multiple logistic regression models adjusted for study center and selected covariates., Results: Compared with never tobacco users, the OR for cigar-only smokers was 1.6 (95% CI: 1.2-2.3), i.e. comparable to that of cigarette-only smokers (OR 1.5; 95% CI 1.4-1.6). The OR was 1.1 (95% CI 0.69-1.6) for pipe-only smokers. There was some evidence of increasing risk with increasing amount of cigar smoked per day (OR 1.82 for ≥ 10 grams of tobacco), although not with duration. The OR for ever smokeless tobacco users as compared with never tobacco users was 0.98 (95% CI 0.75-1.3)., Conclusion: This collaborative analysis provides evidence that cigar smoking is associated with an excess risk of pancreatic cancer, while no significant association emerged for pipe smoking and smokeless tobacco use.

Associations between bladder cancer risk and NAT2 and GSTM1 polymorphisms have emerged as some of the most consistent findings in the genetic epidemiology of common metabolic polymorphisms and cancer, but their interaction with tobacco use, intensity and duration remain unclear. In a New England population-based case-control study of urothelial carcinoma, we collected mouthwash samples from 1088 of 1171 cases (92.9%) and 1282 of 1418 controls (91.2%) for genotype analysis of GSTM1, GSTT1 and NAT2 polymorphisms. Odds ratios and 95% confidence intervals of bladder cancer among New England Bladder Cancer Study subjects with one or two inactive GSTM1 alleles (i.e. the 'null' genotype) were 1.26 (0.85-1.88) and 1.54 (1.05-2.25), respectively (P-trend = 0.008), compared with those with two active copies. GSTT1 inactive alleles were not associated with risk. NAT2 slow acetylation status was not associated with risk among never (1.04; 0.71-1.51), former (0.95; 0.75-1.20) or current smokers (1.33; 0.91-1.95); however, a relationship emerged when smoking intensity was evaluated. Among slow acetylators who ever smoked at least 40 cigarettes/day, risk was elevated among ever (1.82; 1.14-2.91, P-interaction = 0.07) and current heavy smokers (3.16; 1.22-8.19, P-interaction = 0.03) compared with rapid acetylators in each category; but was not observed at lower intensities. In contrast, the effect of GSTM1-null genotype was not greater among smokers, regardless of intensity. Meta-analysis of the NAT2 associations with bladder cancer showed a highly significant relationship. Findings from this large USA population-based study provided evidence that the NAT2 slow acetylation genotype interacts with tobacco smoking as a function of exposure intensity.

Background: In Xuanwei County, Yunnan Province, China, lung cancer mortality rates in both males and females are among the highest in China., Methods: We evaluated differential effects of smoking on lung cancer mortality before and after household stove improvement with chimney to reduce exposure to smoky coal emissions in the unique cohort in Xuanwei, China. Effects of independent variables on lung cancer mortality were measured as hazard ratios and 95% confidence intervals using a multivariable Cox regression model that included separate time-dependent variables for smoking duration (years) before and after stove improvement., Results and Conclusion: We found that the effect of smoking on lung cancer risk becomes considerably stronger after chimney installation and consequent reduction of indoor coal smoke exposure.

Background: Cigarette smoking is a well-established risk factor for bladder cancer. The effects of smoking duration, intensity (cigarettes per day), and total exposure (pack-years); smoking cessation; exposure to environmental tobacco smoke; and changes in the composition of tobacco and cigarette design over time on risk of bladder cancer are unclear., Methods: We examined bladder cancer risk in relation to smoking practices based on interview data from a large, population-based case-control study conducted in Maine, New Hampshire, and Vermont from 2001 to 2004 (N = 1170 urothelial carcinoma case patients and 1413 control subjects). We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. To examine changes in smoking-induced bladder cancer risk over time, we compared odds ratios from New Hampshire residents in this study (305 case patients and 335 control subjects) with those from two case-control studies conducted in New Hampshire in 1994-1998 and in 1998-2001 (843 case patients and 1183 control subjects)., Results: Regular and current cigarette smokers had higher risks of bladder cancer than never-smokers (for regular smokers, OR = 3.0, 95% CI = 2.4 to 3.6; for current smokers, OR = 5.2, 95% CI = 4.0 to 6.6). In New Hampshire, there was a statistically significant increasing trend in smoking-related bladder cancer risk over three consecutive periods (1994-1998, 1998-2001, and 2002-2004) among former smokers (OR = 1.4, 95% CI = 1.0 to 2.0; OR = 2.0, 95% CI = 1.4 to 2.9; and OR = 2.6, 95% CI = 1.7 to 4.0, respectively) and current smokers (OR = 2.9, 95% CI = 2.0 to 4.2; OR = 4.2, 95% CI = 2.8 to 6.3; OR = 5.5, 95% CI = 3.5 to 8.9, respectively) (P for homogeneity of trends over time periods = .04). We also observed that within categories of intensity, odds ratios increased approximately linearly with increasing pack-years smoked, but the slope of the increasing trend declined with increasing intensity., Conclusions: Smoking-related risks of bladder cancer appear to have increased in New Hampshire since the mid-1990s. Based on our modeling of pack-years and intensity, smoking fewer cigarettes over a long time appears more harmful than smoking more cigarettes over a shorter time, for equal total pack-years of cigarettes smoked.

A recent analysis showed that the excess odds ratio (EOR) for lung cancer due to smoking can be modeled by a function which is linear in total pack-years and exponential in the logarithm of smoking intensity and its square. Below 15-20 cigarettes per day, the EOR/pack-year increased with intensity (direct exposure rate or enhanced potency effect), suggesting greater risk for a total exposure delivered at higher intensity (for a shorter duration) than for an equivalent exposure delivered at lower intensity. Above 20 cigarettes per day, the EOR/pack-year decreased with increasing intensity (inverse exposure rate or reduced potency effect), suggesting greater risk for a total exposure delivered at lower intensity (for a longer duration) than for an equivalent exposure delivered at higher intensity. The authors applied this model to data from 10 case-control studies of cancer, including cancers of the lung, bladder, oral cavity, pancreas, and esophagus. At lower intensities, there was enhanced potency for several cancer sites, but narrow ranges for pack-years increased uncertainty, precluding definitive conclusions. At higher intensities, there was a consistent reduced potency effect across studies. The intensity effects were statistically homogeneous, indicating that after accounting for risk from total pack-years, intensity patterns were comparable across the diverse cancer sites.

We examined the effects of dose, type of tobacco, cessation, inhalation, and environmental tobacco smoke exposure on bladder cancer risk among 1,219 patients with newly diagnosed bladder cancer and 1,271 controls recruited from 18 hospitals in Spain. We used unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (95% CI) for the association between bladder cancer risk and various characteristics of cigarette smoking. Current smokers (men: OR, 7.4; 95% CI, 5.3-10.4; women: OR, 5.1; 95% CI, 1.6-16.4) and former smokers (men: OR, 3.8; 95% CI, 2.8-5.3; women: OR, 1.8; 95% CI, 0.5-7.2) had significantly increased risks of bladder cancer compared with nonsmokers. We observed a significant positive trend in risk with increasing duration and amount smoked. After adjustment for duration, risk was only 40% higher in smokers of black tobacco than that in smokers of blond tobacco (OR, 1.4; 95% CI, 0.98-2.0). Compared with risk in current smokers, a significant inverse trend in risk with increasing time since quitting smoking blond tobacco was observed (> or =20 years cessation: OR, 0.2; 95% CI, 0.1-0.9). No trend in risk with cessation of smoking black tobacco was apparent. Compared with men who inhaled into the mouth, risk increased for men who inhaled into the throat (OR, 1.7; 95% CI, 1.1-2.6) and chest (OR, 1.5; 95% CI, 1.1-2.1). Cumulative occupational exposure to environmental tobacco smoke seemed to confer increased risk among female nonsmokers but not among male nonsmokers. After eliminating the effect of cigarette smoking on bladder cancer risk in our study population, the male-to-female incidence ratio decreased from 8.2 to 1.7, suggesting that nearly the entire male excess of bladder cancer observed in Spain is explained by cigarette smoking rather than occupational/environmental exposures to other bladder carcinogens.

In the United States, the incidence rates of multiple myeloma in Blacks are more than twice those in Whites, but the etiology of this cancer is poorly understood. A population-based case-control interview study of 571 subjects (365 White, 206 Black) with multiple myeloma and 2,122 controls (1,155 White, 967 Black) living in three areas of the United States (Georgia, Michigan, New Jersey) offered the opportunity to investigate the relationship with smoking and alcohol drinking and to evaluate whether these factors might contribute to the excess risk of multiple myeloma in Blacks. For Blacks and Whites of either gender, there were no significantly elevated risks associated with ever use of cigarettes or alcoholic beverages and no consistent patterns with either intensity or duration of use. These data support previous studies indicating that smoking and drinking are not related causally to the risk of multiple myeloma, and thus cannot account for the racial disparity in incidence rates.

Background: Cigarette smoking is the most consistently reported risk factor for pancreas cancer, yet the dose-response relationship in many pancreas cancer studies is weak. Because of the poor prognosis for pancreas cancer, many case-control studies have been based largely on interviews with proxy respondents, who are known to report less reliable information on detailed smoking habits than original subjects., Purpose: Our purpose was to evaluate cigarette smoking as a risk factor for pancreas cancer based on data obtained only from direct interviews and to estimate the effects of quitting smoking and of switching from nonfiltered to filtered cigarettes on risk. Our objective also was to estimate the contribution of cigarette smoking toward explaining the higher pancreas cancer incidence experienced by black Americans compared with white Americans., Methods: A population-based, case-control study of pancreas cancer was conducted during 1986-1989 in Atlanta, Ga., Detroit, Mich., and 10 counties in New Jersey. Direct interviews were successfully completed with 526 case patients and 2153 control subjects aged 30-79 years, making this the largest population-based, case-control study of pancreas cancer to date based only on direct interviews., Results: Cigarette smokers had a significant, 70% increased risk of pancreas cancer compared with the risk in nonsmokers. A significant, positive trend in risk with increasing duration smoked was apparent (P < .0001), with long-term (> or = 40 years) smokers experiencing a modest 2.1-fold risk. We also observed a negative trend in risk with increasing years quit smoking. Smokers who quit for more than 10 years experienced about a 30% reduction in risk relative to current smokers; quitters of 10 years or less experienced no risk reduction. Switching from nonfiltered to filtered cigarettes did not appear to decrease risk. Compared with nonsmokers, subjects who smoked only filtered cigarettes had a 50% elevated risk and those who smoked only nonfiltered cigarettes had a 40% elevated risk. The proportion of pancreas cancer attributable to cigarette smoking was 29% in blacks and 26% in whites., Conclusions: The relationship between cigarette smoking and pancreas cancer risk is likely to be causal, despite the weakness of the dose-response data. Long-term smoking cessation clearly reduces risk, whereas switching from nonfiltered to filtered cigarettes may not be beneficial. Cigarette smoking appears to explain little of the excess pancreas cancer risk experienced by blacks., Implications: Elimination of cigarette smoking would eventually prevent approximately 27% of pancreas cancer, saving 6750 lives in the United States annually.

Background: In the United States, incidence rates of squamous cell esophageal cancer are more than five times higher among black men than among white men. Reasons that might explain this large racial disparity are being sought., Purpose: We evaluated whether differential use of alcohol and tobacco can fully account for the excess of squamous cell esophageal cancer among U.S. blacks., Methods: We conducted a population-based, case-control study with in-person interviews with 373 squamous cell esophageal cancer case patients (124 white males and 249 black males) and 1364 control subjects (750 white males and 614 black males) from three U.S. geographic areas. Histologically confirmed cases of squamous cell esophageal cancer newly diagnosed from August 1, 1986, through April 30, 1989, among white and black men aged 30-79 years were included., Results: Alcohol use of more than one drink per day and/or current cigarette use of at least one pack per day accounted for 92.7% (95% confidence interval [CI] = 86.8%-98.5%) of the squamous cell esophageal cancers in blacks, versus 86.3% (95% CI = 75.5%-97.1%) in whites, and for 94% of the difference between the black and white annual incidence rates. The interaction between race and the continuous drinking/smoking variable in a logistic regression analysis was statistically significant (two-sided, P = .02). Exposure rates among controls at all levels of combined alcohol and tobacco use examined were slightly higher among blacks and accounted for a small portion of the racial differences in incidence rates., Conclusion: Although the vast majority of esophageal cancers in both blacks and whites in our data can be explained by use of alcohol and tobacco, it is not clear why heavy consumption of alcohol and/or tobacco is responsible for 14.9 per 100,000 per year more cases of squamous cell esophageal cancer among blacks than among whites. The differences in the odds ratios appear to account for more of the racial differences in incidence rates than do the prevalences of exposure to alcohol and tobacco alone. The reasons for this apparent racial difference in carcinogenic risk from the same level of alcohol and tobacco use are unknown, but they may include qualitative differences in alcohol consumption, differences in other environmental exposures that interact with alcohol and/or tobacco to modify risks, or differences in susceptibility to these factors.

In the United States, the incidence of adenocarcinoma of the esophagus, including the esophagogastric (EG) junction, has been increasing rapidly over the past two decades. Except for an association with Barrett's esophagus, little is known about the etiology of these cancers. A population-based case-control interview study of 174 White men with adenocarcinoma of the esophagus and 750 controls living in three areas of the United States offered the opportunity to investigate the relationship of these cancers with smoking, alcohol drinking, socioeconomic factors, and history of ulcer. There were significantly elevated risks for men who smoked cigarettes (odds ratio [OR] = 2.1) or drank liquor (OR = 1.6). For both cigarette smoking and liquor drinking, there were significant dose gradients with amount consumed. No reduction in risk was observed following smoking cessation. Subjects who switched from nonfilter to filter cigarettes experienced half the risk of those who only smoked nonfilter cigarettes. Inverse risk gradients were seen with increasing recent annual income, with the highest risk (OR = 3.4) for the lowest category. The risk for a history of ulcer (OR = 1.7), especially of the duodenum (OR = 2.2), was also significantly elevated. These data suggest that tobacco and alcohol may be etiologic factors for adenocarcinoma of the esophagus and EG junction, but these factors do not appear to explain the rapid rise in incidence of these tumors. The associations with low social class and history of ulcer need to be explored in greater detail along with other factors that may account for the temporal trends in esophageal adenocarcinomas.

Prostate cancer occurs more frequently in Blacks than Whites in the United States. A population-based case-control study which investigated the association between tobacco use and prostate cancer risk was carried out among 981 pathologically confirmed cases (479 Blacks, 502 Whites) of prostate cancer, diagnosed between 1 August 1986 and 30 April 1989, and 1,315 controls (594 Blacks, 721 Whites). Study subjects, aged 40 to 79 years, resided in Atlanta (GA), Detroit (MI), and 10 counties in New Jersey, geographic areas covered by three, population-based, cancer registries. No excesses in risk for prostate cancer were seen for former cigarette smokers, in Blacks (odds ratio [OR] = 1.1, 95 percent confidence interval [CI] = 0.7-1.5) and in Whites (OR = 1.2, CI = 0.9-1.6), or for current cigarette smokers, in Blacks (OR = 1.0, CI = 0.7-1.4) and in Whites (OR = 1.2, CI = 0.8-1.7). Increases in risk were noted for smokers of 40 or more cigarettes per day, among former (OR = 1.4, CI = 1.0-1.5) and current (OR = 1.5, CI = 1.0-2.4) smokers. Duration of cigarette use and cumulative amount of cigarette use (pack-years) were not associated with prostate cancer risk for Blacks or Whites. By age, only the youngest subjects, aged 40 to 59 years, showed excess risk associated with current (OR = 1.5, CI = 1.0-2.3) and former (OR = 1.7, CI = 1.1-2.6) use of cigarettes, but there were no consistent patterns in this group according to amount or duration of smoking.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for pancreatic cancer were evaluated in a cohort study of 17,633 White men in the United States who responded to a mailed questionnaire in 1966 and were followed-up through 1986 for mortality. Cigarette smoking and alcohol consumption were found to be important risk factors for pancreatic cancer. Risks increased significantly with number of cigarettes smoked, reaching fourfold for smokers of 25 or more cigarettes per day relative to nonsmokers. Alcohol intake also was related significantly to risk, with consumers of 10 or more drinks per month having three times the risk of nondrinkers, but dose-response trends among drinkers were not smooth. Coffee consumption was unrelated to risk. Dietary analyses revealed a rising rate of pancreatic cancer mortality with increasing consumption of meat after adjustment for other risk factors. Men in the highest quartile of meat intake had about three times the risk of those in the lowest quartile. No consistent association, however, was observed for consumption of fruits, vegetables, or grains. This study confirms cigarette smoking as an important risk factor for pancreatic cancer, and provides evidence that elevated intake of alcohol and meat may increase the risk of this fatal malignancy.

A population-based case-control study of bladder cancer (2,982 cases and 5,782 controls) conducted in 10 areas of the United States examined the effect of smoking as a risk factor among Blacks and Whites, after adjustment for occupation and other potential confounders. Although the overall risk for smoking was slightly higher in Blacks than Whites (relative risk = 2.7 and 2.2, respectively), this difference was not statistically significant. Estimation of risk by dose and currency of exposure revealed no consistent racial disparities in smoking-related risks. Race-specific, attributable risk estimates indicated that nearly half of bladder cancers among both Blacks and Whites could have been prevented by elimination of smoking.

A population-based case-control study of renal pelvis and ureter cancers (502 cases, 496 controls) conducted in three areas of the United States found cigarette smoking to be associated with a 3.1-fold increase in risk, with long-term (greater than 45 years) smokers having a 7.2-fold increased risk. Statistically significant dose-response associations were observed for both cancer sites and in both sexes regardless of the measure used: cigarettes per day, duration of use, or pack years. A significant decreasing trend in risk with increasing years quit smoking was also demonstrated for these cancers. Attributable risk estimates indicate that approximately 7 of 10 cancers of the renal pelvis and ureter among men and almost 4 of 10 among women are caused by smoking. The results of this study, the largest to date, confirm that cigarette smoking is the major cause of cancers of the renal pelvis and ureter, and that cessation of smoking could eliminate a large proportion of these tumors.

In nearly all populations studied, the risk of bladder cancer is two to four times as great in men as in women. We estimated what the gender-specific incidence rates would be in the absence of exposure to known carcinogenic factors. The data used were obtained from interviews with 2,806 white individuals with bladder cancer and 5,258 white controls in the National Bladder Cancer Study and from incidence data for 1978 from the National Cancer Institute Surveillance, Epidemiology, and End Results Program. The total age-adjusted incidence of bladder cancer was 27.5 cases per 100,000 person-years for men and 7.0 for women, yielding a ratio of 3.9. Even in the absence of exposure to cigarettes, occupational hazards, or urinary tract infection, the gender-related risk persisted; the incidence of bladder cancer was 11.0 in men and 4.1 in women, yielding a ratio of 2.7. Possible explanations for the excessive risk in men include environmental and dietary exposures not yet identified and innate sexual characteristics such as anatomic differences, urination habits, or hormonal factors.

Lifetime patterns of smoking and occupation based on personal interviews were examined among 3,627 white men and 1,200 white women who were randomly selected from ten areas in the United States during the period 1977-1978. These individuals participated in the control series of the National Bladder Cancer Study. We estimated, based on Axelson's method, the extent to which smoking habits for given occupational groups would confound the estimated relative risk for lung cancer for 62 occupations among men and 18 occupations among women. Among men, confounding by smoking resulted in a 30% or greater increased risk of lung cancer in only three occupational groups--namely, stationary engineers and power station operators (relative risk (RR) = 1.6), printers (RR = 1.3), and fishermen and sailors (RR = 1.3). A decrease in lung cancer risk of 0.8 or less due to smoking habits was observed among the clergy (RR = 0.5) and chemical workers (RR = 0.7). Among women, a 30% increase or greater in the risk of lung cancer based on smoking habits alone was found for food service workers (RR = 1.5), building managers and administrators (RR = 1.3), telephone and telegraph operators (RR = 1.3), and operatives (RR = 1.3). A risk ratio of 0.8 or less was observed for those women employed as farmers (RR = 0.5) and teachers (RR = 0.8). Smoking habits by duration of employment were also examined for 38 occupations among men. The largest increase in the risk of lung cancer based on the smoking habits among long-term workers was only 1.3 and was observed for those men employed 20 or more years as painters and as electricians. These findings suggest that the smoking patterns, in only a few occupational groups that we evaluated, confound estimates of the relative risk by more than 30%, and for most occupational groups under investigation in this study, confounding by smoking alone did not produce trends in relative risks by duration of employment.

To determine whether it is the smoker or smoking per se that explains the observed reduction in birth weight of infants of mothers who smoked during pregnancy, data collected on 1016 pairs of successive births which occurred between 1946 and 1963 in Washington County, Maryland, were studied. The mean birth weight difference between first and second members of pairs of consecutive live births of the same mother was examined in relation to her smoking habits during both pregnancies. A multiple regression technique was used to simultaneously adjust for the effects of maternal smoking habits during pregnancy, infant sex, maternal age, and birth order on birth weight difference. There were no significant differences in mean birth weight difference among pairs in which the mother smoked throughout both pregnancies, pairs in which the mother was a nonsmoker during both pregnancies, and pairs in which the mother smoked during the second pregnancy of the pair, but not the first. When birth weights of only first members of the pair were studied, the mean birth weight of infants of women who were nonsmokers throughout both pregnancies was higher than that of infants of women who smoked during both pregnancies. Infants of first members of pairs in which the mothers smoked only during the second pregnancy tended to have birth weights which were lower than that of infants of nonsmokers and higher than that of infants of smokers. These findings neither confirm nor deny the hypothesis that the smoker rather than the smoking per se causes a reduction in birth weight.