Air pollution and incidence of cancers of the stomach and the upper aerodigestive tract in the European Study of Cohorts for Air Pollution Effects (ESCAPE)

Air pollution has been classified as carcinogenic to humans. However, to date little is known about the relevance for cancers of the stomach and upper aerodigestive tract (UADT). We investigated the association of long‐term exposure to ambient air pollution with incidence of gastric and UADT cancer in 11 European cohorts. Air pollution exposure was assigned by land‐use regression models for particulate matter (PM) below 10 µm (PM₁₀), below 2.5 µm (PM_2.5), between 2.5 and 10 µm (PM_coarse), PM_2.5 absorbance and nitrogen oxides (NO₂ and NO_X) as well as approximated by traffic indicators. Cox regression models with adjustment for potential confounders were used for cohort‐specific analyses. Combined estimates were determined with random effects meta‐analyses. During average follow‐up of 14.1 years of 305,551 individuals, 744 incident cases of gastric cancer and 933 of UADT cancer occurred. The hazard ratio for an increase of 5 µg/m³ of PM_2.5 was 1.38 (95% CI 0.99; 1.92) for gastric and 1.05 (95% CI 0.62; 1.77) for UADT cancers. No associations were found for any of the other exposures considered. Adjustment for additional confounders and restriction to study participants with stable addresses did not influence markedly the effect estimate for PM_2.5 and gastric cancer. Higher estimated risks of gastric cancer associated with PM_2.5 was found in men (HR 1.98 [1.30; 3.01]) as compared to women (HR 0.85 [0.5; 1.45]). This large multicentre cohort study shows an association between long‐term exposure to PM_2.5 and gastric cancer, but not UADT cancers, suggesting that air pollution may contribute to gastric cancer risk.     

Smoking addiction and the risk of upper‐aerodigestive‐tract cancer in a multicenter case–control study

Although previous studies on tobacco and alcohol and the risk of upper‐aerodigestive‐tract (UADT) cancers have clearly shown dose‐response relations with the frequency and duration of tobacco and alcohol, studies on addiction to tobacco smoking itself as a risk factor for UADT cancer have not been published, to our knowledge. The aim of this report is to assess whether smoking addiction is an independent risk factor or a refinement to smoking variables (intensity and duration) for UADT squamous cell carcinoma (SCC) risk in the multicenter case–control study (ARCAGE) in Western Europe. The analyses included 1,586 ever smoking UADT SCC cases and 1,260 ever smoking controls. Addiction was measured by a modified Fagerström score (first cigarette after waking up, difficulty refraining from smoking in places where it is forbidden and cigarettes per day). Adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs) for UADT cancers with addiction variables were estimated with unconditional logistic regression. Among current smokers, the participants who smoked their first cigarette within 5 min of waking up were two times more likely to develop UADT SCC than those who smoked 60 min after waking up. Greater tobacco smoking addiction was associated with an increased risk of UADT SCC among current smokers (OR = 3.83, 95% CI: 2.56–5.73 for score of 3–7 vs. 0) but not among former smokers. These results may be consistent with a residual effect of smoking that was not captured by the questionnaire responses (smoking intensity and smoking duration) alone, suggesting addiction a refinement to smoking variables.     

Ambient air pollution and incident bladder cancer risk: Updated analysis of the Spanish Bladder Cancer Study

Although outdoor air pollution and particulate matter in outdoor air have been consistently linked with increased lung cancer risk, the evidence for associations at other cancer sites is limited. Bladder cancer shares several risk factors with lung cancer and some positive associations of ambient air pollution and bladder cancer risk have been observed. This study examined associations of ambient air pollution and bladder cancer risk in the large-scale Spanish Bladder Cancer Study. Estimates of ambient fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) concentrations were assigned to the geocoded participant residence of 938 incident bladder cancer cases and 973 hospital controls based on European multicity land-use regression models. Adjusted odds ratios (ORs) and 95% confidence intervals (CI) for associations of ambient air pollution and bladder cancer risk were estimated using unconditional logistic regression models. Overall, there was no clear association between either ambient PM_2.5 (OR per 5.9 μg/m³ = 1.06, 95% CI 0.71–1.60) or NO₂ (OR per 14.2 μg/m³ = 0.97, 95% CI 0.84–1.13) concentrations and incident bladder cancer risk. There was no clear evidence for effect modification according to age group, sex, region, education, cigarette smoking status, or pack-years. Results were also similar among more residentially stable participants and in two-pollutant models. Overall, there was no clear evidence for associations of ambient PM_2.5 and NO₂ concentrations and incident bladder cancer risk. Further research in other large-scale population studies is needed with detailed information on measured or modeled estimates of ambient air pollution concentrations and individual level risk factors.     

The association between change in body mass index and upper aerodigestive tract cancers in the ARCAGE project: Multicenter case–control study

Previous studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital‐ and population‐based controls from ten European countries (alcohol‐related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change vs. BMI stability (?5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature.     

Tobacco smoking and the risk of upper aero-digestive tract cancers: A reanalysis of case-control studies using spline models

Although tobacco smoking has long been recognized as a major risk factor for cancer of the upper aero-digestive tract (UADT, i.e., oral cavity, pharynx, larynx, and oesophagus), very few studies have provided estimates of the effect of very low tobacco consumption. Step-functions have been the common statistical methods for risk estimates, but the choice of reference category and of interval cutpoints influence the results, especially when data are sparse. In the present analysis, the dose-response relationship between UADT cancers and tobacco smoking was evaluated through logistic regression spline models. We included 1,241 UADT male cases and 2,835 male controls pooled from a large series of case-control studies conducted in northern Italy and in the Swiss Canton of Vaud during the last 2 decades. For cancers of the pharynx, larynx and oesophagus, the risk steadily increased with number of cigarettes/day. The risk of oral, pharyngeal and oesophageal cancers was significantly higher in smokers than in nonsmokers beginning with as low as 2 cigarettes/day. The effect of tobacco smoking at low levels seemed less evident for laryngeal cancer since the raise in risk begun with 6 cigarettes/day. In conclusion, for all the examined UADT sites, a monotonic dose-response relationship between cancer risk and cigarette smoking emerged. The excess of risk among people smoking 2 cigarettes/day highlights the absence of any harmless level for cigarette smoking, and it further supports the need of public health programs against tobacco smoking.     

Dietary risk factors for squamous cell carcinoma of the upper aerodigestive tract in central and eastern Europe

Objective  The incidence of squamous cell carcinoma of upper aerodigestive tract (UADT: oral cavity, pharynx, larynx, and esophagus) has been increasing in central and eastern European countries. We investigated the relationship between diet and UADT cancers in these high risk areas. Methods  We used data from hospital-based case–control study of 948 UADT cancer cases and 1,228 controls conducted in Romania, Hungary, Poland, Russia, Slovakia, and Czech Republic. Standardized questionnaire were used to collect information on 23 different food items, along with alcohol and tobacco consumptions. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for the UADT cancers after adjusting for center, age, sex, tobacco & alcohol intake, and other food groups. Results  Consumption of dairy product was negatively associated with selected UADT cancers: larynx (OR: 0.38, CI: 0.23–0.62) and esophagus (OR: 0.55, CI: 0.33–0.93). While consumption of yellow/orange vegetables were inversely associated with oral/pharyngeal and laryngeal cancer (OR: 0.53, CI: 0.35–0.81 and OR: 0.62, CI: 0.38–1.00, respectively), preserved vegetable was positively associated with oral/pharyngeal and laryngeal cancer risk (p _trend < 0.01 for both). Conclusion  Specific dietary components may play a role in the development of UADT cancers in the high-risk region of central and eastern Europe.     

The aetiology of upper aerodigestive tract cancers among young adults in Europe: the ARCAGE study

Background

The incidence of cancers of the upper aerodigestive tract (UADT) is increasing throughout the world. To date the increases have been proportionally greatest among young people. Several reports have suggested that they often do not have a history of tobacco smoking or heavy alcohol consumption.

Objective

To determine the contribution of lifestyle factors to the etiology of UADT cancers occurring in those aged less than 50 years.

Methods

A case–control study was conducted in 10 European countries. Cases were cancers of the oral cavity and pharynx, larynx and esophagus, and hospital or population controls were age and sex matched.

Results

There were 356 cases younger than 50 years and 419 controls. Risk was strongly related to current smoking [odds ratio (OR) 5.5 95%; confidence interval (CI) (3.3, 9.2)], and risk increased with number of pack-years smoked. Risk was also related to alcohol consumption for both current (OR 1.8; 0.97, 3.3) and past (OR 3.4; 1.6, 7.4) drinkers, and risk increased with number of drink-years. Persons frequently consuming fruits and vegetables were at significantly reduced risk.

Conclusions

Risk factors already identified as being important for UADT cancers in adults are also important influences on risk in younger adults. The implication of these results is that the public health message in preventing UADT cancers remains the same to young and old alike.     

A case-control study of the association of the polymorphisms and haplotypes of DNA ligase I with lung and upper-aerodigestive-tract cancers

Tobacco smoking is a major risk factor for lung and upper-aerodigestive-tract (UADT) cancers. One possible mechanism for the associations may be through DNA damage pathways. DNA Ligase I (LIG1) is a DNA repair gene involved in both the nucleotide excision repair (NER) and the base excision repair (BER) pathways. We examined the association of 4 LIG1 polymorphisms with lung and UADT cancers, and their potential interactions with smoking in a population-based case-control study in Los Angeles County. We performed genotyping using the SNPlex method from Applied Biosystems. Logistic regression analyses of 551 lung cancer cases, 489 UADT cancer cases and 948 controls showed the expected associations of tobacco smoking with lung and UADT cancers and new associations between the LIG1 haplotypes and these cancers. For lung cancer, when compared to the most common haplotype (rs20581-rs20580-rs20579-rs439132 = T-C-C-A), the adjusted odds ratio (OR) is 1.2 (95% confidence limits (CL) = 0.95, 1.5) for the CACA haplotype, 1.4 (1.0, 1.9) for the CATA haplotype and 1.8 (1.1, 2.8) for the CCCG haplotype, after controlling for age, gender, race/ethnicity, education and tobacco smoking. We observed weaker associations between the LIG1 haplotypes and UADT cancers. Our findings suggest the LIG1 haplotypes may affect the risk of lung and UADT cancers.     

Supraglottic and glottic carcinomas: Epidemiologically distinct entities?

In the time period 1988-2000, a case-control study on laryngeal cancer was conducted in Montevideo, Uruguay. Four-hundred eighty-one (481) cases newly diagnosed and microscopically confirmed as squamous cell carcinomas were included. These cases were frequency matched with 481 nonneoplastic controls, admitted to the same hospitals as the cases. The purpose of our study was to compare odds ratios (ORs) by laryngeal subsite (supraglottis and glottis). ORs of supraglottic cancers displayed much higher risks than glottic carcinomas for most tobacco variables and for red wine intake. The differences between subsites were statistically significant, displaying heterogeneity between both subsites. Moreover, whereas black tobacco smokers displayed a significant increased risk of 1.7 (95% confidence interval [CI] 1.2-2.5) compared to smokers of blond (flue-cured) tobacco among supraglottic tumors, no effect of this type of tobacco was observed in glottic lesions. It could be suggested that concerning tobacco and alcohol effects, supraglottic and glottic squamous cell cancers are probably distinct epidemiologic entities.     

Body mass index change in adulthood and lung and upper aerodigestive tract cancers

Body mass index (BMI) has been inversely associated with lung and upper aerodigestive tract (UADT) cancers. However, only a few studies have assessed BMI change in adulthood in relation to cancer. To understand the relationship between BMI change and these cancers in both men and women, we analyzed data from a population-based case-control study conducted in Los Angeles County. Adulthood BMI change was measured as the proportional change in BMI between age 21 and 1 year before interview or diagnosis. Five categories of BMI change were included, and individuals with no more than a 5% loss or gain were defined as having a stable BMI (reference group). Adjusted odds ratios (ORs) and their 95% confidence intervals (CIs) were estimated using logistic regression models. Potential confounders included age, gender, ethnicity, education, tobacco smoking and energy intake. For UADT cancers, we also adjusted for alcohol drinking status and frequency. A BMI gain of 25% or higher in adulthood was inversely associated with lung cancer (OR 0.53, 95% CI 0.33-0.84) and UADT cancers (OR 0.44, 95% CI 0.27-0.71). In subgroup analyses, a BMI gain of ≥25% was inversely associated with lung and UADT cancers among current and former smokers, as well as among current and former alcohol drinkers. The inverse association persisted among moderate and heavy smokers (≥20 pack-years). The observed inverse associations between adulthood BMI gain and lung and UADT cancers indicate a potential role for body weight-related biological pathways in the development of lung and UADT cancers.     

Case‐control study of cumulative cigarette tar exposure and lung and upper aerodigestive tract cancers

The development of comprehensive measures for tobacco exposure is crucial to specify effects on disease and inform public health policy. In this population‐based case‐control study, we evaluated the associations between cumulative lifetime cigarette tar exposure and cancers of the lung and upper aerodigestive tract (UADT). The study included 611 incident cases of lung cancer; 601 cases of UADT cancers (oropharyngeal, laryngeal and esophageal cancers); and 1,040 cancer‐free controls. We estimated lifetime exposure to cigarette tar based on tar concentrations abstracted from government cigarette records and self‐reported smoking histories derived from a standardized questionnaire. We analyzed the associations for cumulative tar exposure with lung and UADT cancer, overall and according to histological subtype. Cumulative tar exposure was highly correlated with pack‐years among ever smoking controls (Pearson coefficient = 0.90). The adjusted odds ratio (95% confidence limits) for the estimated effect of about 1 kg increase in tar exposure (approximately the interquartile range in all controls) was 1.61 (1.50, 1.73) for lung cancer and 1.21 (1.13, 1.29) for UADT cancers. In general, tar exposure was more highly associated with small, squamous and large cell lung cancer than adenocarcinoma. With additional adjustment for pack‐years, positive associations between tar and lung cancer were evident, particularly for small cell and large cell subtypes. Therefore, incorporating the composition of tobacco carcinogens in lifetime smoking exposure may improve lung cancer risk estimation. This study does not support the claim of a null or inverse association between “low exposure” to tobacco smoke and risk of these cancer types.     

Smoking, alcohol drinking and cancer risk for various sites of the larynx and hypopharynx. A case-control study in France.

The aim of this work was to study the effects of alcohol and tobacco consumption on laryngeal and hypopharyngeal cancer and to compare these across subsites (glottis, supraglottis, epilarynx, hypopharynx). Data from a hospital-based case-control study including 504 male cases (105 glottic cancers, 80 supraglottic cancers, 97 epilaryngeal cancers and 201 hypopharyngeal cancers) and 242 male controls with non-respiratory cancers were used for this analysis. Information about sociodemographic characteristics, detailed alcohol and tobacco consumption was collected through face-to-face interviews. Statistical analysis used logistic regression, and subsites were compared with polytomous logistic regressions. The risk of laryngeal and hypopharyngeal cancer increased with tobacco (duration and amount) and alcohol consumption; the effect of both agents was multiplicative. From the lowest to the highest consumption level, odds ratios ranged from 1.4 to 5.9 among regular drinkers and from 3 to 44 among current smokers. Risks among ex-smokers were approximately one-third of those for current smokers. Slightly elevated odds ratios were associated with consumption of black tobacco (OR=1.2) and hand-rolled cigarettes (OR=1.2). The risk of cancer was not clearly associated with the type of alcoholic beverage. Subsites did not differ significantly according to tobacco smoking, but differed according to alcohol consumption, with a significantly higher increased risk for hypopharyngeal than for glottic and supraglottic cancers.     

Alcohol and tobacco, and the risk of cancers of the upper aerodigestive tract in Latin America: a case�Ccontrol study

Background

Cancers of the upper aerodigestive tract (UADT; including oral cavity, pharynx, larynx and oesophagus) have high incidence rates all over the world, and they are especially frequent in some parts of Latin America. However, the data on the role of the major risk factors in these areas are still limited.

Methods

We have evaluated the role of alcohol and tobacco consumption, based on 2,252 upper aerodigestive squamous-cell carcinoma cases and 1,707 controls from seven centres in Brazil, Argentina, and Cuba.

Results

We show that alcohol drinkers have a risk of UADT cancers that is up to five times higher than that of never-drinkers. A very strong effect of aperitifs and spirits as compared to other alcohol types was observed, with the ORs reaching 12.76 (CI 5.37?C30.32) for oesophagus. Tobacco smokers were up to six times more likely to develop aerodigestive cancers than never-smokers, with the ORs reaching 11.14 (7.72?C16.08) among current smokers for hypopharynx and larynx cancer. There was a trend for a decrease in risk after quitting alcohol drinking or tobacco smoking for all sites. The interactive effect of alcohol and tobacco was more than multiplicative. In this study, 65% of all UADT cases were attributable to a combined effect of alcohol and tobacco use.

Conclusions

In this largest study on UADT cancer in Latin America, we have shown for the first time that a prevailing majority of UADT cancer cases is due to a combined effect of alcohol and tobacco use and could be prevented by quitting the use of either of these two agents.     

Relationship of Lifetime Exposure to Tobacco,Alcohol and Second Hand Tobacco Smoke with Upper aero-digestive tract cancers in India: a Case-Control Study with a Life-Course Perspective

Background: Squamous cell carcinomas of the upper aero-digestive tract (UADTSCC) are a multifaceted public health problem. Effects of lifestyle risk factors, including tobacco (chewing and smoking), alcohol drinking and exposure to second hand tobacco smoke (SHS) at home and their association with UADT cancers was assessed in a case-control study with a life-course perspective. The study was conducted at two different hospitals in Pune, India. Material and methods: The total sample size (N=480) included 240 histopathologically confirmed cases of UADT cancers and an equal number of controls frequency matched with cases by gender and age distribution (+5 years). All the patients were interviewed face-face using structured questionnaires. Self-reported information on socio-demographic and lifestyle risk factors from childhood to the date of diagnosis of disease/cancer was obtained. Frequency, duration and age of initiation of habits were also recorded to study dose-response relationships. Odds ratios and their 95% confidence intervals were calculated through unconditional logistic regression, adjusting for relevant potential confounders. Results: Chewing tobacco emerged as the strongest predictor for UADT cancers (OR=7.61; 95% CI 4.65-12.45) in comparison to smoking and drinking alcohol. Exposure to SHS during childhood (Conclusions: Early exposure to various modifiable lifestyle risk factors has a strong positive association with UADT cancer incidence. Effective future public health interventions with focus on vital time points in life targeting these risk factors could possibly be a major step in primary prevention and control of this cancer at the population level.     

Genetic polymorphisms of glutathione-S-transferase genes (GSTM1, GSTT1 and GSTP1) and upper aerodigestive tract cancer risk among smokers, tobacco chewers and alcoholics in an Indian population

The glutathione-S-transferase (GST) genes are involved in the detoxification of various carcinogens that increase the risk to upper aerodigestive tract (UADT) cancers. In the present study, 408 unrelated histopathologically confirmed cases and 220 population based controls, matched by age and gender, which belonged to the Tamilian population of south India were genotyped for polymorphisms in GSTM1, GSTT1 and GSTP1 using polymerase chain reaction (PCR) based methods. The multivariate logistic regression analyses demonstrated that GSTT1 null genotype was significantly associated with increased risk for UADT cancers (odds ratio (OR) 2.5; 95% confidence intervals (CIs) 1.3–4.7). The combined effects of GST genes have shown that concurrent lack of GSTM1 and GSTT1 had a significantly increased risk (OR 4.6; 95% CI 1.3–15.6), while GSTT1 null genotype along with GSTP1 polymorphic variants further increased the cancer risk (OR 5.3; 95% CI 2.0–13.6). The most remarkable risk was seen among individuals carrying GSTM1 null, GSTT1 null genotypes and GSTP1 polymorphic variants (OR 7.8; 95% CI 1.0–61.0). Tobacco chewers carrying GSTM1 null genotype had an enhanced risk for UADT cancers. An enhanced risk among tobacco chewers and alcoholics (regular) was noted in individuals with GSTT1 null genotype. Similarly, a significant interaction was observed among smokers (>40 pack-year (PY)) and tobacco chewers carrying GSTP1 mutant genotypes. Although the null genotype of GSTT1 is a strong predisposing risk factor for UADT cancers, we conclude that the significant gene–gene and gene–environment interactions of GST genes may confer a substantial risk to UADT cancers in the Tamilian population of south India.     

High-Ambient Air Pollution Exposure Among Never Smokers Versus Ever Smokers With Lung Cancer

IntroductionAir pollution may play an important role in the development of lung cancer in people who have never smoked, especially among East Asian women. The aim of this study was to compare cumulative ambient air pollution exposure between ever and never smokers with lung cancer.MethodsA consecutive case series of never and ever smokers with newly diagnosed lung cancer were compared regarding their sex, race, and outdoor and household air pollution exposure. Using individual residential history, cumulative exposure to outdoor particulate matter (PM_2.5) in a period of 20 years was quantified with a high-spatial resolution global exposure model.ResultsOf the 1005 patients with lung cancer, 56% were females and 33% were never smokers. Compared with ever smokers with lung cancer, never smokers with lung cancer were significantly younger, more frequently Asian, less likely to have chronic obstructive pulmonary disease or a family history of lung cancer, and had higher exposure to outdoor PM_2.5 but lower exposure to secondhand smoke. Multivariable logistic regression analysis revealed a significant association with never-smoking patients with lung cancer and being female (OR = 4.01, 95% confidence interval [CI]: 2.76–5.82, p < 0.001), being Asian (OR_{Asian versus non-Asian} = 6.48, 95% CI: 4.42–9.50, p < 0.001), and having greater exposure to air pollution (OR_{ln_PM2.5} = 1.79, 95% CI: 1.10–7.2.90, p = 0.019).ConclusionsCompared with ever-smoking patients with lung cancer, never-smoking patients had strong associations with being female, being Asian, and having air pollution exposures. Our results suggest that incorporation of cumulative exposure to ambient air pollutants be considered when assessing lung cancer risk in combination with traditional risk factors.     

Multiple occurrence of carcinoma in the upper aerodigestive tract associated with esophageal cancer: Reference to smoking,drinking and family history

Smoking and drinking habits as well as family history were examined in 143 men with esophageal cancer, including 30 who had associated second cancers of the upper aerodigestive tract (UADT) and 113 who did not. The risk of second cancers of UADT associated with the main lesions of the esophagus was evaluated, using odds ratios (ORs). As a result, the ORs of second cancers for current smoking and drinking were 5.3 and 7.6 respectively. The ORs significantly increased to 12.7 and 14.7 in heavy smokers and in heavy drinkers respectively. Furthermore, the risk of second cancer also significantly increased (8-fold) in patients who had close relatives with UADT cancer, compared to those without family history of any cancer. However, there were no differences in smoking or drinking habits regardless of family history. Our data thus suggest that a family history of UADT cancer as well as heavy smoking and drinking are clearly associated with multiple occurrence of UADT cancer. Therefore, careful and frequent examination for appearance of any second lesions are required for patients in these high-risk groups.     

Glutathione S-transferase M1 or T1 null genotype as a risk factor for developing multiple primary neoplasms in the upper aero-digestive tract, in Indian males using tobacco

In this study conducted amongst Indian male tobacco users with upper aero-digestive tract (UADT) squamous carcinoma, 30 patients with multiple primary neoplasms (MPN) were compared with 28 age and sex matched patients with a single primary neoplasm (SPN) for various environmental factors (form of tobacco use, alcohol, radiotherapy for index cancer) and genetic parameters (family history of UADT cancers and GSTT1/GSTM1 genotype). The GSTM1/T1 null genotype, seen in 60% patients with MPN versus 33% patients with SPN (P=0.03) had an odds ratio of 3.7 [CI=1.14-11.99; P=0.03] for developing MPN. Tobacco use in the form of smoking with or without chewing, as opposed to only chewing, and regular alcohol intake were the two other factors with almost three fold increased risk for the development of MPN, although, the effect was not statistically significant. All three patients with a family history of UADT cancer developed MPN, suggesting an inherited predisposition.     

Combined effect of tobacco and alcohol on laryngeal cancer risk: a case-control study

Objective: To provide information on the effects of alcohol and tobacco on laryngeal cancer and its subsites. Methods: This was a case–control study conducted between 1992 and 2000 in northern Italy and Switzerland. A total of 527 cases of incident squamous-cell carcinoma of the larynx and 1297 hospital controls frequency-matched with cases on age, sex, and area of residence were included. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression. Results: In comparison with never smokers, ORs were 19.8 for current smokers and 7.0 for ex-smokers. The risk increased in relation to the number of cigarettes (OR = 42.9 for 25 cigarettes/day) and for duration of smoking (OR = 37.2 for 40 years). For alcohol, the risk increased in relation to number of drinks (OR = 5.9 for 56 drinks per week). Combined alcohol and tobacco consumption showed a multiplicative (OR = 177) rather than an additive risk. For current smokers and current drinkers the risk was higher for supraglottis (ORs 54.9 and 2.6, respectively) than for glottis (ORs 7.4 and 1.8) and others subsites (ORs 10.9 and 1.9). Conclusions: Our study shows that both cigarette smoking and alcohol drinking are independent risk factors for laryngeal cancer. Heavy consumption of alcohol and cigarettes determined a multiplicative risk increase, possibly suggesting biological synergy.     

Long‐term exposure to fine particulate matter air pollution and the risk of lung cancer among participants of the Canadian National Breast Screening Study

Recently, air pollution has been classified as a carcinogen largely on the evidence of epidemiological studies of lung cancer. However, there have been few prospective studies that have evaluated associations between fine particulate matter (PM_2.5) and cancer at lower concentrations. We conducted a prospective analysis of 89,234 women enrolled in the Canadian National Breast Screening Study between 1980 and 1985, and for whom residential measures of PM_2.5 could be assigned. The cohort was linked to the Canadian Cancer Registry to identify incident lung cancers through 2004. Surface PM_2.5 concentrations were estimated using satellite data. Cox proportional hazards models were used to characterize associations between PM_2.5 and lung cancer. Hazard ratios (HRs) and 95% confidence intervals (CIs) computed from these models were adjusted for several individual‐level characteristics, including smoking. The cohort was composed predominantly of Canadian‐born (82%), married (80%) women with a median PM_2.5 exposure of 9.1 µg/m³. In total, 932 participants developed lung cancer. In fully adjusted models, a 10 µg/m³ increase in PM_2.5 was associated with an elevated risk of lung cancer (HR: 1.34; 95% CI = 1.10, 1.65). The strongest associations were observed with small cell carcinoma (HR: 1.53; 95% CI = 0.93, 2.53) and adenocarcinoma (HR: 1.44; 95% CI = 1.06, 1.97). Stratified analyses suggested increased PM_2.5 risks were limited to those who smoked cigarettes. Our findings are consistent with previous epidemiological investigations of long‐term exposure to PM_2.5 and lung cancer. Importantly, they suggest associations persist at lower concentrations such as those currently found in Canadian cities.