Detailed Smoking History Research Articles

Menopausal Hormone Therapy Does Not Influence Lung Cancer Risk: Results from the California Teachers Study

Results from studies examining the association between hormone therapy (HT) and lung cancer risk disagree. We examined the associations between HT use and lung cancer risk among 60,592 postmenopausal women enrolled in the prospective California Teachers Study cohort. Between 1995 and 2007, a total of 727 women had a diagnosis of lung cancer. Multivariable Cox proportional hazards regression models were fit using age as the time metric. No measure of HT use was associated with lung cancer risk (all P(trend) values ≥0.4). In addition, no variations in risk by smoking status (never, ever, former, current), type of HT [estrogen (E)-alone, E + progestin (P) use], type of menopause, or lung cancer histology were observed. Our findings do not support an association between HT and lung cancer. This large-scale, prospective study, which capitalizes on the detailed hormone use, smoking history, and type of menopause information available within this unique cohort, was unable to find any association between intake of HT and lung cancer risk.

Nicotinic acetylcholine receptor polymorphism, smoking history, and tobacco-related cancer in the general population.

1530 Background: Smokers often develop lung and bladder cancer; however, not all smokers develop these diseases. We examined whether the nicotinic acetylcholine receptor gene (CHRNA3) rs1051730 polymorphism can identify smokers in the general population at genetically high risk of tobacco-related cancer, that is, at higher risk than that explained by detailed smoking history alone. Methods: We genotyped 10,322 participants from the Danish general population, the Copenhagen City Heart Study. Detailed smoking history was obtained and validated at baseline. End-points during the following 18 years were lung and bladder cancer from the Danish cancer registry. Follow-up was 100% complete. Results: Among the 7831 ever smokers, CHRNA3 non-carriers (44%) and homozygotes (11%) had daily tobacco consumption of 16 and 18 g/day (Wilcoxon: p = 0.000004), cumulative tobacco consumption of 28 to 31 packyears (p = 0.001), and smoking inhalation of 72% and 78% (chi- square: p = 0.0002). As expected increasing baseline packyears smoked associated with increasing risk of lung and bladder cancer during the following 18 years (trend-tests: p = 4*10-47 and p = 0.0002); the hazard ratios for lung and bladder cancer in those with baseline > 40 packyears smoked vs. never-smokers were 44 (95% CI:14-105) and 2.9 (1.4-5.9) after multifactorial adjustment including genotype. In addition, CHRNA3 homozygotes vs. non-carriers had hazard ratios for lung and bladder cancer of 1.65 (1.18-2.30) and 1.79 (1.05-3.06) after multifactorial adjustment including detailed smoking history. The highest absolute 10-year risks were 11.4% for lung cancer and 4.4% for bladder cancer for homozygous smokers above 60 years who had smoked > 30 packyears at baseline. Conclusions: The nicotinic acetylcholine receptor rs1051730 polymorphism identifies 11% of smokers in the general population at excessive high risk of tobacco-related cancer, even after considering a full smoking history. No significant financial relationships to disclose.

The interaction between smoking status and disease stage on non-small cell lung cancer (NSCLC) survival.

e18021 Background: In cancer, accumulation of somatic and genomic changes occurs from early to late stage disease. Recent data suggest that never smokers (NVS) vs. ever smokers (EVS) develop biologically distinct NSCLCs. We studied whether smoking status (EVS vs. NVS) modified prognosis differently in early (stage I-II) vs. late stages (stage III-IV) of NSCLC. Methods: Detailed smoking history was collected prospectively from patients with newly diagnosed NSCLC as part of a molecular-epidemiologic study (1997-2002) that specifically oversampled never-smokers. Survival data were collected from the Ontario Cancer Registry. Cox proportional hazard models identified variables with prognostic significance. Analyses of patients with early and late stage NSCLC were first performed separately, followed by a model that included a stage- smoking status interaction term. Results: Among 381 patients, 34% were NVS. NVS were younger (median age 60 vs. 65 years in EVS; t- test p = 0.0001), more likely to be female (68% NVS vs. 45% EVS) and non-Caucasian (38% NVS vs. 18% EVS); stage distribution was similar (26% NVS vs. 22% EVS were Stage I/II). Pack-years, intensity or duration of smoking, and years since quitting were not significant univariate predictors of outcome, by stage. Multivariate models were adjusted for significant univariate covariates of age, sex, treatment and stage, along with current vs. former smoking status and race. In early stage patients, NVS had longer survival (adjusted hazard ratio [AHR] 0.43; 95% CI, 0.18-1.03), while in late stage patients, the opposite effect was observed (AHR 1.47; 95% CI, 1.08-2.00). The interaction between disease stage (early vs. late) and smoking status (NVS vs. EVS) was significant (p = 0.006). In the same interaction model, age and sex were no longer significant, after adjusting for smoking, disease stage, and the interaction of these two variables. Conclusions: Never-smokers appear to have better prognosis than ever-smokers in early stage lung cancer, an effect that is reversed in late stage disease; age and gender were not predictive of survival after accounting for smoking and stage. These effects may reflect smoking subpopulations that are biologically heterogeneous. No significant financial relationships to disclose.

The impact of smoking on antimüllerian hormone levels in women aged 38 to 50 years

Smoking is associated with increased follicle-stimulating hormone levels and early menopause. Smoking may directly accelerate ovarian follicular depletion or may act indirectly by increasing the pituitary production of follicle-stimulating hormone. Antimüllerian hormone (AMH), produced by ovarian follicles, is a more direct measure of ovarian reserve. The objective of our study was to determine the extent to which smoking influences ovarian reserve, as measured by AMH levels. A community sample of 284 women aged 38 to 50 years completed a self-administered questionnaire including a detailed smoking history. Serum AMH levels were measured on day 2, 3, or 4 of the menstrual cycle. The association between AMH and smoking was analyzed using linear regression, adjusting for age and body mass index. Participants aged 38 to 42, 43 to 45, and 46 to 50 years had geometric mean AMH values of 6.7 pM (95% CI, 5.2-8.7 pM), 2.7 pM (95% CI, 1.9-3.8 pM), and 1.3 pM (95% CI, 1.0-1.7 pM), respectively. Current smokers, but not past smokers, had 44% lower AMH values than did the reference group (participants with neither active nor former or passive smoke exposure; P = 0.04). Passive smoking had no effect on AMH values when compared with the reference group (P = 0.55). The impact of smoking on AMH values was not dose dependent based on cigarettes per day (P = 0.08) or pack-years (P = 0.22). Finally, prenatal exposure to smoking (either maternal or paternal) had no impact on AMH levels (P = 0.47 and P = 0.89, respectively). Active smoking, but not former smoking, is associated with decreased AMH values in late-reproductive-age and perimenopausal women, suggesting a possible direct effect of smoking on the depletion of the antral but not primordial follicles. The direct impact of active smoking on AMH levels in younger women requires further investigation.

Abstract 937: Nicotinic acetylcholine receptor polymorphisms, secondhand smoke and lung cancer risk

Abstract Introduction: Passive or secondhand smoke (SHS) exposure is an independent risk factor for adult non-small cell lung cancer (NSCLC). In 2008, three genome wide association studies (GWAS) identified a locus on chromosome region 15q24-25.1 that was strongly associated with lung cancer. In this study, we assessed the interaction of the two most significant single nucleotide polymorphisms (SNPs) reported (rs8034191, rs1051730) with SHS on lung cancer risk. We hypothesize that after adjusting for active cigarette smoking, individuals with the risk alleles and the highest cumulative exposure to SHS are at the greatest risk of lung cancer. Methods: This study population is derived from a large ongoing case control study evaluating the molecular epidemiology of lung cancer, which began in 1992 at the Massachusetts General Hospital. The polymorphisms were genotyped by the 5V nuclease assay (Taqman) using the ABI Prism 7900HT Sequence Detection System (Applied Biosystems, Foster City, CA). Interviewer-administered questionnaires collected information on demographics, and detailed smoking histories from each subject. Second hand smoke exposure duration and frequency was self-reported for three different activities (leisure, work and at home). The cumulative SHS exposure was the sum of all durations multiplied by their frequency weight. We used the co-dominant genetic model for individual SNPs, controlling for age, gender, pack years, years since smoking cessation and smoking status. We tested for interaction using the Likelihood Ratio Test by incorporating cross product interaction terms of indicator variables for each SNP and quartiles of cumulative exposure. Results: A total of 2071 cases and 1506 controls were analyzed. Among cases, exposure to SHS at home 1924(93%), work 1727 (83%), leisure 1791 (86%); among controls 1328 (88%), 1044 (69%) and 1233 (82%) respectively. In stratified analysis, for study participants in the highest quartile of cumulative SHS exposure and comparing the homozygous variant to the wildtype, the adjusted odds ratio (AOR) for lung cancer was 1.55 (0.99-2.44) (rs8034191) and 1.66 (1.05-2.62) (rs1051730). In the lowest quartile of SHS exposure the corresponding results were 0.94 (0.47-1.89) (rs8034191) and 0.91(0.45-1.84) (rs1051730). There was no evidence for gene-SHS interaction. Conclusion: Our results indicate that secondhand smoke does not modify the association of rs1051730 and rs8034191 with non-small cell lung cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 937.

Dose effect of cigarette smoking on frequency and spectrum of epidermal growth factor receptor gene mutations in Korean patients with non-small cell lung cancer

This study aimed to determine the dose effect of smoking on the mutational frequency and spectrum of epidermal growth factor receptor (EGFR) gene in Korean non-small cell lung cancer (NSCLC). Detailed smoking histories were obtained from 324 consecutively enrolled Korean NSCLC patients. Mutational status of EGFR (exon 18-21) was determined using nested polymerase chain reaction amplification. A total of 108 EGFR mutations (33.3%) were identified in 107 patients. Decreased EGFR mutation rate with increased smoking dose was observed, with 48.0% (82 of 171) in never smokers, 23.1% (15 of 65) in former smokers, and 11.4% (10 of 88) in current smokers. The incidence of EGFR mutation was significantly lower in patients who smoked for more than 25 pack-years (P < 0.0001) or who stopped smoking cigarettes less than 10 years ago (P < 0.0001). Mutations in exon 19 or 21 were associated with fewer total smoke years (5.0 vs. 25.0 years in exon 20, P = 0.024), fewer total pack-years (6.3 vs. 38.9 pack-years in exon 20, P = 0.079), and more smoke-free years (11.1 vs. 3.6 years in exon 20, P = 0.027), compared with those in exon 20. Mutations in exon 19 or 21 were associated with female (P < 0.0001), never smoker (P < 0.0001), and adenocarcinoma (P < 0.0001), whereas those in exon 20 were not. Smoking dosage affects the incidence of EGFR mutations. EGFR mutations in exon 19 or 21 are associated with low exposure to cigarette smoke, whereas EGFR mutation in exon 20 is more common in smokers.

Increased Frequency of Serrated Aberrant Crypt Foci Among Smokers

The American College of Gastroenterology has published guidelines recently that suggest that smokers with a history of >20 pack years may need screening for colorectal cancer (CRC) at an earlier age than non-smokers. Aberrant crypt foci (ACF) may represent important precursors for colorectal neoplasms and potential surrogate biomarkers. Clarifying the role of ACF in relation to known CRC risk factors such as smoking may have important implications for screening as well as our understanding of tobacco use and colorectal carcinogenesis. Our goal was to examine whether smoking at least 20 pack years was associated with an increased frequency of ACF. We gathered detailed smoking history, personal and family history of CRC, and other epidemiologic data (age, gender, height, weight, ethnicity, and medication use) from 125 patients undergoing routine screening or surveillance colonoscopy. We used a magnifying colonoscope (Olympus Close Focus Colonoscope XCF-Q160ALE, Olympus Corporation, Tokyo, Japan) and examined the distal 20 cm section of colon after staining with 0.5% methylene blue. ACF were counted and characterized histologically. Hyperplastic ACF were further characterized as either serrated or non-serrated. Smoking at least 20 pack years was associated with an increased likelihood (adjusted odds ratio (OR)=3.45; 95% confidence interval (CI)=1.93-6.18) of having more than the median number of ACF (> or = 15) compared with non-smokers. Similarly, patients with a personal history of advanced neoplasia were more likely (adjusted OR=3.42; 95% CI=1.01-11.67) to have a greater than median number of ACF compared with patients without this diagnosis. Smokers were more likely than non-smokers to have serrated ACF (P=0.002). Smoking at least 20 pack years seems to be associated with increased number of ACF in the rectum and distal sigmoid, especially those with serrated histology. Our data support ACG guidelines for earlier screening for CRC among smokers and add to our understanding of how colorectal carcinogenesis is related to tobacco use.

Pack-years of cigarette smoking as a prognostic factor in patients with stage IIIB/IV nonsmall cell lung cancer.

This study was undertaken to characterize the relation between the survival of patients with stage IIIB/IV nonsmall cell lung cancer (NSCLC) and pack-years of cigarette smoking (graded according to the American Joint Committee on Cancer staging system). Data were analyzed from patients with stage IIIB/IV NSCLC who had completed a prospective smoking questionnaire. The impact of pack-years of cigarette smoking, age, sex, Karnofsky performance status (KPS), and the presence of weight loss >5% was evaluated on overall survival using univariate and multivariate analyses. Smoking history and clinical data were available for 2010 patients with stage IIIB/IV NSCLC (1004 women and 1006 men). Approximately 70% of patients (1409 patients) had smoked >15 pack-years, 13% (270) were former and current smokers who had smoked < or = 15 pack-years, and 16% (331) were never-smokers (<100 lifetime cigarettes). Never-smokers had a longer median survival compared with former or current smokers (17.8 months vs 11.3 months; log-rank P < .001). Among smokers, patients with a < or = 15 pack-year history of smoking had a longer median survival than patients who had smoked >15 pack-years (14.6 months vs 10.8 months; log-rank P = .03). As the number of pack-years increased, the median overall survival decreased (log-rank P < .001). Multivariate analysis indicated that a history of smoking was an independent prognostic factor (hazard ratio, 1.36; P < .001). More cigarette smoking, measured in pack-years, was associated with decreased survival after a diagnosis of stage IIIB/IV NSCLC. Trials assessing survival in patients with stage IIIB/IV NSCLC should report a detailed cigarette smoking history for all patients.

Relationships between hand‐rolled cigarettes and primary lung cancer: A Norwegian experience

Detailed smoking history of patients developing lung cancer is rarely known, especially not for users of hand-rolled cigarettes. In Norway, smoking hand-rolled tobacco is still popular, accounting for one-third of the total tobacco consume. A questionnaire-based study revealing detailed information about tobacco consume with consecutive inclusion of all persons developing lung cancer in Southern Norway 2002-2005. In this unselected population with 479 patients with newly diagnosed lung cancer, 95% had a smoking history and 88% of ever-smokers had smoked primarily hand-rolled cigarettes. The hand-rolled cigarette smokers had smoked fewer cigarettes daily (15) and less pack-years of tobacco (34) than fabricated cigarette smokers (20, P < 0.0001 and 42, P = 0.021, respectively). Smoking hand-rolled cigarettes was considerably more frequent than expected from official sales statistics. Hand-rolled cigarette smoking revealed an odds ratio of 13 for developing lung cancer compared with smoking fabricated cigarettes. In this unselected population with newly diagnosed lung cancer, nine out of 10 ever-smokers had smoked primarily hand-rolled cigarettes. Patients smoking hand-rolled cigarettes had a smoking history of fewer daily cigarettes and less pack-years tobacco consumed than fabricated cigarette smokers. In this study, hand-rolled cigarettes are more frequently used than shown in national statistics. Smokers of hand-rolled cigarettes may have a greatly increased risk for lung cancer compared with smokers of fabricated cigarettes.

Influence of smoking dose on the outcome of Japanse patients with non-small cell lung cancer who had gefitinib treatment

e19004 Background: Non-smoking history and epidermal growth factor receptor (EGFR) mutation are associated with increased sensitivity to gefitinib in non-small cell lung cancer (NSCLC). However, it is still unclear how much smoking dose is associated with survival and response to gefitinib among smokers. Methods: NSCLC patients (pts) with detailed smoking history who received gefitinib at our institution between 9/02 and 9/04 were reviewed. An analysis was conducted to the pts for association between smoking dose, EGFR mutations, performance status (PS), response and overall survival using multivariate analysis. Results: Data were available for 100 pts including 30 females and 70males. We expressed smoking dose as pack year (Py).The median dose of smoking was 32 Py (0.1–100 Py). We defined the group of &lt;10 Py as light smokers(17 pts) and the other group of 10 Py or more as heavy smokers(83 pts). We detected 31(31%) EGFR mutation (median 14 Py 0.1–75 Py) with exon 18 / 19 /21 mutation;3/17/11 pts .Cox survival analysis showed that overall survival was preferably associated with small dose of smoking(&lt;10 Py)(HR=0.505; [95% CI 0.277–0.921; P=0.013]), EGFR mutation(HR=0.452[95% CI 0.235–0.87;P=0.035])and PS;0–1(HR=0.347 [95% CI 0.207–0.583 P&lt;0.001]). EGFR mutations were significantly more frequently observed in light (12/17:71%) than heavy smokers(19/83:23%) (p&lt;0.001). Disease control rate(DCR) was significantly higher in light (13/17;76%;PR 6, SD 7) than heavy smokers(29/83;35%;PR 15, SD 14)(P=0.002), but there was not significant difference between those groups in terms of response rate (RR)(P=0.187). There were significant differences between pts with EGFR mutations (PR 13 SD 14; RR 42%,DCR 87%) and pts without EGFR mutations (PR 8 SD 15; RR 12%, DCR 33%) in terms of RR(P&lt;0.001) and DCR(P&lt;0.001). In pts with EGFR mutation, there was no significant difference between light and heavy smokers in terms of RR (light smokers 5/10, heavy smokers 8/21; P=0.701) and DCR (light smokers 10/10, heavy smokers17/21; P= 0.277). Conclusions: EGFR mutations were predictive factor and prognostic factor. Small dose of smoking (&lt; 10 Py) was prognostic factor, however it was not a predictive factor of smokers with NSCLC. No significant financial relationships to disclose.

Smoking and Colorectal Neoplasia

Purpose: While it has been shown that smoking is associated with a 2 fold risk for important colorectal neoplasia in screening populations (Lieberman et al JAMA 2003; Anderson et al AJG 2003), less is known about the exposure quantity needed. Furthermore, there is little data regarding the gender difference for the tobacco dose. Our hypothesis was that women demonstrate this 2 fold increase in risk from smoking with a lower pack year exposure than men. Methods: Data collected included, age, height, weight, family history of colon cancer, medication use (aspirin, insulin, statins, multivitamins, folic acid, hormone replacement therapy, calcium supplementation, medical history including diabetes, surgery (including cholecystectomy), exercise and 5 year dietary including servings of fruits/vegs and red meat. We also collected a detailed smoking history in pack years and defined three smoking categories:1) No Exposure: No tobacco use 2) Heavy Exposure: smoking more than 10 pack years and still smoking or quit in past 10 yrs 3) Low Exposure: those who smoked less than 10 pack yrs or those who quit over 10 yrs prior. Significant neoplasia was the main outcome and included, villous, large (>1 cm), high grade dysplasia, adenocarcinoma and multiple (>2) adenomas. Results: 2707 patients (average age 57.3) were screened from 11/99 to 7/06. For the analysis, the Low Exposure smokers were removed. The Heavy Exposure smokers were then divided into 2 new groups: 1) Heavy Exposure A: Those who smoked < or = to 30 pack years and 2) Heavy Exposure B: Those who smoked >30 pack years. The analysis controlling for age, BMI and family history was performed. The results comparing the two groups of smokers to the No Exposure patients for males and females are shown in the Table. As seen in the table women who smoked less than 30 pack years were almost twice as likely to have significant colorectal neoplasia as the female No Exposure patients (OR = 1.91; 95% CI:1.08–3.41). The anaylsis was performed using advanced adenomas as an outcome and the same increased risk for the < or = 30 pack year smokers when compared to the No Exposure patients was observed (OR = 2.15; 95% CI: 1.14–4.09) Conclusion: Although males and females have a similar 2 fold risk for significant colorectal neoplasia from smoking, women require less exposure in pack years to have an increase in risk.Table: Risk for Significant Colorectal Neoplasia.

Low-level arsenic exposure in drinking water and bladder cancer: A review and meta-analysis

Although exposure to high levels of arsenic in drinking water is associated with excess cancer risk (e.g., skin, bladder, and lung), lower exposures (e.g., <100–200 μg/L) generally are not. Lack of significant associations at lower exposures may be attributed to methodologic issues (e.g., inadequate statistical power, exposure misclassification), or to differences in the dose–response relationship at high versus low exposures. The objectives of this review and meta-analysis were to evaluate associations, examine heterogeneity across studies, address study design and sample size issues, and improve the precision of estimates. Eight studies of bladder cancer and low-level arsenic exposure met our inclusion criteria. Meta-analyses of never smokers produced summary relative risk estimates (SRREs) below 1.0 (highest versus lowest exposure). The SRRE for never and ever smokers combined was elevated slightly, but not significantly (1.11; 95% CI: 0.95–1.30). The SRRE was somewhat elevated among ever smokers (1.24; 95% CI: 0.99–1.56), and statistical significance was observed in some subgroup analyses; however, heterogeneity across studies was commonly present. Although uncertainties remain, low-level arsenic exposure alone did not appear to be a significant independent risk factor for bladder cancer. More studies with detailed smoking history will help resolve whether smoking is an effect modifier.

Risk of hypertension amongst Swedish male snuff users: a prospective study

The scientific evidence on whether long-term use of snuff is associated with high blood pressure is limited, inconsistent and based only on cross-sectional data. We aimed at studying the risk of hypertension in relation to long-term use of snuff based on longitudinal data. Repeated health check-ups were offered to all employees in the Swedish construction industry between 1978 and 1993. Blood pressure was measured at the health check-up and information on tobacco use and other risk factors was collected through questionnaires. In total, 120 930 never smoking men with information on blood pressure and snuff use at baseline were included. The association of high blood pressure and snuff use at baseline was estimated by logistic regression. Further, 42 055 men were identified as normotensive at baseline and had at least one subsequent health check-up. Through repeated blood pressure measurements and linkage to the Swedish National Inpatient Register, information on hypertension was obtained. Relative risk estimates were derived from Cox proportional hazards regression model. Almost 30% of all men had used snuff. The adjusted odds ratio of high blood pressure amongst snuff users at baseline was 1.23 (95% CI 1.15-1.33) compared to never snuff users. The relative risk of high blood pressure during follow-up was 1.39 (95% CI 1.08-1.79) amongst snuff users and 1.36 (95% CI 1.07-1.72) for hypertension as recorded in the Inpatient Register. Use of Swedish moist snuff appears to be associated with a moderately increased risk of hypertension.

Pack years of cigarette smoking as a predictor of survival in 2,013 patients with stage IIIb/IV non-small cell lung cancer (NSCLC)

8005 Background: Cigarette smoking is a negative prognostic factor for patients with NSCLC. It is unclear how the number of pack years (py) smoked affects survival. EGFR mutations, which have been associated with a good prognosis, are more common in patients who never smoked cigarettes. The frequency of EGFR mutations in patients who smoked up to 15 py is not significantly different from that observed in never smokers (Pham JCO 2006). In order to characterize the relationship between patient survival and pack years of cigarette smoking, we reviewed prospectively collected smoking data for patients with stage IIIb/IV NSCLC. Methods: Detailed smoking history was obtained using a patient-completed smoking questionnaire. Age, gender, stage and survival from time of diagnosis were obtained with Institutional Review Board approval. Results: Smoking history and clinical data were available for 2,013 patients with Stage IIIb/IV NSCLC (1007 women, 1006 men). Median age was 64. Seventy % (1416) smoked >15 py, 14% (270) were former or current smokers who had smoked ≤ 15 py, and 16% (331) were never smokers (<100 lifetime cigarettes). Never smokers had an increased median survival relative to current/former smokers (18 mo vs 11 mo, p<0.0001). Among smokers, patients with ≤ 15 py history of smoking had a longer median survival than patients with > 15 py (14 mo vs 11 mo, p =0.001). These differences for smoking remain significant after adjustment for gender (p<0.001). Increasing py of cigarette smoking was associated with a decrease in overall survival (Table). Conclusions: This is the largest reported evaluation of smoking history in patients with Stage IIIb/IV NSCLC. More cigarette smoking, measured in pack years, was associated with decreased survival after diagnosis. Smoking history, including pack years, should be a stratification factor for randomized clinical trials of patients with NSCLC. Pack Years median survival (months) 95% CI (months) never 18 15–21 <5 16 13–20 6–10 14 10–19 11–15 13 9–15 16- 25 13 10–15 26–50 11 9–11 51–75 10 8–11 >75 11 9–13 No significant financial relationships to disclose.

Periodontal disease, tooth loss, and cancer risk in male health professionals: a prospective cohort study

Studies suggest that tooth loss and periodontal disease might increase the risk of developing various cancers; however, smoking might have confounded the reported associations. We aimed to assess whether periodontal disease or tooth loss is associated with cancer risk. The analysis was done in a prospective study (the Health Professionals Follow-Up Study [HPFS]), which was initiated in 1986 when US male health professionals aged 40-75 years responded to questionnaires posted by the Department of Nutrition, Harvard University School of Public Health, Boston, MA, USA. In addition to the baseline questionnaires, follow-up questionnaires were posted to all living participants every 2 years and dietary questionnaires every 4 years. At baseline, participants were asked whether they had a history of periodontal disease with bone loss. Participants also reported number of natural teeth at baseline and any tooth loss during the previous 2 years was reported on the follow-up questionnaires. Smoking status and history of smoking were obtained at baseline and in all subsequent questionnaires. Additionally at baseline, participants reported their mean frequency of food intake over the previous year on a 131-item semiquantitative food-frequency questionnaire. Participants reported any new cancer diagnosis on the follow-up questionnaires. Endpoints for this study were risk of total cancer and individual cancers with more than 100 cases. Multivariate hazard ratios (HRs) and 95% CIs were calculated by use of Cox proportional hazard models according to periodontal disease status and number of teeth at baseline. In the main analyses, 48 375 men with median follow-up of 17.7 years (1986 to Jan 31, 2004) were eligible after excluding participants diagnosed with cancer before 1986 (other than non-melanoma skin cancer, n=2076) and those with missing data on periodontal disease (n=1078). 5720 incident cancer cases were documented (excluding non-melanoma skin cancer and non-aggressive prostate cancer). The five most common cancers were colorectal (n=1043), melanoma of the skin (n=698), lung (n=678), bladder (n=543), and advanced prostate (n=541). After adjusting for known risk factors, including detailed smoking history and dietary factors, participants with a history of periodontal disease had an increased risk of total cancer (HR 1.14 [95% CI 1.07-1.22]) compared with those with no history of periodontal disease. By cancer site, significant associations for those with a history of periodontal disease were noted for lung (1.36 [1.15-1.60]), kidney (1.49 [1.12-1.97]), pancreas (1.54 [1.16-2.04]; findings previously published), and haematological cancers (1.30 [1.11-1.53]). Fewer teeth at baseline (0-16) was associated with an increase in risk of lung cancer (1.70 [1.37-2.11]) for those with 0-16 teeth versus those with 25-32 teeth. In never-smokers, periodontal disease was associated with significant increases in total (1.21 [1.06-1.39]) and haematological cancers (1.35 [1.01-1.81]). By contrast, no association was noted for lung cancer (0.96 [0.46-1.98]). Periodontal disease was associated with a small, but significant, increase in overall cancer risk, which persisted in never-smokers. The associations recorded for lung cancer are probably because of residual confounding by smoking. The increased risks noted for haematological, kidney, and pancreatic cancers need confirmation, but suggest that periodontal disease might be a marker of a susceptible immune system or might directly affect cancer risk.

Agricultural Exposures in Patients with COPD in Health Systems Serving Rural Areas

ABSTRACT Background: Agricultural exposure is a risk factor for the development of chronic obstructive pulmonary disease (COPD). However, there are no good estimates of the number of COPD patients with a history of agricultural exposure. Methods: We conducted a telephone interview of subjects with COPD identified by reviewing all pulmonary function tests at the Omaha Veterans Administration Hospital between November 2004 and March 2005. Obstructive lung disease was defined as a FEV1/FVC ratio of less than 70%. The survey detailed demographic data, smoking history, pulmonary symptoms, and history of agricultural exposures. Results: Participants included 150 veterans (mean age 68.2 years ±10.8). A history of agricultural exposure was elicited in 68% of subjects. Of those who had worked in agriculture, the types of exposures varied, with 14% in hog confinement barns, 20% on dairy farms, 8% on poultry farms, and 87% exposed to grain dust. There was a trend of diminishing FEV1 with increasing years of agricultural exposure. Conclusions: In health systems that serve rural areas, patients with COPD commonly have a history of agricultural exposures that may contribute to the development of COPD. Health care workers in these areas should include agricultural exposures as an important part of the social/occupational history in these patients.

Association Between Cigarette Smoking and Colorectal Cancer in the Women's Health Initiative

The evidence linking cigarette smoking to the risk of colorectal cancer is inconsistent. We investigated the associations between active and passive smoking and colorectal cancer among 146,877 Women's Health Initiative participants. Women reported detailed smoking histories at enrollment. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the association between smoking and overall and site-specific risk of colorectal cancer. Invasive colorectal cancer was diagnosed in 1242 women over an average of 7.8 years (range = 0.003-11.2 years) of follow-up. In adjusted analyses, statistically significant positive associations were observed between most measures of cigarette smoking and risk of invasive colorectal cancer. Site-specific analyses indicated that current smokers had a statistically significantly increased risk of rectal cancer (HR = 1.95, 95% CI = 1.10 to 3.47) but not colon cancer (HR = 1.03, 95% CI = 0.77 to 1.38), compared with never smokers. Passive smoke exposure was not associated with colorectal cancer in adjusted analyses. Thus, active exposure to cigarette smoking appears to be a risk factor for rectal cancer.

Smoking status and adiponectin in healthy Japanese men and women

Background. Recent studies promisingly indicate that adiponectin plays an important and fundamental role in the development and progression of metabolic and atherosclerosis disorders. Smoking is known as one of the most important risk factors of atherosclerosis, and its relation with metabolic disorders has also been reported. We therefore investigated the association between cigarette smoking and adiponectin concentration in a large sample of Japanese men and women. Method. The cross-sectional study was carried out in 2002. The subjects were 3260 men and 953 women local government workers aged 35 to 59 in Japan. Lifestyle-related variables including detailed smoking history were inquired in a self-administered questionnaire. Results. Significant differences in adiponectin levels related to smoking status were observed in both men and women ( p = 0.001). A dose-dependent association was found between the intensity of smoking and adiponectin levels in current smokers, and was statistically significant in men ( p for trend = 0.006 in the multivariate-adjusted model). Men who quit smoking for more than 20 years and women for more than 10 years had an adiponectin concentration similar to that observed in non-smokers. Conclusion. We not only revealed that current smoking habit was associated with low adiponectin level but also found a dose-dependent association between smoking intensity and adiponectin level in current smokers. The present finding may provide further evidence of the importance of a causal relationship between smoking status and adiponectin concentrations.

Smoking history and frequency of somatic KRAS mutations in adenocarcinoma of the lung

7573 Background: Somatic mutations in the epidermal growth factor receptor (EGFR) gene are more common in patients with adenocarcinoma, especially those who smoked &lt; 15 pack years (py). KRAS mutations are found in ∼25% of lung adenocarcinomas, most commonly in codons 12 and 13 of exon 2 (∼85%) and have been associated with poor prognosis in resected disease [Winton NEJM 2005] and resistance to EGFR tyrosine kinase inhibitors [Pao PLoS Med 2005]. KRAS mutations are uncommon in non-small cell lung cancer histologies other than adenocarcinoma. We sought to determine the association between quantitative measures of cigarette smoking and presence of KRAS mutations in lung adenocarcinomas. Methods: Standard direct sequencing techniques were used to identify KRAS codon 12 and 13 mutations in lung adenocarcinoma specimens from surgical resections between 2001 and 2006 and tumor specimens sent for KRAS molecular analysis in 2006. Surgical specimens were obtained from an institutional tumor bank. Detailed smoking history (age at first cigarette, packs per day, years smoked, years since quitting smoking) was obtained from the medical record and a patient-completed smoking questionnaire. Results: KRAS mutational analysis was performed on 408 lung adenocarcinomas from 242 women and 166 men. Median age was 68 (range 33–89). KRAS mutations were present in 19% (78/408, 95% CI 15 to 23%). The frequency of KRAS mutation was not associated with age or gender. The presence of KRAS mutations was not related to smoking history with 15% (9/61) of never smokers having KRAS mutations compared with 19% (51/275) of former smokers. When compared with never smokers, there was no significant difference in frequency of KRAS mutations for tumors from patients with 1–5 py (5%, p=0.44), 6- 10 py (12%, p=0.99), 11–15 py (25%, p=0.45), 16–25 py (16%, p=0.99), 26–50 py (25%, p=0.129), 51–75 py (20%, p=0.48), &gt;75 py (20%, p=0.47) history of cigarette smoking. Conclusions: While the incidence of EGFR mutations has a strong inverse relationship with the amount of cigarettes smoked, allowing the selective molecular testing for EGFR mutations, the frequency of KRAS mutations cannot be predicted by age, gender, or smoking history. KRAS mutational analysis of all adenocarcinomas is required to reliably identify patients with KRAS mutations. No significant financial relationships to disclose.

Effects of active non-smoking programmes on smoking behaviour in oral precancer patients

Smoking is the commonest risk factor for oral cancer and precancer. The objective of this study was to characterize smoking behaviour and attitude in a cohort of oral precancer patients in Newcastle upon Tyne, UK, and to determine changes in behaviour during diagnosis, treatment and follow-up. Twenty-seven consecutive, smoking patients with dysplastic oral lesions were recruited to the study and a detailed smoking history obtained, quantifying types and numbers of cigarettes smoked, length of smoking history, and changes in smoking behaviour during treatment episodes and long-term follow-up. All patients underwent an interventional management protocol comprising risk-factor education, histopathological diagnosis by incisional biopsy and laser excision of lesions. Patients were followed up for 5 years. Whilst there was a significant decrease in the number of cigarettes smoked at patients’ most recent follow-up compared with initial presentation ( p < 0.001), 74% continued to smoke. Patients received advice from a smoking cessation adviser on support available to them from the local NHS (National Health Service) Stop Smoking services. Six out of 10 patients who set a ‘quit date’ and attended a programme had quit at the 4-week follow-up but only 5 remained non-smokers. Smoking remains a considerable problem in oral precancer patients even after interventional treatment, with the risk of further precancerous lesions and malignant transformation.