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Background: Smoking has been associated with colorectal cancer (CRC) incidence and mortality in previous studies, but current evidence on smoking in association with survival after CRC diagnosis is limited., Methods: We pooled data from 12 345 patients with stage I-IV CRC from 11 epidemiologic studies in the International Survival Analysis in Colorectal Cancer Consortium. Cox proportional hazards regression models were used to evaluate the associations of prediagnostic smoking behavior with overall, CRC-specific, and non-CRC-specific survival., Results: Among 12 345 patients with CRC, 4379 (35.5%) died (2515 from CRC) over a median follow-up time of 7.5 years. Smoking was strongly associated with worse survival in stage I-III patients, whereas no association was observed among stage IV patients. Among stage I-III patients, clear dose-response relationships with all survival outcomes were seen for current smokers. For example, current smokers with 40 or more pack-years had statistically significantly worse overall, CRC-specific, and non-CRC-specific survival compared with never smokers (hazard ratio [HR] =1.94, 95% confidence interval [CI] =1.68 to 2.25; HR = 1.41, 95% CI = 1.12 to 1.78; and HR = 2.67, 95% CI = 2.19 to 3.26, respectively). Similar associations with all survival outcomes were observed for former smokers who had quit for less than 10 years, but only a weak association with non-CRC-specific survival was seen among former smokers who had quit for more than 10 years., Conclusions: This large consortium of CRC patient studies provides compelling evidence that smoking is strongly associated with worse survival of stage I-III CRC patients in a clear dose-response manner. The detrimental effect of smoking was primarily related to noncolorectal cancer events, but current heavy smoking also showed an association with CRC-specific survival., (© The Author(s) 2021. Published by Oxford University Press.)

The changing profile of lifestyles and their intricate relationships with smoking indicate the importance of accounting for smoking status when assessing cancer preventability. We assessed the association of body mass index, weight change, alcohol intake and physical activity with risk of total carcinoma among 53,195 smokers and 62,842 nonsmokers in two prospective cohorts. Then, leveraging the national prevalence estimates, we calculated the population attributable risk (PAR) for healthy lifestyle defined as body mass index ≥18.5 and <27.5 kg/m 2 , mid-life weight change of ≤20 pounds, no or moderate alcohol drinking (≤1 and 2 drinks/day for women and men, respectively) and weekly moderate or vigorous physical activity of at least 150 min. The PAR (95% CI) for healthy lifestyle was 18% (14-22%) in nonsmokers and 14% (10-19%) in smokers among women, and 20% (12-27%) in nonsmokers and 11% (5-17%) in smokers among men. While adiposity accounted for a substantially higher proportion of carcinoma cases in nonsmokers than smokers (16% vs. 2% in women, 15% vs. 2% in men), alcohol contributed more in smokers than nonsmokers (7% vs. 3% in women, 8% vs. 1% in men). When more strict criteria were used to define healthy lifestyle, the PAR estimates further increased (for women: 37% in smokers and 32% in nonsmokers; for men: 15% and 24%, respectively). In conclusion, lifestyle modification has great potential to reduce cancer risk in both smokers and nonsmokers. Weight control and reducing alcohol consumption should be prioritized for cancer prevention in nonsmokers and smokers, respectively., (© 2019 UICC.)

Background: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type., Methods: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression., Results: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR ≥7 drinks/day  = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR ≥5 drinks/day  = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR >0-<0.5 drinks/day  = 0.77, 95% CI: 0.67-0.89; HR >0.5-<1 drinks/day  = 0.57, 95% CI: 0.44-0.73; HR 1-<3 drinks/day  = 0.71, 95% CI: 0.58-0.87), but not ICC., Conclusions: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.

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.)

Objectives: Cigarette smoking has been linked to somatic genetic and epigenetic aberrations, including CpG island methylator phenotype (CIMP)-high, microsatellite instability (MSI)-high and BRAF mutation. These molecular features have been associated with synchronous primary colorectal cancers (CRCs). Thus, we examined the hypothesis that smoking might be associated with the risk of synchronous CRCs., Methods: Within the Health Professionals Follow-up Study and Nurses' Health Study, we examined the relationship of smoking and incidence of CRC according to tumor synchronicity, using duplication-method Cox proportional hazards regression analysis., Results: We confirmed 1,981 solitary CRC and 45 synchronous CRC cases during follow-up of 134,305 individuals. CRC risk associated with smoking differed significantly by tumor synchronicity status (P heterogeneity <0.001). When comparing current smokers with never smokers, multivariable hazard ratios (HR) were 5.27 (95% confidence interval (CI), 2.08-13.40) for synchronous CRCs and 0.97 (95% CI, 0.83-1.14) for solitary CRC. Similarly, differential associations were observed when examining cumulative pack-years smoked (P heterogeneity =0.006). Smoking cessation for ≥10 years relative to current smoking might reduce the risk of synchronous CRCs (multivariable HR=0.42; 95% CI, 0.19-0.95), but not solitary CRC (multivariable HR=1.10; 95% CI, 0.94-1.29; P heterogeneity =0.001). Comparing current and former smokers with never smokers, multivariable HRs for synchronous CRCs were significantly higher than those of solitary CRC positive for either CIMP-high, MSI-high, or BRAF mutation (P heterogeneity =0.002)., Conclusions: Smoking is associated with an elevated risk of synchronous CRCs. Our data support a model where smoking contributes to an etiologic field effect that favors these somatic molecular alterations and the development of multiple primary tumors.

Importance: Lifestyle factors are important for cancer development. However, a recent study has been interpreted to suggest that random mutations during stem cell divisions are the major contributor to human cancer., Objective: To estimate the proportion of cases and deaths of carcinoma (all cancers except skin, brain, lymphatic, hematologic, and nonfatal prostate malignancies) among whites in the United States that can be potentially prevented by lifestyle modification., Design, Setting, and Participants: This prospective cohort study analyzes cancer and lifestyle data from the Nurses' Health Study, the Health Professionals Follow-up Study, and US national cancer statistics to evaluate associations between lifestyle and cancer incidence and mortality., Exposures: A healthy lifestyle pattern was defined as never or past smoking (pack-years <5), no or moderate alcohol drinking (≤1 drink/d for women, ≤2 drinks/d for men), BMI of at least 18.5 but lower than 27.5, and weekly aerobic physical activity of at least 75 vigorous-intensity or 150 moderate-intensity minutes. Participants meeting all 4 of these criteria made up the low-risk group; all others, the high-risk group., Main Outcomes and Measures: We calculated the population-attributable risk (PAR) by comparing incidence and mortality of total and major individual carcinomas between the low- and high-risk groups. We further assessed the PAR at the national scale by comparing the low-risk group with the US population., Results: A total of 89 571 women and 46 339 men from 2 cohorts were included in the study: 16 531 women and 11 731 men had a healthy lifestyle pattern (low-risk group), and the remaining 73 040 women and 34 608 men made up the high-risk group. Within the 2 cohorts, the PARs for incidence and mortality of total carcinoma were 25% and 48% in women, and 33% and 44% in men, respectively. For individual cancers, the respective PARs in women and men were 82% and 78% for lung, 29% and 20% for colon and rectum, 30% and 29% for pancreas, and 36% and 44% for bladder. Similar estimates were obtained for mortality. The PARs were 4% and 12% for breast cancer incidence and mortality, and 21% for fatal prostate cancer. Substantially higher PARs were obtained when the low-risk group was compared with the US population. For example, the PARs in women and men were 41% and 63% for incidence of total carcinoma, and 60% and 59% for colorectal cancer, respectively., Conclusions and Relevance: A substantial cancer burden may be prevented through lifestyle modification. Primary prevention should remain a priority for cancer control., Competing Interests: Disclosures: None.

Background: Many modifiable lifestyle factors have been associated with colon cancer risk, but less is known about their effect on disease when considered together. Estimating the proportion of colon cancer cases that could be prevented by the adoption of combined modifiable lifestyle behaviors will provide important insights into disease prevention., Methods: In the Nurses' Health Study, we defined a low-risk group according to a combination of six factors: body mass index < 25 kg/m(2), physical activity of ≥ 21 metabolic equivalent of task per week, alcohol consumption ≤ 30 g/day, cigarette smoking <10 pack-years before the age of 30, current use of multivitamins for ≥ 15 years, and total calcium intake ≥ 700 mg/day. A composite risk score index was created and the population attributable risk (PAR%) was calculated after accounting for other known risk or protective factors., Results: We documented 1,127 colon cancer cases among 81,092 over 24 years of follow-up. Compared with women in the lowest risk category, the women at all other exposure levels had a hazard ratio of colon cancer of 1.81 (95% confidence interval 1.15-2.85). The score index was significantly and linearly related to an increasing risk of colon cancer (p value for trend <0.0001). The PAR% of the six risk factors considered together in relation to colon cancer was 0.37 (95% CI 0.09-0.60). When regular aspirin use (two tablets/week for six or more years) was included with the other low-risk behaviors, the PAR% increased to 0.43 (95% CI 0.14-0.65)., Conclusions: Beyond the known benefit from colonoscopy/sigmoidoscopy, key behavior modifications and adherence to a healthy lifestyle could avoid approximately 37% of colon cancer cases among women.

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.)

Background: Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer (CRC). What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for CRC modify this association., Methods: We conducted a pooled analysis of eight studies, including 6,796 CRC cases and 7,770 controls, to evaluate the association between cigarette smoking history and CRC risk and to investigate potential effect modification by other risk factors., Results: Current smokers [OR, 1.26; 95% confidence interval (CI), 1.11-1.43] and former smokers (OR, 1.18; 95% CI, 1.09-1.27), relative to never smokers, showed higher risks of CRC. Former smokers remained at higher CRC risk, relative to never smokers, for up to about 25 years after quitting. The impact of time since quitting varied by cancer subsite: The excess risk due to smoking decreased immediately after quitting for proximal colon and rectal cancer but not until about 20 years post-quitting for distal colon cancer. Furthermore, we observed borderline statistically significant additive interactions between smoking status and body mass index [BMI; relative excess risk due to interaction (RERI]), 0.15; 95% CI, -0.01 to 0.31; P = 0.06] and significant additive interaction between smoking status and fruit consumption (RERI, 0.16; 95% CI, 0.01-0.30; P = 0.04)., Conclusion: CRC risk remained increased for about 25 years after quitting smoking, and the pattern of decline in risk varied by cancer subsite. BMI and fruit intake modified the risk associated with smoking., Impact: These results contribute to a better understanding of the mechanisms through which smoking impacts CRC etiology., (©2012 AACR.)

Context: Studies of smoking in relation to prostate cancer mortality or recurrence in prostate cancer patients are limited, with few prostate cancer-specific outcomes., Objective: To assess the relation of cigarette smoking and smoking cessation with overall, prostate cancer-specific, and cardiovascular disease (CVD) mortality and biochemical recurrence among men with prostate cancer., Design, Setting, and Participants: Prospective observational study of 5366 men diagnosed with prostate cancer between 1986 and 2006 in the Health Professionals Follow-Up Study., Main Outcome Measures: Hazard ratios (HRs) for overall, prostate cancer-specific, and CVD mortality, and biochemical recurrence, defined by an increase in prostate-specific antigen (PSA) levels., Results: There were 1630 deaths, 524 (32%) due to prostate cancer and 416 (26%) to CVD, and 878 biochemical recurrences. Absolute crude rates for prostate cancer-specific death for never vs current smokers were 9.6 vs 15.3 per 1000 person-years; for all-cause mortality, the corresponding rates were 27.3 and 53.0 per 1000 person-years. In multivariable analysis, current vs never smokers had an increased risk of prostate cancer mortality (HR, 1.61; 95% confidence interval [CI], 1.11-2.32), as did current smokers with clinical stage T1 through T3 (HR, 1.80; 95% CI, 1.04-3.12). Current smokers also had increased risk of biochemical recurrence (HR, 1.61; 95% CI, 1.16-2.22), total mortality (HR, 2.28; 95% CI, 1.87-2.80), and CVD mortality (HR, 2.13; 95% CI, 1.39-3.26). After adjusting for clinical stage and grade (likely intermediates of the relation of smoking with prostate cancer recurrence and survival), current smokers had increased risk of prostate cancer mortality (HR, 1.38; 95% CI, 0.94-2.03), as did current smokers with clinical stage T1 through T3 (HR, 1.41; 95% CI, 0.80-2.49); they also had an increased risk of biochemical recurrence (HR, 1.47; 95% CI, 1.06-2.04). Greater number of pack-years was associated with significantly increased risk of prostate cancer mortality but not biochemical recurrence. Current smokers of 40 or more pack-years vs never smokers had increased prostate cancer mortality (HR, 1.82; 95% CI, 1.03-3.20) and biochemical recurrence (HR, 1.48; 95% CI, 0.88-2.48). Compared with current smokers, those who had quit smoking for 10 or more years (HR, 0.60; 95% CI, 0.42-0.87) or who have quit for less than 10 years but smoked less than 20 pack-years (HR, 0.64; 95% CI, 0.28-1.45) had prostate cancer mortality risks similar to never smokers (HR, 0.61; 95% CI, 0.42-0.88)., Conclusions: Smoking at the time of prostate cancer diagnosis is associated with increased overall and CVD mortality and prostate cancer-specific mortality and recurrence. Men who have quit for at least 10 years have prostate cancer-specific mortality risks similar to those who have never smoked.

Although tobacco use has been recognized as one of the leading causes of cancer morbidity and mortality, a role of smoking in the occurrence of prostate cancer has not been established. However, evidence indicates that factors that influence the incidence of prostate cancer may differ from those that influence progression and fatality from the disease. Thus, we reviewed and summarized results from prospective cohort studies that assessed the relation between smoking and fatal prostate cancer risk, as well as epidemiological and clinical studies that focused on aggressive behavior in prostate cancer, such as poorer survival, advanced stage, or poorer differentiation at diagnosis. The majority of the prospective cohort studies showed that current smoking is associated with a moderate increase of ~30% in fatal prostate cancer risk compared to never/non-smokers. This association is likely to be an underestimate of the effect of smoking because most studies had a single assessment of smoking at baseline and long follow-up times, and the association was considerably stronger in some sub-groups of heaviest smokers, or when smoking was assessed in a relatively short period (within 10 years) prior to cancer mortality. Using aggressive behavior of prostate cancer as outcome, current smoking was associated with significantly elevated risk, ranging from around twofold to threefold or higher. Although alternative explanations, such as publication bias, residual confounding, screening bias, and the influence of smoking-related comorbidities cannot be ruled out entirely, these findings suggest that smoking is associated with aggressive behavior of prostate cancers or with a sub-group of rapidly progressing prostate cancer. Based on evidence presented in this review, cigarette smoking is likely to be a risk factor for prostate cancer progression and should be considered as a relevant exposure in prostate cancer research and prevention of mortality from this cancer.

The association between cigarette smoking and colorectal cancer (CRC) has been controversial. To synthesize the available data, we conducted a comprehensive meta-analysis of all prospective studies. A total of 36 studies were included in our meta-analysis. We examined the association between smoking and CRC, colon cancer and rectal cancer in terms of incidence and mortality. Separate analyses were conducted for smoking status, daily cigarette consumption, duration, pack-years and age of initiation. Relative to nonsmokers, current and former smokers had a significantly increased risk of CRC incidence and mortality, respectively. When CRC data were combined with colon/rectal cancer data, current smokers had a significantly increased risk of CRC incidence. All 4 dose-response variables examined-daily cigarette consumption (RR = 1.38 for an increase of 40 cigarettes/day), duration (RR = 1.20 for an increase of 40 years of duration), pack-years (RR = 1.51 for an increase of 60 pack-years) and age of initiation (RR = 0.96 for a delay of 10 years in smoking initiation)-were significantly associated with CRC incidence (all p-values < 0.0001). The relationship between duration of smoking and rectal cancer incidence was also significant. Among the subset of studies that distinguished cancer by site, a higher risk was seen for rectal cancer than for colon cancer for all analyses. Among prospective studies, a consistent association exists between smoking and CRC. The association is stronger for rectal cancer than for colon cancer in the subset of studies that differentiated cancer by site., ((c) 2008 Wiley-Liss, Inc.)

Microsomal epoxide hydrolase (mEH) and cytochrome P450 2C9 (CYP2C9) are involved in the bioactivation and detoxification of polycyclic aromatic hydrocarbons (PAHs) derived from tobacco smoke. Two coding-region mEH variants (Tyr113His, His139Arg) and CYP2C9 variants (Arg144Cys, Ile359Leu) have been described and affect enzyme specific activity. We investigated these polymorphisms and tested interactions with smoking in relationship to risk of colorectal carcinoma in two case-control studies nested in the Nurses' Health Study (NHS) and Physicians' Health Study (PHS) cohorts. mEH Tyr113His and His139Arg polymorphisms were not associated with the risk of cancer among 197 incident cases and 490 controls from the NHS. Among 273 incident cases and 453 controls from the PHS, carrying one or two copies of the 'rapid' 139Arg allele was associated with a significantly reduced risk of colorectal cancer (OR=0.70, 95% CI 0.49--0.99) when compared with His139 wild-type individuals. Risk of colorectal cancer was significantly reduced among men carrying the CYP2C9 *1/*2 genotype (OR=0.62, 95% CI 0.42--0.92) or at least one CYP2C9 variant allele (OR=0.72, 95% CI 0.52--1.00) when compared with *1/*1 wild-type individuals. For women, carrying at least one variant CYP2C9 allele was inversely associated with the risk of colorectal cancer (OR=0.85, 95% CI, 0.57--1.27) when compared with *1/*1 wild-type individuals. No statistically significant genotype-smoking or gene-gene interactions were found in this study. Our results indicate that individuals exposed to tobacco carcinogens were at increased risk of colorectal cancer and that overall risk is related to mEH and CYP2C9 genotype, although the results were not consistent between men and women., ((c) 2005 Wiley-Liss, Inc.)

Objectives: To examine the association of cigarette smoking, alcohol consumption and physical activity with lower urinary tract symptoms (LUTS) in older men., Subjects and Methods: The study included 2797 men participating in the Third National Health and Nutrition Examination Survey (NHANES III), who were aged > or = 60 years. During an interview, LUTS, smoking history, alcohol consumption and physical activity were assessed. Cases comprised men with at least three of the symptoms of nocturia, hesitancy, weak stream and incomplete emptying. Men who had had prostate surgery unrelated to cancer were not included as cases. Controls were men with no symptoms or surgery. We adjusted for age and race in logistic regression models and used sampling weights to account for selection probability., Results: Current cigarette smokers had no higher odds of LUTS than 'never' smokers, but former heavy smokers (> or = 50 pack-years) had a higher odds of LUTS than never smokers (odds ratio 2.01; 95% confidence interval 1.04-3.89). Men who drank alcohol daily had a lower chance of LUTS than non-drinkers (0.59; 0.37-0.95; P trend, 0.07). All levels of moderate and vigorous activity were statistically significantly inversely associated with LUTS (P trend, 0.06), whereas men who reported no leisure-time physical activity had a greater odds of LUTS (2.06; 1.26-3.39)., Conclusions: Moderate alcohol consumption and physical activity may be protective against LUTS. Current cigarette smoking was not consistently associated with the condition. The possible association in former smokers warrants further investigation.

Epidemiologic evidence indicates an inverse association of folate intake with risk of colorectal cancer, but whether this association is modified by intake of caffeine (in coffee and tea) or cigarette smoking--factors that possibly interfere with folate--has not been studied. Thus, we examined whether the association between dietary folate intake and incidence of colorectal cancer is modified by caffeine intake and smoking. Cox proportional hazards modeling was used to estimate rate ratios relating dietary folate intake to colorectal cancer incidence among 61,433 women ages 40 to 75 years at recruitment into the Swedish Mammography Cohort in 1987 to 1990. From March 1987 through June 2004, a total of 805 incident cases of colorectal cancer were diagnosed. After controlling for age and other potential confounders, we observed an inverse association between dietary folate intake and risk of colon cancer (rate ratio for the highest versus the lowest quintile, 0.61; 95% confidence interval, 0.41-0.91; P(trend) = 0.02), but not of rectal cancer (rate ratio, 0.93; 95% confidence interval, 0.55-1.56; P(trend) = 0.97). The inverse association between dietary folate intake and colon cancer risk was most pronounced among smokers (P(interaction) = 0.03). We found no apparent modification of risk by caffeine intake. Findings from this population-based cohort study support an inverse association between dietary folate intake and risk of colon cancer and suggest that smokers might benefit most from a high dietary folate intake.

Microsomal epoxide hydrolase (mEH) is involved in the bioactivation and detoxification of polycyclic aromatic hydrocarbons derived from tobacco smoke and charred meat intake. Two coding region mEH variants located in exon 3 (Tyr113His) and exon 4 (His139Arg) have been described and may affect the enzyme's specific activity. We investigated these polymorphisms and tested interactions with smoking and charred meat intake in relation to risk of colorectal adenoma in two case-control studies nested in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts. mEH exon 3 and exon 4 polymorphisms were not associated with overall risk of adenoma among 556 incident cases and 557 controls from the NHS or 376 prevalent cases and 725 controls from the HPFS. A statistically significant interaction was found between the exon 4 polymorphism and smoking for men (P = 0.03) and a borderline significant interaction was found between the exon 3 polymorphism and smoking for women (P = 0.06). Women having the exon 3 'rapid' Tyr/Tyr genotype were at increased risk when exposed to either > or =25 pack-years smoking [relative risk (RR) = 2.43, 95% confidence interval (CI) 1.47-4.01] or <25 pack-years of smoking (RR = 1.73, 95% CI 1.10-2.73) relative to non-smokers. Men with the exon 4 'slow' His/His genotype were at increased risk when exposed to > or =25 pack-years smoking (RR = 2.21, 95% CI 1.43, 3.41) or <25 pack-years smoking (RR = 1.71, 95% CI 1.13-2.59) relative to non-smokers. Charred meat intake was not associated with adenoma risk and there was no significant interaction with either mEH polymorphism. Our results indicate that individuals exposed to > or =25 pack-years smoking were at increased risk for colorectal adenoma and that risk is related to dose of tobacco carcinogens and mEH activity level, but the results were not consistent between men and women.

Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk.

There is some evidence that alpha-linolenic acid might be positively related to prostate cancer risk. Associations between serum fatty acid composition as well as fatty acid intakes and prostate cancer risk were examined in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. The cohort included 29,133 male smokers aged 50-69 years. During 5-8 years of follow-up, 246 prostate cancer cases were diagnosed. One control was selected and matched by age (+/- 1 month) for each case from the cohort subjects alive and free of prostate cancer at the time the case was diagnosed. This study included 198 case-control pairs with baseline serum sample available for both. Fatty acids of serum cholesterol esters were measured as a percentage of total fatty acids, using capillary gas chromatography. Intakes of fatty acids were assessed from a validated self-administered dietary questionnaire. Serum and dietary fatty acids had no consistent association with prostate cancer risk. Serum alpha-linolenic acid was not related to prostate cancer risk. Twofold risk was found in the highest quartile of serum myristic acid compared with the lowest quartile (odds ratio, 1.93; 95% confidence interval, 1.02-3.64). alpha-Tocopherol supplementation modified the association between serum linoleic acid and prostate cancer risk (P for interaction 0.03); odds ratio was 0.17 (95% confidence interval, 0.04-0.68) in the highest quartile of serum linoleic acid compared with the lowest quartile in men who received alpha-tocopherol, whereas no association was found in men who did not receive alpha-tocopherol. In conclusion, we found no overall association between serum or dietary alpha-linolenic acid or any other unsaturated fatty acid and prostate cancer risk, but high serum linoleic acid was associated with lower risk in men supplemented with alpha-tocopherol. High serum myristic acid associated with an increased risk of prostate cancer.

Carcinogens from tobacco reach the colorectal mucosa through either the alimentary tract or the circulatory system and could possibly damage or alter expression of important cancer-related genes. Twenty-one of 22 studies found that long-term, heavy cigarette smokers have a 2-3-fold elevated risk of colorectal adenoma. Risk of large adenomas, immediate cancer precursors, was elevated in smokers in 12 of 12 studies. The studies of smoking and colorectal cancer risk conducted earlier in the twentieth century consistently did not show any association. However, 27 studies in various countries, including the vast majority of those that have been analyzed in the past several years, now show an association between tobacco use and colorectal cancer. In the United States, 15 of 16 studies conducted after 1970 in middle-age men and elderly men and, in the 1990s, in women demonstrate an association. This temporal pattern is consistent with an induction period of three to four decades between genotoxic exposure and the diagnosis of colorectal cancer and with men as a group having begun smoking several decades earlier than women. Overall, accumulating evidence, much within the past decade, strongly supports the addition of colorectal cancer to the list of tobacco-associated malignancies and the possibility that up to one in five colorectal cancers in the United States may be potentially attributable to tobacco use.

Studies that have examined the relationship between cigarette use and prostate cancer incidence have yielded inconsistent results, although most studies have suggested that smoking is related to the occurrence of fatal prostate cancer. We evaluated prospectively the relationship between cigarette smoking and total, distant metastatic, and fatal prostate cancer in 47,781 male health professionals throughout the United States followed with questionnaires. From 1986 to 1994, we documented 1369 men with prostate cancer (excluding stage A1). One hundred fifty-two of the men had distant metastatic disease at diagnosis, and 103 fatal cases occurred from 1986 to 1994. Early (before age 30), late (within recent 10 years), and lifetime cumulative smoking history were unrelated to risk of total prostate cancer. However, men who had smoked 15 or more pack-years of cigarettes within the preceding 10 years were at higher risk of distant metastatic prostate cancer [multivariate relative risk (RR), 1.81; 95% confidence interval (CI), 1.05-3.11; P (trend), 0.03] and fatal prostate cancer [RR, 2.06; CI, 1.08-3.90; P (trend), 0.02] relative to nonsmokers. Within 10 years after quitting, the excess risk among smokers is eliminated. The higher rate of fatal prostate cancer among smokers did not appear to result from confounding by diet or other lifestyle factors, different screening behavior between smokers and nonsmokers, or from other smoking-related comorbidities. Our results indicate that although smoking was unrelated to prostate cancer incidence, recent tobacco use had a substantial impact on the occurrence of fatal prostate cancer.

Alcohol consumption and cigarette smoking were evaluated in relation to development of benign prostatic hyperplasia (BPH) among 29,386 members of the Health Professionals Follow-up Study. Men who were 40-75 years old in 1986 and free of prior BPH surgery, diagnosed cancer at baseline, and prostate cancer at baseline and during follow-up were followed for incidence of BPH surgery from 1986 to 1994. Cases were men who reported BPH surgery between 1986 and 1994 (n = 1,813) or who scored > or = 15 points of 35 on seven lower urinary tract symptom questions modified from the American Urological Association symptom index in 1992 and 1994 (n = 1,786); noncases were men who scored < or = 7 points (n = 20,840). After controlling for age, race/ethnicity, body mass index, physical activity, and mutually for alcohol intake and smoking, moderate alcohol consumption was inversely related with total BPH (30.1-50 g/day vs. 0: odds ratio (OR) = 0.59, 95% confidence interval (CI) 0.51-0.70; p trend < 0.0001), although the relation was attenuated at high intake (> or = 50.1 g/day vs. 0: OR = 0.72, 95% CI 0.57-0.90). Current cigarette smoking was positively related to total BPH only among those who smoked 35 or more cigarettes/day (compared with never smokers: OR = 1.45, 95% CI 1.07-1.97). These findings suggest that moderate alcohol consumption and avoidance of smoking may benefit BPH.

The associations between smoking, caffeine, and alcohol intake and the risk of duodenal ulcer have rarely been investigated prospectively. We examined these associations in a prospective cohort of 47,806 men, 40-75 years of age, using a mailed baseline questionnaire in 1986, with follow-up every 2 years through 1992. During 6 years of follow-up, we documented 138 newly diagnosed cases of duodenal ulcer. After adjustment for age, energy-adjusted dietary fiber, body mass index, and use of aspirin or other nonsteroidal antiinflammatory drugs, current smoking was not associated with a substantial risk of duodenal ulcer [relative risk (RR) = 1.07; 95% confidence interval (CI) = 0.61-1.89]. Overall, past smokers were not at increased risk compared with never-smokers (RR = 0.99; 95% CI = 0.69-1.42). Adjusting for other risk factors, alcohol intake (comparing those who drink > 30 gm of alcohol per day to nondrinkers) was not associated with higher risk of duodenal ulcer (RR = 0.74; 95% CI = 0.42-1.29). We observed little association between caffeine, caffeine-containing beverages, and decaffeinated coffee and the risk of duodenal ulcer. These results indicate that smoking is not associated with a substantial increase in risk of duodenal ulcer, nor is high intake of alcohol and caffeine.

Although tobacco has been clearly implicated as a cause of a number of cancers, earlier studies had not generally found cigarette smokers to be at higher risk for cancers of the large bowel. Unlike the earlier studies, more recent studies have tended to find cigarette smokers to be at higher risk of colorectal cancer. In addition, cigarette smoking has been consistently associated with a higher risk of colorectal adenomas, precursors of cancers. We hypothesize that smoking is an initiator of colorectal carcinogenesis. The consistent finding of a positive association between smoking and risk of adenomas may reflect the presumably shorter induction period for these lesions. Recent studies indicate that an increased risk for large-bowel cancer emerges only after about four decades after one begins smoking, perhaps accounting for the null studies that were conducted earlier during the smoking epidemic. Most studies had not taken into account an induction period between timing of smoking and risk for cancer. The increasing male-to-female mortality ratio from colorectal cancer over the latter half of this century in the United States may have been a result of tobacco use by men earlier in the century. If the associations observed with colorectal adenomas and cancers in recent studies are causal, approximately 20% of the large-bowel cancers in men would be attributable to smoking. On the basis of the strength of the available evidence, intensified effort to prevent smoking among young people is warranted.

Objectives: To prospectively examine the excess incidence of pancreatic cancer among cigarette smokers and to examine the influence of smoking cessation on the risk of pancreatic cancer., Methods: We obtained data on cigarette smoking and other risk factors for pancreatic cancer from 118,339 women aged 30 to 55 years and 49,428 men aged 40 to 75 years who were without diagnosed cancer. During the 2,116,229 persons-years of follow-up, pancreatic cancer was diagnosed in 186 participants., Results: The multivariate relative risk of pancreatic cancer for current smokers was 2.5 (95% confidence interval, 1.7-3.6). A significant, positive trend in risk with increasing pack-years of smoking was observed (P for trend = .004), although this association was confined to cigarette consumption within the past 15 years. Compared with participants who continued to smoke, former smokers had a 48% reduction in pancreatic cancer risk within 2 years of quitting. Ultimately, the relative risk of pancreatic cancer among former smokers approached that for never smokers after less than 10 years of smoking cessation. Overall, the proportion of pancreatic cancers attributable to cigarette smoking was 25%., Conclusions: Cigarette smoking is associated with an increased risk of pancreatic cancer. The rapid reduction in risk associated with quitting suggests that smoking cessation could eliminate 25% of the 27,000 deaths from pancreatic cancer occurring annually in the United States.

The relationship between smoking, caffeine, and alcohol intake and the risk of symptomatic diverticular disease has not been investigated directly. We examined these associations in a prospective cohort of 47,678 US men, 40 to 75 years old. During 4 years of follow-up (1988 to 1992), we documented 382 newly diagnosed cases of symptomatic diverticular disease. After adjustments for age, physical activity, and energy-adjusted intake of dietary fiber and total fat, alcohol intake (comparing those who drink > 30 g of alcohol/d to nondrinkers) was only weakly and nonsignificantly associated with risk of symptomatic diverticular disease (relative risk (RR) = 1.36; 95 percent confidence interval (CI), 0.94 to 1.97; P for trend = 0.37). We observed no association between caffeine, specific caffeinated beverages, and decaffeinated coffee and the risk of symptomatic diverticular disease. Current smoking was not appreciably associated with risk of symptomatic diverticular disease compared to nonsmokers (RR = 1.25; 95 percent CI, 0.75 to 2.09) after adjustment for age, physical activity, and energy-adjusted intake of dietary fiber and total fat. In a subset analysis restricted to men who had undergone sigmoidoscopy or colonoscopy, a modest positive association was seen between smoking and risk of symptomatic diverticular disease. These results suggest that smoking, caffeine, and alcohol intake are not associated with any substantially increased risk of symptomatic diverticular disease.

Background: A positive correlation between smoking and colorectal cancer has been reported for men, but not for women, who began smoking in substantial numbers in the late 1940s and early 1950s. We hypothesized that smoking acts as an initiator of colorectal neoplasia and that an association with cancer in women has been missed because of the long period between initiation and diagnosis of cancer., Purpose: Our purpose was to assess the association between smoking and risk of colorectal adenoma and colorectal cancer in women and to estimate the minimum induction period between the onset of smoking and cancer diagnosis., Methods: Our data came from the ongoing Nurses' Health Study, in which current and lifetime smoking histories and other potential confounding factors were assessed by questionnaire at baseline and at 2-year intervals. We documented 586 new cases of colorectal cancer from 1976 to 1990 from a group of 118,334 women and 564 new cases of adenoma among 12,143 women who had a first colonoscopy or sigmoidoscopy between 1980 and 1990. We then assessed the relative risk (RR) of small adenoma, large adenoma (> or = 1 cm), and colorectal cancer in terms of pack-years of smoking., Results: The amount smoked in the prior 20 years was related to the prevalence of small adenomas (multivariate RR = 1.45; 95% confidence interval [CI] = 1.25-1.68; P < .0001) and less strongly with large adenomas (RR = 1.31; 95% CI = 1.17-1.47; P < .0001), adjusting for age, intake of saturated fat, dietary fiber, folate, and alcohol, body mass, family history of colorectal cancer, and pack-years of cigarettes smoked within the prior 20 years. Pack-years of cigarettes smoked more than 20 years in the past was associated with risk of large adenoma (multivariate RR for a 20 pack-year increment = 1.29; 95% CI = 1.01-1.64; P trend = .04), but not of small adenoma (RR = 1.11; 95% CI = 0.93-1.34). Cigarette smoking was unrelated to colorectal cancer until 35 years after smoking began, but then became progressively more strongly related with time. Among women who had started smoking more than 10 cigarettes per day 35-39 years in the past, the RR for cancer was 1.47 (95% CI = 1.07-2.01), progressing to 1.63 (95% CI = 1.14-2.33) after 40-44 years and 2.00 (95% CI = 1.14-3.49) after 45 years., Conclusions: Because the minimum induction period for colorectal cancer appears to be at least 35 years, an association between smoking and colorectal cancer in women may just now be showing up., Implications: Our findings suggest that cigarette smoking may be a previously unrecognized, preventable cause of colorectal cancer among women.

Background: Epidemiologic studies of men consistently demonstrate a positive association between tobacco smoking and risk of colorectal adenomas, precursors of cancer, but have not consistently shown an association between smoking and colorectal cancer. We hypothesized that smoking acts as an initiator of colorectal neoplasia and that the association with cancer has been obscured because the time is long between onset of smoking and diagnosis of cancer., Purpose: Our purpose was to examine the association between cigarette smoking and risk of colorectal adenoma and colorectal cancer in men and to estimate the minimum induction period between the start of smoking and the diagnosis of cancer., Methods: Using data from the ongoing Health Professionals Follow-up Study, we assessed the relative risk (RR) of small adenoma, large adenoma (> or = 1 cm), and cancer according to pack-years of smoking. Current and lifetime histories of smoking and other confounding factors were assessed by questionnaire at baseline and at 2-year intervals. Between 1986 and 1992, we documented 238 new cases of colorectal cancer among 47,935 U.S. males and 626 new cases of colorectal adenomas among 12,854 of the men who had a sigmoidoscopy or colonoscopy., Results: Smoking during the prior two decades was associated with the prevalence of small adenomas (RR = 2.96; 95% confidence interval [CI] = 1.47-5.98; for > or = 35 pack-years versus 0 pack-years within the 20 years preceding the endoscopy, P trend = .04) but not with large adenomas (RR = 0.46; 95% CI = 0.11-1.94; P trend = .56). However, smoking more than 20 years in the past was associated with large adenomas (RR = 2.38; 95% CI = 1.56-3.63; P trend = .004 for smoking > or = 16 pack-years versus 0 pack-years). Smoking was related to risk of colorectal cancer only after allowing for an induction period of at least 35 years (RR = 1.94; 95% CI = 1.13-3.35; P trend = .008 for smoking > or = 16 versus 0 pack-years more than 35 years in the past)., Conclusions: Smoking in the prior 20 years has a strong relation to small colorectal adenomas, smoking at least 20 years in the past is related to larger adenomas, and the induction period for colorectal cancers is at least 35 years., Implications: Our results highlight the need to intensify efforts to prevent smoking, especially among the young, and suggest a reduced threshold for screening for colorectal cancer among long-term smokers.

Background:Increasing nut intake has been associated with reduced risk of diabetes mellitus, which is a risk factor for pancreatic cancer.Methods:We prospectively followed 75 680 women in the Nurses' Health Study, and examined the association between nut consumption and pancreatic cancer risk. Participants with a previous history of cancer were excluded. Nut consumption was assessed at baseline and updated every 2 to 4 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models.Results:We documented 466 incident cases of pancreatic cancer. After adjusting for age, height, smoking, physical activity, and total energy intake, women who consumed a 28-g (1 oz) serving size of nuts 2 times per week experienced a significantly lower risk of pancreatic cancer (RR, 0.65; 95% CI, 0.47-0.92; P for trend=0.007) when compared with those who largely abstained from nuts. The results did not appreciably change after further adjustment for body mass index (BMI) and history of diabetes mellitus (RR, 0.68; 95% CI, 0.48-0.95; P for trend=0.01). The inverse association persisted within strata defined by BMI, physical activity, smoking, and intakes of red meat, fruits, and vegetables.Conclusion:Frequent nut consumption is inversely associated with risk of pancreatic cancer in this large prospective cohort of women, independent of other potential risk factors for pancreatic cancer. [ABSTRACT FROM AUTHOR]

Background: Studies evaluating vitamin D status in relation to pancreatic cancer risk have yielded inconsistent results.Methods: We prospectively followed 118 597 participants in the Nurses' Health Study and Health Professionals Follow-up Study from 1986 to 2006. We calculated a 25-hydroxyvitamin D (25(OH)D) score from known predictors of vitamin D status for each individual and then examined the predicted 25(OH)D levels in relation to pancreatic cancer risk. Relative risks (RRs) and 95% confidence intervals (95% CIs) were estimated using Cox proportional hazards models adjusted for age, sex, race, height, smoking, and diabetes. We then further adjusted for body mass index (BMI) and physical activity in a sensitivity analysis.Results: During 20 years of follow-up, we identified 575 incident pancreatic cancer cases. Higher 25(OH)D score was associated with a significant reduction in pancreatic cancer risk; compared with the lowest quintile, participants in the highest quintile of 25(OH)D score had an adjusted RR of 0.65 (95% CI=0.50-0.86; P(trend)=0.001). Results were similar when we further adjusted for BMI and physical activity.Conclusions: Higher 25(OH)D score was associated with a lower risk of pancreatic cancer in these two prospective cohort studies. [ABSTRACT FROM AUTHOR]

The article presents a study related to colorectal adenomas in men. Adenomas larger than 1 cm, with a villous histology or severe dysplasia are postulated to have the highest risk of progression to colorectal cancer. Logistic regression was used to compare the distribution of risk factors between advanced and non-advanced adenomas, and controls. Smoking at baseline was more strongly associated with advanced than with non-advanced adenomas; past smoking was positively associated with both to a similar extent, and a family history of colorectal cancer was also similarly associated with increased risk of advanced and non-advanced adenomas.

Background At the population level, it is useful to estimate the liver cancer risk based on lifestyle factors and regular biomarkers to encourage high-risk people to be screened. Therefore, we conducted the current study to develop a prediction model for the stratification of liver cancer risk among the general population in China. Methods 112 440 subjects aged 20-80 years from Kailuan Cohort were included in the current study. A total of 326 incident primary liver cancer occurred during 913 078.51 person-years of follow-up. We used the Cox proportional hazards regression model to obtain coefficients for each predictor in the 8-year prediction models among a random two thirds of participants. The prediction models were validated in the remaining one third of participants. Hosmer-Lemeshow's statistic and Harrell's C-index were used to evaluate calibration and discrimination, respectively. Results A full prediction model that comprised of nine predictors, including age, sex, smoking pack-years, alcohol drinking, tea consumption, diabetes and fasting blood glucose (FBG) level, total cholesterol (TC), alanine aminotransferase (ALT), and hepatitis B virus surface antigen (HBsAg), was derived. The model showed good calibration (χ2=3.57, P = 0.89) and discrimination (Harrell's C-index=0.85; 95% confidence interval [CI]: 0.81, 0.88) in the validation data set. Conclusions A practical liver prediction model based on accessible indicators combined with lifestyle factors, regular blood biomarkers, and hepatitis virus status was developed, which allows to stratify the risk of liver cancer among the general population. Because the factors in this model are able to be acquired from questionnaire and blood detection, it has great potential to be translated into practical use for public health. Legal entity responsible for the study The authors. Funding National Key R& D Program. Disclosure All authors have declared no conflicts of interest. [ABSTRACT FROM AUTHOR]