Reduced Risk Of Lung Cancer Research Articles

Red meat, Mediterranean diet and lung cancer risk among heavy smokers in the COSMOS screening study

BackgroundTo assess whether intake of selected foods and food groups and adherence to a Mediterranean diet are associated with lung cancer risk in heavy smokers. Patients and methodsIn the context of a lung cancer screening programme, we invited asymptomatic volunteers, aged 50 years or more, current smokers or recent quitters, who had smoked at least 20 pack-years, to undergo annual low-dose computed tomography. We assessed participants' diet at baseline using a self-administered food frequency questionnaire and calculated their average daily food intake using an ad hoc computer program and determined their alternate Mediterranean diet (aMED) score. We used Cox proportional hazards regression to assess the association between selected food items, beverages and the aMED score and lung cancer risk. ResultsDuring a mean screening period of 5.7 years, 178 of 4336 participants were diagnosed with lung cancer. At multivariable analysis, red meat consumption was associated with an increased risk of lung cancer [hazard ratio (HR) Q4 versus Q1, 1.73; 95% confidence interval (CI) 1.15–2.61; P-value for trend 0.002], while tea consumption (HR for one or more cup/day versus none, 0.56; 95% CI 0.31–0.99; P-value for trend 0.04) and adherence to a Mediterranean diet (HR for aMED≥8 versus ≤1, 0.10; 95% CI 0.01–0.77) were significantly associated with reduced lung cancer risk. ConclusionsAmong heavy smokers, high red meat consumption and low adherence to a Mediterranean diet are associated with increased risk of lung cancer.

Exposure-Response Analysis and Risk Assessment for Lung Cancer in Relationship to Silica Exposure: A 44-Year Cohort Study of 34,018 Workers

Crystalline silica has been classified as a human carcinogen by the International Agency for Research on Cancer (Lyon, France); however, few previous studies have provided quantitative data on silica exposure, silicosis, and/or smoking. We investigated a cohort in China (in 1960-2003) of 34,018 workers without exposure to carcinogenic confounders. Cumulative silica exposure was estimated by linking a job-exposure matrix to work history. Cox proportional hazards model was used to conduct exposure-response analysis and risk assessment. During a mean 34.5-year follow-up, 546 lung cancer deaths were identified. Categorical analyses by quartiles of cumulative silica exposure (using a 25-year lag) yielded hazard ratios of 1.26, 1.54, 1.68, and 1.70, respectively, compared with the unexposed group. Monotonic exposure-response trends were observed among nonsilicotics (P for trend < 0.001). Analyses using splines showed similar trends. The joint effect of silica and smoking was more than additive and close to multiplicative. For workers exposed from ages 20 to 65 years at 0.1 mg/m(3) of silica exposure, the estimated excess lifetime risk (through age 75 years) was 0.51%. These findings confirm silica as a human carcinogen and suggest that current exposure limits in many countries might be insufficient to protect workers from lung cancer. They also indicate that smoking cessation could help reduce lung cancer risk for silica-exposed individuals.

Hormone use and risk for lung cancer: a pooled analysis from the International Lung Cancer Consortium (ILCCO)

Background:The association between oral contraceptive (OC) use, hormone replacement therapy (HRT) and lung cancer risk in women is still debated.Methods:We performed a pooled analysis of six case–control studies (1961 cases and 2609 controls) contributing to the International Lung Cancer Consortium. Potential associations were investigated with multivariable unconditional logistic regression and meta-analytic models. Multinomial logistic regressions were performed to investigate lung cancer risk across histologic types.Results:A reduced lung cancer risk was found for OC (odds ratio (OR)=0.81; 95% confidence interval (CI): 0.68–0.97) and HRT ever users (OR=0.77; 95% CI: 0.66–0.90). Both oestrogen only and oestrogen+progestin HRT were associated with decreased risk (OR=0.76; 95% CI: 0.61–0.94, and OR=0.66; 95% CI: 0.49–0.88, respectively). No dose-response relationship was observed with years of OC/HRT use. The greatest risk reduction was seen for squamous cell carcinoma (OR=0.53; 95% CI: 0.37–0.76) in OC users and in both adenocarcinoma (OR=0.79; 95% CI: 0.66–0.95) and small cell carcinoma (OR=0.37; 95% CI: 0.19–0.71) in HRT users. No interaction with smoking status or BMI was observed.Conclusion:Our findings suggest that exogenous hormones can play a protective role in lung cancer aetiology. However, given inconsistencies with epidemiological evidence from cohort studies, further and larger investigations are needed for a more comprehensive view of lung cancer development in women.

Association between diabetes or antidiabetic therapy and lung cancer: A meta‐analysis

Diabetes can increase the risk of cancers at several sites, but the association between diabetes and lung cancer remains unclear. We aimed to provide the quantitative estimates for the association between diabetes or antidiabetic treatment and lung cancer risk in the present meta-analysis. Cohort studies were identified by searching the PubMed database (January 1960 through October 2012) and manually assessing the cited references in the retrieved articles. Study-specific relative risks (RRs) and 95% confidence intervals (CIs) were estimated using a random-effects model. Study quality was assessed using the Newcastle-Ottawa scale. A total of 19 cohort studies were included in the present meta-analysis. Of these, 14 studies focused on the association between diabetes and lung cancer incidence, and seven studies focused on the association between antidiabetic treatment and lung cancer incidence. Compared with non-diabetic individuals, diabetic patients do not have an increased risk of lung cancer (RR=1.04, 95% CI 0.87-1.24). The association between diabetes and lung cancer remained not statistically significant in subgroup analysis stratified by study characteristics, study quality, diabetes ascertainment or important confounders. A null association between insulin or biguanides therapy and lung cancer risk was found. However, the diabetic patients receiving thiazolidinedione (TZD) treatment had a 20% reduced risk of lung cancer than those without TZD treatment. No association between diabetes and lung cancer risk was found. However, TZD treatment might reduce lung cancer risk in diabetic patients.

Asbestos, Asbestosis, Smoking, and Lung Cancer. New Findings from the North American Insulator Cohort

Asbestos, smoking, and asbestosis increase lung cancer risk in incompletely elucidated ways. Smoking cessation among asbestos-exposed cohorts has been little studied. To measure the contributions of asbestos exposure, asbestosis, smoking, and their interactions to lung cancer risk in an asbestos-exposed cohort and to describe their reduction in lung cancer risk when they stop smoking. We examined lung cancer mortality obtained through the National Death Index for 1981 to 2008 for 2,377 male North American insulators for whom chest X-ray, spirometric, occupational, and smoking data were collected in 1981 to 1983 and for 54,243 non-asbestos-exposed blue collar male workers from Cancer Prevention Study II for whom occupational and smoking data were collected in 1982. Lung cancer caused 339 (19%) insulator deaths. Lung cancer mortality was increased by asbestos exposure alone among nonsmokers (rate ratio = 3.6 [95% confidence interval (CI), 1.7-7.6]), by asbestosis among nonsmokers (rate ratio = 7.40 [95% CI, 4.0-13.7]), and by smoking without asbestos exposure (rate ratio = 10.3 [95% CI, 8.8-12.2]). The joint effect of smoking and asbestos alone was additive (rate ratio = 14.4 [95% CI, 10.7-19.4]) and with asbestosis, supra-additive (rate ratio = 36.8 [95% CI, 30.1-45.0]). Insulator lung cancer mortality halved within 10 years of smoking cessation and converged with that of never-smokers 30 years after smoking cessation. Asbestos increases lung cancer mortality among nonsmokers. Asbestosis further increases the lung cancer risk and, considered jointly with smoking, has a supra-additive effect. Insulators benefit greatly by quitting smoking.

Association between folate intake, serum folate levels and the risk of lung cancer: a systematic review and meta-analysis

Background Folate plays a critical role in nucleotide synthesis and DNA methylation, and was considered to be associated with anti-carcinogenesis. Results from studies that concern the relationship between the folate intake or serum folate levels and lung cancer risk showed no consistency, which requires our further comprehensive metaanalysis. Methods Systematic literature search was conducted to identify the relevant studies (published prior to February 2013) according to standard protocol. Estimated effects were calculated under both random-effects and fixed-effects models. Heterogeneity between studies and publication bias were also evaluated. Results A total of 4390 cases and 6138 controls from 6 case-control studies revealed a significant overall inverse association between folate intake and lung cancer risk (OR = 0.74, 95% CI = 0.65-0.84, P&lt; 0.001). Summary of 1438 cases and 2582 controls from 4 case-control studies and 44 cases out of a cohort of 1988 participants suggested a marginal association without significance (OR = 0.78, 95% CI = 0.60-1.02, P = 0.075) between high serum folate levels and less lung cancer susceptibility; however, subgroup analysis about population-based case-control studies showed that high serum folate levels significantly associated with the reduced lung cancer risk (OR = 0.76, 95% CI = 0.58-1.00, P = 0.048). Conclusion Higher folate intake can be a protective factor against lung cancer risk, and higher serum folate level is probably associated with reduced lung cancer risk in marginal manner, though more studies are warranted to confirm these associations.

Abstract 4581: Interaction between DRD1 and childhood exposure to environmental tobacco smoke modulates lung cancer risk in smokers and never smokers.

Abstract In searching for a role for genetic variation in susceptibility to lung cancer, we postulated that miRNA modulating SNPs within smoking behavior associated genes, such as the nicotinic acetylcholine and dopamine receptor families, could modulate susceptibility to tobacco carcinogens and lung cancer risk. Bioinformatic analyses of these gene families identified 5 SNPs predicted to modulate a miRNA binding site. We assessed these SNPs in the National Cancer Institute-MD case-control study (European American [EA] &amp; African Americans [AA] n=1,438). rs686 in DRD1 (dopamine receptor D1) was associated with a reduced risk of lung cancer after adjustment for age, gender and race (OR 0.63, 95% C.I. 0.47-0.85; P=0.002). As DRD1 mediates dopamine signaling following nicotine exposure, we reasoned that the rs686 variant associates with lung cancer risk via modulation of the nicotine reward pathway. However, adjustment for smoking both in terms of smoking status and pack-years did not significantly modulate the association (OR 0.57, 95% C.I. 0.40-0.81, P=0002). In addition, age at smoking initiation, pack-years of smoking and levels of urinary nicotine metabolites (cotinine and hydroxycotinine) did not vary across rs686 genotypes. Moreover, in an analysis of a never smoking cohort from Mayo Clinic, rs686 was also associated with a reduced risk of lung cancer (OR 0.77, 95% C.I. 0.62-0.97; P=0.027; n=629) (pooled analysis OR 0.61, 95% C.I. 0.47-0.78; P&amp;lt;0.0001; n=2,067). Intriguingly, the association between rs686 and lung cancer risk was only observed in subjects exposed to tobacco smoke during childhood (EA smokers: [OR 0.63, 95% C.I. 0.45-0.88; P=0.007] EA never smokers [OR 0.64, 95% C.I. 0.49-0.85; P=0.002] AA smokers OR 0.31, 95% C.I. 0.11-0.89; P=0.029) (model adjusted as above and for education, adult-second-hand smoke exposure). To further explore a relationship between tobacco and DRD1, we exposed lung cancer cell lines to increasing doses of nicotine and observed a significant increase in DRD1 expression (P=0.009). As DRD1 lies within a CpG island, we are currently testing if this regulation occurs via epigenetic modulation of the DRD1 promoter. While a direct role for DRD1 in lung cancer has not previously been reported, a recent report linked DRD to the cancer stem cell hypothesis. Indeed, our work demonstrates that DRD1 is significantly upregulated in lung cells with cancer stem-like properties. Furthermore, miR-296, predicted to bind to variant rs686 allele, is increased in paired lung cancer tissues (P=0.0003), thus linking a decrease in DRD1 with reduced lung cancer risk. Collectively, our work suggests a novel lung cancer pathway whereby rs686 in DRD1 counteracts the increase in DRD1 imposed by exposure to tobacco smoke in both current and never smokers. Furthermore, it hints at a novel role for the dopamine receptor/signaling pathway in lung carcinogenesis. Citation Format: Brid M. Ryan, Ana I. Robles, Andrew C. McClary, Elise Bowman, Kirsi Vahakangas, Susan Olivo-Marston, Ping Yang, Jin Jen, Curtis C. Harris. Interaction between DRD1 and childhood exposure to environmental tobacco smoke modulates lung cancer risk in smokers and never smokers. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4581. doi:10.1158/1538-7445.AM2013-4581

Associations between Dietary Intake of Choline and Betaine and Lung Cancer Risk

Evidence from human and animal research indicates that choline metabolic pathways may be activated during a variety of diseases, including cancer. We report results of a case-control study of 2821 lung cancer cases and 2923 controls that assessed associations of choline and betaine dietary intakes with lung cancer. Using multivariable logistic regression analyses, we report a significant association between higher betaine intake and lower lung cancer risk that varied by smoking status. Specifically, no significant association was observed between betaine intake and lung cancer among never-smokers. However, higher betaine intake was significantly associated with reduced lung cancer risk among smokers, and the protective effect was more evident among current than former smokers: for former and current smokers, the ORs (95% CI) of lung cancer for individuals with highest as compared to lowest quartiles of intake were 0.70(0.55–0.88) and 0.51(0.39–0.66) respectively. Significant linear trend of higher betaine intake and lower lung cancer risk was observed among both former (ptrend = 0.002) and current (ptrend<0.0001) smokers. A similar protective effect was also observed with choline intake both in overall analysis as well as among current smokers, with p-values for chi-square tests being 0.001 and 0.004 respectively, but the effect was less evident, as no linear trend was observed. Our results suggest that choline and betaine intake, especially higher betaine intake, may be protective against lung cancer through mitigating the adverse effect of smoking.

Investigating Multiple Candidate Genes and Nutrients in the Folate Metabolism Pathway to Detect Genetic and Nutritional Risk Factors for Lung Cancer

PurposeFolate metabolism, with its importance to DNA repair, provides a promising region for genetic investigation of lung cancer risk. This project investigates genes (MTHFR, MTR, MTRR, CBS, SHMT1, TYMS), folate metabolism related nutrients (B vitamins, methionine, choline, and betaine) and their gene-nutrient interactions.MethodsWe analyzed 115 tag single nucleotide polymorphisms (SNPs) and 15 nutrients from 1239 and 1692 non-Hispanic white, histologically-confirmed lung cancer cases and controls, respectively, using stochastic search variable selection (a Bayesian model averaging approach). Analyses were stratified by current, former, and never smoking status.ResultsRs6893114 in MTRR (odds ratio [OR] = 2.10; 95% credible interval [CI]: 1.20–3.48) and alcohol (drinkers vs. non-drinkers, OR = 0.48; 95% CI: 0.26–0.84) were associated with lung cancer risk in current smokers. Rs13170530 in MTRR (OR = 1.70; 95% CI: 1.10–2.87) and two SNP*nutrient interactions [betaine*rs2658161 (OR = 0.42; 95% CI: 0.19–0.88) and betaine*rs16948305 (OR = 0.54; 95% CI: 0.30–0.91)] were associated with lung cancer risk in former smokers. SNPs in MTRR (rs13162612; OR = 0.25; 95% CI: 0.11–0.58; rs10512948; OR = 0.61; 95% CI: 0.41–0.90; rs2924471; OR = 3.31; 95% CI: 1.66–6.59), and MTHFR (rs9651118; OR = 0.63; 95% CI: 0.43–0.95) and three SNP*nutrient interactions (choline*rs10475407; OR = 1.62; 95% CI: 1.11–2.42; choline*rs11134290; OR = 0.51; 95% CI: 0.27–0.92; and riboflavin*rs8767412; OR = 0.40; 95% CI: 0.15–0.95) were associated with lung cancer risk in never smokers.ConclusionsThis study identified possible nutrient and genetic factors related to folate metabolism associated with lung cancer risk, which could potentially lead to nutritional interventions tailored by smoking status to reduce lung cancer risk.

Soy food intake and risk of lung cancer: evidence from the Shanghai Women's Health Study and a meta-analysis.

The authors prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and performed a meta-analysis of published data. Included in the analysis were 71,550 women recruited into the Shanghai Women's Health Study (Shanghai, China) in 1997-2000. Usual soy food intake was assessed at baseline and reassessed during follow-up through in-person interviews. During a mean follow-up period of 9.1 years, 370 incident lung cancer cases were identified; 340 patients were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer (P(trend) = 0.004); the hazard ratio for the highest quintile of intake compared with the lowest was 0.63 (95% confidence interval: 0.44, 0.90). This inverse association appeared predominately among women with later age at menopause (P(interaction) = 0.01) and for aggressive lung cancer as defined by length of survival (<12 months vs. ≥12 months; P(heterogeneity) = 0.057). Meta-analysis of 7 studies conducted among nonsmokers found a summary relative risk of 0.59 (95% confidence interval: 0.49, 0.71) for the highest categories of soy or isoflavone intake versus the lowest. This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive tumors, and its effect may be modified by endogenous estrogens.

The link between lung cancer and indoor air pollution

www.thelancet.com/oncology Vol 13 October 2012 e415 A retrospective cohort study of more than 37 000 residents of Xuanwei County in China’s Yunnan Province has concluded that the domestic use of smoky (bituminous) coal substantially increases the risk of lung cancer. The study—led by scientists at the National Cancer Institute (NCI), Bethesda, MD, USA—found that male users of smoky coal had an 18% absolute risk of dying from lung cancer before they reached the age of 70 years. Female users, nearly all of whom were non-smokers, had a 20% risk. Male and female users of smokeless coal (anthracite), by contrast, had a lung cancer risk of less than 0·5%. “Lung cancer alone accounted for about 40% of all deaths before age 60 among individuals using smoky coal”, wrote the authors. About half the world’s population relies on solid fuels or coal for cooking and heating. The International Agency for Research on Cancer (IARC; Lyon, France) classifi es indoor emissions from the combustion of coal as a group 1 carcinogen. 2 years ago the UN Foundation launched the Global Alliance for Clean Cook Stoves, aiming to ensure universal access to such devices. In China, where most people live in rural areas, the use of coal is especially prevalent. Moreover, households in Xuanwei, which has some of the highest lung cancer rates in the world, are poorly ventilated, so the internal concentration of coal smoke is particularly intense. “There are several factors that come together in Xuanwei, but the risk for lung cancer in using smoky coal, compared with smokeless coal, is much higher”, co-author Qing Lan (NCI) told The Lancet Oncology. The study period (1976–96) saw a total of 8976 deaths, 2377 of which were due to lung cancer. Co-author Nathaniel Rothman (NCI) described the fi ndings as a “striking example of an environmental contribution to cancer”. Lan added that “the use of less carcinogenic types of coal or other fuels would likely translate to a substantial reduction in lung cancer risk in Xuanwei”. However, this strategy might not always be feasible: good quality coal might not be locally available. Fortunately, other interventions can be highly eff ective. “Construct a chimney and ensure that people’s exposure to coal smoke is reduced”, urges IARC’s Robert Baan. Indeed, an earlier study co-authored by Lan showed that simply installing a household stove with a chimney can halve the risk of lung cancer.

Risk of lung cancer associated with domestic use of coal in Xuanwei, China: retrospective cohort study

Objective To estimate the risk of lung cancer associated with the use of different types of coal for household cooking and heating.Setting Xuanwei County, Yunnan Province, China.Design Retrospective cohort study...

UGT1A6 Polymorphisms Modulated Lung Cancer Risk in a Chinese Population

Uridine diphosphoglucuronosyltransferases (UGTs) 1A6 is the only UGT1A isoform expressed in lung tissue. It is responsible for the detoxification of carcinogens such as benezo[a]pyrene from cigarette smoke. The purpose of this study was to evaluate the association of UGT1A6 polymorphisms and haplotypes with lung cancer risk and to evaluate the functional significance of UGT1A6 polymorphisms. Genomic DNA was isolated from leukocytes. Eight UGT1A6 polymorphisms were sequenced in a test set of 72 Chinese lung cancer patients and 62 healthy controls. Potential risk modifying alleles were validated in a separate set of 95 Chinese lung cancer patients and 100 healthy controls. UGT1A6 19T>G, 541A>G and 552A>C showed significant association with increased lung cancer risk, while UGT1A6 105C>T and IVS1+130G>T were significantly associated with reduced lung cancer risk. Multivariate logistic regression analysis demonstrated a significant association of lung cancer with UGT1A6 541A>G (OR: 3.582, 95% CI: 1.27–10.04, p = 0.015), 552A>C (OR: 5.364, 95% CI: 1.92–14.96, p = 0.001) and IVS1+130G>T (OR: 0.191, 95% CI: 0.09–0.36, p<0.001). Functional test demonstrated that UGT1A6 105C>T increased mRNA stability, providing a plausible explanation of its association with reduced lung cancer risk. Thus UGT1A6 polymorphisms may be used to identify people with increased risk of developing lung cancer.

Abstract 5478: Indoor coal smoke exposure, tobacco use, and lung cancer risk in Xuanwei, China

Abstract Introduction: Lung cancer rates in Xuanwei County, Yunnan Province are among the highest in China. We have previously reported that indoor combustion of smoky coal for home heating and cooking was associated with increased risk of lung cancer and that this effect varies markedly by coal type. Further, improved stove ventilation is followed by reduction in lung cancer risk. We explored the joint relationship between tobacco use and coal use in Xuanwei men. Methods: We analyzed data from a population-based case-control study of lung cancer in Xuanwei. Cases were identified from four Xuanwei hospitals and controls were selected from the general population by probability sampling. Controls were matched one-to-one with cases on age. In total, 260 cases and 260 controls were analyzed in this study. Tobacco, coal, and solid fuel exposures were tabulated from questionnaires and reported in cigarette pack-years, duration of smoking, and average tons of coal used annually. Odds ratios and 95% confidence intervals were estimated by conditional logistic regression with the main effects of coal, smoking, and coal-smoking interaction terms. Results: Overall, smoking was positively and significantly, although only modestly, associated with lung cancer risk (OR per pack-year: 1.02; 95% CI: 1.01-1.04). The risk of lung cancer per pack-year of smoking decreased as cumulative lifetime use of smoky coal increased (0-50 tons coal: OR: 1.07; 95% CI: 1.01-1.15; &amp;gt;50-150 tons coal: OR: 1.05; 95% CI: 1.01-1.10; &amp;gt;150 tons coal: OR: 1.00; 95% CI: 0.99-1.03; P-interaction: 0.041). Discussion: Our results suggest that the effect of tobacco on lung cancer risk was weaker in men exposed to higher amounts of coal. Results are consistent with previous cohort study findings in Xuanwei. Constituents of coal combustion, such as polycyclic aromatic hydrocarbons, could plausibly act to diminish the carcinogenicity of tobacco through metabolic competition or other possible mechanisms. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5478. doi:1538-7445.AM2012-5478

Abstract 646: Soy food intake and risk of lung cancer: Evidence from the Shanghai Women's Health Study and a meta-analysis

Abstract Background: Recent large-scale clinical trials raised concerns regarding increased risk of aggressive lung cancer and lung cancer mortality among users of postmenopausal estrogen therapy. Soy and its phytoestrogens have been shown to act as a natural estrogen antagonist and have cancer-inhibitory activities in experimental studies. Objective: We prospectively evaluated the association of soy food intake with lung cancer risk, overall and by tumor aggressiveness, and perform a meta-analysis of published data. Methods: Included in this analysis were 71,550 women recruited in the Shanghai Women's Health Study, a population-based cohort study. Usual soy food intake was assessed at baseline and re-assessed during follow-up through in-person interviews. Previous studies were identified through a MEDLINE search. Results: During a mean follow-up of 9.1 years, 370 incident lung cancer cases were identified; 340 were lifetime never smokers. After adjustment for potential confounders, soy food intake was inversely associated with subsequent risk of lung cancer; the hazard ratio (HR) for the highest compared with lowest quintile of intake was 0.63 (95% CI: 0.44 - 0.90; P trend = 0.004). This inverse association appeared predominately among women with a later age at menopause (P interaction = 0.01) and varied by tumor aggressiveness as defined by length of survival (&amp;lt;12 versus β12 months), with corresponding HR of 0.49 for more aggressive lung cancer versus 0.76 for less aggressive lung cancer (P heterogeneity = 0.057). Similar inverse associations were observed for isoflavone intake. A meta-analysis of seven studies conducted among never smokers found a summary odds ratio of 0.59 (95% CI: 0.49 - 0.71) for the highest versus lowest categories of soy or isoflavone intake. Conclusion: This study suggests that soy food consumption may reduce lung cancer risk in nonsmoking women, particularly for aggressive lung cancer, and its effect may be modified by endogenous estrogens. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 646. doi:1538-7445.AM2012-646

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31–0.81 in non-smokers; OR 0.38, 95%CI 0.16–0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

Research links heavy alcohol consumption with lung cancer

Heavy alcohol consumption was found to be related to an increased risk of lung cancer, according to several studies presented at the Annual Meeting of the American College of Chest Physicians in Honolulu, Hawaii, on October 22–26, 2011. At the same time, black tea consumption was shown to reduce lung cancer risk in nonsmoking women whereas higher body mass index (BMI) and increased fruit consumption were linked to a lower risk of the disease in both men and women. Further findings showed that specific ethnic groups, including African American men and Asian women, had slightly higher risks for lung cancer. Researchers did not note a connection between moderate drinking and the development of lung cancer. Stanton Siu, MD, of Kaiser Permanente in Oakland, California, and colleagues studied 126,293 individuals who provided baseline data from 1978 to 1985, and followed them until 2008 (abstracts 305A and 937A). They sought to determine the participants' risk for developing lung cancer in relation to smoking, alcohol consumption, gender, ethnicity, BMI, and level of education. Of the 1852 people who developed lung cancer, cigarette smoking was a strong predictor for all types. In addition, heavy alcohol consumption (more than 3 drinks per day) also was found to increase risk. The risk was slightly higher in relation to beer consumption compared with wine and liquor consumption, researchers note. Dr. Siu and colleagues also found that higher education levels were associated with a lower risk of developing lung cancer, possibly because, in general, more highly educated individuals may lead a healthier lifestyle. Researchers from the Czech Republic presented a separate study that examined the relationship between smoke exposure, diet and exercise, and lung cancer risk (abstract 952A). They found that consumption of black tea helped protect nonsmoking women and that fruit had a protective effect on both men and women.

Abstract B7: Comparison of diet diversity scores for fruit and vegetables and plasma carotenoids levels in the cross-sectional study of the European Prospective Investigation into Cancer and Nutrition (EPIC)

Abstract Research on the relationship between cancer risk and fruit and vegetable consumption is primarily focused on the quantity of consumption. However, simply looking at the quantity of fruit and vegetable consumption or at one specific component of fruits and vegetables might not fully capture the mechanism(s) responsible for a lower cancer risk. Looking at the diversity of fruit and vegetable consumption, reflecting an intake of many different bioactive compounds present in fruit and vegetables, may complement the research on fruit and vegetable consumption and cancer risk. We have previously linked the variety in fruit and vegetable consumption, as measured by diet diversity scores (DDS), to lung and bladder cancer risk in the European Prospective Investigation into Nutrition and Cancer (EPIC). We found no relation between the DDS and bladder cancer risk and a reduced lung cancer risk with increased variety in vegetable consumption. In this current study we evaluated whether the DDS indeed captures a mixed intake of bioactive compounds by comparing the DDS to plasma concentrations of six carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein and zeaxanthin). Within the cross-sectional study of the EPIC (including 3,089 subjects), we calculated four different DDS based on dietary questionnaires: one represents diversity in vegetable and fruit consumption, two represent diversity in vegetable consumption and one represents diversity in fruit consumption. Plasma carotenoids samples (200 μl) were analyzed by reversed-phase high-performance liquid chromatography (HPLC; HPLC-1100 system, Hewlett Packard). To standardize the six plasma carotenoids, concentrations were re-scaled using a rank difference method; higher values represent larger and lower values represent smaller intra-individual variation in the concentrations of the six plasma carotenoids. Conceptually, the rank difference score should be inversely correlated with the DDS. Correlation coefficients between the DDS and the rank difference score were calculated for the full study population and stratified by subgroups of potential effect modifiers. Complete data on the DDS and plasma levels of carotenoids were available for 2,675 participants. The correlation coefficient (r) between the diversity in vegetable and fruit consumption and the rank difference score was −0.13. Diversity in vegetable consumption was not correlated to the rank difference score. The strongest, although still weak, correlation was found between the diversity in fruit consumption and the rank difference score (r=-0.19). Correlations were somewhat stronger for fasting samples, in women, and in Southern Europe. The diet diversity scores show only weak correlations with rescaled plasma levels of six carotenoids. This might suggest that either questionnaire information or one measurement of plasma carotenoid levels or both cannot fully capture variety in fruit and vegetable consumption. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B7.

Meta-Analysis on the Association Between Nonsteroidal Anti-Inflammatory Drug Use and Lung Cancer Risk

Background Nonsteroidal anti-inflammatory drugs (NSAIDs), especially aspirin, have emerged as the most potential chemopreventive agents. However, epidemiologic studies reported a controversial association between NSAID use and lung cancer risk. We conducted a meta-analysis to summarize the evidence for such relationship. Methods Eligible studies were identified by searching the electronic literature PubMed, Medline, Embase, and ScienceDirect databases for relevant reports and bibliographies. Studies were included if they designed as cohort study, case-control study, or clinical trial on the NSAID exposure and lung cancer with sufficient raw data to analyzes. Relative risk (RR) or odds ratio (OR) was used to evaluate the association between NSAIDs and lung cancer. Stratified analysis was also performed. Results A total of 19 studies including 20,266 lung cancer cases met the inclusion criteria. To the effect of aspirin on lung cancer, the combined RR for cohort studies was 0.96 (95%confidence interval [CI]: 0.78-1.19) and OR for case-control studies was 0.87 (95%CI: 0.69-1.09). When restricted in exposure of aspirin use to 7 tablets per week, the OR was 0.80 (95%CI: 0.67-0.95). The summary risk estimates showed no significant association between non-aspirin NSAID or overall NSAID use and lung cancer risk. Conclusions Aspirin use with a dose of 7 tablets per week can significantly reduce lung cancer risk, whereas non-aspirin NSAIDs showed no chemopreventive value. Greater attention should be paid to identifying appropriate individuals for this new indication of aspirin and the optimal dose and duration as a chemopreventive agent.

Dietary Patterns Affect Lung Cancer Risk in Never Smokers

A number of studies suggest a role of dietary factors as risk predictors of lung cancer in never smokers. However, it is difficult to interpret the observed associations of lung cancer risk with any particular dietary item due to high correlation among different dietary items. In this study, we derived uncorrelated patterns of dietary items in the never smokers and evaluated the association of these patterns with lung cancer risk, using food frequency data from 299 never-smoker lung cancer patients and 317 controls enrolled in an ongoing case–control lung cancer study. We identified 2 major dietary patterns in never smokers: a “healthy eating” pattern including vegetables, fruits, and low-fat food items, and a “mixed dishes” pattern including most foods with positive loadings. Using multivariable regression analysis, we show that the healthy eating pattern is associated with a significant reduction of lung cancer risk among never smokers. The effect of the healthy eating pattern remained significant after adjustment for age, gender, education, caloric intake, secondhand smoke exposure, and family history of cancer. This finding, if confirmed in a prospective study, has a clear preventive significance, by promoting interventions encouraging healthier diets.