Decreased Risk Of Lung Cancer Research Articles

Fatty liver index and development of lung cancer: a nationwide cohort study.

This study aimed to evaluate the impact of steatotic liver disease severity on the cumulative incidence of lung cancer utilizing data from the Korea National Health Insurance Service (NHIS). This study examined the risk of lung cancer in the general population in conjunction with the incidence of steatotic liver disease. The study population consisted of 3,261,438 individuals aged 20 years or older who underwent a general health examination in 2009. Individuals with fatty liver index (FLI) of 30-59 exhibited a 1.08-fold increased risk of lung cancer (95% CI: 1.04-1.11), while FLI ≥ 60 was associated with a 1.22-fold elevated risk of lung cancer (95% CI: 1.17-1.28) compared to those with FLI < 30. The risk varied with smoking status; in current smokers, the adjusted HR for the FLI 30-59 group was 1.05 (95% CI: 1.00-1.10), while that in the FLI ≥ 60 group was 1.11 (95% CI: 1.04-1.18). In never- or past-smokers, the adjusted HR for the FLI 30-59 group was 1.10, and that for the FLI ≥ 60 group was 1.31. Subgroup analysis revealed an incidence rate of 1.06 per 1,000 person-years in the consistently high FLI group compared to 1.15 in those with improved FLI. Improving FLI over time was associated with a 0.93-fold decrease in lung cancer risk. Our study demonstrated a correlational relationship between lung cancer incidence and the severity of steatotic liver disease as measured by FLI.

Association of genetic variants in soy isoflavones metabolism-related genes with decreased lung cancer risk

BackgroundSoy isoflavones have been reported to exhibit anti-tumor effects. We hypothesize that genetic variants in soy isoflavone metabolism-related genes are associated with the risk of lung cancer. MethodsA two-stage case-control study design was conducted in this study. The discovery stage included 300 lung cancer cases and 600 healthy controls to evaluate the association of candidate genetic variants with lung cancer risk. The validation stage involved 1200 cases and 1200 controls to validate the associations found. Furthermore, qPCR was performed to assess the mRNA expression levels of different genotypes of the SNP. ELISA was used to explore the association between genotype and soy isoflavone levels, as well as the association between soy isoflavone levels and lung cancer risk. ResultsA nonlinear association was observed between plasma soy isoflavone levels and lung cancer risk, with higher soy isoflavone levels associated with lower lung cancer risk (P < 0.001). The two-stage case-control study identified that UGT1A1 rs3755319 A > C was associated with decreased lung cancer risk (Recessive model: adjusted OR = 0.69, 95 %CI = 0.57–0.84, P < 0.001). Moreover, eQTL analysis showed that the expression level of UGT1A1 in the rs3755319 CC genotype was lower than in the AA + AC genotype (P < 0.05). The plasma concentration of soy isoflavones in the rs3755319 CC genotype was higher than in the AA + AC genotype (P = 0.008). ConclusionsWe identified a potentially functional SNP, UGT1A1 rs3755319 A > C, as being associated with decreased lung cancer risk. Further experiments will be needed to explore the mechanisms underlying the observed associations.

Is certain food and nutrients associated with the risk of lung cancer? A systematic review

This review explores the intricate relationship between dietary factors and lung cancer risk based on a thorough examination of relevant literature and articles. The findings highlight a significant association between specific dietary elements and lung cancer risk. Increased intake of fiber, fruit, and vitamin C is linked to a notable 9% reduction in risk, particularly for squamous cell carcinoma. Notably, vegetables exhibit a risk reduction for current smokers, while offal, red meat, and processed meat may elevate risk, especially in heavy smokers. Contradictory evidence surrounds dairy products, with fermented dairy inversely correlated. Beer and cider consumption are associated with an increased risk, primarily among current smokers. In contrast, avocados demonstrate a promising link to decreased lung cancer risk. Vitamin K intake shows an inverse relationship, particularly in males and ever smokers. High retinol intake may elevate risk, potentially modifying the effects of tobacco exposure. Nuts consumption is significantly linked to reduced lung cancer risk and overall cancer mortality. Dietary polyunsaturated fatty acids (PUFA) demonstrate a noteworthy risk reduction for lung cancer, with supplementation improving overall survival in patients with the disease. Palmitic acid, a component of saturated fatty acids, is implicated in promoting lung metastasis, emphasizing the intricate nature of dietary influences on cancer. In summary, while lung cancer is primarily associated with tobacco smoking, this review underscores the multifaceted interplay between diet and lung cancer risk. Further research is crucial to unravel underlying mechanisms and provide definitive evidence on the impact of specific dietary factors, emphasizing the importance of continued exploration in this complex field.

Causal effect of beta-blockers on the risk of lung cancer: a Mendelian randomization study.

It remains uncertain whether there is a causal association of the use of beta-blockers (BBs) on lung cancer risk. We used a two-sample Mendelian randomization (MR) approach to identify the causal association of BBs and lung cancer risk. Twenty-two BB-related single-nucleotide polymorphisms (SNPs) were obtained from the UK Biobank as the instrumental variables (IVs). Genetic summary data information of lung cancer was extracted from the International Lung Cancer Consortium, with a total of 11,348 cases and 15,861 controls. We adopted the inverse-variance weighted (IVW) approach to conduct the MR analyses. Egger-intercept analysis was further performed as sensitivity analysis for pleiotropy evaluation. Additionally, we investigated whether BBs could causally affect the risk of lung cancer through their pharmacological effects. The current IVW analysis suggested a decreased lung cancer risk in BB users [odds ratio (OR) =0.83; 95% confidence interval (CI): 0.73-0.95; P<0.01]. Results of Egger-intercept analysis demonstrated that no pleiotropy was found (P=0.94), which suggested the robustness of the causality. However, there was little evidence that pharmacological effects mediate the association between BBs and lung cancer. The current analysis suggested that BBs could decrease the risk of lung cancer but may be not via its pharmacological effects. Further research is in need for elucidating the underlying mechanisms.

Patient Preferences for Lung Cancer Interception Therapy

Interception therapy requires individuals to undergo treatment to prevent a future medical event, but little is known about preferences of individuals at high risk for lung cancer and whether they would be interested in this type of treatment. To explore preferences of individuals at high risk for lung cancer for potential interception therapies to reduce this risk. This survey study used a discrete-choice experiment and included hypothetical lung cancer interception treatments with 4 attributes: reduction in lung cancer risk over 3 years, injection site reaction severity, nonfatal serious infection, and death from serious infection. Respondents were assigned to a baseline lung cancer risk of 6%, 10%, or 16% over 3 years. The discrete-choice experiment was administered online (July 13 to September 6, 2022) to US respondents eligible for lung cancer screening according to US Preventive Services Task Force guidelines. Participants included adults aged 50 to 80 years with at least a 20 pack-year smoking history. Statistical analysis was performed from September to December 2022. Attribute-level preference weights were estimated, and conditional relative attribute importance, maximum acceptable risks, and minimum acceptable benefits were calculated. Characteristics of respondents who always selected no treatment were also explored. Of the 803 survey respondents, 495 (61.6%) were female, 138 (17.2%) were African American or Black, 55 (6.8%) were Alaska Native, American Indian, or Native American, 44 (5.5%) were Asian or Native Hawaiian or Other Pacific Islander, 104 (13.0%) were Hispanic, Latin American, or Latinx, and 462 (57.5%) were White, Middle Eastern or North African, or a race or ethnicity not listed; and mean (SD) age was 63.0 (7.5) years. Most respondents were willing to accept interception therapy and viewed reduction in lung cancer risk as the most important attribute. Respondents would accept a greater than or equal to a 12.0 percentage point increase in risk of nonfatal serious infection if lung cancer risk was reduced by at least 20.0 percentage points; and a greater than or equal to 1.2 percentage point increase in risk of fatal serious infection if lung cancer risk was reduced by at least 30.0 percentage points. Respondents would require at least a 15.4 (95% CI, 10.6-20.2) percentage point decrease in lung cancer risk to accept a 12.0 percentage point increase in risk of nonfatal serious infection; and at least a 23.1 (95% CI, 16.4-29.8) percentage point decrease in lung cancer risk to accept a 1.2 percentage point increase in risk of death from serious infection. Respondents who were unwilling to accept interception therapy in any question (129 [16.1%]) were more likely to be older and to currently smoke with no prior cessation attempt, and less likely to have been vaccinated against COVID-19 or examined for skin cancer. In this survey study of individuals at high risk of lung cancer, most respondents were willing to consider interception therapy. These results suggest the importance of benefit-risk assessments for future lung cancer interception treatments.

Investigating Causal Effects of Hematologic Traits on Lung Cancer: A Mendelian Randomization Study.

Observational studies have suggested blood cell counts may act as predictors of cancer. It is not known whether these hematologic traits are causally associated with lung cancer. Two-sample bidirectional univariable Mendelian randomization (MR) and multivariable MR (MVMR) were performed to investigate the causal association between hematologic traits and the overall risk of lung cancer and three histologic subtypes [lung adenocarcinoma, squamous cell lung cancer, and small cell lung cancer (SCLC)]. The instrumental variables of 23 hematologic traits were strictly selected from large-scale genome-wide association studies. Inverse-variance weighted method and five extra methods were used to obtain robust causal estimates. We found evidence that genetically influenced higher hematocrit [OR, 0.845; 95% confidence interval (CI), 0.783-0.913; P = 1.68 × 10-5] and hemoglobin concentration (OR, 0.868; 95% CI, 0.804-0.938; P = 3.20 × 10-4) and reticulocyte count (OR, 0.923; 95% CI, 0.872-0.976; P = 5.19 × 10-3) decreased lung carcinoma risk, especially in ever smokers. MVMR further identified hematocrit independently of smoking as an independent predictor. Subgroup analysis showed that a higher plateletcrit level increased the risk of small cell lung carcinoma (OR, 1.288; 95% CI, 1.126-1.474; P = 2.25 × 10-4). Genetically driven higher levels of reticulocyte count and hematocrit decreased lung cancer risk. Higher plateletcrit had an adverse effect on SCLC. Hematologic traits may act as low-cost factors for lung cancer risk stratification. Further studies are required to elucidate the potential mechanisms underlying the dysregulation of homeostasis related to hematologic traits, such as subclinical inflammation.

MiRNA-423 rs6505162and miRNA-6811 rs2292879SNP AssociatedwithLung Cancer in Hainan, China.

MicroRNAs (miRNAs) are known to exert significant influence on various physiological processes and diseases, including cancers. The primary objective of this present study was to examine the impact of eightsingle nucleotide polymorphisms(SNPs)in miRNA on the susceptibility to lung cancer (LC) within the Chinese Southernpopulation. Thegenotypes of these eight polymorphisms weredeterminedin132 LC patients and 214cancer-free controls. In overall analyses, GG genotype of miRNA-6811 rs2292879 polymorphismwas significantly correlated with increased risk ofLC (GG vs. AA,adjusted OR = 5.10, 95% CI = 1.02 ~ 25.43, P= 0.047), yet the genotype frequenciesof rs2292879SNP in controlsdid notmet the Hardy-Weinberg equilibrium (HWE)(P= 0.001) in present study. Stratified analysesby smoking revealed that miRNA-423 rs6505162 variants significantly decreased the LC risk in heterozygous (CA vs. CC, adjusted OR = 0.14, 95% CI = 0.03 ~ 0.81, P= 0.028), recessive(AA vs. CA + CC, adjusted OR = 0.17, 95% CI = 0.03 ~ 0.90, P= 0.038)genetic models in smoking population. However, miRNA-196A2rs11614913, miRNA-196A2rs12304647, miRNA-146Ars2910164, miRNA-16-1rs1022960, miRNA-608rs4919510, andmiRNA-27a rs895819polymorphisms were not significantly associated withLC. The findings of our study indicate a potential decrease inLC risk among smokers with the miRNA-423 rs6505162variants, while an increase in risk is associated with miRNA-6811 rs2292879 polymorphismsin the population of SouthernChinese. However, further well-designed researchis necessary to fully understand the precise impact of these twoSNPs on the development of LC.

Integrating genomics and proteomics data to identify candidate plasma biomarkers for lung cancer risk among European descendants.

Plasma proteins are potential biomarkers for complex diseases. We aimed to identify plasma protein biomarkers for lung cancer. We investigated genetically predicted plasma levels of 1130 proteins in association with lung cancer risk among 29,266 cases and 56,450 controls of European descent. For proteins significantly associated with lung cancer risk, we evaluated associations of genetically predicted expression of their coding genes with the risk of lung cancer. Nine proteins were identified with genetically predicted plasma levels significantly associated with overall lung cancer risk at afalse discovery rate (FDR) of <0.05. Proteins C2, MICA, AIF1, and CTSH were associated with increased lung cancer risk, while proteins SFTPB, HLA-DQA2, MICB, NRP1, and GMFG were associated with decreased lung cancer risk. Stratified analyses by histological types revealed the cross-subtype consistency of these nine associations and identified an additional protein, ICAM5, significantly associated with lung adenocarcinoma risk (FDR < 0.05). Coding genes of NRP1 and ICAM5 proteinsare located at two loci that have never been reported by previous GWAS. Genetically predicted blood levels of genes C2, AIF1, and CTSH were associated with lung cancer risk, in directions consistent with those shown in protein-level analyses. Identification of novel plasma protein biomarkers provided new insights into the biology of lung cancer.

Associations of chest X-ray trajectories, smoking, and the risk of lung cancer in two population-based cohort studies.

Despite the increasing use of computed tomography (CT), chest X-ray (CXR) remains the first-line investigation for suspected lung cancer (LC) in primary care. However, the associations of CXR trajectories, smoking and LC risk remain unknown. A total of 52,486 participants from the PLCO and 22,194 participants from the NLST were included. The associations of CXR trajectories with LC risk were evaluated with multivariable COX regression models and pooled with meta-analyses. Further analyses were conducted to explore the stratified associations by smoking status and the factors associated with progression and regression in CXR. Compared to stable negative CXR (CXRSN), HRs (95%CIs) of LC incidence were 2.88(1.50-5.52), 3.86(2.03-7.35), and 1.08(0.80-1.46) for gain of positive CXR (CXRGP), stable positive CXR (CXRSP), and loss of positive CXR (CXRLP), while the risk of LC mortality were 1.58(1.33-1.87), 2.56(1.53-4.29), and 1.05(0.89-1.25). Similar trends were observed across different smoking status. However, LC risk with CXRGP overweighed that with CXRSP among ever smokers [2.95(2.25-3.88) vs. 2.59(1.33-5.02)] and current smokers [2.33(1.70-3.18) vs. 2.26(1.06-4.83)]. Moreover, compared to CXRSN among never smokers, even no progression in CXR, the HRs(95%CIs) of LC incidence were 7.39(5.60-9.75) and 31.45(23.58-41.95) for ever and current smokers, while risks of LC mortality were 6.30(5.07-7.81) and 27.17(21.65-34.11). If participants gained positive CXR, LC incidence risk significantly climbed to 22.04(15.37-31.60) and 71.97(48.82-106.09) for ever and current smokers, while LC mortality risk climbed to 11.90(8.58-16.50) and 38.92(27.04-56.02). CXRLP was associated with decreased LC risk. However, even smokers lost their positive CXR, and the increased risks of LC incidence and mortality did not decrease to non-significant level. Additionally, smoking was significantly associated with increased risk of CXRGP but not CXRLP. LC risk differed across CXR trajectories and would be modified by smoking status. Comprehensive intervention incorporating CXR trajectories and smoking status should be recommended to reduce LC risk.

Associations of the inflammatory diet index and smoking status with the risk of chronic obstructive pulmonary disease and lung cancer.

It remains unknown whether a low-inflammatory diet could modify the chronic obstructive pulmonary disease (COPD) and lung cancer risk related to smoking. To investigate the association between a low-inflammatory diet, smoking status, and the risk of COPD and lung cancer. A total of 171 050 COPD-free and lung cancer-free (mean age: 55.80) individuals were included in this study. COPD and lung cancer were defined as hospital admission. An inflammatory diet index (IDI) was developed based on C-reactive protein levels and was a weighted sum of 34 food groups. Participants were grouped into tertiles corresponding to IDI scores (lowest, middle, and highest). Over 2 091 071 person-years of follow-up, a total of 4007 individuals developed COPD (person-years: 2 075 579), and 1049 developed lung cancer. In comparison with the highest tertile of the IDI score, hazard ratios (HRs) and 95% confidence intervals (CIs) of COPD and lung cancer related to a low-inflammatory diet were 0.66 (0.61, 0.72) and 0.76 (0.65, 0.89), respectively. A low-inflammatory diet may prolong COPD onset by 1.88 (1.50, 2.27) years and lung cancer onset by 1.05 (0.45, 1.65) years. In joint effect analyses, participants with the lowest/middle IDI score and smoking had a significant 37% decrease in COPD risk and a 35% decrease in lung cancer risk compared to the participants with the highest IDI score and smoking. Replacing each standard deviation unit (≈1080.426 g day-1) of pro-inflammatory foods with anti-inflammatory foods was associated with a 30% lower COPD risk. Our findings suggest that a low-inflammatory diet may significantly mitigate the risk of smoking on COPD development, and delay the COPD onset by about 2 years. However, a low-inflammatory diet is associated with a reduced risk of lung cancer among only smokers. Substituting equal intake of pro-inflammatory foods with anti-inflammatory foods is related to a decreased risk of COPD, but not lung cancer.

Preventive and therapeutic effects of green tea on lung cancer: a narrative review of evidence from clinical and basic research.

Green tea is a popular beverage worldwide and has numerous health-promoting properties. Accumulating evidence indicates that green tea has preventive and therapeutic effects on lung cancer. This study aimed to investigate the association between green tea consumption and lung cancer. We performed a narrative review to summarized the association between green tea consumption and lung cancer. Green tea consumption is known to decrease lung cancer risk in the general population, as indicated by meta-analyses of observational studies. Two active components of green tea, theabrownin and (-)-epigallocatechin gallate (EGCG), mediate the antitumor activity of green tea. Theabrownin promotes apoptosis, induces cell cycle arrest, and inhibits the migration, clone formation, and proliferation of lung cancer cell lines in vitro and in vivo. EGCG inhibits lung cancer cell proliferation and promotes apoptosis, agenesis, and epithelial-mesenchymal transition (EMT). In addition, EGCG sensitizes lung cancer cells to cisplatin and tyrosine kinase inhibitors (TKIs). The possible molecular mechanisms underlying the antitumor activity of EGCG and theabrownin were reviewed. Observational studies have indicated that green tea has preventive effects on lung cancer. In vitro and animal studies have indicated that green tea has therapeutic effects on lung cancer. Further clinical trials are needed to illustrate the therapeutic effects of green tea or its active components (i.e., theabrownin, EGCG) on lung cancer.

Variants in CYP2J2 and CYP2C9 Contribute to Susceptibility of Lung Cancer.

Cytochrome P450 (CYP) enzymes are involved in the metabolism of xenobiotic and carcinogen. In the study, we evaluated the association of CYP2J2 and CYP2C9 variants with lung cancer. Five polymorphisms in CYP2J2 and four polymorphisms in CYP2C9 were genotyped in 507 lung cancer patients and 505 controls with Agena MassARRAY platform. The linkage of variants with lung cancer risk was evaluated by odds ratio (OR) and 95% confidence interval (CI) in genetic models and haplotype analyses. We found that CYP2C9 rs1934967 alleles were associated with lung cancer risk (P < 0.05). In stratified analysis, rs2280274 (women, non-smoker, non-drinker and lymphatic metastasis), rs11207535 (non-smoker and non-drinker), rs10889159 (non-smoker and non-drinker) of CYP2J2, whereas rs1934967 (age ≤ 60m, BMI > 24, squamous carcinoma) of CYP2C9 decreased lung cancer risk (P < 0.05). In addition, the results of linkage disequilibrium (LD) analysis showed that rs2280274|rs4388726 - TG (with adjustment: P = 0.042) of CYP2J2 and rs10509679|rs1934967|rs1934968|rs9332220 - GTGG (without adjustment: P = 0.044) of CYP2C9 were linked with a significantly decreased lung cancer risk. Our results indicated genetic variants in CYP2J2 and CYP2C9 might contribute to the susceptibility of lung cancer in Chinese population.

DNA repair in lung cancer: a large-scale quantitative analysis for polymorphisms in DNA repairing pathway genes and lung cancer susceptibility

ABSTRACT Background The results of associations between single nucleotide polymorphisms (SNPs) of genes in DNA repairing pathway and lung cancer (LC) risk are inconsistent. Methods We applied allele, dominant and recessive models to explore the risk of researched variants to LC in total LC and subgroups by ethnicity or LC subtypes with a cutoff point of p < 0.05. Results A total of 76,935 cases and 88,649 controls from 192 articles were included. Among the analyzed 40 variants from 20 genes, we found 9 statistically significant variants in overall populations by allele model, including five SNPs (rs1760944, rs9344, rs13181, rs1001581, and rs915927) increasing LC risk (odd ratios [ORs] = 1.10–1.71) and four SNPs (rs1042522, rs3213245, rs11615, and rs238406) decreasing the risk (ORs = 0.75–0.94). We identified rs1042522 and rs13181 as significant variants for LC in three models. Additionally, we identified differential significant SNPs in ethnic and subtype’s analysis with comparison to total population. Conclusions There are five SNPs in DNA repairing pathway associated with increased LC risk and four others decreased LC risk. Besides, the risky SNPs in different ethnicities and various LC subtypes were partly different, and the contribution of different genotypes to risk alleles were various as well.

The 2018 World Cancer Research Fund/American Institute for Cancer Research Score and Cancer Risk: A Longitudinal Analysis in the NIH-AARP Diet and Health Study.

We examined associations between adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention Recommendations using the standardized 2018 WCRF/AICR Score and cancer risk among older U.S. adults. Participants included 215,102 adults in the NIH-AARP Diet and Health Study followed between 2004 and 2011 (mean 7.0 person-years). Scores (range: 0-7 points) were calculated from self-reported weight, physical activity, and diet and alcohol intake measures. Outcomes included 17 cancers reviewed by WCRF/AICR (cases: male n = 11,066; female n = 8,865) and top three U.S. cancers in males (total n = 4,658; lung n = 2,211; prostate n = 920; colorectal n = 1,527) and females (total n = 5,957; lung n = 1,475; post-menopausal breast n = 3,546; colorectal n = 936). Cox proportional hazard ratios (HRs) were estimated for score and cancer risk associations, stratifying by sex and smoking status. Each one-point score increase was associated with 6% to 13% reduced cancer risk across combined outcomes, except for male never smokers' risk for top three cancers and male current smokers' risk for both combined cancer outcomes. Higher scores were associated with decreased lung cancer risk only among male former smokers (HR, 0.84; 95% CI, 0.79-0.89) and female current smokers (HR, 0.89; 95% CI, 0.82-0.96). Higher scores were associated with 7% to 19% decreased breast cancer risk across smoking strata and 10% to 14% decreased colorectal cancer risk among male and female never and former smokers. Greater recommendations adherence was associated with reduced cancer risk. Findings emphasize the importance of considering combined contributions of multiple lifestyle factors for cancer prevention among older adults and the potential modifying role of smoking history.

Epigenome–wide DNA methylation signature of plasma zinc and their mediation roles in the association of zinc with lung cancer risk

Essential trace element zinc is associated with decreased lung cancer risk, but underlying mechanisms remain unclear. This study aimed to investigate role of DNA methylation in zinc-lung cancer association. We conducted a case-cohort study within prospective Dongfeng-Tongji cohort, including 359 incident lung cancer cases and a randomly selected sub–cohort of 1399 participants. Epigenome-wide association study (EWAS) was used to examine association of plasma zinc with DNA methylation in peripheral blood. For the zinc-related CpGs, their mediation effects on zinc-lung cancer association were assessed; their diagnostic performance for lung cancer was testified in the case-cohort study and further validated in another 126 pairs of lung cancer case-control study. We identified 28 CpGs associated with plasma zinc at P < 1.0 × 10−5 and seven of them (cg07077080, cg01077808, cg17749033, cg15554270, cg26125625, cg10669424, and cg15409013 annotated to GSR, CALR3, SLC16A3, PHLPP2, SLC12A8, VGLL4, and ADAMTS16, respectively) were associated with incident risk of lung cancer. Moreover, the above seven CpGs were differently methylated between 126 pairs of lung cancer and adjacent normal lung tissues and had the same directions with EWAS of zinc. They could mediate a separate 7.05%∼22.65% and a joint 29.42% of zinc-lung cancer association. Compared to using traditional factors, addition of methylation risk score exerted improved discriminations for lung cancer both in case-cohort study [area under the curve (AUC) = 0.818 vs. 0.738] and in case-control study (AUC = 0.816 vs. 0.646). Our results provide new insights for the biological role of DNA methylation in the inverse association of zinc with incident lung cancer.

Association of oral microbiota with lung cancer risk in a low-income population in the Southeastern USA.

Oral microbiome plays an important role in oral health and systemic diseases, including cancer. We aimed to prospectively investigate the association of oral microbiome with lung cancer risk. We analyzed 156 incident lung cancer cases (73 European Americans and 83 African Americans) and 156 individually matched controls nested within the Southern Community Cohort Study. Oral microbiota were assessed using 16S rRNA gene sequencing in pre-diagnostic mouth rinse samples. Paired t test and the permutational multivariate analysis of variance test were used to evaluate lung cancer risk association with alpha diversity or beta diversity, respectively. Conditional logistic regression models were used to evaluate the association of individual bacterial abundance or prevalence with lung cancer risk. No significant differences were observed for alpha or beta diversity between lung cancer cases and controls. Abundance of families Lachnospiraceae_[XIV], Peptostreptococcaceae_[XI], and Erysipelotrichaceae and species Parvimonas micra was associated with decreased lung cancer risk, with odds ratios (ORs) and 95% confidence intervals (CIs) of 0.76 (0.59-0.98), 0.80 (0.66-0.97), 0.81 (0.67-0.99), and 0.83 (0.71-0.98), respectively (all p < 0.05). Prevalence of five pre-defined oral pathogens were not significantly associated with overall lung cancer risk. Prevalence of genus Bacteroidetes_[G-5] and species Alloprevotella sp._oral_taxon_912, Capnocytophaga sputigena, Lactococcus lactis, Peptoniphilaceae_[G-1] sp._oral_taxon_113, Leptotrichia sp._oral_taxon_225, and Fretibacterium fastidiosum was associated with decreased lung cancer risk, with ORs and 95% CIs of 0.55 (0.30-1.00), 0.36 (0.17-0.73), 0.53 (0.31-0.92), 0.43 (0.21-0.88), 0.43 (0.19-0.94), 0.57 (0.34-0.99), and 0.54 (0.31-0.94), respectively (all p < 0.05). Species L. sp._oral_taxon_225 was significantly associated with decreased lung cancer risk in African Americans (OR [95% CIs] 0.28 [0.12-0.66]; p = 0.00012). Results from this study suggest that oral microbiota may play a role in the development of lung cancer.

Dietary phytoestrogen intake and lung cancer risk: an analysis of the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial

Phytoestrogens (PEs) have estrogen-like activity and were found to lower incidences of several hormone-dependent cancers. Emerging evidence suggests that estrogen may play a role in lung cancer carcinogenesis. We aim to evaluate dietary PE intake and lung cancer risk using data from the Prostate, Lung, Colorectal and Ovarian cancer screening trial. A total of 1706 lung cancer cases were identified. The association between lung cancer risk and PE intake (in quartiles) was calculated using the Cox proportional hazard models adjusting for potential confounders. Stratified analyses by smoking status, sex and histology were also performed. The highest quartile of total PE intake was associated with a reduced risk of lung cancer compared with the lowest quartile [hazard ratio (HR) = 0.85, 95% confidence interval (CI): 0.73-0.99 for >1030 μg/day versus <290 μg/day] (P trend = 0.56). Similar patterns were observed among ever smokers (HR = 0.84, 95% CI: 0.71-0.98), non-small cell histology (HR = 0.84, 95% CI: 0.72-0.99), male (HR = 0.84, 95% CI: 0.69-1.03) and female (HR = 0.80, 95% CI: 0.64-0.99 for 510-1030 μg/day, HR = 0.84, 95% CI: 0.67-1.06 for >1030 μg/day versus <290 μg/day) subjects with no significant linear trend observed. Despite a lower consumption compared with the Asian population, increased PE intake still appears to decrease lung cancer risk in a Caucasian-dominant population. Future studies are needed to replicate these results in independent cohorts and shed a light on the potential mechanism of the protective effect of PEs on lung carcinogenesis and the interaction between PEs, smoking and endogenous estrogens.

Genetic evidence for the causal association between programmed death-ligand 1 and lung cancer.

PD-1/PD-L1 might have a causal role in operating lung cancer risk. However, such an association has not been investigated in the general population. We assessed whether PD-L1 has an independent effect on lung cancer risk using two-sample Mendelian randomization (MR) based on a proteomic genome-wide association study (3301 health participants) of European ancestry and the International Lung cancer Consortium (11,348 cases and 15,861 controls). Negative control analyses using chronic obstructive pulmonary disease (COPD)/asthma/interstitial lung disease (ILD)-related infection (~ 22,730 cases and ~ 112,908 controls) were also conducted to enhance the credibility of the selected instruments and MR-based estimates. This study found that genetically predicted PD-1/PD-L1 were not significantly associated with lung cancer after adjustment for multiplicity. However, suggestive evidence was observed for the total effect of higher PD-1 with decreased lung cancer risk and the direct effect (i.e., not mediated by PD-1 and smoking) of lower PD-L1 with decreased lung cancer risk. No association between genetically predicted PD-L1 and COPD/asthma/ILD related infection was noted. Taken together, our findings suggest that interventions decreasing PD-L1 might have a role in lowering lung cancer risk.

Relationship between glucosamine use and the risk of lung cancer: data from a nationwide prospective cohort study.

Research on glucosamine shows anti-inflammatory and anti-cancer benefits with minimal adverse effects. We aimed to explore the relationship between use of glucosamine and risk of lung cancer and lung cancer mortality based on data from the large-scale nationwide prospective UK Biobank cohort study. Participants were enrolled between 2006 and 2010 and followed-up to 2020. The Cox proportional hazards model was used to assess the relationship between glucosamine use and risk of lung cancer and lung cancer mortality. Subgroup analyses and sensitivity analyses were performed to explore the potential effect modifications and the robustness of the main findings. 439 393 participants (mean age 56 years; 53% females) with a mean follow-up of 11 years were included for analyses. 82 603 (18.80%) participants reported regular use of glucosamine at baseline. During follow-up, 1971 (0.45%) lung cancer events were documented. Glucosamine use was significantly associated with a decreased risk of lung cancer (hazard ratio (HR) 0.84, 95% CI 0.75-0.92; p<0.001) and lung cancer mortality (HR 0.88, 95% CI 0.81-0.96; p=0.002) in fully adjusted models. A stronger association between glucosamine use and decreased lung cancer risk was observed in participants with a family history of lung cancer when compared with those without a family history. Regular use of glucosamine was significantly related with decreased risk of lung cancer and lung cancer mortality, based on data from this nationwide prospective cohort study.

Rheumatoid arthritis and risk of lung cancer: Meta-analysis and Mendelian randomization study

ObjectiveObservational studies suggest that rheumatoid arthritis (RA) may be associated with lung cancer (LC) risk, while the evidence is inconsistent. We conducted a meta-analysis and a Mendelian randomization study to investigate the association and causality between RA and the LC risk. MethodsWe conducted a systematic search of cohort studies and performed a meta-analysis (PROSPERO ID CRD42020159082) to calculate the relative risks (RRs) and their 95% confidence intervals (95%CIs). Subgroup analyses based on sex and initiation year of follow-up were carried out. E‐values of each study were calculated to evaluate if existing studies were sensitive to unmeasured confounding. Furthermore, we investigated the correlation between genetically predisposed RA and LC risk using summary statistics from the International Lung Cancer Consortium (11,348 cases and 15,861 controls) and 90 RA-related single nucleotide polymorphisms from European and East Asian descent as instrumental variables. A two-sample Mendelian randomization (MR) analysis was performed to detect the findings based on LC and histological subtypes. Sensitivity analyses were performed to test the robustness of our findings. ResultsIn the meta-analysis of 11 cohort studies involving 183,888 patients, an increased risk of LC was observed among RA patients (RR = 1.44, 95%CI = 1.31–1.57). Subgroup analyses suggested that male patients have a relatively higher LC risk than female patients, and an increased incidence of LC in RA patients was found from 1950 to 2010. Conversely, in the MR analysis, we found that genetically predisposed RA was associated with a decreased risk of LC overall, while neither causally associated with the risk of lung adenocarcinoma nor squamous cell lung cancer. Nevertheless, genetically predisposed RA was associated with a decreased LC risk among the East Asian population, but not in Europeans. These results were robust against extensive sensitivity analyses. ConclusionOur meta-analysis suggested that although RA was associated with a relatively higher LC risk, the causal relationship between genetically predisposed RA and LC risk was not supported by the MR study. Further studies are warranted to elucidate the possible association between RA and the risk of LC, as well as its underlying mechanisms.