History of periodontal disease diagnosis and lung cancer incidence in the Women’s Health Initiative Observational Study

Purpose

While some evidence suggests that periodontal disease (PD) might be positively associated with lung cancer, prospective studies in women are limited. Previous findings may reflect residual confounding by smoking. The study aims to determine whether history of PD diagnosis is associated with incident lung cancer in a large cohort of postmenopausal women.

Methods

Prospective analyses were conducted in a cohort of 77,485 postmenopausal women enrolled in the Women’s Health Initiative Observational Study. History of PD (prevalence of 26.1 %) was self-reported, and 754 incident lung cancer cases occurred during an average 6.8 (SD ± 2.6) years of follow-up. Cox proportional hazards regression analysis was used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs).

Results

Overall, PD was positively associated with lung cancer risk after adjusting for detailed smoking history including smoking status and pack-years of smoking (HR 1.24, 95 % CI 1.07–1.45). There was a positive additive interaction between PD with pack-years of smoking (p = 0.02), suggesting a potential synergistic effect between PD and smoking intensity on lung cancer. The association between PD and lung cancer was stronger in former smokers. When restricted to never-smokers, PD was not associated with lung cancer (HR 1.02, 95 % CI 0.68–1.53).

Conclusions

Periodontal disease was not independently associated with lung cancer in non-smoking postmenopausal women. However, smoking and PD jointly increased lung cancer risk beyond that expected from the sum of the each effect separately. The potential synergism between PD and smoking on lung cancer warrants further examination.     

Attributes of brain metastases from breast and lung cancer

Background

Most brain metastases arise from breast and lung cancers. Few studies compare the brain regions they involve, their numbers and intrinsic attributes.

Methods

Records of all patients referred to Radiation Oncology for treatment of symptomatic brain metastases were obtained. Computed tomography (n = 56) or magnetic resonance imaging (n = 72) brain scans were reviewed.

Results

Data from 68 breast and 62 lung cancer patients were compared. Brain metastases presented earlier in the course of the lung than of the breast cancer patients (p = 0.001). There were more metastases in the cerebral hemispheres of the breast than of the lung cancer patients (p = 0.014). More breast than lung cancer patients had cerebellar metastases (p = 0.001). The number of cerebral hemisphere metastases and presence of cerebellar metastases were positively correlated (p = 0.001). The prevalence of at least one metastasis surrounded with >2 cm of edema was greater for the lung than for the breast patients (p = 0.019). The primary tumor type, rather than the scanning method, correlated with differences between these variables.

Conclusions

Brain metastases from lung occur earlier, are more edematous, but fewer in number than those from breast cancers. Cerebellar brain metastases are more frequent in breast cancer.     

Effect of progesterone receptor status on maspin synthesis via nitric oxide production in neutrophils in human breast cancer

Background

Although progesterone receptor (PR) status, similarly to estrogen receptor status, is of prognostic importance in breast cancer, the involvement of the PR in breast cancer remains obscure. Studies were conducted to determine the function of the PR in neutrophils in the nitric oxide-induced synthesis of maspin, an anti-breast-cancer protein produced in nonmalignant mammary cells and in neutrophils in the circulation.

Methods

PR status was determined by immunohistochemistry. Maspin synthesis was determined by in-vitro translation of messenger RNA and quantified by enzyme-linked immunosorbent assay. Nitric oxide was determined by the methemoglobin method.

Results

It was found that PR status in neutrophils was identical with that in malignant breast tissues. A Scatchard plot for progesterone binding to normal and PR-positive (PR+) neutrophils revealed that whereas normal neutrophils had 11.5 × 10¹⁰ PR sites/cell with K _d = 47.619 nM, PR+ neutrophils had 6.6 × 10¹⁰ PR sites/cell with K _d = 47.619 nM. The progesterone negative (PR?) neutrophils failed to bind to progesterone. Incubation of normal and PR+ neutrophils with 25 nM progesterone produced 1.317 μM NO and 2.329 nM maspin; the PR+ neutrophils produced 0.72 μM NO and 1.138 nM maspin. The PR? neutrophils failed to produce any NO or maspin in the presence of progesterone. Inhibition of progesterone-induced NO synthesis led to complete inhibition of maspin synthesis in all neutrophils.

Conclusion

These results suggest that estrogen and progesterone complement each other in NO-induced maspin synthesis, and do not necessarily antagonize in the synthesis of the anti-breast-cancer protein.     

Lung cancer risk from radon in Ontario, Canada: how many lung cancers can we prevent?

Purpose

To calculate the burden of lung cancer illness due to radon for all thirty-six health units in Ontario and determine the number of radon-attributable lung cancer deaths that could be prevented.

Methods

We calculated the population attributable risk percent, excess life-time risk ratio, life-years lost, the number of lung cancer deaths due to radon, and the number of deaths that could be prevented if all homes above various cut-points were effectively reduced to background levels.

Results

It is estimated that 13.6 % (95 % CI 11.0, 16.7) of lung cancer deaths in Ontario are attributable to radon, corresponding to 847 (95 % CI 686, 1,039) lung cancer deaths each year, approximately 84 % of these in ever-smokers. If all homes above 200 Bq/m³, the current Canadian guideline, were remediated to background levels, it is estimated that 91 lung cancer deaths could be prevented each year, 233 if remediation was performed at 100 Bq/m³. There was important variation across health units.

Conclusions

Radon is an important contributor to lung cancer deaths in Ontario. A large portion of radon-attributable lung cancer deaths are from exposures below the current Canadian guideline, suggesting interventions that install effective radon-preventive measures into buildings at build may be a good alternative population prevention strategy to testing and remediation. For some health units, testing and remediation may also prevent a portion of radon-related lung cancer deaths. Regional attributable risk estimates can help with local public health resource allocation and decision making.     

Potential causal links of long-term air pollution with lung cancer incidence: From the perspectives of mortality and hospital admission in a large cohort study in southern China

Evidence on the potential causal links of long-term air pollution exposure with lung cancer incidence (reflected by mortality and hospital admission) was limited, especially based on large cohorts. We examined the relationship between lung cancer and long-term exposure to particulate matter (PM, including PM_2.5, PM₁₀ and PM_10-2.5) and nitrogen dioxide (NO₂) among a large cohort of general Chinese adults using causal inference approaches. The study included 575 592 participants who were followed up for an average of 8.2 years. The yearly exposure of PM and NO₂ was estimated through satellite-based random forest approaches and the ordinary kriging method, respectively. Marginal structural Cox models were used to examine hazard ratios (HRs) of mortality and hospital admission due to lung cancer following air pollution exposure, adjusting for potential confounders. The HRs of mortality due to lung cancer were 1.042 (95% confidence interval [CI]: 1.033-1.052), 1.032 (95% CI:1.024-1.041) and 1.052 (95% CI:1.041-1.063) for each 1 μg/m³ increase in PM_2.5, PM₁₀ and NO₂, respectively. In addition, we observed statistically significant effects of PMs on hospital admission due to lung cancer. The HRs (95%CI) were 1.110 (1.027-1.201), 1.067 (1.020-1.115) and 1.079 (1.010-1.153) for every 1 μg/m³ increase in PM_2.5, PM₁₀, PM_10-2.5, respectively. Furthermore, we found larger effect estimates among the elderly and those who exercised more frequently. We provided the most comprehensive evidence of the potential causal links between two outcomes of lung cancer and long-term air pollution exposure. Relevant policies should be developed, with special attention to protecting the vulnerable groups of the population.     

Assessing environmental and occupational risk factors for lung cancer in Mexican–Americans

Background

We investigated environmental and occupational exposures and smoking history (while controlling for demographics) in a population of Mexican–American lung cancer cases and controls from the Houston metropolitan area.

Methods

Data were collected between 1991 and 2005 as part of an on-going multi-racial/ethnic, lung cancer case–control study. Cases included 212 Mexican–American lung cancer cases from UT MD Anderson Cancer Center. Controls (n = 328) were recruited from Houston’s largest multispecialty group practice and frequency matched to the cases by age (±5 years), sex, and ethnicity. Environmental and occupational factors were analyzed and odds ratios and 95% confidence intervals were calculated using logistic regression.

Results

We detected elevated risks of lung cancer associated with pesticide exposure and found conventional and antimicrobial (e.g., sterilizers, disinfectants, antiseptics) pesticides were associated with an increased risk of lung cancer in Mexican–Americans (conventional pesticides and antimicrobial pesticides combined: OR = 1.80, 95% CI 1.13–2.86; conventional pesticides: OR = 2.05, 95% CI 1.23–2.39; antimicrobial pesticides: OR = 2.48, 95% CI 1.46–4.21).

Conclusions

Although we found over a two-fold increased risk of lung cancer among Mexican–Americans for pesticides, we could not identify individual pesticides. Our findings are an important preliminary step in identifying factors that are specifically associated with lung cancer risk among Mexican Americans.     

Significant association of combination of OCT4, NANOG,and SOX2 gene polymorphisms in susceptibility and response to treatment in North Indian breast cancer patients

Purpose

Dysregulations of regulatory genes in embryonic stem cells (ESCs) gene polymorphisms may lead to breast cancer cell growth, differentiation, and tumor metastasis.

Methods

Polymorphisms in OCT4 (rs3130932), NANOG (rs11055786), LIN28 (rs4274112), and SOX2 (rs11915160) genes were evaluated for susceptibility in 297 breast cancer females and 273 healthy controls from north Indian population. Response to neo-adjuvant chemotherapy was followed in 128 locally advanced breast cancer patients along with clinicopathological features. Genotyping was done using TaqMan allelic discrimination assays. Statistical analysis was performed using SPSS and multifactor dimensionality reduction (MDR).

Results

For OCT4 gene polymorphism, protective effect of genotypes AC [P _corr = 0.031, OR = 0.63 (0.44–0.91)] and AC+CC [P _corr = 0.031, OR = 0.68 (0.48–0.95)] was seen in patients. However, no association of NANOG, LIN28, and SOX2 gene polymorphisms was found with overall breast cancer susceptibility. Further, significant association of AG+GG genotype [P _corr = 0.021, OR = 6.08 (1.83–20.15)] and G allele [P _corr = 0.021, OR = 3.07 (1.21–7.77)] of rs4274112 polymorphism was seen with positive lymph node. For OCT4, significant association of allele C was seen with patients having negative hormone receptor [P _corr = 0.021, OR = 0.51 (0.29–0.90)], but no association of any of the studied polymorphisms individually was found with response to NACT. On MDR analysis, we found combination of SNPs SOX2 rs11915160, OCT4 rs3130932, and NANOG rs11055786 to be the best interaction model for predicting breast cancer risk [p for permutation test <10^?3, OR = 2.04 (1.43–2.910] and response to NACT [p for permutation test = 0.005, OR = 2.09 (1.24–3.52)].

Conclusion

Combination of genetic variants of ESCs gene may have a profound effect in breast cancer risk and response to NACT.     

The effect of atmospheric particulate matter on survival of breast cancer among US females

Short-term effects of ambient particulate matter (PM) on cardiopulmonary morbidity and mortality have been consistently documented. However, no study has investigated its long-term effects on breast cancer survival. We selected all female breast cancer cases (n = 255,128) available in the California Surveillance Epidemiology and End Results cancer data. These cases were linked to 1999–2009 California county-level PM daily monitoring data. We examined the effect of PM on breast cancer survival. Results from Kaplan–Meier survival analysis show that female breast cancer cases living in areas with higher levels of PM₁₀ and PM_2.5 had a significant shorter survival than those living in areas with lower exposures (p < 0.0001). The results from marginal cox proportional hazards models suggest that exposure to higher PM₁₀ (HR 1.13, 95 % CI 1.02–1.25, per 10 μg/m³) or PM_2.5 (HR 1.86, 95 % CI 1.12–3.10, per 5 μg/m³) was significantly associated with early mortality among female breast cancer cases after adjusting for individual-level covariates such as demographic factors, cancer stage and year diagnosed, and county-level covariates such as socioeconomic status and accessibility to medical resources. Interactions between cancer stage and PM were also observed; the effect of PM on survival was more pronounced among individuals diagnosed with early stage cancers. This study suggests that exposure to high levels of PM may have deleterious effects on the length of survival from breast cancer, particularly among women diagnosed with early stage cancers. The findings from this study warrant further investigation.     

Dietary inflammatory index,Mediterranean diet score,and lung cancer: a prospective study

Purpose

To investigate prospectively the associations of Dietary Inflammatory Index (DII) and Mediterranean Diet Score (MDS) with lung cancer.

Methods

We used data from men and women aged 40–69 years at recruitment in 1990–1994, who were participants in the Melbourne Collaborative Cohort Study (n = 35,303). A total of 403 incident lung cancer cases were identified over an average 18-year follow-up. Hazard ratios (HR) were estimated using Cox regression, adjusting for smoking status and other risk factors, with age as the time metric.

Results

An inverse correlation was observed between the DII and MDS (ρ = ?0.45), consistent with a higher DII being pro-inflammatory and less ‘healthy,’ while a high MDS reflects a ‘healthier’ diet. The DII was positively associated with risk of lung cancer in current smokers [HR_{Q4 vs Q1} = 1.70 (1.02, 2.82); P_trend = 0.008] (p interaction between DII quartiles and smoking status = 0.03). The MDS was inversely associated with lung cancer risk overall [HR_{7–9 vs 0–3} = 0.64 (0.45, 0.90); P_trend = 0.005] and for current smokers (HR_{7–9 vs 0–3} = 0.38 (0.19, 0.75); P_trend = 0.005) (p interaction between MDS categories and smoking status = 0.31).

Conclusions

The MDS showed an inverse association with lung cancer risk, especially for current smokers. A high DII, indicating a more pro-inflammatory diet, was associated with risk of lung cancer only for current smokers. A healthy diet may reduce the risk of lung cancer, especially in smokers.

     

Leukocyte telomere length in a population-based case–control study of ovarian cancer: a pilot study

Objectives

Telomeres are structures at chromosome ends that contribute to maintaining genomic integrity. Telomere shortening with repeated cell divisions may lead to genomic instability and carcinogenesis. Studies suggest that shorter telomeres in constitutional DNA are associated with bladder, breast, lung, and renal cancer. Ovarian cancer tissues also have shortened telomeres and increased telomerase activity, suggesting that telomere abnormalities may be related to ovarian cancer.

Methods

We investigated leukocyte telomere length in 99 women with serous ovarian adenocarcinoma and 100 age-matched cancer-free controls enrolled in a population-based case–control study.

Results

Cases tended to have shorter telomeres than controls (P _wilcoxon = 0.002). Compared to subjects with telomere lengths in the longest tertile, those in the middle and shortest tertiles showed respective age-adjusted odds ratios (95% confidence intervals) of 2.69 (1.23–5.88) and 3.39 (1.54–7.46) (P _trend = 0.002). Strongest associations were found for subjects with poorly differentiated carcinomas (OR = 4.89, 95% CI 1.93–12.34).

Conclusions

This study shows that short leukocyte telomeres are associated with serous ovarian adenocarcinoma. These findings should be confirmed in large, prospective studies.     

Phase II clinical trial of PM00104 (Zalypsis®) in urothelial carcinoma patients progressing after first-line platinum-based regimen

Purpose

This exploratory phase II clinical trial evaluated the antitumor activity, safety profile and pharmacokinetics of PM00104 (Zalypsis^®) 3 mg/m² 1 h every 3-week intravenous infusion in patients with advanced and/or metastatic urothelial carcinoma progressing after first-line platinum-based chemotherapy.

Methods

The primary efficacy end point was the disease control rate (DCR), defined as the percentage of patients with confirmed objective response or progression-free at 3 months, according to the response evaluation criteria in solid tumors.

Results

In a first stage (n = 19 patients evaluable for efficacy), only one patient achieved DCR (stable disease as best response and progression-free survival of 3.1 months). According to the 2-stage design used, the primary efficacy objective was unmet, and therefore, the trial was finalized without opening the second stage. The most common adverse events related to PM00104 were fatigue, anorexia, nausea, troponin I increase and neutropenia, which were transient and manageable with dose modifications or administration delays. Mean PK results (C _max = 48.57 μg/l and area under the curve (AUC) = 154.97 h μg/l) were similar to those observed in a previous phase I trial evaluating the same dose and schedule. Few troponin I concentrations were higher than 0.10 ng/ml, and none of them were related to parameters of PM00104 exposure such as AUC or C _max.

Conclusions

No recommendation is given for further evaluation of PM00104 as single-agent treatment of patients with pretreated advanced and/or metastatic urothelial carcinoma. No new safety signals were observed.     

13C-uracil breath test to predict 5-fluorouracil toxicity in gastrointestinal cancer patients

Purpose

Up to 30 % of patients undergoing 5-fluorouracil (5FU)-based chemotherapy experience severe toxicity. Dihydropyrimidine dehydrogenase (DPD) deficiency explains 36–61 % of cases. Predicting toxicity is an unmet challenge. Uracil breath test (UraBT) consists of measuring ¹³CO₂ in exhaled breath after ingestion of 2-¹³C-uracil to evaluate pyrimidine (and 5FU) catabolism.

Methods

We studied 33 gastrointestinal cancer patients previously exposed to 5FU: Thirteen had grade 3–4 and 20, grade 0–1 toxicity. The following tests were used to evaluate pyrimidine catabolism: (1) sequencing of three exons of DPYD; (2) plasma dihydrouracil/uracil ratio (UH₂/U); and (3) UraBT. We tested the performance of UraBT to discriminate patients who had grade 0–1 toxicity versus grade 3–4 toxicity and patients with and without proven DPD deficiency.

Results

Of the thirteen patients, four grade 3–4 toxicity patients were proved to be DPD-deficient: Three had deleterious mutations (IVS14 + 1G>A in one; single nucleotide polymorphism 2846A>T in two), and one had low UH₂/U ratio. Mean delta over baseline in 50 min (DOB₅₀) significantly differed between groups. DOB₅₀≤161.4 discriminated individuals with grade 3–4 versus grade 0–1 toxicity (sensitivity = 61.5 %; specificity = 85 %) and DPD-deficient versus non-DPD-deficient (sensitivity = 75 %; specificity = 85 %).

Conclusion

UraBT has moderate accuracy in discriminating individuals who manifested severe toxicity from those who had mild or no toxicity to 5FU.     

Age at first childbirth and oral contraceptive use are associated with risk of androgen receptor-negative breast cancer: the Malmö Diet and Cancer Cohort

Purpose

Risk factors for breast cancer vary according to breast cancer subtype. This study analyzes the impact of potential risk factors in breast cancer by androgen receptor (AR) status.

Methods

A total of 17,035 women were followed in the population-based prospective Malmö Diet and Cancer Study. Baseline data included lifestyle factors including anthropometry, reproductive history, and exogenous hormone use. During follow-up (mean: 12.8 years), 747 invasive breast cancers were diagnosed. Expression of AR was determined by immunohistochemistry in tumor tissue microarrays.

Results

AR status was assessable in 516 of 747 tumors (69%). Among these, 467 tumors (90.5%) were AR positive (AR⁺) and 49 tumors (9.5%) were AR negative (AR^-). AR negativity was significantly associated with estrogen receptor (ER) and progesterone receptor negativity, higher grade and proliferation (Ki67). Cox regression analyses stratified by AR status showed significant associations between reproductive factors and AR^- breast cancer. The older the woman at first childbirth the higher the risk of AR^- breast cancer; adjusted HR_≤20yrs = 0.35, HR_{>20–≤25yrs} = 0.62, HR_nulliparous = 1.00, HR_{>25–≤30yrs} = 1.29, HR_>30yrs = 1.92, p _trend = 0.001. No such association was seen for AR⁺ tumors. Similarly, ever oral contraceptive use increased the risk of AR^- breast cancer [Adj. HR = 2.59, 95% CI (1.26–5.34)] compared to never use, but not for AR⁺ breast cancer.

Conclusions

Advanced age at first child birth and use of oral contraceptives were associated with increased risk of AR^? breast cancer. This study may contribute to enhanced understanding of the role of the AR in breast carcinogenesis and improve risk stratification tools for personalized breast cancer prevention.     

Association of Mosaic Loss of Chromosome Y with Lung Cancer Risk and Prognosis in a Chinese Population

Introduction

Mosaic loss of chromosome Y (mLOY) is the most commonly detectable mosaic chromosomal event in cancers; however, its underlying relationship with tumorigenesis is still unclear.

Mechanisms of enhanced tumoricidal efficacy of multiple small dosages of ranpirnase, the novel cytotoxic ribonuclease, on lung cancer

Purpose

The effect of multiple small dosages of the cytotoxic RNase, ranpirnase (ONCONASE^®, ONC), on lung cancer was studied. The possible mechanisms for the enhanced tumoricidal efficacy of multiple small dosages of ONC were also investigated.

Methods

Hematoxylin and eosin staining, TUNEL labeling, and caspase-3-antibody labeling were used for in vivo analysis of apoptosis. A growth-delay assay was applied to detect the therapeutic potential of small and multiple dosages of ONC in vivo. ONC-induced changes in blood flow in A549 tumors and the kidney were measured non-invasively by dynamic contrast enhanced magnetic resonance imaging (DCE-MRI).

Results

In cell culture studies, ONC significantly inhibited tumor growth of A549 human NSCLC cells without damaging non-cancerous cells (HLF-1 human lung fibroblast). Multiple small dosages of ONC significantly prolonged tumor growth delay of A549 tumors, with increased apoptosis in vivo from 0.5 ± 0.3 to 70.1 ± 1.1% (by TUNEL labeling, N = 3, P < 0.05). Interestingly, multiple small doses of ONC were more effective than a single large dose for the inhibition of tumor growth with reduced side effect. Using non-invasive DCE-MRI methods, we found that the mean of the K ^trans median values increased to 49.3 ± 7.5% from the pre-ONC values by ONC (N = 4 mice, P < 0.05). A subsequent T ₁ map of the kidney showed that T ₁ values were temporarily decreased for up to 2 days (however, fully recovered ～4 days post-treatment).

Conclusions

Multiple small dosages of ONC significantly inhibited tumor growth of A549 NSCLC cells in vivo, with markedly increased apoptosis. This investigation suggests important potential clinical uses of ONC for the treatment of NSCLC cancer patients.     

C-reactive protein and postmenopausal breast cancer risk: results from the E3N cohort study

Background

C-reactive protein (CRP), a marker of low-grade inflammation, has been associated with breast cancer risk, but results are scarce and inconsistent.

Methods

A case–control study nested within the E3N prospective cohort included 549 postmenopausal breast cancer cases and 1,040 matched controls, all free of breast cancer at baseline. Serum levels of CRP were measured in samples collected between 1995 and 1999. Unconditional logistic regression models were used to evaluate the association between CRP and breast cancer risk, adjusting for matching factors and known breast cancer risk factors.

Results

No association was observed between CRP levels and breast cancer risk overall. However, a significant interaction was observed between CRP levels and body mass index (BMI). A statistically significant increase in breast cancer risk was observed in overweight and obese women (BMI ≥ 25 kg/m²) (OR 1.92, 95 % CI 1.20–3.08 for CRP ≥ 2.5 mg/L compared with CRP < 1.5 mg/l, p _trend = 0.003, p _interaction between CRP and BMI = 0.03). Similar results were observed in women with waist circumference (WC) ≥ 88 cm (p _trend = 0.01, p _interaction = 0.06) and waist-to-hip ratio (WHR) ≥ 0.80 (p _trend = 0.06, p _interaction = 0.35). CRP levels were not associated with breast cancer risk in women with normal BMI, WC, or WHR.

Conclusions

We found a positive association between CRP levels and postmenopausal breast cancer risk restricted to women with excess adiposity. The suggested relationship between low-grade inflammation, abdominal adiposity, and postmenopausal breast cancer risk deserves further investigation.     

Gastric cancers with microsatellite instability exhibit high fluorodeoxyglucose uptake on positron emission tomography

Background

Gastric cancers exhibit various degrees of ¹⁸F-fluorodeoxyglucose (FDG) uptakes on positron emission tomography/computed tomography (PET/CT) imaging. The aim of this study was to evaluate whether FDG uptake in gastric cancer varies according to the microsatellite instability (MSI) status.

Methods

Consecutive gastric cancer patients who underwent PET/CT imaging and MSI analysis were included in the study. The maximum standardized uptake value (SUV_max) of gastric cancer was assessed using PET/CT imaging.

Results

Of 131 gastric cancers, 16 exhibited a high incidence of MSI (MSI-H) and 3 exhibited a low incidence of MSI (MSI-L). In 29 subjects who showed no uptake on PET/CT imaging the gastric cancers were all microsatellite stable (MSS). Gastric cancers with MSI were related to age older than 60 years (p = 0.002), cancer volume larger than 10 cm³ (p = 0.015), and the presence of FDG uptake on PET/CT imaging (p = 0.001). A higher SUV_max of gastric cancer was linked to the presence of MSI (p < 0.001).

Conclusion

The presence of MSI is related to FDG uptake in gastric cancer. Care should be taken with MSS gastric cancers, because they show lower SUV_max on PET/CT imaging than MSI gastric cancers.     

Risk factors for primary lung cancer among never smokers by gender in a matched case–control study

Objective

Lung cancers that occur in never smokers differ from those that occur in smokers. We performed an analysis of potential epidemiological risk factors for lung cancer among never smokers.

Methods

In this hospital-based matched case–control study, all 1,540 matched case–control pairs were Han Chinese in Taiwan. The data on demographic characteristics, smoking habit, exposure to environmental tobacco smoke, medical history of lung diseases, family history of lung cancer, and female characteristics were collected from a structured questionnaire. A multiple conditional logistic regression was used to estimate odds ratios and 95 % confidence intervals after adjusting for possible confounders.

Results

Overall, several epidemiological factors of lung cancer in never smokers were different between males and females. For the female population, subjects who were exposed to environmental tobacco smoke (OR = 1.39, 95 % CI = 1.17–1.67) with a history of pulmonary tuberculosis and with family history of lung cancer in first-degree relatives (OR = 2.44, 95 % CI = 1.79–3.32) had higher risk of lung cancer, while subjects with a history of hormone replacement therapy and using fume extractors for those who cooked were protective. For the male population, only subjects with family history of lung cancer in first-degree relatives (OR = 2.77, 95 % CI = 1.53–5.01) were significantly associated with risk of lung cancer.

Conclusion

This study provides insights about the epidemiological factors of lung cancer in never smokers, adding to existing evidence that family history of lung cancer and environmental tobacco smoke may moderate lung cancer risk.     

Identification of the methylation of p14ARF promoter as a novel non-invasive biomarker for early detection of lung cancer

Background

Recent diagnostic procedure advances have greatly improved early lung cancer detection. However, the invasive, unpleasant and inconvenient nature of current diagnostic procedures limits their application. There is a great need of novel non-invasive biomarkers for early lung cancer diagnosis. In the present study, we intend to determine whether the blood signatures of p14ARF promoter methylation are suitable for early detection of lung cancer.

Methods

The study aimed to assess the probability of p14ARF promoter methylation in plasma samples to detect early lung cancer using nested methylation-specific PCR in the training set consisted of tumor tissues and paired blood. Besides, we were further to discuss the difference in time to progression between methylation and unmethylation of p14ARF promoter using univariate and multivariate analysis.

Results

The methylation of p14ARF promoter was detected in 33.6 % of tumor tissues, and 12.1 and 25.2 % in distant-cancer mucosa and matched plasma, respectively, and our study has also demonstrated the positive correlation between them by Pearson’s test (r = 0.300). The tumor-free survival time of the unmethylation of p14ARF promoter is significantly longer than that of the methylation of p14ARF promoter in tumor tissues (χ ² = 7.149, P = 0.008).

Conclusion

The methylation of p14ARF promoter in plasma samples has strong potential as a novel non-invasive biomarker for early detection of lung cancer, and the methylation of p14ARF promoter was considered as prognostic factor in our study.     

Tobacco smoking, NBS1 polymorphisms, and survival in lung and upper aerodigestive tract cancers with semi-Bayes adjustment for hazard ratio variation

Purpose

Although single nucleotide polymorphisms (SNPs) of NBS1 have been associated with susceptibility to lung and upper aerodigestive tract (UADT) cancers, their relations to cancer survival and measures of effect are largely unknown.

Methods

Using follow-up data from 611 lung cancer cases and 601 UADT cancer cases from a population-based case–control study in Los Angeles, we prospectively evaluated associations of tobacco smoking and 5 NBS1 SNPs with all-cause mortality. Mortality data were obtained from the Social Security Death Index. We used Cox regression to estimate adjusted hazard ratios (HR) for main effects and ratios of hazard ratios (RHR) derived from product terms to assess hazard ratio variations by each SNP. Bayesian methods were used to account for multiple comparisons.

Results

We observed 406 (66 %) deaths in lung cancer cases and 247 (41 %) deaths in UADT cancer cases with median survival of 1.43 and 1.72 years, respectively. Ever tobacco smoking was positively associated with mortality for both cancers. We observed an upward dose–response association between smoking pack-years and mortality in UADT squamous cell carcinoma. The adjusted HR relating smoking to mortality in non-small cell lung cancer (NSCLC) was greater for cases with the GG genotype of NBS1 rs1061302 than for cases with AA/AG genotypes (semi-Bayes adjusted RHR = 1.97; 95 % limits = 1.14, 3.41).

Conclusions

A history of tobacco smoking at cancer diagnosis was associated with mortality among patients with lung cancer or UADT squamous cell carcinoma. The HR relating smoking to mortality appeared to vary with the NBS1 rs1061302 genotype among NSCLC cases.