Increasing incidence of adenocarcinoma of the lung

Review of the histology of 219 lung cancers initially diagnosed at Lutheran General Hospital, Park Ridge, Illinois, in 1963-1967 and 1974-1976, confirms the increasing incidence of adenocarcinoma. This is due to an increase of adenocarcinoma in men. In women, the incidence of adenocarcinoma was higher than squamous carcinoma in the earliest period (44% adeno, 18% squamous). The percentage of women with lung cancer has also significantly increased from 19% to 31%, which increases the overall incidence of adenocarcinoma of the lung. As the number of women with lung carcinoma has increased, there has been no change in the percentage of adenocarcinoma in women.     

Changing incidence of adenocarcinoma of the lung: a brief review

The autopsy of lung cancer at Hines Veterans Administration Hospital was reviewed for a 27-year period, between 1957 and 1983. There has been a changing histologic pattern with a recent increase in adenocarcinoma and a relative decrease of the other cell types. This observation, based on a virtually all-male patient population, is partly attributed to better and improved diagnostic procedures.     

GST genetic polymorphisms and lung adenocarcinoma susceptibility in a Chinese population

Lung adenocarcinoma (AC) has been increasing over the last several decades in many countries, including China. Some of the glutathione S-transferases (GSTs) demonstrate polymorphisms which may play a role in lung AC susceptibility. Our previous study of a Chinese population found the GSTM1 null genotype to be associated with an increased risk of lung AC, and the combination of GSTM1 null genotype and CYP2E1 wild type conferred a significantly elevated risk. Here, we extended the study to investigate the potential role of GSTT1 and GSTP1 polymorphisms in likelihood of development of lung AC, either separately or in combination. This case-control study encompassed 112 cases with lung ACs and 119 age- and gender-matched cancer-free controls from Beijing. The frequencies for the GSTM1 null genotype were 61.6 and 50.4% among cases and controls, and for the GSTT1 null genotype 47.3 and 45.4%, respectively. The distribution of the GSTP1 Ile/Ile, Ile/Val and Val/Val genotypes was 59.8, 39.3 and 0.9% in cases, and 70.6, 28.6 and 0.8% in controls, respectively. No relationship between lung AC and the GSTT1 genotype was observed in the present study, either separately or in combination with the GSTM1 or GSTP1 genotypes. Although separate GSTM1 and GSTP1 polymorphisms were not statistically related to lung AC, the combination of GSTM1 null and GSTP1 Val was significantly associated with an elevated lung AC risk (OR=2.4, 95% CI 1.1-5.1).     

Oral bisphosphonate use and lung cancer incidence among postmenopausal women

BackgroundBisphosphonates are common medications for the treatment of osteoporosis in older populations. Several studies, including the Women’s Health Initiative (WHI), have found inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little is known about its association with other common malignancies. The objective of this study was to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI.Patients and methodsThe association between oral bisphosphonate use and lung cancer risk was examined in 151 432 postmenopausal women enrolled into the WHI in 1993–1998. At baseline and during follow-up, participants completed an inventory of regularly used medications including bisphosphonates.ResultsAfter a mean follow-up of 13.3 years, 2511 women were diagnosed with incident lung cancer. There was no evidence of a difference in lung cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio = 0.91; 95% confidence intervals, 0.80–1.04; P = 0.16). However, an inverse association was observed among those who were never smokers (hazard ratio = 0.57, 95% confidence interval, 0.39–0.84; P < 0.01).ConclusionIn this large prospective cohort of postmenopausal women, oral bisphosphonate use was associated with significantly lower lung cancer risk among never smokers, suggesting bisphosphonates may have a protective effect against lung cancer. Additional studies are needed to confirm our findings.     

COX-2/EGFR expression and survival among women with adenocarcinoma of the lung

Previous studies suggest that cyclooxygenase-2 (COX-2) expression may predict survival among patients with non-small cell lung cancer. COX-2 may interact with epidermal growth factor receptor (EGFR), suggesting that combined COX-2/EGFR expression may provide predictive value. The extent to which their independent or combined expression is associated with prognosis in women with adenocarcinoma of the lung is unknown. In the present study, we examined relationships between COX-2 expression (n = 238), EGFR expression (n = 158) and dual COX-2/EGFR expression (n = 157) and survival among women with adenocarcinoma of the lung. Overall survival was estimated by constructing Cox proportional hazards models adjusting for other significant variables and stratifying by stage at diagnosis and race. Clinical or demographic parameters were not associated with either COX-2 or EGFR expression. Patients with COX-2-positive tumors tended to have poorer prognosis than did patients with COX-2-negative tumors [hazard ratio (HR) 1.67, 95% confidence interval (CI) 1.01-2.78]. African-Americans with COX-2-positive tumors had a statistically non-significant higher risk of death than African-Americans with COX-2-negative tumors (HR 5.58, 95% CI 0.64-48.37). No association between COX-2 expression and survival was observed among Caucasians (HR 1.29, 95% CI 0.72-2.30). EGFR expression was associated with a 44% reduction in the risk of death (HR 0.56, 95% CI 0.32-0.98). COX-2-/EGFR+ tumor expression, but not COX-2+/EGFR+ tumor expression, was associated with survival when compared with other combined expression results. In conclusion, COX-2 and EGFR expression, but not combined COX-2+/EGFR+ expression, independently predict survival of women with adenocarcinoma of the lung.     

Smoking-adjusted incidence of lung cancer by occupation among Norwegian men

OBJECTIVE: To use aggregated data on smoking habits and lung cancer incidence in occupations assumed to carry no lung cancer risk to control for confounding in other occupational groups. METHODS: Lung cancer incidence was observed from 1971 to 1991 for 53 occupational groups and a group of economically inactive men in a national cohort study. Data on occupation and smoking habits were collected from national surveys during 1965-1980. The relationship between smoking habits and lung cancer incidence was estimated on aggregated level using data from 12 occupational groups that were initially assumed not to be exposed to occupational lung carcinogens. The estimated relationship was used to control confounding from smoking in the other groups. The results were presented as smoking-adjusted incidence ratios. RESULTS: A significant excess risk was found for 26 groups. It was estimated that about 20% of all lung cancer among men could be related to occupation after adjusting for the effect of smoking. CONCLUSIONS: Our method provided a clearer picture of the occupational risk and could be useful in other situations where individual information on smoking habits is lacking.     

Brain metastases in lung adenocarcinoma: impact of EGFR mutation status on incidence and survival

Background

The brain represents a frequent progression site in lung adenocarcinoma. This study was designed to analyse the association between the epidermal growth factor receptor (EGFR) mutation status and the frequency of brain metastases (BM) and survival in routine clinical practice.

Patients and methods

We retrospectively analysed the medical records of 629 patients with adenocarcinoma in Slovenia who were tested for EGFR mutations in order to analyse the cumulative incidence of BM, the time from the diagnosis to the development of BM (TDBM), the time from BM to death (TTD) and the median survival.

Results

Out of 629 patients, 168 (27%) had BM, 90 patients already at the time of diagnosis. Additional 78 patients developed BM after a median interval of 14.3 months; 25.8 months in EGFR positive and 11.8 months in EGFR negative patients, respectively (p = 0.002). EGFR mutations were present in 47 (28%) patients with BM. The curves for cumulative incidence of BM in EGFR positive and negative patients demonstrate a trend for a higher incidence of BM in EGFR mutant patients at diagnosis (19% vs. 13%, p = 0.078), but no difference later during the course of the disease. The patients with BM at diagnosis had a statistically longer TTD (7.3 months) than patients who developed BM later (3.1 months). The TTD in EGFR positive patients with BM at diagnosis was longer than in EGFR negative patients (12.6 vs. 6.8, p = 0.005), while there was no impact of EGFR status on the TTD of patients who developed BM later.

Conclusions

Except for a non-significant increase of frequency of BM at diagnosis in EGFR positive patients, EGFR status had no influence upon the cumulative incidence of BM. EGFR positive patients had a longer time to CNS progression. While EGFR positive patients with BM at diagnosis had a longer survival, EGFR status had no influence on TTD in patients who developed BM later during the course of disease.     

Socioeconomic status and prostate cancer incidence and mortality rates among the diverse population of California

Background  

The racial/ethnic disparities in prostate cancer rates are well documented, with the highest incidence and mortality rates observed among African-Americans followed by non-Hispanic Whites, Hispanics, and Asian/Pacific Islanders. Whether socioeconomic status (SES) can account for these differences in risk has been investigated in previous studies, but with conflicting results. Furthermore, previous studies have focused primarily on the differences between African-Americans and non-Hispanic Whites, and little is known for Hispanics and Asian/Pacific Islanders.     

Cigarette smoking is strongly associated with mutation of the K-ras gene in patients with primary adenocarcinoma of the lung.

BACKGROUND: The majority of lung carcinoma cases occur in current or former smokers. K-ras gene mutations are common in lung adenocarcinoma and have been associated with cigarette smoking, asbestos exposure, and female gender. METHODS: In the current study, the authors examined the contribution of cigarette smoking to K-ras gene mutations in patients with primary lung adenocarcinoma. Smoking histories were obtained from 106 prospectively enrolled patients with primary adenocarcinoma of the lung. RESULTS: K-ras mutations were detected in the primary tumor using an allele-specific ligation assay. Ninety-two of the 106 patients (87%) with lung adenocarcinoma were smokers. Nonsmokers with this tumor were more likely to be women (11 of 14; 79%), whereas the majority of smokers (57%) were men. K-ras mutations were detected in 40 of 106 tumors (38%) and were significantly more common in smokers compared with nonsmokers (43% vs. 0%; P = 0.001). CONCLUSIONS: The results of the current study confirm and extend previous observations that smokers with adenocarcinoma of the lung are more likely to have K-ras mutant tumors compared with nonsmokers. The strong link between cigarette smoking and K-ras mutations in adenocarcinoma of the lung supports the role of specific tobacco carcinogens in the etiology of this malignancy.     

Identification and characterization of side population cells in human lung adenocarcinoma SPC-A1 cells

Objective  

There has been an increasing interest in recent years in the role of stem cells. With an extensive understanding of their biology, a major role for stem cells in the malignant process has been proposed and the existence of cancer stem cells (CSCs) has been confirmed in hematopoietic malignancies and solid organ malignancies including brain cancer, breast, prostate, colon, and pancreatic cancer. Lung cancer is the leading cause of cancer mortality in most large cities of China. It is possible that lung cancer contains cancer stem cells responsible for its malignancy. The aim of this study is to identify, characterize and enrich the CSC population that drives and maintains lung adenocarcinoma growth and metastasis.     

Hepatoid adenocarcinoma in the lung

We have experienced a very rare case of hepatoid adenocarcinoma in the lung. A 55-year-old male with a history of smoking was diagnosed as adenocarcinoma of the right S2, and underwent resection of the right upper lobe and dissection of the hilum and mediastinal lymph nodes (complete resection). Pathological examination revealed cuboid atypical cells arranged in a papillary or trabecular fashion, and a proliferating pattern in most part of the tumor resembling that of hepatocellular carcinoma. Immunohistochemistry study showed alpha-fetoprotein (AFP)-positive tumor cells, hence the diagnosis of hepatoid adenocarcinoma was confirmed. Postoperative pathological staging classified the patient as having as p-T2NOMO, p-stage I B disease. The serum AFP level was not determined before surgery, but the value decreased gradually after surgery and has since remained within the normal range. At present, 32 months after the operation, no signs of recurrence have been observed. Hepatoid adenocarcinoma in the lung has been reported in eight patients with the present one being the ninth case. All were males, the tumor diameter was large and the patient prognoses were mostly poor, but at early stage two cases of long-term survival have been reported indicating that the stage is the most important prognostic factor also for rare tumor.     

人肺腺癌A549细胞系干细胞相关亚群的分离与鉴定

目的 分离人肺腺癌A549细胞系中的侧群(SP)细胞亚群并探讨其细胞特性.方法 采用免疫组化法检测人肺腺癌A549细胞系中ABCG2蛋白的表达.采用流式细胞术分选A549细胞系中的SP和非SP细胞亚群,并检测两亚群细胞的分化功能.采用逆转录聚合酶链反应(RT-PCR)方法检测两亚群细胞的ABCG2蛋白表达,通过两亚群细胞的生长曲线、细胞分裂指数、细胞周期各时相分布、平板克隆形成实验、体外侵袭和迁移实验、化疗药敏试验、细胞内药物浓度测定以及裸鼠移植瘤实验,比较两亚群细胞的生物学行为,并用RT-PCR和免疫组化方法检测移植瘤组织中ABCG2的表达.结果 A549细胞系中ABCG2蛋白的阳性表达率为2.13%.通过流式细胞术能成功分选得到SP细胞和非SP细胞,SP细胞亚群可产生SP及非SP两种细胞,而非SP细胞只能产生非SP细胞.SP细胞表达ABCG2,非SP细胞则不表达.两细胞亚群的增殖、迁移能力相似,吸光度、分裂指数、细胞周期时相分布和细胞体外迁移实验穿过滤膜的细胞数差异均无统计学意义(均P＞0.05),但SP细胞的侵袭能力和成瘤能力强于非SP细胞,细胞体外侵袭实验穿过滤膜的细胞数、体外细胞克隆形成数和移植瘤成瘤率均高于非SP细胞(P＜0.01,P＜0.01,P＜0.05).SP细胞和非SP细胞对顺铂(DDP)的敏感性和细胞内药物浓度相似,非SP细胞对5-氟尿嘧啶(5-Fu)、依托泊苷(VP-16)、长春瑞滨(NVB)和吉西他滨(GEM)的敏感性及细胞内药物浓度则高于SP细胞(均P＜0.01).结论 人肺腺癌A549细胞系SP细胞亚群富集了肺癌干细胞,通过流式细胞仪分选肺腺癌SP细胞亚群是分离肺腺癌干细胞的有效方法.

Abstract：

Objective To isolate and characterize the side population cells(SP cells) in the lung adenocarcinomas cell line A549. Methods The protein expression of ABCG2 in human lung adenocarcinoma cell line A549 was detected by immunohistochemistry.SP and NSP cells in the cell line A549 were isolated by FACS,and their differentiation was analysed.ABCG2 expression in the two cell subsets was detected by RT-PCR.The cell growth curves,cell division indexes,cell cycles,plate clone formation tests,migration and invasion assays,chemotherapeutic susceptibility tests,tests of the intracellular drug levels,and the tumor cell implantation experiments on nude mice were applied to study the biological properties of the two cell subsets.The expression of ABCG2 in the transplanted tumor in nude mice was detected by immunohistochemistry and RT-PCR. Results The positive rate of ABCG2 expression in the A549 cells by immunohistochemistry was 2.13%.SP and NSP cells were isolated by FACS.The SP cells could produce both SP and NSP cells,while NSP cells only produced NSP cells.SP cells expressed ABCG2,but NSP cells did not.The proliferation and migration abilities of the two cell subsets were similar,but the invasion and tumorigenic ability of SP cells was significantly higher than that of NSP cells.The susceptibilities to DDP and its intracellular levels of the two cell subsets were similar,but the susceptibilities to 5-FU,VP16,NVB and GEM and their intracellular levels of NSP cells were significantly higher than those of the SP cells. Conclusions SP cells in the human lung adenocarcinomas cell line A549 is enriched with tumor stem cells.An effective way to get lung adenocarcinomas stem cells is to isolate SP cells by FACS.     

Chemotherapy in adenocarcinoma of the lung

Adenocarcinoma of the lung (ACL) attracts increasing attention because of the fast rising incidence. Systemic chemotherapy with cytostatic agents has been widely used for patients with inoperable ACL, but a standard treatment has not yet been defined. A review of the literature revealed that the highest response rates observed for single agents and combination chemotherapy in ACL in randomized studies were 22% and 38%, respectively, while the longest median survivals were 35 weeks and 34 weeks. Independent prognostic factors for survival in ACL patients were performance status, prior non-radical resection, liver metastases, white blood cell count and serum values of lactate dehydrogenase and aspartic aminotransaminase. Using logistic regression analysis, the only significant predictor of response was measurable disease parameter, while 26 other variables were not significant. Response to chemotherapy was not a major prognostic factor for survival, probably because of the low rate of complete responses (4%). Chemotherapy in ACL remains experimental and the prognosis for these patients is poor. High priority should therefore be given to the identification of new agents or combination regimens with appreciable activity. The knowledge of prognostic factors should be used for optimal design of trials and interpretation of the results.     

Trends in esophageal adenocarcinoma incidence and mortality

BACKGROUND:

Over the past several decades, the incidence of esophageal adenocarcinoma (EAC) has rapidly increased. The purpose of this analysis was to examine temporal trends in EAC incidence and mortality within the US population and, in addition, to explore these trends within subgroups of the population.

METHODS:

The National Cancer Institute (NCI) Surveillance, Epidemiology and End Results (SEER 9) data were used to examine incidence and incidence‐based (IB) mortality in EAC from 1975 to 2009. Secular trends in incidence and IB mortality by cancer stage, sex, and race were further characterized using the NCI's Joinpoint Regression program.

RESULTS:

Based on SEER 9 data, EAC incidence and IB mortality continues to increase in the United States. However, since the mid‐1990s, the overall rate of increase in both EAC incidence and IB mortality appears to be slowing. In addition, in early‐stage cancers, there is a noticeable leveling off of IB mortality rates and divergence from incidence starting in the late 1990s. Over the study period, the average annual percentage increase in incidence was 6.1% in men and 5.9% in women.

CONCLUSIONS:

EAC incidence and IB mortality rates continue to rise in the United States, although at a slower rate in more recent years. In early‐stage cancers, IB mortality and incidence rates have diverged primarily because IB mortality rates have plateaued beginning in the late 1990s. Although EAC continues to be less common in women, the rate of increase in EAC incidence is similar in both sexes. Cancer 2013. © 2012 American Cancer Society.     

Patterns of cancer incidence among the population of qatar: a worldwide comparative study.

Background: Cancer is a major public health problem all over the world. Monitoring the evolution of the cancer burden in the State of Qatar is of great value but has never been explored in depth. Aims: The aim of the study was to determine the incidence patterns of cancer cases, assess trends during the period 1991 - 2006 and make comparisons with other countries. Methods: This was a retrospective cohort study based on the Cancer disease registry of Al Amal Cancer hospital, State of Qatar, from 1991 - 2006. All Qataris and non-Qataris, males and females, who were diagnosed with any type of cancer were included in this study. The diagnostic classification of definite cancer cases was made according to the International Classification of Disease 10th revision (ICD-10). Results: A total of 5,825 cancer cases were registered in Qatar during the period 1991 - 2006 with 56.7% in males and 43.3% in females, 35.6% in Qataris and 64.4% in non-Qataris. Incidence rates per 100,000 population showed that lung (5.9), lymph node (5.9), bone marrow (4.1) and connective tissue (3.9) were the top major cancers in men. In women, breast (30.1), genital organs (9), lymph node (6.8), rectum (6.1) and thyroid (5.7) cancers were the leading cancers. There was a sharp rise in the total number of cancer cases during the period 2002-2006 of 57.1% compared to the period 1991-1996. The incidence rate of cancer cases increased with increasing age in all cancer types except for breast cancer in women above 65 years old. During the study period, the five most common cancers among women were different from those in men. The incidence rate per 100,000 population of all cancer types in Qatar (63.1) was remarkably lower than the other Middle East countries and the UK. Conclusions: Cancer is an important public health problem in Qatar, with increase in incidence with age. Incidence rates of all cancers were higher across all age groups of women compared to men. Lung cancer was the most frequent cancer diagnosed in men and breast cancer in women. More epidemiological studies are now required to elucidate the patterns of cancer and related risk factors.     

Increasing incidence of adenocarcinoma of the proximal stomach.

A retrospective study was performed on patients with histologically proven gastric adenocarcinoma during the periods 1972 to 1976 (n = 368) and 1986 to 1990 (n = 870) to analyse the potential changes in tumour distribution within the stomach. A recent increase in gastric cancer patients admitted to our institution represents a change in the referral patterns of the patients. The mean age and male:female ratio according to site distribution of the tumour were not found to differ between the two periods. The proportion of carcinomas of the upper third of the stomach was, however, significantly increased (P less than 10(-6)) in the recent series (36.4%) compared with the old series (20.6%). Since the incidence of gastric cancer in our population seems to be unchanged, this may suggest a true increase in proximal gastric tumours. The data may indicate possible changes in aetiological influences.