Parathyroid hormone-related protein regulates the growth of orthotopic human lung tumors in athymic mice.

BACKGROUND: Parathyroid hormone-related protein (PTHrP) has growth regulatory effects for many malignant cells and may influence the progression of carcinomas of the breast, prostate, and lung. In the current study, the authors investigated the in vivo and in vitro effects of PTHrP neutralizing antibody and PTHrP treatment on the growth of BEN cells, a human lung squamous cell carcinoma line that expresses PTHrP and its receptor. METHODS: Orthotopic lung tumors were produced in 20 athymic mice with BEN-GFP cells (a clonal line that stably expresses green fluorescent protein [GFP]) by instilling suspensions of 3 x 10(6) cells per mouse into the lungs of anesthetized animals. The mice were divided into 2 groups receiving either subcutaneous mouse antihuman PTHrP antibodies or irrelevant mouse immunoglobulin (Ig) G (150 microg) twice weekly. RESULTS: After 30 days, 6 of 10 mice receiving anti-PTHrP antibodies had lung tumors visible on macroscopic inspection, but only 1 of the 10 mice treated with irrelevant IgG had a lung tumor that was of that size (P < 0.01). GFP fluorescence was significantly greater in lung homogenates of the PTHrP antibody-treated mice than in the mice treated with IgG (6006 +/- 411 vs. 2907 +/- 282 relative fluorescent units, respectively; P < 0.001). Although neutralizing antibodies stimulated BEN cell lung tumor growth, exogenous PTHrP 1-34 treatment (0.01-1 nM) inhibited the growth of cultured BEN cells by approximately 40%. CONCLUSIONS: Although PTHrP expression has been reported to be associated with more aggressive malignancies, the data from the current study suggest that PTHrP 1-34 was a paracrine growth inhibitor in BEN human lung carcinoma cells. The growth-related effects of PTHrP are complex, and can be both stimulatory and inhibitory.     

Gender differences in UVB-induced skin carcinogenesis, inflammation, and DNA damage

The American Cancer Society reports the incidence of squamous cell carcinoma in males to be thrice the incidence in females. This increased squamous cell carcinoma incidence has been attributed to men accumulating more sun exposure and using less sun protection than women. To date, there have been no controlled studies examining the effect of gender on skin tumor development following equal doses of UVB. Gender differences in UVB-induced skin carcinogenesis were examined using the Skh-1 mouse model. After chronic exposure to equal doses of UVB, male mice developed tumors earlier and had more tumors than female mice; tumors in male mice tended to be larger, and the total tumor burden was greater than in females. In addition, tumors in males were of more advanced histologic grade compared with those of female mice. To evaluate the contribution of differences in inflammation and DNA damage to differences in skin carcinogenesis, male and female Skh-1 mice were exposed once to 2,240 J/m(2) UVB and examined 48 h after exposure. Surprisingly, male mice developed less of an inflammatory response, as determined by skin fold thickness and myeloperoxidase activity, compared with females. Interestingly, male mice showed more cutaneous oxidative DNA damage than the females and lower antioxidant levels. These results show a gender bias in skin carcinogenesis and suggest that the gender difference in tumor development is more influenced by the extent of oxidative DNA damage and antioxidant capacities than by inflammatory response.     

Inhibition by erlotinib of primary lung adenocarcinoma at an early stage in male mice

PURPOSE: Erlotinib, a small molecule inhibitor of the tyrosine kinase (TK) domain of epidermal growth factor receptor (EGFR), increases survival of advanced non-small cell lung cancer patients who failed standard chemotherapy (Phase III study). We evaluated whether erlotinib is also effective at an early stage of primary lung tumorigenesis in a carcinogen-induced lung tumor model in mice. METHODS: Sixteen weeks after carcinogen (urethane) injection, when small self-contained adenomas are evident, male and female A/J mice were treated IP with 10 mg/kg erlotinib or Captisol vehicle daily over 3.5 weeks (15 mice per group). The efficacy, metabolism and mechanism of action of erlotinib were evaluated. RESULTS: Erlotinib reduced tumor burden in males by twofold compared to vehicle (12.7 +/- 1.2 vs 26.2 +/- 2.5 mg, respectively; p < 0.0001), while tumor burden in erlotinib-treated females slightly increased compared to vehicle by 21% (15.1 +/- 1.2 vs 11.9 +/- 0.9 mg, respectively; p < 0.05). Tumor multiplicity, in contrast, was unaffected by erlotinib. The levels of erlotinib that accumulated in plasma, lung tumor tissue and adjacent uninvolved (UI) lung were comparable in males and females. Males, however, accumulated more OSI-420, an active and pharmacologically equipotent metabolite of erlotinib, than females in plasma, lung tumors, and UI lung. In both genders, 80% of tumors contained Kras mutations at codon 61, but no EGFR mutations were detected. The cellular distribution and concentration of EGFR were also similar between genders. In control mice, however, phosphorylated EGFR (pEGFR) levels were nearly 2.5-fold higher in males compared to females in UI lungs and sevenfold higher in lung tumors. Further, erlotinib decreased the contents of pEGFR in UI lungs and lung tumors, particularly in males. CONCLUSIONS: Adenomas from male mice in this early lung cancer model are responsive to erlotinib treatment, possibly because of a greater dependence of male tumor growth on the EGFR pathway compared to females. Importantly, these results indicate that small lung adenomas from male mice that utilize EGFR signaling but also harbor Kras mutations shrink in response to erlotinib, suggesting that erlotinib may be beneficial for some patients very early during lung cancer progression.     

Gender susceptibility for cigarette smoking-attributable lung cancer: A systematic review and meta-analysis

Objectives

As the primary cause of lung cancer, whether smoking confers the same risk of lung cancer for women as men is unclear. Therefore, we aimed to compare male and female susceptibility for cigarette smoking-attributable lung cancer.

Methods

A systematic review and meta-analysis was conducted by searching articles published up to July 2013 in three online databases (MEDLINE, EMBASE, and Cochrane Database). All studies estimated the association of cigarette smoking with the risk of lung cancer between men and women, respectively. A random effects model with inverse variance weighting was used to pool data. Male to female ratio of relative risk (RRR) was calculated to compare male and female susceptibility for cigarette smoking-attributable lung cancer.

Results

47 articles containing 404,874 individuals were included in the final analysis. Compared with non-smokers, male to female RRR was 1.61 (95%CI: 1.37, 1.89) among current smokers. Based on pathological type, adenocarcinoma had the highest RRR (1.42; 95%CI: 0.86, 2.35), followed by squamous cancer and small cell lung cancer. Furthermore, compared with non-smoking men, current smoking men had higher risk of lung cancer than women in spite of smoking quantity, smoking duration or years since quitting.

Conclusions

These findings indicated that males had higher susceptibility for cigarette smoking-attributable lung cancer than females. It is contradicted with traditional opinion that females would be more easily suffered from cigarette smoking-attributable health problems than males. Hence, tobacco control is very crucial in both males and females.     

Gender differences in non-small cell lung cancer: a population-based study.

BACKGROUND: A retrospective study including all patients with non-small cell lung cancer carcinoma in a population-based registry was performed to characterize gender differences in lung cancer and to analyze the factors influencing prognosis in women. METHODS: We retrieved through the Tuscan Cancer Registry (RTT) archive 2,523 lung tumor cases diagnosed during the period 1996-1998 in the provinces of Florence and Prato, central Italy. We compared the prognosis within 464 non-small lung cancer women and 1,798 men in a population-based case series. The influence of the following variables on postoperative survival were analyzed: age, cell type, pathologic T and N status, site of tumor and type of surgical resection. RESULTS: The age at diagnosis was similar in women and in men. Women were significantly more likely to have adenocarcinoma but less likely to have squamous cell carcinoma compared with men. Fewer pneumonectomies were performed in women than in men. Nevertheless, prognosis was similar in both sexes and type of surgical resection was significant prognostic factor. CONCLUSIONS: Lung cancer was more frequent in men than in women, but overall survival is similar. Differences in lung cancer histology and rate of pneumonectomies were found between men and women.     

女性肺癌的临床特点

 本文报道我院1978年1月～1992年7月间经外科治疗、病理证实的女性肺癌210例,占同期收治肺癌的20.8%,男女比例为3.8:1.女性肺癌有其明显的临床特点:1.发病年龄低于男性,年龄越小女性肺癌比例越大,<30岁者女性占43.5%(10/23);2.肺癌的组织类型中,女性腺癌发生率最高达44.8%,鳞癌占22.4%,与男性肺癌相比较其腺癌、类癌及其他低恶性肿瘤发生率较高(P<0.01),无大细胞癌;3.女性肺癌切除率为77.1%,低于男性,手术死亡率4.3%,高于男性;4.切除术后1、3、5年生存率为74.1%,39.3%及34.4%,均高于男性.预后较好可能与女性腺癌细胞浆中雌激素激体有关,其性别可作为估计预后的一个因素.     

陕西省神木县2012-2015年肿瘤发病分析

目的:分析中国西北陕西省神木县2012至2015年间癌症发病的流行特点.方法:收集2012至2015年就诊于神木县医院或外出就医返回医保机构报销例的2 752新发癌症患者,分析影响癌症发病的高危因素及年龄、性别、地域分布等流行病学特征.结果:2012至2015年4年间神木县癌症新发病例2 752例,其中男性 1 495 例(54%),女性1 257 例(46%),男女比约为1.2∶1.2012年新发555例,2013年新发593例,2014年新发673例,2015年新发931例,发病率呈逐年上升趋势.发病率居前五位的癌症分别是胃癌、肺癌、宫颈癌、食管癌和肝癌,总计新发病例1 845例,男性1 124例(61%),女性721例(39%).城镇和农村、男性和女性癌症谱有明显的差异.农村男女胃癌均明显高发于城镇,城镇男性肺癌显著高于农村男性,城镇女性乳腺癌高于农村女性.主要发病地区为神木镇、高家堡、锦界、乔岔滩、万镇.61~70岁为癌症高发年龄段.县医院就诊和外出就诊的住院天数及总花费的均数比较,都具有显著性差异.结论:神木县消化道肿瘤发病仍处于高发水平,恶性肿瘤是神木县地区威胁居民健康的重要疾病.     

Sex-specific survival advantage with parathyroid hormone-related protein in non-small cell lung carcinoma patients.

PURPOSE: Parathyroid hormone-related protein (PTHrP) is commonly expressed in non-small cell lung carcinomas (NSCLC). Expression of the protein could have implications for progression of the disease because it regulates cancer cell growth, apoptosis, and angiogenesis. However, its relationship with survival has not been evaluated in a large-scale investigation. EXPERIMENTAL DESIGN: PTHrP expression was assessed in paraffin-embedded tumor samples from 407 patients with NSCLC by immunohistochemistry. A pathologist unaware of the clinical history classified specimens as PTHrP positive or PTHrP negative. The log-rank test was used to compare survivals of PTHrP-positive and PTHrP-negative groups, and Cox regression was used to adjust for additional covariates. RESULTS: Median survival was 55 versus 22 months (P < 0.001) in female patients with and without tumor PTHrP, respectively. Male survival was 38 months independent of PTHrP status. Stage, histology, age, and smoking history were also associated with increased longevity. PTHrP remained a significant predictor of survival for female patients after controlling for stage, histology, and age. CONCLUSIONS: In this study, PTHrP expression was associated with a survival advantage in female patients. Additional investigations must be done to ascertain whether the result is reproducible and independent of potential confounding covariates. Sex-dependent effects of PTHrP in lung cancer would open new avenues of research into the role of sex in cancer progression.     

Trends in lung cancer mortality among young adults in Japan

BACKGROUND: Trends in lung cancer mortality among young adults, which are important for projecting future trends, have not been explored previously in Japan. METHODS: Using data from the National Vital Statistics between 1958 and 2003, we compiled lung cancer mortality by sex and 5-year birth cohort among young adults aged 20-49. RESULTS: Mortality among those aged 20-29 has consistently decreased regardless of sex. There were birth cohort effects in mortality from lung cancer, although these were less evident among women than among men. Both men and women born in the 1930s had lower mortality rates, while those born after 1940 had higher lung cancer mortality rates. Mortality rates appear to be declining for male birth cohorts born after 1950 and female birth cohorts after 1960, although these trends may not be stable due to the small number of deaths in these cohorts. CONCLUSION: Lung cancer mortality trends appear to be decreasing among young adults. This might be associated with the lower mortality of birth cohorts after 1950 for men and the 1960s birth cohorts for women. Careful monitoring is needed to confirm continuation of these declining trends.     

Lung Cancer in Malabar Cancer Center in Kerala - A Descriptive Analysis

The burden of lung cancer in terms of mortality is the highest among all types of cancers globally. Thepresent study aimed to evaluate lifestyle related habits, clinico-pathological profile and treatment details of lungcancer patients who were registered at Malabar Cancer Centre (MCC), Kerala, during the calendar year 2010.A retrospective evaluation was made from medical records to gather data from 281 registered lung cancer casesin 241 males and 40 females, with a male to female ratio of 6.03: 1. Approximately 89% of the cases were above50 years of age. Among males about 91% of the cases were smokers and 62% of them had a chronic smokinghabit. Adenocarcinomas, squamous cell carcinomas, non-small cell carcinomas and small cell cancers accountedfor 10.7, 13.9, 17.0 and 5.7% respectively. Out of 281 cases around 67% were diagnosed with distant metastasisand the remainder had regional lymph node involvement. However, no statistically significant difference wasobserved for secondary site of tumor according to gender. As majority of the cases reported at MCC were in anadvanced stage of the disease, histology of the secondary site from supraclavicular lymph nodes or liver was takenfor diagnosis. Initiation of population based screening for early detection of cancer, and primary and secondaryprevention strategies for reducing the prevalence of tobacco consumption are high priorities to reduce the lungcancer burden in Kerala.     

小于30岁低龄肺癌患者的临床分析

背景与目的青年肺癌患者肿瘤恶性程度高,侵袭性强,预后差,已成为多数共识。既往对青年肺癌患者的研究多以40岁或45岁为界,而<30岁的低龄肺癌患者临床资料少见报道。本文回顾分析了解放军总医院从1993年至今17年来诊疗过的<30岁的低龄肺癌患者的病史、分期、治疗及病理特点,为这一年龄段肺癌患者的诊疗提供参考。方法检索解放军总医院收治的1993年以来所有<30岁的肺癌患者,共计53例。其中非小细胞癌患者34例,小细胞癌患者19例。男女比例1.5:1。非小细胞肺癌患者中,腺癌27例,鳞癌6例,腺鳞癌1例,无大细胞癌患者。其中12例接受手术治疗,38例化放疗,3例放弃治疗。结果全组无住院死亡病例,12例手术患者中,手术根治性切除8例,姑息性切除4例。结论低龄肺癌患者腺癌,小细胞癌比例大,多数出现症状就诊时处于晚期,预后差。改善预后应重视常规体检,早期诊断。     

International lung cancer trends by histologic type: male:female differences diminishing and adenocarcinoma rates rising

Lung cancer rates have peaked among men in many areas of the world, but rates among women continue to rise. Most lung cancers are squamous cell carcinoma, small cell carcinoma, or adenocarcinoma; trends vary according to type. We compiled population-based morphology-specific incidence data from registries contributing to the International Agency for Research on Cancer (IARC) databases. Unspecified cancers and carcinomas were reallocated based on a registry, time period, sex and age group-specific basis. Where available, data from several registries within a country were pooled for analysis. Rates per 100,000 person-years for 1980-1982 to 1995-1997 were age-adjusted by the direct method using the world standard. Squamous cell carcinoma rates among males declined 30% or more in North America and some European countries while changing less dramatically in other areas; small cell carcinoma rates decreased less rapidly. Squamous and small cell carcinoma rates among females generally rose, with the increases especially pronounced in the Netherlands and Norway. In contrast, adenocarcinoma rates rose among males and females in virtually all areas, with the increases among males exceeding 50% in many areas of Europe; among females, rates also rose rapidly and more than doubled in Norway, Italy and France. Rates of all lung cancer types among women and adenocarcinoma among men continue to rise despite declining cigarette use in many Western countries and shifts to filtered/low-tar cigarettes. Renewed efforts toward cessation and prevention are mandatory to curb the prevalence of cigarette smoking and to reduce lung cancer rates eventually.     

Incidence of lung cancer by histological type from a population-based registry

Using data from a population-based registry, the Cancer Surveillance Program of Orange County, we examined patterns in lung cancer incidence by histological type for 1984 in Orange County, CA. Age-adjusted incidence rates per 100,000 population are 66.4 for men and 34.1 for women. Compared to 1983 rates for whites from all SEER areas combined, Orange County incidence rates are lower for men but equal for women. Squamous cell carcinoma incidence shows a strong male predominance [male/female 3.4; 95% confidence interval = (2.6, 4.4)], whereas the male/female incidence ratios for adenocarcinoma [male/female 1.4; 95% confidence interval = (1.1, 1.8)] and small cell carcinoma [male/female = 1.8; 95% confidence interval = 1.3, 2.4)] are closer to unity. Smoking habits were abstracted from medical records for 79% of cases. Only 8% of lung cancer cases (5% of men and 12% of women) with known smoking habits are nonsmokers. Adenocarcinoma is the most common cell type among women smokers and nonsmokers, while squamous cell carcinoma predominates in both male smokers and nonsmokers. Cases who smoked were younger at diagnosis than nonsmokers (P less than 0.001) for each cell type. Despite a greater proportion of nonsmokers, cases with adenocarcinoma were younger at diagnosis compared to small cell carcinoma (P less than 0.01) and squamous cell carcinoma (P less than 0.05). The observed patterns of incidence rates by histological type are not entirely explained by current knowledge of the relationship between smoking and cell type.     

Incidence and Clinicopathologic Features of Primary LungCancer: A North-Eastern Anatolia Region Study in Turkey(2006-2012)

Background: Lung cancer is the most frequent cancer among men and second highest among womenoverall, including in Turkey. Cigarette smoking is the most important etiologic factor for the development ofcancer in both men and women. Objective: To determine the lung cancer incidence in Northeastern AnatoliaRegion of Turkey with a focus on clinical properties, cancer subtypes, the relationships of tumors with cigarettesmoking and radiological properties of the lesions. Materials and Methods: In a retrospective study design,566 lung cancer cases diagnosed at the Pathology Department of Ataturk University in Erzurum over the lastseven years extending from January 2006 to June 2012 were investigated. The results were compared withstatistical analyses. Results: The most common histopathological subtype of primary bronchogenic carcinomain our study was found to be the squamous cell carcinoma, 46.1% (261 out of 566), and the second was smallcell lung carcinoma 15.7% (89 out of 566). Based on our data, an overall male predominance was noted with amale/female ratio of 6.1/1. While 296 (52.2%) of the patients were found to be smokers at the time of diagnosis,125 (22.0%) were nonsmokers and 145 (25.6%) were ex-smokers. Smoking status was found to have a strongcorrelation with primary lung cancer (p <0.05), and there were significant differences between males and females(p<0.001). Conclusion: Although relative prominence of subtypes of lung cancers differ between Turkish andother populations, lung cancer overall remains as an important health problem in Turkey. Our findings stressthe critical need for effective cancer prevention programs such as anti-smoking campaigns.     

The association of human papillomavirus 16/18 infection with lung cancer among nonsmoking Taiwanese women

Lung cancer is the leading cause of cancer death in Taiwanese women since 1982. High lung cancer mortality ratio of male:female in Taiwan (2:1) was observed, although less than 10% of female lung cancer patients are smokers. Until now, the etiological factor remains unknown. We hypothesize that high-risk human papillomavirus (HPV) 16/18 may be associated with lung cancer development based on high prevalence of p53 negative immunostainings in female lung tumors compared with that of male lung tumors. In this study, 141 lung cancer patients and 60 noncancer control subjects were enrolled to examine whether HPV 16/18 DNA existed in lung tumor and normal tissues by nested PCR and in situ hybridization (ISH), respectively. The concordant detection of HPV 16 and 18 DNA between nested PCR and ISH method was 73 and 85.5%, respectively. Our data showed that 77 (54.6%) of 141 lung tumors had HPV 16/18 DNA compared with 16 (26.7%; P = 0.0005) of 60 noncancer control subjects. In addition, ISH data showed that HPV 16/18 DNA was uniformly located in lung tumor cells, but not in the adjacent nontumor cells. When study subjects were stratified by gender, age, and smoking status, nonsmoking female lung cancer patients who were older than 60 years old had significantly high prevalence of HPV 16/18 infection. The odds ratio of HPV 16/18 infection of nonsmoking female lung cancer patients is much higher at 10.12 (95% confidence interval, 3.88-26.38) compared with 1.98 (95% confidence interval, 0.84-4.76) of nonsmoking male lung cancer patients. This result strongly suggests that HPV infection is associated with lung cancer development of nonsmoking female lung cancer patients. The high prevalence of HPV 16/18 infection may explain to a certain extent why Taiwanese women nonsmokers had a higher lung cancer mortality rate.     

Murine mammary tumor virus related antigen in human male mammary carcinoma

An antigen immunologically related to mouse mammary tumor virus (MuMTV) and the major envelope glycoprotein, gp52 of MuMTV, was identified in tissue sections of human male and female mammary carcinomas using the peroxidase-antiperoxidase technique. The specificity of the reaction was established by absorption studies. Positive reactions with the gp52 antiserum were seen in mouse and human mammary carcinomas, but not in normal mammary tissues, mammary tissues with benign diseases and in other primary malignant neoplasms. Almost all (32/36, 89%) male mammary carcinomas were positive for the gp52 related antigen. A lesser proportion of tumors among female patients (14/50, 28%) were positive. The gp52 positive tumors were significantly larger than the gp52 negative tumors in female patients (P less than 0.05). Gp52 positive tumors were also larger than gp52 negative tumors in male patients, but the difference was not statistically significant. Gp52 reactivity was also detected in metastatic mammary carcinoma in axillary lymph nodes of male and female patients. The presence of gp52 related antigen was not apparently related to tumor grade or lymphocytic infiltrate in the primary tumor. The data do not permit a firm conclusion regarding nodal status in men; no correlation of gp52 activity and nodal status in women was evident. These results indicate that mammary carcinomas in men as well as in women have an antigen related immunologically to MuMTV gp52. Other than tumor size, the antigen seems to be unrelated to major prognostic factors. The significance of the antigen with respect to etiologic features and prognosis in breast cancer remains to be determined.     

Lung cancer in women: age, smoking, histology, performance status, stage, initial treatment and survival. Population-based study of 20 561 cases.

BACKGROUND: The community-based cancer registry was set up and results were analysed to assess differences in clinicopathological parameters between women and men. PATIENTS AND METHODS: The Pulmonary Outpatient Departments supplied data on 20 561 lung cancer patients diagnosed in Poland from 1995 to 1998. Data regarding demographics, smoking, histology, treatment and survival were obtained. RESULTS: There were 2875 women and 17 686 men with lung cancer. Women were younger than men (60.02 versus 62.18 years; P <0.001). Age <50 years was more frequent in women than in men (23.3% versus 12%; P <0.001). Women with small-cell lung cancer (SCLC) and adenocarcinoma were significantly younger than women with squamous cancer (58.2 and 58.2 versus 61 years; P = 0.05). Also, men with adenocarcinoma and SCLC were younger than men with squamous cancer (60.6 and 60.2 versus 62.3 years; P = 0.05). Squamous cancer was the predominant type of lung cancer both in women (32.5%) and men (55.2%). However, SCLC (26.6% versus 19.9%: P <0.001) and adenocarcinoma (21.6% versus 9.6%; P <0.001) were more frequent in women than in men. Women were more frequently non-smokers than men (18.8% versus 2.4%; P <0.001). Adenocarcinoma patients smoked less intensively than patients with squamous and SCLC both in women (31.4 versus 35.8 and 33.7 packs/year; P <0.02) and in men (38.2 versus 42 and 41.9 packs/year; P <0.002). In multivariate analysis, bad performance status, advanced stage, non-surgical treatment, age >50 years at diagnosis and male gender were significant independent negative prognostic factors. CONCLUSIONS: Lung cancer was six times more frequent in men than in women. Women with lung cancer were younger than men and smoked less intensively. Over-representation of adenocarcinoma and SCLC was observed in the women. Women with lung cancer had a better prognosis than men.     

The Variation of Cell Type Distribution in Lung Cancer: A Study of 10,910 Cases at a Medical Center in Taiwan between 1970 and 1993

The rise in the incidence of lung cancer has been associatedwith shifts in histologic distribution. A study was conductedto investigate changes in the cell type distribution in lungcancer in relation to age, sex, and smoking history, based ona retrospective analysis of 10,910 proven cases of lung cancerat the Veterans General Hospital-Taipei during the period from1970 to 1993. The diagnosis in each case was substantiated byhistologic samples from the original tumor site in the lung.Detailed smoking histories were obtaind by personal interviewat the time of the first admission. Adenocarcinoma (38.3%) wasthe most common type of lung cancer, followed by squamous cellcarcinoma (37.1%) and small cell carcinoma (12.2%). Over thestudy period, the incidence of squamous cell carcinoma decreasedfrom 46.4% to 36.2% in men (P < 0.005), adenocarcinoma increasedfrom 30% to 36% in men (P = 0.001) and 50.7% to 64.8% in women(P = 0.008), and small cell carcinoma increased from 7% to 14%in men but showed no significant change in women. Adenocarcinomaexhibited a marked increase in both men and women, and surpassedsquamous cell carcinoma as the most frequent type of lung cancer.Lung cancer among younger men, and among non-smoking older menand women, was more often adenocarcinoma. Small cell carcinomashowed a significant increase among males, differing from thetrend for squamous cell carcinoma in men, though both are stronglyassociated with smoking. These findings suggest factors otherthen cigarette smoking could influence the development and distributionof lung cancer.     

Lung cancer in women

Lung cancer is one of the most important avoidable causes of death around the world, it is the most widespread carcinoma with a very poor prognosis, and is the leading cause of cancer death in both developed and developing countries. At present more men than women die each year from lung cancer, but in recent years a rapid increase in lung cancer mortality has been observed among women in developed countries, contrasting with a levelling off or decrease among men. The rising trend in female lung cancer mortality has been observed to parallel with the past and current prevalence of cigarette smoking among women in the United States and elsewhere. An important role of other factors acting either as independent risk factors or interacting with the effect of smoking has been suggested by some studies among women, among them genetic, biologic and hormonal factors, and probably some factors related to the environment and lifestyle. There is a controversy concerning the claim that women have a different susceptibility to tobacco carcinogens, which might or might not be greater than men do. Since tobacco is far and away the strongest epidemiological risk factor for the development of lung cancer, comprehensive smoking control efforts are the priority in the prevention of lung cancer among women.