CLPTM1L polymorphism as a protective factor for lung cancer: a case-control study in southern Chinese population.

Variants of the cleft lip and palate trans-membrane 1 like (CLPTM1L) gene, located on chromosome 5p15.33, were previously determined to influence lung cancer susceptibility. Here, we performed a case-control study to examine the potential association of CLPTM1L single nucleotide polymorphisms (SNPs) with lung cancer in a Chinese Han population. We selected four SNPs in the CLPTM1L gene that were previously reported to be associated with lung cancer. Odds ratios (ORs) and 95 % confidence intervals (CIs) were calculated to estimate the strength of the relationship between each CLPTM1L SNP and lung cancer risk. Allelic model analysis revealed that the minor alleles of all four SNPs were significantly associated with decreased lung cancer risk. Similar significant results were detected using genetic model analysis. In addition, we observed a protective effect of haplotype "TT" in the CLPTM1L gene. Our results verified that certain CLPTM1L polymorphisms are protective factors against lung cancer in a southern Chinese Han population and may be potential diagnostic and molecular markers for lung cancer patients.

Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China.

BACKGROUND: We performed a multicenter evaluation of the Elecsys® progastrin-releasing peptide (ProGRP) immunoassay in Europe and China. METHODS: The assay was evaluated at three European and two Chinese sites by imprecision, stability, method comparison and differentiation potential in lung cancer. RESULTS: Intermediate imprecision across five analyte concentrations ranged from 2.2% to 6.0% coefficient of variation. Good stability for plasma and serum samples was shown for various storage conditions. There was excellent correlation between the Elecsys® and ARCHITECT assays in plasma (slope 1.02, intercept -2.72pg/mL). The Elecsys® assay also showed good correlation between serum and plasma samples (slope 0.93, intercept 2.35pg/mL; correlation coefficient 0.97). ProGRP differentiated small-cell and non-small-cell lung cancer (NSCLC; area under the curve 0.90, 95% CI 0.87-0.93; 78.3% sensitivity, 95% specificity; at 84pg/mL), with no relevant effects of ethnicity, age, gender or smoking. Median ProGRP concentrations were low in benign diseases (38pg/mL), other malignancies (40pg/mL) or NSCLC (39pg/mL), except chronic kidney disease above stage 3 (>100pg/mL). CONCLUSIONS: Increased stability of the Elecsys® ProGRP assay in serum and plasma offers clear benefits over existing assays. This first evaluation of a ProGRP assay in China demonstrated comparable differentiation potential among different ethnicities.

Analysis of the impact of platinum-based combination chemotherapy in small cell cervical carcinoma: a multicenter retrospective study in Chinese patients.

BACKGROUND: Small cell cervical carcinoma (SCCC) is a rare, aggressive tumor with a poor prognosis. However, information in relation to its treatment is scarce due to the limited numbers of patients. The aim of this study was to establish whether platinum-based combination chemotherapy may by beneficial in this patient population. METHODS: We carried out a multicenter, retrospective study comprising of 72 Chinese patients with SCCC. The patients were treated between 1995 and 2010 at Sun Yat-sen Memorial Hospital or the Cancer Center of Sun Yat-Sen University, and at the First Affiliated Hospital of Shantou University Medical College, China. RESULTS: Of the 72 patients, 46/72 (63.9%) had Federation of Gynecology and Obstetrics (FIGO) stage Ia-Ib2 and 26/72 (36.1%) had stage IIa-IV disease. Surgery was performed in 63/72 (87.5%) patients, 61/72 (84.7%) patients received chemoradiotherapy and 35/72 (48.6%) received radiotherapy. The 3-year overall survival (OS) and disease-free survival (DFS) rates were as follows: Ia (100%, 100%); Ib1 (62%, 57%); Ib2 (53%, 48%); IIa (36%, 23%); IIb (29%, 21%); IIIb (50%, 50%); and IV (0%, 0%), respectively. The estimated 3-year OS and DFS rates in patients who received platinum-based combination chemotherapy (etoposide + cisplatin [EP], or paclitaxel + cisplatin [TP]) as part of their adjuvant treatment were 64.8% and 63.0%, respectively, compared to 25.2% and 22.0% in those who did not (P = 0.0003; P = 0.0003). Univariate analysis showed that platinum-based combination chemotherapy was associated with improved survival compared to other chemotherapy techniques or no chemotherapy (OS: HR = 0.227; 95% CI, 0.099-0.524; P = 0.001; DFS: HR = 0.210; 95% CI, 0.087-0.506; P = 0.001). Multivariate analysis identified FIGO stage, lymphatic metastasis and platinum-based combination chemotherapy as independent prognostic factors for improved survival in patients with SCCC. CONCLUSIONS: Platinum-based combination chemotherapy (with EP or TP) can improve the 3-year survival outcomes in patients with SCCC. Therefore, it should be considered an important component in a future standardized treatment strategy for SCCC.

High-incidence of PTEN mutations in Chinese patients with primary small cell carcinoma of the esophagus.

BACKGROUND: Primary small cell carcinoma of the esophagus (PSCCE) is a rare and aggressive tumor with poor prognosis. The aim of this study was to investigate the existence of EGFR, KRAS, PIK3CA and PTEN mutations in PSCCE. METHODS: Clinical-pathological data and paraffin-embedded specimens were collected from 38 patients. Exons 18 to 21 of EGFR, KRAS and PIK3CA status were analyzed by real-time PCR based on ARMS and Scorpion technology in all patients, and the PTEN gene was also screened using real-time PCR and high-resolution melting curve analysis (HRMA). RESULTS: Only 1 (2.63%) out of 38 patients had EGFR mutations in L858R missense, and KRAS and PIK3CA were not found in the mutational spot in all patients. However, PTEN mutations presented in 14 (36.84%) out of 38 patients, including exon 5 coding for PTEN missense mutation (n =4, 10.53%), exon 6 (n =7, 18.42%), concurrent exon 5 and exon 6 (n =2, 5.26%), and exon 8 (n =1, 2.63%). Concurrent mutations of these genes were not detected in all samples. No statistically significant associations were found between the clinicopathological features and the mutation status of PTEN. CONCLUSIONS: The incidence of PTEN mutations in Chinese patients with PSCCE was higher than that of previous reports in other histological subtypes of esophageal cancer.

Significant association of 5p15.33 (TERT-CLPTM1L genes) with lung cancer in Chinese Han population.

Lung cancer is a leading cause of cancer-related deaths throughout the world. Recent genome-wide association studies and consecutive validation supported that the 5p15.33 region containing telomerase reverse transcriptase gene (TERT) and cleft lip and palate transmembrane protein 1-like (CLPTM1L) gene showed significant association with lung cancer in multiple populations. Here we studied a large Chinese Han cohort consisting of 1759 cases and 1804 controls. In the 1st stage (784 cases versus 782 controls) we genotyped 13 tag SNPs within 5p15.33 region to further investigate the association. After the 2nd stage validation (975 cases versus 1022 controls), the study clarified the association that rs2736100 of the TERT gene conferred the highest significant risk of lung cancer (P=4×10(-3) in the 1st stage association, P=4×10(-4) in the 2nd stage validation, and P=1×10(-5), odds ratio=1.24 in the combined population). The results provided the evidence of a cross-race susceptibility of the lung cancer locus.

Risk of lung cancer by histology among immigrants to Sweden.

BACKGROUND: We wanted to define lung cancer incidence rates by histological subtype among immigrants in Sweden to explore the effect of new environments on the incidence of lung cancer by histological subtype in different ethnic populations. METHODS: The nationwide Swedish Family-Cancer Database w used to calculate age-standardized incidence rates (ASR) (per 100,000) and standardized incidence ratios (SIRs). The patient series covered 19,255 male and 14,601 female Swedes, and 3236 male and 1751 female immigrants. RESULTS: By time since immigration, Former Yugoslavian (ASR=46.4) and Asian Arab (38.8) men, and Danish (23.3), Norwegian (19.5) and Finnish (14.5) women had the highest rates for lung cancer, while the lowest rate was seen among Asian Arab women (5.8). The highest adenocarcinoma rates were seen among South European men (11.5), and Danish (7.4) and Norwegian (6.9) women, while squamous cell (SCC) and small cell carcinomas rates were the highest among former Yugoslavian (16.0) and Baltic (8.8) men, respectively. Former Yugoslavian men (2.6) had the highest rate for large cell carcinoma. Compared to Swedes, former Yugoslavian men had the highest significant risk for SCC (SIR=3.62), small cell (3.14) and large cell (4.21) carcinomas, whereas the highest adenocarcinoma risk was seen among Asian Arabs (2.35). Danish women had the highest risks for SCC (1.91) and small cell carcinoma (2.56). CONCLUSION: The ethnic-specific lung cancer rates by histology followed the rates in the countries of origin. Our findings may suggest that preservation of smoking habits in the host country is linked to the ethnic diversity of lung cancer incidence by histology.

Replication of lung cancer susceptibility loci at chromosomes 15q25, 5p15, and 6p21: a pooled analysis from the International Lung Cancer Consortium.

BACKGROUND: Genome-wide association studies have identified three chromosomal regions at 15q25, 5p15, and 6p21 as being associated with the risk of lung cancer. To confirm these associations in independent studies and investigate heterogeneity of these associations within specific subgroups, we conducted a coordinated genotyping study within the International Lung Cancer Consortium based on independent studies that were not included in previous genome-wide association studies. METHODS: Genotype data for single-nucleotide polymorphisms at chromosomes 15q25 (rs16969968, rs8034191), 5p15 (rs2736100, rs402710), and 6p21 (rs2256543, rs4324798) from 21 case-control studies for 11 645 lung cancer case patients and 14 954 control subjects, of whom 85% were white and 15% were Asian, were pooled. Associations between the variants and the risk of lung cancer were estimated by logistic regression models. All statistical tests were two-sided. RESULTS: Associations between 15q25 and the risk of lung cancer were replicated in white ever-smokers (rs16969968: odds ratio [OR] = 1.26, 95% confidence interval [CI] = 1.21 to 1.32, P(trend) = 2 x 10(-26)), and this association was stronger for those diagnosed at younger ages. There was no association in never-smokers or in Asians between either of the 15q25 variants and the risk of lung cancer. For the chromosome 5p15 region, we confirmed statistically significant associations in whites for both rs2736100 (OR = 1.15, 95% CI = 1.10 to 1.20, P(trend) = 1 x 10(-10)) and rs402710 (OR = 1.14, 95% CI = 1.09 to 1.19, P(trend) = 5 x 10(-8)) and identified similar associations in Asians (rs2736100: OR = 1.23, 95% CI = 1.12 to 1.35, P(trend) = 2 x 10(-5); rs402710: OR = 1.15, 95% CI = 1.04 to 1.27, P(trend) = .007). The associations between the 5p15 variants and lung cancer differed by histology; odds ratios for rs2736100 were highest in adenocarcinoma and for rs402710 were highest in adenocarcinoma and squamous cell carcinomas. This pattern was observed in both ethnic groups. Neither of the two variants on chromosome 6p21 was associated with the risk of lung cancer. CONCLUSIONS: In this international genetic association study of lung cancer, previous associations found in white populations were replicated and new associations were identified in Asian populations. Future genetic studies of lung cancer should include detailed stratification by histology.

Lung cancer incidence among American Indians and Alaska Natives in the United States, 1999-2004.

BACKGROUND: Lung cancer incidence rates among American Indians and Alaska Natives (AI/ANs) in the United States have not been described well, primarily because of race misclassification and, until the 1990s, incomplete coverage of their population by cancer registries. Smoking, the predominant cause of lung cancer, is particularly prevalent among this population. METHODS: Data from the National Program of Cancer Registries and the Surveillance, Epidemiology, and End Results Program were combined to estimate age-adjusted incidence rates of lung cancer during 1999 through 2004. Cases were linked to Indian Health Service (IHS) registration databases to identify AI/ANs whose race may have been misclassified. Age-adjusted rates were calculated for Contract Health Service Delivery Area (CHSDA) counties and for all counties by IHS region, and comparisons were made between AI/ANs and non-Hispanic whites (NHWs). RESULTS: Among populations living in CHSDA counties, NHWs overall had higher rates of lung cancer than AI/ANs. However, the rates (per 100,000 population) among AI/ANs varied substantially between IHS regions from 14.9 (Southwest) to 87.1 (Southern Plains), 93.2 (Alaska), and 104.3 (Northern Plains). Approximately 41.6% of AI/AN lung cancer cases were diagnosed before age 65 years compared with approximately 29.8% of NHW lung cancer cases. The overall percentage stage distribution was not different between AI/ANs and NHWs. Squamous cell carcinomas were slightly more common and adenocarcinomas were less common among AI/ANs than among NHWs. Lung cancer rates were not decreasing for AI/ANs as they were for NHWs. CONCLUSIONS: Data from this study clarified the need for culturally appropriate tobacco prevention and control policies and resources for AI/ANs in all regions, and especially in the Plains and Alaska.

Ethnic differences in the management of lung cancer in New Zealand.

BACKGROUND: Major ethnic disparities in lung cancer survival exist in New Zealand, with Mäori having a higher case-fatality ratio than non-Mäori. AIM: To assess whether secondary care management of lung cancer differed by ethnicity and could contribute to ethnic survival disparities. METHODS: An audit of secondary care management in Auckland and Northland of lung cancer patients diagnosed in 2004 permitted comparison of the management of lung cancer in different ethnic groups. RESULTS: The 565 eligible cases comprised: European 378 (67%), Mäori 95 (17%), Pacific Peoples 56 (10%), Asian 23 (4%), and other or unknown ethnicity 13 (2%). In multivariate analysis (adjusting for tumor and patient factors including comorbidity), Mäori were 2.5 times more likely to have locally advanced disease than localized disease compared with Europeans (p < 0.01), and four times less likely to receive curative rather than palliative anticancer treatment compared with Europeans (p < 0.01). Mäori had longer transit times from diagnosis to treatment (p < 0.001). Mäori were more likely to decline treatment and miss appointments than Europeans, although this only partially explained management differences. CONCLUSION: Multiple factors are potentially responsible for the higher case-fatality ratio in Mäori. Such factors include presentation with more advanced disease, lower rates of curative treatment for nonmetastatic disease, and longer transit times from diagnosis to treatment. In this retrospective study, socioeconomic deprivation, comorbidity levels, and failure to accept treatment did not fully explain ethnic differences in management. Further assessment of the underlying issues by prospective evaluation is warranted.

Polymorphisms in excision repair cross-complementing group 4 (ERCC4) and susceptibility to primary lung cancer in a Chinese Han population.

ERCC4/XPF protein plays an important role in the nucleotide excision repair (NER) pathway, and deficiencies in the gene encoding it can lead to a repair-deficiency syndrome, xeroderma pigmentosum group F (XP-F). Common variants on this gene are assumed to be foreboding markers for lung cancer, and 4 selected SNPs in the ERCC4 gene were genotyped in a multi-center case-control study involving 1010 lung cancer patients and 1011 cancer-free controls in a Chinese Han population to test the hypothesis. A significant association to decreased risk of lung cancer was observed in major allele C of rs3136038 carriers (adjusted OR=0.57, 95% CI=0.39-0.84 for CT; adjusted OR=0.75, 95% CI=0.52-1.10 for CC; adjusted OR=0.68, 95% CI=0.46-0.99 for CT+CC, compared with genotype TT), and additionally, referenced with homozygote TT, the heterozygous genotype CT showed a distinct protective effect in younger subjects (adjusted OR=0.47, 95% CI=0.26-0.86), in males (adjusted OR=0.59, 95% CI=0.37-0.93), in non-smokers (adjusted OR=0.38, 95% CI=0.20-0.72), in subjects without family history of cancer (adjusted OR=0.52, 95% CI=0.34-0.80) and in adenocarcinomas patients (adjusted OR=0.51, 95% CI=0.31-0.84). Our finding indicated, for the first time, the polymorphism rs3136038 on the promotor region of ERCC4 may contribute to the etiology of lung cancer. Further functional studies on this locus and/or other genetic variants in highly linkage disequilibrium with it are warranted to elucidate the underlying molecular mechanisms of the association.

Changes in the distribution of lung cancer cell types and patient demography in a developing multiracial Asian country: experience of a university teaching hospital.

A comparison of patients with lung cancer diagnosed at the University of Malaya Medical Centre, Kuala Lumpur, Malaysia from October 1991 to September 1999 with another group of lung cancer patients diagnosed at the same hospital during an earlier period of 1967-1976 was undertaken to determine whether there had been a change in the distribution of lung cancer cell types and patient demography. The number of histologically and/or cytologically proven lung cancer cases was 583 from October 1991 to September 1999 and 278 from 1967 to 1976. The mean (S.D.) age of the patients during the period 1991-1999, 60.1 (12.0) years was similar to that of patients during the period 1967-1976, 60.3 (12.2) years. There was no shift of the peak age distribution of lung cancer (i.e., the 7th decade) between the two periods. In the recent period, the percentage of patients with adenocarcinoma had increased significantly to 43.2% from 25.2% while that of large cell carcinoma had decreased to 3.3% from 11.9%. The percentages of patients with squamous cell carcinoma (SCC) and small cell lung cancer remained stable. In the period 1967-1976, SCC was the commonest cell type in men and in smokers while adenocarcinoma was the commonest cell type in women and in never smokers. In the period 1991-1999, adenocarcinoma was the commonest cell type in both men and women as well as in smokers and never smokers.

Similar outcomes between African American and non-African American patients with extensive-stage small-cell lung carcinoma: report from the Cancer and Leukemia Group B.

PURPOSE: Among patients with small-cell lung carcinoma, African Americans have lower survival rates than non-African Americans. We investigated whether the disparity in survival would persist when patients were treated with similar therapies (ie, phase II/III Cancer and Leukemia Group B [CALGB] trials). PATIENTS AND METHODS: We assessed 995 patients (928 non-African American and 67 African American) receiving chemotherapy in CALGB studies for extensive-stage small-cell lung cancer (ES-SCLC). Clinical and demographic characteristics, treatment received, and survival data were obtained from the CALGB database. The Cox proportional hazards model was used to assess the effect of race/ethnicity on survival after adjustment for other known prognostic factors. All statistical tests were two sided. RESULTS: The unadjusted survival distribution of African American patients was not significantly different from that of non-African American patients; median survival was 11.5 months (95% CI, 9.4 to 13.4 months) for African American patients versus 9.9 months (95% CI, 9.6 to 10.3 months) for non-African American patients. Multivariable adjustment for the effect of treatment arm, histology, and metastatic site at presentation did not alter the outcome for African American patients. Survival was similar even though African American patients were more likely to have a poorer performance status, present with significant weight loss, and be Medicaid recipients (20% v 6%), which is an indicator of lower socioeconomic status. CONCLUSION: African American patients tended to present with prognostic features associated with a worse survival. However, when offered equivalent therapy, the outcome for African American patients was the same as that observed for non-African American patients.

Relative and absolute risks of cigarette smoking on major histologic types of lung cancer in Korean men.

OBJECTIVES: Most prospective cohort studies of lung cancer focus on the relative risk rather than the absolute risk of smoking. METHODS: This prospective study included 437,976 Korean men (cohort for the National Health Insurance Cooperation Study), > or = 40 years old, who were free of cancer and smoking-related chronic disease at the time of enrollment. Based on new incidence cases, relative risk and excess risk, and their 95% confidence intervals (95% CI), were estimated with the standard Poisson regression model after adjustment for age or other demographic factors and other confounders. RESULTS: During the 6-year follow-up period of 3,142,451 person-years, 1,357 new lung cancer cases were identified. Based on the multivariate-adjusted relative risk for current smokers, the strongest association with smoking was shown for small-cell lung cancer (relative risk, 21.7; 95% CI, 8.0-58.5) followed by squamous cell carcinoma (relative risk, 11.7; 95% CI, 7.1-19.4) and then adenocarcinoma (relative risk, 2.1; 95% CI, 1.6-2.7). In current smokers with > or = 40 pack-years of exposure, excess risk was highest for squamous cell carcinoma (excess risk, 33.8; 95% CI, 10.2-109.8) followed by adenocarcinoma (excess risk, 26.7; 95% CI, 10.3-64.4), and then small-cell carcinoma (excess risk, 16.3; 95% CI, 1.8-144.3). CONCLUSIONS: In Korean men, cigarette smoking was as important a risk factor for adenocarcinoma as it was for squamous cell and small-cell lung cancer.

Epstein-Barr virus plays little role in cervical carcinogenesis in Korean women.

We examined whether Epstein-Barr virus (EBV) infection plays a role in cervical carcinogenesis in Korean women. EBV infection was examined using polymerase chain reaction (PCR) with two different primer pairs flanking the BamHI "W" fragment of EBV and by EBV-encoded small RNAs (EBER) in situ hybridization in various histologic types of cervical cancer, including 17 cases of squamous cell carcinoma, 36 cases of adenocarcinoma, and 3 cases of small-cell carcinoma. We also evaluated 20 cases of cervical intraepithelial neoplasia and 20 cases of normal uterine cervix. One case of squamous cell carcinoma and three cases of cervical intraepithelial neoplasia were positive for EBV DNA using PCR, but EBER in situ hybridization analysis showed that none of the PCR-positive cases expressed EBER. EBV DNA was not found using PCR in any of the 20 normal uterine cervices. From our results, EBV infection does not seem to play a role in cervical carcinogenesis in Korean women.

Combinations of glutathione S-transferase genotypes and risk of early-onset lung cancer in Caucasians and African Americans: a population-based study.

Polymorphisms in GSTM1, GSTT1 and GSTP1 genes in humans are associated with the reduction of enzymatic activity toward several substrates, including those in tobacco smoke. To investigate the potential role these polymorphisms have, as modulators of early-onset lung cancer risk, a population-based case-control study involving early-onset lung cancer cases was performed. Biological samples were available for 350 individuals diagnosed <50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 410 cases of age, race and sex-matched controls ascertained through random digit dialing. African Americans carrying at least one G allele at the GSTP1 locus were 2.9-fold more likely to have lung cancer compared with African Americans without a G allele after adjustment for age, sex, pack years of smoking and history of lung cancer in a first-degree relative (95% CI 1.29-6.20). African Americans with either one or two risk genotypes at the GSTM1 and GSTP1 loci were at increased risk of having lung cancer compared with those having fully functional GSTM1 and GSTP1 genes (OR = 2.8, 95% CI 1.1-7.2 and OR = 4.0, 95% CI 1.3-12.2, respectively). No significant single gene associations between GSTM1, GSTT1 or GSTP1 and early-onset lung cancer were identified in Caucasians, after adjusting for age, sex, pack years and family history of lung cancer. However, our results suggest that specific combinations of glutathione S-transferase polymorphisms increase the risk of early-onset of lung cancer. Joint analysis of these genotypes may identify individuals who are at a higher risk of developing early-onset lung cancer with a greater certainty than single gene studies.

Impact of race in lung cancer: analysis of temporal trends from a surveillance, epidemiology, and end results database.

STUDY OBJECTIVES: We analyzed data from a community-based cancer database over a 26-year period in order to characterize clinicopathologic differences between black and white patients with lung cancer, and to identify relevant temporal trends in incidence and survival. DESIGN, SETTING, AND PATIENTS: Data on demographics, stage, histology, and survival were obtained on all black and white patients with primary bronchogenic carcinoma registered in the community-based metropolitan Detroit Surveillance, Epidemiology, and End Results database from 1973 to 1998. RESULTS: Of 48,318 eligible patients, 23% were black. Lung cancer incidence rates decreased for men of both races from 1985 to 1998, with a greater decline occurring in black men (p < 0.0001). Although incidence rates declined over time for men of both races < 50 years of age, this decrease was greater in white men, resulting in an increase in the racial differential in younger men. Temporal trends in incidence rates were similar for women of both races. The incidence of distant-stage disease was higher among blacks throughout the study period. The incidence of local-stage disease decreased for both races, though this decline was greater in blacks. A significant racial difference in 2-year and 5-year survival rates developed during the study period, due to a distinct lack of improvement in black patients. In a multivariate model, the relative risks of death for black patients, relative to white patients, were 1.24 (p < 0.0001) for local stage, 1.14 (p < 0.0001) for regional stage, and 1.03 (p = 0.045) for distant stage. CONCLUSION: Significant racial differences exist in the incidence and survival rates for lung cancer in metropolitan Detroit. Since 1973, several disturbing trends have developed, particularly with regard to the lack of improvement in overall survival in black patients. Further study is required to determine the factors responsible for these temporal trends.

Lung cancer in patients younger than 40 years in a multiracial Asian country.

OBJECTIVE: This study aimed to determine whether the clinicopathological features of lung cancer in patients younger than 40 years differ from that of older patients in an Asian country. METHODOLOGY: We undertook a review of the clinicopathological data of all patients with confirmed primary lung cancer at the Department of Medicine, University of Malaya Medical Centre, Kuala Lumpur, Malaysia, from October 1991 to September 1999. RESULTS: Of the 580 patients with lung cancer, 36 (6.2%; 23 males, 13 females) were 21-39 years old at diagnosis. The percentage of people who had never smoked was higher among the younger patients (58.3% vs 19.1%, P < 0.001). Although adenocarcinoma was the most common cell type in both groups, its incidence was higher in the younger patients (24/36 (66.7%) vs 228/544 (41.9%), P = 0.007). The mean World Health Organization performance status at presentation was worse in the younger patients (2.4 vs 2, P = 0.007). In the case of non-small cell lung cancer, all the younger patients presented with either stage IIIb or metastatic disease compared to 77.2% of the older patients (P < 0.001). CONCLUSIONS: Younger lung cancer patients were more likely than older patients to have never smoked, to have adenocarcinoma, and to present with poorer performance status and with more advanced-stage non-small cell lung cancer.

NAT2 slow acetylator genotype is associated with increased risk of lung cancer among non-smoking Chinese women in Singapore.

Among non-smokers, the factors resulting in lung carcinogenesis are poorly understood. We conducted a hospital-based case-control analysis of 294 Chinese women, of whom 217 were non-smokers, to evaluate the role of polymorphic N-acetyltransferase (NAT2) as a susceptibility factor for the disease. The proportion of slow acetylator genotypes among non-smoking cases (n = 92) and controls (n = 125) was 38.0 and 24.0%, respectively [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.7]. No effect of NAT2 genotype was seen among smokers. Among non-smokers, the effect was marked for adenocarcinomas (OR 2.1, 95% CI 1.1-4.0). As NAT2 activity is known to modify risk of arylamine-induced carcinogenesis, our results suggest that exposure to arylamines in the environment may play a role in risk of lung cancer among non-smokers.

Lung cancer among Chinese females in Singapore 1968-1992: time trends, dialect group differences and implications for aetiology.

BACKGROUND: Chinese females are distinguished internationally as having relatively high lung cancer incidence rates despite a low prevalence of cigarette smoking. In Singapore, this population comprises several dialect groups which have origins in different regions in China, each with its own traditional cultural practices. METHODS: An analysis of 4029 incident cases of the disease notified to the Singapore Cancer Registry for 1968-1992 was undertaken to provide some insight into important aetiologic factors among these women. RESULTS: The age-standardized incidence rate of lung cancer rose from 17.3 per 100,000 woman-years in 1968-1972 to 23.0 in 1978-1982 before falling off in more recent years. Age-period-cohort analysis indicated significant period and birth cohort effects, with the risk being highest for women born around 1908. Between the major dialect groups, Cantonese women had a significantly high rate compared with Hokkiens (relative risk [RR] = 2.6, 95% CI: 2.4-2.8). Histologically, there appears to be an increase in the proportion of adenocarcinomas diagnosed over this period (25.8% in 1968-1972 to 51.3% in 1988-1992). CONCLUSION: Our results suggest that traditional practices which have decreased over the years, and are more prominent among Southern Chinese, may play a part in the aetiology of lung cancer locally.