Female Lung Cancer Cases Research Articles

PM2.5 exposure and risk of lung adenocarcinoma in women of Taiwan: A case-control study with density sampling.

The prevalence of smoking among women in Taiwan is <5%, but the incidence of lung cancer remains high. This study determined the association between PM2.5 (fine particulate matter with an aerodynamic diameter of ≤2.5μm) exposure and lung cancer among women in Taiwan. In total, 21,301 female lung cancer cases nationwide were newly diagnosed between 2012 and 2017. Each case was age-, sex- and calendar year-matched with four controls randomly selected from the general population. Allowing a latent period of 5 years, we estimated the PM2.5 and nitrogen dioxide (NO2 ) exposures for each individual according to the residential changes from 2000. We adopted self-reported smoking statuses for the cases, while those of controls were estimated using annual surveys in each residential county. We performed multiple logistic regression analyses to examine the associations between PM2.5 and NO2 exposures and incident lung cancer cases. The ORs of lung adenocarcinoma for the third (30.5-35.1μg/m3 ), fourth (35.1-39.3μg/m3 ) and fifth PM2.5 exposure quintiles (39.3-48.1μg/m3 ) relative to the first quintile were 1.10 (95% CI: 1.04-1.16), 1.12 (95% CI: 1.06-1.19) and 1.10 (95% CI: 1.04-1.16), respectively, after adjusting for smoking, residence and comorbidities. A dose-response relationship (p=0.004) was found. The associations persisted with a 10-year latency and were not detected for small-cell and squamous cell carcinoma after control for smoking. We did not observe a similar effect for NO2 exposure. Residential PM2.5 exposure higher than 30 μg/m3 was associated with an increased risk of lung adenocarcinoma in women of Taiwan.

Abstract 2254: Risk models for lung cancer in never-smoking women in Shanghai with implications for screening

Abstract Background: The majority of female lung cancer cases in Asia are never-smokers with distinct risk factor profiles. Given the high burden of disease in this population, there is an increasing need to improve the understanding of lung cancer. Current risk models for lung cancer focus on active smokers and individuals of European ancestry. Therefore, we developed statistical models by integrating genetic and environmental risk factors to estimate absolute and population attribute risk of lung cancer among never-smoking women in Asia. Methods: We built absolute risk models for lung cancer among never-smoking women using data from 71,300 women (760 incident cases) in the Shanghai Women’s Health Study (SWHS), a population-based prospective cohort study. Relative risks were estimated using a multivariable Cox regression model with questionnaire-based risk factors. To account for missing genetic data for some subjects, we simulated genotypes for 10 common single nucleotide polymorphisms (SNP) using information on minor allele frequencies (MAF) and odds ratio estimates from previous genome-wide association studies (GWAS), conditional on family history of lung cancer. We used the iCARE tool to build two models for predicting lifetime (40 years) and 6-year absolute risk of lung cancer using age-specific lung cancer incidence rates, age-specific competing mortality rates, and risk factor distribution with: 1) questionnaire-based risk factors only and 2) questionnaire and genetic data. We then used the full absolute risk model to estimate the population attributable risk (PAR) due to modifiable risk factors, namely coal use and exposure to environmental tobacco smoke (ETS). Results: The questionnaire-based only model included family history of lung cancer, coal use, exposure to ETS, and body mass index (BMI). The full model also included data on 10 lung cancer related SNPs from our previous GWAS and had a wider spread in distribution of absolute lifetime risk (median=2.41%; range=0.43-12.36) compared to the questionnaire-based only model (median=2.72%; range=1.93-4.87). We used the full model to estimate the PAR and found that 1.74% and 6.33% of lung cancer cases could be prevented if never-smoking women in Shanghai did not use coal and were not exposed to ETS, respectively. Furthermore, we found that the full model estimated that 2.5% of the study population had a 6-year absolute risk of lung cancer higher than 1.51%, which is the suggested risk threshold for screening by existing risk models. Conclusion: We built risk models for never-smoking Asian women and estimated the contribution of coal use and ETS to the burden of lung cancer in Shanghai. This initial work shows promise for expanding and validating risk models in this population with potential translational implications, such as providing insight to identifying high risk individuals that may be eligible for lung cancer screening and primary prevention efforts. Citation Format: Batel Blechter, Parichoy Pal Choudhury, Xiao-ou Shu, Wei Zheng, Qiuyin Cai, Gong Yang, Jason Y.Y. Wong, Bu-Tian Ji, Wei Hu, Anne Rositch, Nilanjan Chatterjee, Nathaniel Rothman, Qing Lan. Risk models for lung cancer in never-smoking women in Shanghai with implications for screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2254.

Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones

BackgroundPublished findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women.MethodsThe PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed.ResultsForty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87–0.98) and exogenous (OR: 0.86, 95% CI: 0.80–0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86–0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78–0.99) than in smoking women (OR: 0.98, 95% CI: 0.77–1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74–0.96).ConclusionsOur meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.

Forecasting of Lung Cancer Incident Cases at the Small-Area Level in Victoria, Australia.

Predicting lung cancer cases at the small-area level is helpful to quantify the lung cancer burden for health planning purposes at the local geographic level. Using Victorian Cancer Registry (2001–2018) data, this study aims to forecast lung cancer counts at the local government area (LGA) level over the next ten years (2019–2028) in Victoria, Australia. We used the Age-Period-Cohort approach to estimate the annual age-specific incidence and utilised Bayesian spatio-temporal models that account for non-linear temporal trends and area-level risk factors. Compared to 2001, lung cancer incidence increased by 28.82% from 1353 to 1743 cases for men and 78.79% from 759 to 1357 cases for women in 2018. Lung cancer counts are expected to reach 2515 cases for men and 1909 cases for women in 2028, with a corresponding 44% and 41% increase. The majority of LGAs are projected to have an increasing trend for both men and women by 2028. Unexplained area-level spatial variation substantially reduced after adjusting for the elderly population in the model. Male and female lung cancer cases are projected to rise at the state level and in each LGA in the next ten years. Population growth and an ageing population largely contributed to this rise.

Gender-based epidemiological study of lung cancer patients

Background In Egypt, lung cancer represents 5.0–7.0% of all cancers and ranks the fifth in males and both sexes, and ninth among females. The current study aims to characterize a cohort of patients with lung cancer based on their sex regarding risk factors, clinical presentation, and results of investigations. Patients and methods A retrospective comparative cross-sectional study was conducted that included all female lung cancer cases that were referred to the Clinical Oncology and Nuclear Medicine Department from year 2014 to year 2018. An equal number of males were randomly selected within the same year interval (as a comparative group). Data (included epidemiological data, relevant medical history, and the histopathologic type of cancer) were retrieved from the electronic database. Results The family history of malignancy was higher among females (8.8 vs. 0%), but the difference was not significant. There were no significant differences in performance status between male and female group. Apart from chronic obstructive pulmonary disease, the prevalence of most chronic diseases was significantly higher among females than males. Adenocarcinoma is the most common histologic subtype regardless of sex, whereas squamous cell carcinoma represented 18.5% among males and 1.9% among females, with significant difference (P=0.001). Bone was the most common site of metastasis. Overall, 14% of males had suprarenal metastasis, compared with 3.5% of females, with significant difference (P=0.047). Conclusion This 4-year single-center analysis concluded that both male and female present at a late stage of lung cancer. Suprarenal metastasis was more common in males than females. Squamous cell carcinoma was the most common among males. There were no sex differences regarding age of diagnosis, performance status, presenting symptoms, and radiological site of tumor.

The effect of susceptibility variants, identified in never-smoking female lung cancer cases, on male smokers.

Background/AimsGenome wide and candidate gene association studies have identified polymorphisms associated with the risk of lung cancer in never-smokers. This study was conducted to evaluate the association between 11 polymorphisms identified in female never smokers and the lung cancer risk in male smokers.MethodsThis study included 714 lung cancer patients and 626 healthy controls. The polymorphisms were genotyped using SEQUENOM MassARRAY iPLEX assay or Taq-Man assay.ResultsTwo polymorphisms were associated with the risk of lung cancer in male smokers, as in female never smokers. Male smokers carrying the rs4975616 variant allele had a significantly decreased risk of lung cancer (in a codominant model: odds ratio, 0.77; 95% confidence interval, 0.61 to 0.96; p = 0.02). The rs9387478 polymorphism also reduced lung cancer risk in male smokers (in a codominant model: odds ratio, 0.85; 95% confidence interval, 0.73 to 0.997; p = 0.046). In a stratified analysis, the association between these polymorphisms and the risk of lung cancer was predominant in lighter smokers and for cases of adenocarcinoma.ConclusionsThese results suggest that a subset of polymorphisms known to be associated with the risk of lung cancer in female never smokers is also associated with the risk of lung cancer in male smokers.

Cancers Due to Smoking and High Alcohol Consumption.

Tobacco and alcohol consumption are known causes of cancer. We set out to estimate the absolute numbers and proportions of cancer attributable to smoking and high alcohol consumption in Germany in 2018. Numbers and proportions (population-attributable fractions, PAF) were calculated by sex and age group for ages 35 to 84 years based on population projections, national cancer incidence and exposure data, and published relative risks. For the year 2018 we estimated the smoking-attributable cancer burden to be 85 072 cases (men 58 760, women 26 312), corresponding to 19% of all incident cancers. The highest PAF was seen for lung cancer: 89% of male and 83% of female lung cancer cases are attributable to smoking. The cancer burden attributable to high alcohol consumption was estimated to be 9588 (men 8117, women 1471) cases (2% of all incident cancers). The highest PAF were observed for cancer of the oral cavity and pharynx (men 34%, women 6%) and squamous cell carcinoma of the esophagus (men 30%; women 5%). A considerable proportion of cancer cases are attributable to smoking and high alcohol consumption. More rigorous prevention efforts are required to achieve significant reductions in the prevalence of these risk factors and the attributable cancer burden.

Trends in Lung Cancer Incidence in Delhi, India 1988-2012: Age-Period-Cohort and Joinpoint Analyses

Introduction:Lung cancer (LC) has been one of the most commonly diagnosed cancers worldwide, both in terms of new cases and mortality. Exponential growth of economic and industrial activities in recent decades in the Delhi urban area may have increased the incidence of LC. The primary objective of this study was to evaluate the time trend according to gender.Method:LC incidence data over 25 years were obtained from the population based urban Delhi cancer registry. Joinpoint regression analysis was applied for evaluating the time trend of age-standardized incidence rates. The age-period-cohort (APC) model was employed using Poisson distribution with a log link function and the intrinsic estimator method.Results:During the 25 years, 13,489 male and 3,259 female LC cases were registered, accounting for 9.78% of male and 2.53% of female total cancer cases. Joinpoint regression analysis revealed that LC incidence in males continued to increase during the entire period, a sharp acceleration being observed starting from 2009. In females the LC incidence rate remained a plateau during 1988-2002 and thereafter increased. The cumulative risks for 1988-2012 were 1.79% and 0.45%. The full APC (IE) model showed best fit for an age-period-cohort effect on LC incidence, with significant increase with age peaking at 70-74 years in males and 65-69 years in females. A rising period effect was observed after adjusting for age and cohort effects in both genders and a declining cohort effect was identified after controlling for age and period effects.Conclusion:The incidence of LC in urban Delhi showed increasing trend from 1988-2012. Known factors such as environmental conservation, tobacco control, physical activity awareness and medical security should be implemented more vigorously over the long term in our population.

Abstract 4596: Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: A report from the Female Lung Cancer Consortium in Asia

Abstract Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of 7 telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of 7 telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, P-value = 4.54×10−14) even after removing rs2736100 (P-value = 4.81×10−3), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk. Citation Format: Mitchell J. Machiela, Chao A. Hsiung, Xiao-Ou Shu, Wei J. Seow, Zhaoming Wang, Keitaro Matsuo, Yun-Chul Hong, Adeline Seow, Chen Wu, H Dean Hosgood, Kexin Chen, Jiu-Cun Wang, Wanqing Wen, Tangchun Wu, Maria P. Wong, Yi-Long Wu, Pan-Chyr Yang, Baosen Zhou, Min-Ho Shin, Joseph F. Fraumeni, Wei Zheng, Dongxin Lin, Stephen J. Chanock, Nathaniel Rothman, Qing Lan. Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: A report from the Female Lung Cancer Consortium in Asia. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4596. doi:10.1158/1538-7445.AM2015-4596

Genetic variants associated with longer telomere length are associated with increased lung cancer risk among never-smoking women in Asia: a report from the female lung cancer consortium in Asia.

Recent evidence from several relatively small nested case-control studies in prospective cohorts shows an association between longer telomere length measured phenotypically in peripheral white blood cell (WBC) DNA and increased lung cancer risk. We sought to further explore this relationship by examining a panel of seven telomere-length associated genetic variants in a large study of 5,457 never-smoking female Asian lung cancer cases and 4,493 never-smoking female Asian controls using data from a previously reported genome-wide association study. Using a group of 1,536 individuals with phenotypically measured telomere length in WBCs in the prospective Shanghai Women's Health study, we demonstrated the utility of a genetic risk score (GRS) of seven telomere-length associated variants to predict telomere length in an Asian population. We then found that GRSs used as instrumental variables to predict longer telomere length were associated with increased lung cancer risk (OR = 1.51 (95% CI = 1.34-1.69) for upper vs. lower quartile of the weighted GRS, p value = 4.54 × 10(-14) ) even after removing rs2736100 (p value = 4.81 × 10(-3) ), a SNP in the TERT locus robustly associated with lung cancer risk in prior association studies. Stratified analyses suggested the effect of the telomere-associated GRS is strongest among younger individuals. We found no difference in GRS effect between adenocarcinoma and squamous cell subtypes. Our results indicate that a genetic background that favors longer telomere length may increase lung cancer risk, which is consistent with earlier prospective studies relating longer telomere length with increased lung cancer risk.

Histological subtypes of lung cancer in Chinese women from 2000 to 2012.

The aim of the study was to characterize the histological and epidemiological features of lung cancer in Chinese women. Demographic and histological information on female lung cancer cases identified during 1 January 2000 through 31 December 2012 from the Cancer Hospital of the Chinese Academy of Medical Sciences were collected. The International Classification of Diseases for Oncology system was used to classify the histological subtypes. Relative frequencies (RF) were estimated for major histological subtypes and compared by the years of diagnosis and birth, and among residential areas. Statistical differences were tested for RFs in the time periods with a trend test and with Pearson Chi square tests for distribution. Of 7070 female Chinese lung cancer cases, the major histological subtypes were adenocarcinoma (ADC) 65.79%; squamous cell carcinoma (SCC) 10.21%; small cell cancer 8.12%; large cell carcinoma, 2.79%; and adeno-squamous carcinoma (ASC), 2.19%. ADC increased, with RFs from 46.72% in the cases identified in 2000-2002 to 76.49% in 2011-2012 (Z = 16.998, P < 0.0001); SCC decreased from 15.69% to 5.97% (Z = -8.750, P < 0.0001). Compared to the cases identified in 2000-2006, the age-adjusted RFs of ADC in 2007-2012 consistently increased in all study areas. The significant increase of ADC of the lung in Chinese women suggests that a persistently strong exposure to potential carcinogens in the Chinese population should be further and fully investigated.

Longer Telomere Length in Peripheral White Blood Cells Is Associated with Risk of Lung Cancer and the rs2736100 (CLPTM1L-TERT) Polymorphism in a Prospective Cohort Study among Women in China

A recent genome-wide association study of lung cancer among never-smoking females in Asia demonstrated that the rs2736100 polymorphism in the TERT-CLPTM1L locus on chromosome 5p15.33 was strongly and significantly associated with risk of adenocarcinoma of the lung. The telomerase gene TERT is a reverse transcriptase that is critical for telomere replication and stabilization by controlling telomere length. We previously found that longer telomere length measured in peripheral white blood cell DNA was associated with increased risk of lung cancer in a prospective cohort study of smoking males in Finland. To follow up on this finding, we carried out a nested case-control study of 215 female lung cancer cases and 215 female controls, 94% of whom were never-smokers, in the prospective Shanghai Women’s Health Study cohort. There was a dose-response relationship between tertiles of telomere length and risk of lung cancer (odds ratio (OR), 95% confidence interval [CI]: 1.0, 1.4 [0.8–2.5], and 2.2 [1.2–4.0], respectively; P trend = 0.003). Further, the association was unchanged by the length of time from blood collection to case diagnosis. In addition, the rs2736100 G allele, which we previously have shown to be associated with risk of lung cancer in this cohort, was significantly associated with longer telomere length in these same study subjects (P trend = 0.030). Our findings suggest that individuals with longer telomere length in peripheral white blood cells may have an increased risk of lung cancer, but require replication in additional prospective cohorts and populations.

Genome-wide association analysis identifies new lung cancer susceptibility loci in never-smoking women in Asia

To identify common genetic variants that contribute to lung cancer susceptibility, we conducted a multistage genome-wide association study of lung cancer in Asian women who never smoked. We scanned 5,510 never-smoking female lung cancer cases and 4,544 controls drawn from 14 studies from mainland China, South Korea, Japan, Singapore, Taiwan and Hong Kong. We genotyped the most promising variants (associated at P < 5 × 10(-6)) in an additional 1,099 cases and 2,913 controls. We identified three new susceptibility loci at 10q25.2 (rs7086803, P = 3.54 × 10(-18)), 6q22.2 (rs9387478, P = 4.14 × 10(-10)) and 6p21.32 (rs2395185, P = 9.51 × 10(-9)). We also confirmed associations reported for loci at 5p15.33 and 3q28 and a recently reported finding at 17q24.3. We observed no evidence of association for lung cancer at 15q25 in never-smoking women in Asia, providing strong evidence that this locus is not associated with lung cancer independent of smoking.

EGFR Somatic Mutations in Lung Tumors: Radon Exposure and Passive Smoking in Former- and Never-Smoking U.S. Women

Patients with lung cancer with mutations in EGF receptor (EGFR) tyrosine kinase have improved prognosis when treated with EGFR inhibitors. We hypothesized that EGFR mutations may be related to residential radon or passive tobacco smoke. This hypothesis was investigated by analyzing EGFR mutations in 70 lung tumors from a population of never and long-term former female smokers from Missouri with detailed exposure assessments. The relationship with passive smoking was also examined in never-smoking female lung cancer cases from the Mayo clinic. Overall, the frequency of EGFR mutation was 41% [95% confidence interval (CI), 32%-49%]. Neither radon nor passive-smoking exposure was consistently associated with EGFR mutations in lung tumors. The results suggest that EGFR mutations are common in female, never-smoking lung cancer cases from the United States, and EGFR mutations are unlikely due to exposure to radon or passive smoking.

Abstract 5479: Somatic driver mutations among never smoking female lung cancer cases in China identify unique mutation pattern that may be associated with household coal burning

Abstract Globally, about 53% of lung cancer cases in women and 15% of lung cancer cases in men are not attributable to active tobacco use, making lung cancer in never smokers the seventh leading cause of cancer death. Experimental and epidemiological evidence suggest that lung cancer in never smokers has unique risk factors, clinical features, and histological distributions as compared to those lung cancer cases attributed to tobacco smoking. In general, lung cancer in never smokers presents predominately as adenocarcinoma and in females. The lung cancer rate among females in Xuanwei, China is among the highest in the world for nonsmoking females, and has been attributed to indoor air pollution from domestic fuel combustion, particularly from bituminous coal. To further explore the clinical and histological aspects of lung cancer in Xuanwei, we collected formalin-fixed paraffin embedded (FFPE) tissue samples from a series of 76 female lung cancer cases. The mean age of the patients was 47.7 years old (±9.2 years). Expert consensus review found 54 (71%) of the female lung cancer cases were adenocarcinomas (ADCs), 11 (14.5%) were squamous cell carcinomas (SCCs), 1 (1.3%) was an adenosquamous carcinoma (ADSC), 8 (10.5%) were large cell carcinomas, and 2 (2.7%) were other subtypes. We then used two multiplexed assays to detect in DNA from FFPE tissue more than 40 recurrent mutations in nine genes relevant to existing and emerging targeted lung cancer therapies among subjects who were confirmed never smoking female lung cancer cases (32 ADCs, 7 SCCs, 1 ADSC). These assays include amplification of DNA through Applied Biosystem's SNaPshot technology to detect 38 different recurrent somatic point mutations in 8 driver genes (EGFR, KRAS, BRAF, NRAS, PIK3CA, MEK1, AKT1, and PTEN) and a PCR-based sizing assay that assesses for EGFR exon 19 deletions, EGFR exon 20 insertions, and HER2 exon 20 insertions. We detected 15 EGFR mutations [E20-6bp-ins. (n=1); EGFR_19-15bpDel (n=4); EGFR_G719A_2156G&amp;gt;C (n=2); EGFR_G719C_2155G&amp;gt;T (n=3); EGFR_G719S _2155G&amp;gt;T (n=1); EGFR_G719S_2155G&amp;gt;A (n=1); EGFR_L858R_2573T&amp;gt;G (n=2); EGFR L861Q_2582T&amp;gt;A (n=1)] in 12 ADCs and 2 SCCs. Six KRAS mutations, all of which were KRAS G12C_34G&amp;gt;T, were detected in 5 ADCs and 1 SCC. EGFR and KRAS mutations were mutually exclusive and no mutations were observed for BRAF, NRAS, PIK3CA, MEK1, HER2, AKT1, or PTEN. The high percentage of samples with KRAS mutations (15.0% overall; 15.6% ADCs; 14.3% SCCs) in our series is of interest, primarily because KRAS mutations are reportedly more rare in other populations from Asia (∼5%) and populations of never smokers from Asia (∼2%). Given that all subjects with KRAS mutations burned coal indoors for heating and cooking, our findings may provide new insights into the pathogenesis of lung cancer among never smoking females exposed to indoor air pollution from coal. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5479. doi:1538-7445.AM2012-5479

Environmental and Dietary Factors and Lung Cancer Risk Among Chinese Women: A Case-Control Study in Southeast China

After decades of increase, lung cancer has become the leading cause of cancer death among women. The mortality rate from lung cancer is ascending at a relatively steady rate, which has greatly affected the health of the female population and become a serious issue. A case-control study of 226 female lung cancer cases and 269 controls was conducted from 2006 to 2010 in Fujian Province. A structured questionnaire was used to gather information on demographic characteristics as well as dietary and environmental factors. Odds ratios and 95% confidence intervals were estimated by using univariate logistic regression. Multivariate unconditional logistic regression analysis was applied to evaluate the potential interactions of variables or confounders. The consumption of fruit, eggs, and tea was inversely associated with the risk of lung cancer. As expected, cooking oil fumes and environmental tobacco exposure were positively associated with elevated risk. In addition, frequent physical activity and late age at menarche were identified as protective factors of female lung cancer. The results demonstrate that some environmental and dietary factors are related to the risk of lung cancer among the female population in southeast China.

Aspirin and non-aspirin non-steroidal anti-inflammatory drug use and risk of lung cancer

There is evidence that aspirin and non-aspirin non-steroidal anti-inflammatory drug (NSAID) have anti-carcinogenic properties, but their effect on lung cancer, in particular in never-smokers, is unclear. Information on past or current use of anti-inflammatory medication was obtained in 398 Chinese female primary lung cancer cases and 814 controls in a hospital-based study in Singapore. 65% of cases and 88% of controls were never-smokers. Controls were excluded if they had been admitted for conditions associated with aspirin or NSAID use (n=174). Regular aspirin use (twice a week or more, for a month or more) was associated with a reduced risk of lung cancer (adjusted odds ratio [OR] 0.50, 95% confidence intervals [95%CI] 0.31–0.81 in non-smokers; OR 0.38, 95%CI 0.16–0.93 in smokers). Regular use of non-aspirin NSAID, paracetamol, steroid creams and steroid pills was uncommon and no association with lung cancer was detected. Our results suggest that aspirin consumption may reduce lung cancer risk in Asian women and are consistent with current understanding of the role of cyclooxygenase in lung carcinogenesis.

Genetic variant in TP63 on locus 3q28 is associated with risk of lung adenocarcinoma among never-smoking females in Asia.

A recent genome-wide association study (GWAS) of subjects from Japan and South Korea reported a novel association between the TP63 locus on chromosome 3q28 and risk of lung adenocarcinoma (p = 7.3 × 10(-12)); however, this association did not achieve genome-wide significance (p ≤ 10(-7)) among never-smoking males or females. To determine if this association with lung cancer risk is independent of tobacco use, we genotyped the TP63 SNPs reported by the previous GWAS (rs10937405 and rs4488809) in 3,467 never-smoking female lung cancer cases and 3,787 never-smoking female controls from 10 studies conducted in Taiwan, Mainland China, South Korea, and Singapore. Genetic variation in rs10937405 was associated with risk of lung adenocarcinoma [n = 2,529 cases; p = 7.1 × 10(-8); allelic risk = 0.80, 95% confidence interval (CI) = 0.74-0.87]. There was also evidence of association with squamous cell carcinoma of the lung (n = 302 cases; p = 0.037; allelic risk = 0.82, 95% CI = 0.67-0.99). Our findings provide strong evidence that genetic variation in TP63 is associated with the risk of lung adenocarcinoma among Asian females in the absence of tobacco smoking.

Female Reproductive Factors, Gene Polymorphisms in the Estrogen Metabolism Pathway, and Risk of Lung Cancer in Chinese Women

The authors examined relations between reproductive factors and 5 estrogen pathway gene polymorphisms (CYP17 rs743572, CYP19A1 rs10046, ERβ rs1256049, ERβ rs4986938, and COMT rs4680) among 702 Singapore Chinese female lung cancer cases and 1,578 hospital controls, of whom 433 cases (61.7%) and 1,375 controls (87.1%) were never smokers. Parity (per child, odds ratio (OR) = 0.92, 95% confidence interval (CI): 0.87, 0.97) and menstrual cycle length (for ≥30 days vs. <30 days, OR = 0.50, 95% CI: 0.32, 0.80) were inversely associated with lung cancer in never smokers, while age at first birth (for ages 21-25, 26-30, and ≥31 years vs. ≤20 years, ORs were 1.54, 2.17, and 1.30, respectively), age at menopause (for ages 49-51 and ≥52 years vs. ≤48 years, ORs were 1.37 and 1.59; P(trend) = 0.003), and reproductive period (for 31-33, 34-36, 37-39, and ≥40 years vs. ≤30 years, ORs were 1.06, 1.25, 1.45, and 1.47; P(trend) = 0.026) were positively associated. Among smokers, parity was inversely associated with lung cancer, but there was no association with other reproductive factors. The COMT rs4680 A allele was positively associated with lung cancer in never smokers (for G/A or A/A vs. G/G, OR = 1.46, 95% CI: 1.12, 1.90) but not in ever smokers. No associations were seen with other polymorphisms. These results support a risk-enhancing role of estrogens in lung carcinogenesis among never smokers.

Lung cancer in patients under the age of 40 years

Aim of the studyIn the paper clinical cases of individuals diagnosed with lung cancer below the age of 40 years have been analyzed.Material and methodsThe analysis included: sex, age, clinical symptoms found before and at the moment of diagnosis, character of changes visible in radiological imaging, time that passed from the first symptoms to reporting to a doctor and to establishing a diagnosis, type of diagnostic method used in establishing the final diagnosis, histopathologic type of cancer, degree of cancer progression.ResultsThe results have been compared with a peer group who had been diagnosed 20 years earlier. Currently 7% of patients were diagnosed at the age of 25 or younger, whereas in the previous cohort patients in this age constituted 2%. The predominant pathological type was adenocarcinoma (currently 33%, previously 4%) in contrast to the earlier group in which 57% of patients had small cell lung cancer (57%). The incidence is equally distributed between both sexes, although there is an evident increase in female lung cancer cases. In the majority of patients the clinical presentation is a peripheral mass on chest X-ray. 20% of patients present pleural effusion on diagnosis. Patients reported the following complaints: breathlessness, chest pain, weight loss and fatigue. The majority of cases were diagnosed in advanced stages on the basis of a bronchoscopy acquired specimen. Time course from symptoms to diagnosis tends to be shorter than 20 years ago.