Lung Cancer In African Americans Research Articles

Abstract B61: Insights into lung cancer survival in African Americans from a study of germline variation in the microRNA network

Abstract Lung cancer remains one of the leading public health issues of our time. Moreover, it engenders prominent disparities in incidence and mortality across populations from diverse ethnic backgrounds. Specifically, African Americans, and particularly African American men, have an increased incidence and poorer survival from lung cancer compared to Caucasians. Previously, studies have looked at how populations differ in their susceptibility to lung cancer based on inheritance of deleterious or favorable alleles. However, germline variation in the microRNA network, and how it might contribute to racial disparities in lung cancer have not been studied to date. Using the NCI/UMD case control study, we collated a list of single nucleotide polymorphisms (SNPs) within the machinery that processes microRNA genes and subsequently guides them to their mRNA target transcripts. We then analyzed the association between these SNPs with lung cancer risk and survival in a Caucasian (n=567) and African American population (n=445). Associations with risk were determined using unconditional logistic regression adjusted for age, gender and smoking. Cox proportional hazards were used to compute hazard ratio estimates in a model adjusted for age, gender, stage and histology. A variant in the gene GEMIN3, a key partner in the complex that guides the microRNA to the mRNA strand was associated with an increased risk of lung cancer in African Americans, but not after adjustment for smoking status. However, the variant A allele was associated with adverse survival in an additive model in African Americans (HR AA vs. CC 2.27 [1.30–3.93] p=0.004). Notably, the association with risk was particularly prominent in late stage tumors (HR AA vs. CC 3.08 [1.72–5.54] p<0.001). Interestingly, no associations were seen in Caucasians, suggesting that this association is race-specific. In a follow up analysis, we observed that the deleterious AA genotype for GEMIN3 is present at 12% in African Americans, yet just 1% in Caucasians, perhaps in part explaining higher mortality rates in African Americans. Moreover, we analyzed a portion of these samples on which we had tumor tissue by microarray and observed that levels of GEMIN3 are significantly increased in tumor versus normal tissue from African Americans, but not Caucasians (fold enrichment 1.45, p=0.0015, FDR=0.014). This again suggests that GEMIN3 is somehow preferentially involved in lung cancer biology distinctly between the two populations. Further work is ongoing to study how this gene and indeed the variant allele of GEMIM3, contributes to poor survival in African Americans. The literature contains numerous examples of how tumor biology differs between individuals from various geographic areas, in part due to genetic heterogeneity and lifestyle. Understanding how these variations manifest and contribute to lung cancer pathogenesis will have novel insight for the rational and targeted treatment of tumors. Citation Information: Cancer Epidemiol Biomarkers Prev 2011;20(10 Suppl):B61.

Abstract A14: Qualitative study of African American smokers regarding lung cancer

Abstract Background: The differences in mortality and incidence for lung cancer in African Americans are well-documented; however, the underlying reasons for these disparities are not well-delineated. The role that patient preferences and knowledge play in exploring these patterns among African American patients is unclear. This qualitative study was designed to explore potential themes involving treatment, and assess the level of general knowledge about lung cancer in African Americans. Methods: 32 African American smokers with ages ranging from 26 to 70 years of age, (mean, 47.5 years), who did not have a cancer diagnosis were recruited to a series of focus groups held in a Boston housing complex. Four focus groups were held over an 8-week period. The groups were evenly divided between men and women. Focus groups were facilitated by a trained qualitative researcher and the sessions were audio taped. The data was transcribed and analyzed using standard anthropology coding and thematic formulation processes. Results: Participants understood the link between smoking and lung cancer, as well as the common signs and symptoms of the disease. Regarding prevention, participants wanted the information to be in-depth, and tailored to their situation. They were familiar with the lethality of lung cancer, and had a good working knowledge of the treatment modalities. The impact of patient preferences and mistrust on treatment choice was minimal. When asked specifically about the role of race in getting appropriate treatment for lung cancer; most participants felt that insurance and socioeconomic factors were more important than race. Conclusions: This study suggests that African American smokers are informed about the link between smoking and lung cancer, and have a good working knowledge of the disease. Participants did not feel that their race prevented them from accessing high-quality cancer care, but were concerned about the effect of socioeconomic status and insurance on this process. Our study suggests that African Americans are interested in access to quality cancer treatment and information, and that patient preferences and mistrust of clinicians may not be major factors in lung cancer treatment disparities. Citation Information: Cancer Epidemiol Biomarkers Prev 2010;19(10 Suppl):A14.

Drilling Down to the Causes of Racial Disparities in Lung Cancer

A recent study of early-stage lung cancer patients found that African Americans are statistically significantly less likely than whites to receive definitive — i.e., potentially curative — surgery. That finding, which the Journal of the American Medical Association published in June, appeared soon after an American Lung Association (ALA) report that also underscored the need for systematic change in the approach to lung cancer in African Americans. Together, the two reports confi rm the disparity between blacks and whites in lung cancer rates, treatment, and outcomes while exploring some of the reasons — biological, clinical, and socioeconomic — that may explain these differences. African Americans are more likely to develop lung cancer and less likely to respond to available treatments than whites. Cigarette smoking rates can’t account for the disparity, because although white men smoke 30% – 40% more cigarettes, African American men have a higher incidence of lung cancer (75 per 100,000 vs. 64 per 100,000). According to a meta-analysis published in the September 2008 issue of PLoS Medicine , the disparity exists even among nonsmokers (16 per 100,000 among blacks vs. 12 per 100,000 among whites). This disproportionate burden prompted the April 2010 ALA report, which called for a concerted effort to examine underlying biological differences; to reduce cigarette advertising, particularly for menthol cigarettes, in African American communities ( see sidebar); and to educate physicians on how to overcome communication barriers with African American patients.

CYP1A1/2 Haplotypes and Lung Cancer and Assessment of Confounding by Population Stratification

Prior studies of lung cancer and CYP1A1/2 in African-American and Latino populations have shown inconsistent results and have not yet investigated the haplotype block structure of CYP1A1/2 or addressed potential population stratification. To investigate haplotypes in the CYP1A1/2 region and lung cancer in African-Americans and Latinos, we conducted a case-control study (1998-2003). African-Americans (n = 535) and Latinos (n = 412) were frequency matched on age, sex, and self-reported race/ethnicity. We used a custom genotyping panel containing 50 single nucleotide polymorphisms in the CYP1A1/2 region and 184 ancestry informative markers selected to have large allele frequency differences between Africans, Europeans, and Amerindians. Latinos exhibited significant haplotype main effects in two blocks even after adjusting for admixture [odds ratio (OR), 2.02; 95% confidence interval (95% CI), 1.28-3.19 and OR, 0.55; 95% CI, 0.36-0.83], but no main effects were found among African-Americans. Adjustment for admixture revealed substantial confounding by population stratification among Latinos but not African-Americans. Among Latinos and African-Americans, interactions between smoking level and haplotypes were not statistically significant. Evidence of population stratification among Latinos underscores the importance of adjusting for admixture in lung cancer association studies, particularly in Latino populations. These results suggest that a variant occurring within the CYP1A2 region may be conferring an increased risk of lung cancer in Latinos.

Current imaging techniques to detect brain metastasis and its findings in correlation with histopathological diagnosis in african american population with lung cancer

19107 Background: To assess the incidence of brain metastasis in lung cancer with current imaging techniques, in correlation with their respective histopathologic diagnosis in african americans. Methods: Retrospective analysis of 69 african american patients with histopathologic diagnosis of lung cancer between January 2005 and December 2007 with appropriate metastatic workup were done. Results: We reviewed the data of 69 african american patients with lung cancer, and were found to have the following histological pattern. Adenocarcinoma is the commonest histological type with 34.8%(n=24), followed by 18.8%(n=13) squamous cell carcinoma, 5.8% (n=4) small cell carcinoma, 5.8% (n=4) large cell neuroendocrine carcinoma, 5.8%(n=4) poorly differentiated carcinoma, 2.9% (n=2) sarcoma, 1.44% (n=1) bronchoalveolar carcinoma and 24.6% (n=17) NSCLC(unspecified histology). Brain metastasis were found in a total of 9 patients. CT head with contrast and MRI showed multiple brain metastasis in 10.14%(n=7) and 13.04%(n=9) respectively. Among the histological types mentioned above,3 (75%) patients with poorly differentiated lung cancer, 2 (50%) patients with small cell carcinoma, 1 (25%) patient with large cell neuroendocrine tumor and 3(12.5%)patients with adenocarcinoma had brain metastasis. Conclusion: Brain metastasis were found increasingly in poorly differentiated carcinoma in patients lung cancer in african americans. Brain imaging may be considered as a part of routine staging workup for histopathologies other than small cell lung cancer. Larger studies are needed to validate these results. Frequency of brain metastasis in african Americans according to histology. Histology Adenocarcinoma Poorly differentiated small cell Large cell neuro endocrine Total no. of patients 24 4 4 4 No. of patients with brain mets 3 (12.5%) 3 (75%) 2 (50%) 1(25%) No significant financial relationships to disclose.

Small cell lung cancer in African Americans

18194 Background: Several factors associated with prognosis in patients with small cell lung cancer (SCLC) have been established. The association between these known prognostic factors and race, in particular in African Americans has not been reported. This study was conducted to detect differences in presentation and prognostic factors among African Americans when compared to Caucasians. Methods: A retrospective chart review was performed identifying patients diagnosed with SCLC between July 1998 and December 2005. Data collected included demographic information (age, gender and race) as well as clinical information: stage at time of diagnosis, date of diagnosis, date of death, sites of metastases, response to chemotherapy as well as presenting symptoms and lab values including serum sodium, hemoglobin, WBC, platelets, LDH and any evidence of a neurological presentation. Results: Data was available for 198 patients. There was no significant association between race and stage (p=0.594), gender and stage (p=0.731), age and stage (p=0.505) or presence of a neurological symptom at time of diagnosis and stage (p=0.63). There was a trend that African Americans were more likely to present with a neurological symptom when compared to Caucasians (25% vs. 17% respectively) but this was not statistically significant (p=0.285). There was a significant association between race and gender (p=0.019). Of African Americans with SCLC, 71.4% were female while among Caucasians there was a more even distribution between sexes (51% female, 49% male). No significant difference was detected in overall survival when gender or race were examined (p=0.595 and p=0.953 respectively) and the difference when evaluating those with a neurological presentation was marginal (p=0.086). Other prognostic factors were similar amongst Caucasians and African Americans. Conclusions: When compared with Caucasian females, African American females are more likely to be diagnosed with SCLC than their male counterparts. Although not statistically significant, there is also a trend that African Americans with SCLC are more likely to present with neurological symptoms. No significant financial relationships to disclose.

Common Genetic Variation in TP53 Is Associated with Lung Cancer Risk and Prognosis in African Americans and Somatic Mutations in Lung Tumors

Lung cancer is primarily caused by tobacco smoking, but susceptibility is likely modified by common genetic variation. In response to many forms of cellular stress, including DNA damage, the p53 protein functions to induce cell cycle arrest, DNA repair, senescence, or apoptosis. We hypothesized that common TP53 haplotypes modulate pathways of lung carcinogenesis and lung cancer susceptibility or prognosis. To investigate our hypothesis, 14 polymorphisms in TP53, including haplotype tagging and coding single nucleotide polymorphisms, were genotyped in two studies from the greater Baltimore, Maryland area. One study is a case-control study and the second is a case-only study for which TP53 mutational spectra data are available. African Americans with Pro-T-A-G-G haplotypes of the combined TP53 polymorphisms TP53_01 (rs1042522), TP53_65 (rs9895829), TP53_66 (rs2909430), TP53_16 (rs1625895), and TP53_11 (rs12951053) had both an increased risk for lung cancer (odds ratio, 2.32; 95% confidence interval, 1.18-4.57) and a worsened lung cancer prognosis (hazards ratio, 2.38; 95% confidence interval, 1.38-4.10) compared with those with Arg-T-A-G-T haplotypes. No associations of TP53 polymorphisms with lung cancer were observed in Caucasians. In the case-only study, several polymorphisms in TP53 and TP53 haplotypes, overlapping regions of TP53 associated with risk and prognosis in African Americans, were associated with increased odds of somatic TP53 mutation in lung tumors in Caucasians. In conclusion, common genetic variation in TP53 could modulate lung cancer pathways, as suggested by the association with lung cancer in African Americans and somatic TP53 mutation frequency in lung tumors.

Less Efficient G2-M Checkpoint Is Associated with an Increased Risk of Lung Cancer in African Americans

Cell cycle checkpoints play critical roles in the maintenance of genomic integrity. The inactivation of checkpoint genes by genetic and epigenetic mechanisms is frequent in all cancer types, as a less-efficient cell cycle control can lead to genetic instability and tumorigenesis. In an on-going case-control study consisting of 216 patients with non-small cell lung cancer, 226 population-based controls, and 114 hospital-based controls, we investigated the relationship of gamma-radiation-induced G2-M arrest and lung cancer risk. Peripheral blood lymphocytes were cultured for 90 hours, exposed to 1.0 Gy gamma-radiation, and harvested at 3 hours after gamma-radiation treatment. gamma-Radiation-induced G2-M arrest was measured as the percentage of mitotic cells in untreated cultures minus the percentage of mitotic cells in gamma-radiation-treated cultures from the same subject. The mean percentage of gamma-radiation-induced G2-M arrest was significantly lower in cases than in population controls (1.18 versus 1.44, P < 0.01) and hospital controls (1.18 versus 1.40, P = 0.01). When dichotomized at the 50th percentile value in combined controls (population and hospital controls), a lower level of gamma-radiation-induced G2-M arrest was associated with an increased risk of lung cancer among African Americans after adjusting for baseline mitotic index, age, gender, and pack-years of smoking [adjusted odd ratio (OR), 2.25; 95% confidence interval (95% CI), 0.97-5.20]. A significant trend of an increased risk of lung cancer with a decreased level of G2-M arrest was observed (P(trend) = 0.02) among African Americans, with a lowest-versus-highest quartile adjusted OR of 3.74 (95% CI, 0.98-14.3). This trend was most apparent among African American females (P(trend) < 0.01), with a lowest-versus-highest quartile adjusted OR of 11.75 (95% CI, 1.47-94.04). The results suggest that a less-efficient DNA damage-induced G2-M checkpoint is associated with an increased risk of lung cancer among African Americans. Interestingly, we observed a stronger association of DNA damage-induced G2-M arrest and lung cancer among African Americans when compared with Caucasians. If replicated, these results may provide clues to the exceedingly high lung cancer incidence experienced by African Americans.

Glutathione S-transferase M1 polymorphism and lung cancer risk in African-Americans.

Glutathione S:-transferase M1 (GSTM1) can detoxify many carcinogens, including polycyclic aromatic hydrocarbons such as those from cigarette smoke. Though a number of studies have been published about the association between GSTM1 polymorphism and lung cancer, this association has received limited attention in the African-American population. We conducted a case-control study to investigate the role of GSTM1 polymorphism in the development of lung cancer in African-Americans. Specimens of DNA from 117 lung cancer cases and 120 controls were assayed for detection of GSTM1 genotype by polymerase chain reaction (PCR). The odds ratios (ORs) and 95% confidence intervals (CIs) for lung cancer associated with homozygous deletion of the GSTM1 gene and other risk factors were estimated by logistic regression. Thirty-seven of the 117 cases (31. 6%) and 24 of the 120 controls (20.0%) had the GSTM1 null genotype; the OR was 2.10 (95% CI 1.07-4.11) after adjustment for age, gender and smoking. The association was higher for squamous cell carcinoma (OR 2.98, 95% CI 1.09-8.19) than for adenocarcinoma (OR 1.95, 95% CI 0.81-4.66). We observed a stronger association between GSTM1 null genotype and lung cancer among heavy smokers with > or =30 pack-years (OR 4.35, 95% CI 1.16-16.23). This association was also found in squamous cell carcinoma (OR 6.26, 95% CI 1.31-29.91). In the analysis combining GSTM1 polymorphism and smoking, smokers with the null genotype had high risk (OR 8.19, 95% CI 2.35-28.62) compared with non-smokers with the wild-type genotype, and the risk increased with smoking cigarette pack-years (P: = 0.0001 for trend). Our results suggest that GSTM1 polymorphism plays a role in the development of lung cancer and modifies the risk for smoking-related lung cancer in African-Americans.

Lung cancer in African Americans. A call for action.

The authors present information about current trends in the incidence, risk factors, types, presentation, and treatment for lung cancer common to all Americans and highlight factors that are unique to African Americans. Barriers to effective care and strategies for implementing culturally competent programs for lung cancer are outlined. Disparity in the incidence and mortality rates of cancer between African Americans and white Americans has been increasing at an alarming rate since 1950. For African-American men and women, lung cancer accounted for the largest increase in the incidence of cancer between 1988 and 1992: African-American men experienced an increase of 170%, and African-American women had a dramatic increase of 464%. Lung cancer is by far the most common cause of cancer death in this population, accounting for 32% of the mortality rate in men and 20% in women. Unfortunately, lung cancer in African Americans has received little attention, and culturally competent programs are needed urgently to promote lung cancer prevention, early detection, and treatment in this population. Healthcare providers' lack of knowledge about cultural influences on care is a barrier to providing adequate healthcare to individuals of different ethnic groups. Knowledge about cultural differences, respect for individual opinions about health and illness, and ability to negotiate differences are essential qualities for health professionals who serve culturally diverse populations. Because of the morbidity and mortality rates associated with lung cancer in the African-American population, prevention, early detection, and treatment programs are needed urgently. However, for these programs to succeed, the multidisciplinary cancer care team (nurses, physicians, social workers, psychologists, health educators, clergy) must provide information and care in culturally appropriate ways. Partnerships with family, extended kin networks, and religious and community leaders are essential. Finally, to minimize morbidity and maximize quality of life during the illness trajectory, comprehensive education and supportive care services are needed for those who have been diagnosed with lung cancer.

A race-specific genetic polymorphism in the CYP1A1 gene is not associated with lung cancer in African Americans: Kelsey KT, Wiencke JK, Spitz MR. Lab for Molecular Epidemiology, Dept of Epidemiol and Biostatistics, University of California, San Francisco, CA 94143. Carcinogenesis 1994;15:1121–1124

A race-specific genetic polymorphism in the CYP1A1 gene is not associated with lung cancer in African Americans: Kelsey KT, Wiencke JK, Spitz MR. Lab for Molecular Epidemiology, Dept of Epidemiol and Biostatistics, University of California, San Francisco, CA 94143. Carcinogenesis 1994;15:1121–1124

A race-specific genetic polymorphism in the CYP1A1 gene is not associated with lung cancer in African Americans.

In a case-control study, we tested the hypothesis that a previously described African American-specific polymorphism in an intron 3' to the coding region of the CYP1A1 gene was associated with the occurrence of lung cancer. The study population included 72 African Americans with newly diagnosed, untreated lung cancer who presented to collaborating clinicians at the University of Texas M.D. Anderson Cancer Center and from county, community and Veterans Administration hospitals in the Houston metropolitan area. Controls were 97 African Americans, frequency-matched on gender and age, recruited from community centers, churches, cancer screening programs and from among hospital employees. The prevalence of the variant CYP1A1 genotype did not differ between the cases and controls. The odds ratio for individuals with one or more copies of the variant allele was 0.64 [95% confidence interval (CI) 0.3-1.4]. Overall, 20.7% of the population had one or more variant alleles; the prevalence in cases was 16.7% and in controls it was 23.7%. Two individuals with the homozygous variant genotype were controls while one individual with lung cancer was found to have the homozygous variant genotype. The lack of an association between genotype and lung cancer persisted after subgroup analysis for lifetime cigarette smoking history and tumor histology was performed. The sample size of this study is sufficient to detect odds ratios of three or greater; associations of this magnitude are similar to those reported in studies of a different polymorphism in the same region of the CYP1A1 gene in Japanese. Thus, it is unlikely that this polymorphism is associated with sizable risks for tobacco-induced lung cancer in this population subgroup.