Smoking and genetic risk variation across populations of European, Asian, and African American ancestry--a meta-analysis of chromosome 15q25.

Recent meta-analyses of European ancestry subjects show strong evidence for association between smoking quantity and multiple genetic variants on chromosome 15q25. This meta-analysis extends the examination of association between distinct genes in the CHRNA5-CHRNA3-CHRNB4 region and smoking quantity to Asian and African American populations to confirm and refine specific reported associations. Association results for a dichotomized cigarettes smoked per day phenotype in 27 datasets (European ancestry (N = 14,786), Asian (N = 6,889), and African American (N = 10,912) for a total of 32,587 smokers) were meta-analyzed by population and results were compared across all three populations. We demonstrate association between smoking quantity and markers in the chromosome 15q25 region across all three populations, and narrow the region of association. Of the variants tested, only rs16969968 is associated with smoking (P < 0.01) in each of these three populations (odds ratio [OR] = 1.33, 95% CI = 1.25-1.42, P = 1.1 × 10(-17) in meta-analysis across all population samples). Additional variants displayed a consistent signal in both European ancestry and Asian datasets, but not in African Americans. The observed consistent association of rs16969968 with heavy smoking across multiple populations, combined with its known biological significance, suggests rs16969968 is most likely a functional variant that alters risk for heavy smoking. We interpret additional association results that differ across populations as providing evidence for additional functional variants, but we are unable to further localize the source of this association. Using the cross-population study paradigm provides valuable insights to narrow regions of interest and inform future biological experiments.

Financial Hardship by Age at Diagnosis Including in Young Adulthood among African American Cancer Survivors.

BACKGROUND: Financial hardship is most common among cancer survivors with the fewest financial resources at diagnosis; however, little is known about the financial outcomes of young adult (YA) survivors (ages 20-39 at diagnosis), despite their having fewer financial reserves than older adults. METHODS: We utilized data from 3,888 participants in the population-based Detroit Research on Cancer Survivors cohort. Participants self-reported several forms of material and behavioral financial hardship (MFH and BFH, respectively). Psychological financial hardship (PFH) was measured using the Comprehensive Score for financial Toxicity (COST) score. Modified Poisson models estimated prevalence ratios (PR) and 95% confidence intervals (CI) for financial hardship by age at diagnosis controlling for demographic, socioeconomic, and cancer-related factors. RESULTS: MFH prevalence was inversely associated with age such that 72% of YA survivors reported MFH, 62% ages 40 to 54, 49% ages 55 to 64, and 33% ages 65 to 79 (PRadjusted YA vs. 65+: 1.75; 95% CI, 1.49-2.04; Ptrend < 0.001). BFH was also more common among YA survivors (26%) than those ages 65 to 79 (20%; PRadjusted: 1.50; 95% CI, 1.08-2.08; Ptrend = 0.019). Age was positively associated with financial wellbeing. COST scores ranged from 20.7 (95% CI, 19.0-22.4) among YA survivors to 27.2 (95% CI, 26.1-28.2) among adults 65 to 79 years old (Ptrend < 0.001). CONCLUSIONS: In this population of African American cancer survivors, MFH and BFH were more common, and PFH was more severe, in YA survivors compared with those diagnosed as older adults. IMPACT: Young adulthood at diagnosis should be considered a risk factor for cancer-related financial hardship and addressed in work designed to reduce the adverse financial impacts of cancer.

Cytokine SNPs: Comparison of allele frequencies by race and implications for future studies.

The role of inflammation is being considered in chronic diseases. Previous studies have examined SNPs in a few key inflammatory genes and have included small numbers of African American participants. Variation in the frequencies of inflammatory pathway SNPs may help to explain racial disparities in disease risk. Through a population-based study of 103 African American and 380 Caucasian unrelated, healthy women, we examined the relationships between race and allele frequencies of 70 cytokine and cytokine receptor SNPs. The associations between genotypic and haplotype frequencies and race were also analyzed. Allelic frequencies for 52 out of the 70 SNPs meeting criteria for analysis differed significantly by race. Of the 32 pro-inflammatory and 20 anti-inflammatory SNPs for which the allele frequencies varied significantly by race, variant allele frequency differences between Caucasians and African Americans ranged between 6-37% and 7-53% for pro-inflammatory SNPs and anti-inflammatory SNPs, respectively. Our findings suggest that while allele frequencies do vary by race, racial groups are not simplistically represented by a pro-inflammatory or anti-inflammatory genetic profile. Given the racial variability in allele frequencies in inflammatory gene SNPs, studies examining the association between these SNPs and disease should at least incorporate self-reported race in their analyses.

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

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

Regular adult aspirin use decreases the risk of non-small cell lung cancer among women.

BACKGROUND: Prior studies indicate that use of aspirin or other nonsteroidal anti-inflammatory drugs (NSAID) is associated with a decreased risk of non-small cell lung cancer (NSCLC); however, results have been contradictory in part because of variation in study design. Few studies have examined the use of aspirin or other NSAIDs on risk of NSCLC in women. METHODS: Through a case-control study of African American and Caucasian women with and without NSCLC, we examined the relationship between use of aspirin, NSAIDs, and acetaminophen and risk of NSCLC. Risk was estimated by calculating odds ratios and 95% confidence intervals for ever/never use, duration of use, and duration of use category (never, 1-5 years, >5 years) after adjusting for major risk factors for lung cancer. Risk estimates were stratified by race, age, smoking history, and body mass index. RESULTS: Every use of adult-strength aspirin was associated with a significant reduction in risk of NSCLC (odds ratio, 0.66; 95% confidence interval, 0.46-0.94). Additionally, there was a significant trend toward a reduced risk of NSCLC in adult-strength aspirin users with increasing duration of use (P(trend) = 0.02). In stratified analyses, aspirin use was associated with a significantly reduced risk of lung cancer among Caucasians and 55- to 64-year-olds. Baby aspirin and NSAID use was associated with a significant reduction in risk of NSCLC only among 65- to 74-year-olds. CONCLUSION: Our results suggest that long-term use of adult-strength aspirin may reduce the risk of NSCLC in women.

The relationship between chronic obstructive pulmonary disease and lung cancer in African American patients.

RATIONALE: Airflow obstruction and/or emphysema have been associated with lung cancer risk; however, this relationship and the joint occurrence of these conditions are not well studied in the African American population OBJECTIVE: To describe the prevalence of airflow obstruction and/or emphysema in African Americans with lung cancer and to evaluate their impact on the management and outcome of lung cancer. METHODS: Medical records of 114 African Americans who had participated in population-based case-control studies of lung cancer and who sought medical care at the Karmanos Cancer Center in Detroit, Michigan, were reviewed. The medical records of these patients were reviewed for demographics, type and stage of lung cancer, spirometry, treatment, and outcome. Computed tomographies (CT) of the chest about the time of the diagnosis of lung cancer were reviewed by a radiologist for evidence of emphysema. COPD was diagnosed when there were changes consistent with emphysema on CTs and/or airflow obstruction by spirometry. RESULTS: There were no differences by sex for age at lung cancer diagnosis (P = .78) and tumor histology (P = .43). The men were more likely to present at a later stage of lung cancer diagnosis compared with the women (P = .04), and the women were more likely to have surgery than the men (P = .03). Overall, 94% of the men and 78% of the women in this population had spirometry and/or CT evidence of COPD. The men were somewhat more likely to have COPD diagnosed by either CT or spirometry than were the women (P = .06), but the Global Obstructive Lung Disease Classification scores did not differ by sex among those with spirometry-diagnosed COPD (P = .34). Seventy-eight percent of individuals who did not report a previous diagnosis of COPD had clinical evidence of COPD, whereas 94% of individuals who reported a previous diagnosis of COPD also had clinical evidence of COPD (P = .03). Among individuals who had both spirometry and CT data available, 29% had CT evidence of emphysema but normal spirometry. No differences in COPD diagnosis (P = .82) or emphysema diagnosis (P = .51) were noted by tumor histology. Stage at diagnosis also did not differ by COPD or emphysema diagnosis (P = .30 and P = .06, respectively), nor did treatment modality (P = .54 and P = .10, respectively). Patients with lung cancer and with COPD, diagnosed either via spirometry or CT, did not show an increased risk of death compared with patients with lung cancer and without COPD after adjusting for age at diagnosis, sex, and stage (hazard ratio, 1.31 [95% CI, 0.68-2.53]). CONCLUSION: There is a high incidence of COPD, emphysema in particular, in a selected group of African American patients with lung cancer. A significant number of these patients were not aware that they had COPD. There was no significant difference in the outcome of lung cancer in relation to the presence or absence of COPD.

Cytokine and cytokine receptor single-nucleotide polymorphisms predict risk for non-small cell lung cancer among women.

Studies on the relationships between inflammatory pathway genes and lung cancer risk have not included African-Americans and have only included a handful of genes. In a population-based case-control study on 198 African-American and 744 Caucasian women, we examined the association between 70 cytokine and cytokine receptor single-nucleotide polymorphisms (SNPs) and risk of non-small cell lung cancer (NSCLC). Unconditional logistic regression was used to estimate odds ratios and 95% confidence intervals in a dominant model adjusting for major risk factors for lung cancer. Separate analyses were conducted by race and by smoking history and history of chronic obstructive pulmonary disease among Caucasians. Random forest analysis was conducted by race. On logistic regression analysis, IL6 (interleukin 6), IL7R, IL15, TNF (tumor necrosis factor), and IL10 SNP were associated with risk of non-small cell lung cancer among African-Americans; IL7R and IL10 SNPs were also associated with risk of lung cancer among Caucasians. Although random forest analysis showed IL7R and IL10 SNPs as being associated with risk for lung cancer among African-Americans, it also identified TNFRSF10A SNP as an important predictor. On random forest analysis, an IL1A SNP was identified as an important predictor of lung cancer among Caucasian women. Inflammatory SNPs differentially predicted risk for NSCLC according to race, as well as based on smoking history and history of chronic obstructive pulmonary disease among Caucasian women. Pathway analysis results are presented. Inflammatory pathway genotypes may serve to define a high risk group; further exploration of these genes in minority populations is warranted.