Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women.

To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.

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.

INSPstI polymorphism and prostate cancer in African-American men.

BACKGROUND: Both prostate cancer and diabetes mellitus are common diseases in African-American men. High insulin levels and insulin resistance have been implicated in prostate cancer development, which has prompted a recent investigation of a possible role for germline variation in the insulin gene (INS) and prostate cancer risk. METHODS: Four hundred sixty-six African-American men with and without prostate cancer from the Flint Men's Health Study were typed for the INS Pst1 genotype using restriction digest and direct sequencing. An association between the Pst1 genotype and prostate cancer was examined using crude and age-adjusted logistic regression models. RESULTS: African-American men who were homozygous for the INS PstI CC genotype were 1.59 times more likely to be diagnosed with prostate cancer compared to men with the TT or TC genotypes (95% CI = 0.93-2.72). The association appeared stronger among diabetics compared to non-diabetics; however this observation was not statistically significant. CONCLUSIONS: Our study, taken together with the report of Ho et al., suggests that the INS Pst1 CC genotype is associated with prostate cancer risk in African-American men. Germline variation in the INS gene should be more fully explored in multiethnic studies to elucidate the molecular variant(s) associated with prostate carcinogenesis.

Risk perception and concern among brothers of men with prostate carcinoma.

BACKGROUND: It is important for clinicians, researchers, and others who shape public health policy to understand the demographic correlates and psychologic factors that drive health behaviors, such as screening for early detection of cancer, particularly among individuals at high risk for developing the disease. METHODS: One-hundred eleven men whose brothers were diagnosed with prostate carcinoma completed a computer-assisted telephone interview aimed to assess their perception of absolute risk and concern about developing prostate carcinoma over the next 10 years and across their lifetime. Comparisons were made between selected demographic, behavioral, family pedigree characteristics, and measures of perceived risk and concern. RESULTS: The majority of men perceived their personal risk of developing prostate carcinoma to be > or =50%. Men who at the time of the interview were younger than their affected brother were significantly more concerned about prostate carcinoma and perceived their risk to be higher than men who were older than their brother. Estimates of personal risk and concern were also uniformly higher among men with more than one first-degree relative affected with prostate carcinoma compared to men with only one affected first-degree relative. Risk perception and concern about an impending prostate carcinoma diagnosis were associated with the use of supplements marketed for prostate health. CONCLUSIONS: The findings indicated that birth order in relation to a brother diagnosed with prostate carcinoma is significantly associated with risk perception and concern in unaffected family members. These results highlight the need for further study of the familial dynamics and characteristics that drive health behaviors and stress importance of public health education to inform men of personal risk assessment as well as the risks and benefits of screening. These studies ultimately can contribute to the success of strategies for the primary prevention and early detection of cancer.