Michele L Cote

Karmanos Cancer Institute, Detroit, Michigan, United States

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Publications (22)103.58 Total impact

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    ABSTRACT: Lung cancer is the leading cause of worldwide cancer deaths. While smoking is its leading risk factor, few prospective cohort studies have reported on the association of lung cancer with both active and passive smoking. This study aimed to determine the relationship between lung cancer incidence with both active and passive smoking (childhood, adult at home, and at work).
    Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 10/2014;
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    ABSTRACT: Women with benign proliferative breast disease (BPBD) are at increased risk for developing breast cancer. Evidence suggests that accumulation of adipose tissue can influence breast cancer development via hyperinsulinemia, increased estrogen, and/or inflammation. However, there are limited data investigating these pathways with respect to risk of BPBD. We evaluated serologic markers from these pathways in a case-control study of postmenopausal women nested within the Women's Health Initiative Clinical Trial. Cases were the 667 women who developed BPBD during follow-up and they were matched to 1321 controls. Levels of insulin, estradiol, C-reactive protein (CRP) and adiponectin were measured in fasting serum collected at baseline. Conditional logistic regression models were used to estimate odds ratios for the association of each factor with BPBD risk. Among non-users of hormone therapy, fasting serum insulin was associated with a statistically significant increase in risk of BPBD (OR for highest vs. lowest quartile=1.80; 95%CI=1.16-2.79; ptrend=0.003) as were levels of estradiol (OR for highest vs. lowest tertile=1.89; 95%CI=1.26-2.83; ptrend=0.02) and CRP (OR for highest vs. lowest quartile=2.46; 95%CI=1.59-3.80; ptrend<0.001). Baseline adiponectin level was inversely associated with BPBD risk (OR for highest vs. lowest quartile=0.47; 95%CI=0.31-0.71; ptrend<0.001). These associations persisted after mutual adjustment but were not observed among users of either estrogen alone or of estrogen plus progestin hormone therapy. Our results indicate that serum levels of estrogen, insulin, CRP and adiponectin are independent risk factors for BPBD and suggest that the estrogen, insulin and inflammation pathways are associated with the early stages of breast cancer development.
    Cancer Research 04/2014; · 9.28 Impact Factor
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    ABSTRACT: Objective Endometrial cancer mortality disproportionately affects black women and whether greater prevalence of obesity plays a role in this disparity is unknown. We examine the effect of race on post-surgical complications, length of stay, and mortality specifically in a morbidly obese population. Methods Black and white women with endometrial cancer diagnosed from 1996 to 2012 were identified from the University Pathology Group database in Detroit, Michigan, and records were retrospectively reviewed to obtain clinicopathological, demographic, and surgical information. Analysis was limited to those with a body mass index of 40 kg/m2 or greater. Differences in the distribution of variables by race were assessed by chi-squared tests and t-tests. Kaplan–Meier and Cox regression analyses were performed to examine factors associated with mortality. Results 97 white and 89 black morbidly obese women were included in this analysis. Black women were more likely to have type II tumors (33.7% versus 15.5% of white women, p-value = 0.003). Hypertension was more prevalent in black women (76.4% versus 58.8%, p-value = 0.009), and they had longer hospital stays after surgery despite similar rates of open vs minimally invasive procedures and lymph node dissection (mean days = 5.4) compared to whites (mean days = 3.5, p-value = 0.036). Wound infection was the most common complication (16.5% in whites and 14.4% in blacks, p-value = 0.888). Blacks were more likely to suffer other complications, but overall the proportions did not differ by race. In univariate analyses, black women had higher risk of endometrial cancer-related death (p-value = 0.090). No racial differences were noted in adjusted survival analyses. Conclusion A more complete investigation, incorporating socio-demographic factors, is warranted to understand the effects of morbid obesity and race on endometrial cancer.
    Gynecologic Oncology 01/2014; 133(1):38–42. · 3.93 Impact Factor
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    ABSTRACT: Background: Statins are a class of cholesterol lowering drugs that affect many intracellular pathways which may have implications for chemo prevention against cancer. Epidemiological data on statins and breast cancer is conflicting. We analyzed updated data from the Women's Health Initiative (WHI) to assess the relationship between statins and breast cancer risk. Methods: The population included 154,587 post-menopausal women ages 50-79 years, with 7,430 pathologically confirmed cases of breast cancer identified over an average of 10.8 (SD 3.3) years. Information on statins was collected at baseline and years 1, 3, 6, and 9. Self- and interviewer-administered questionnaires were used to collect information on risk factors. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) to evaluate the relationship between statin use and cancer risk. Statistical tests were two-sided. Results: Statins were used by 11,584 (7.5%) women at baseline. The annualized rate of breast cancer was 0.42% among statin users and 0.42% among nonusers. The multivariable adjusted HR of breast cancer for users versus non-users was 0.94 (95% C.I. 0.83-1.06). In the multivariable adjusted time-dependent model, the HR for simvastatin was 0.87 (95% CI, 0.71-1.07). There was no significant trend by overall duration of use (p value for trend 0.68). There was no effect of tumor stage, grade or hormone receptor status. Conclusion: Overall statins were not associated with breast cancer risk. Impact: Our study adds to the literature suggesting no relationship between statins and breast cancer risk.
    Cancer Epidemiology Biomarkers &amp Prevention 08/2013; · 4.56 Impact Factor
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    ABSTRACT: OBJECTIVE: Uterine serous carcinoma (USC) constitutes 10% of uterine cancers but ~40% of deaths. Tumor size is a known prognostic factor in other solid tumors. In endometriod cancers it is one element used to identify the need for complete staging, while its significance in USC is debated. Therefore tumor size was examined as an independent prognostic factor. METHODS: Clinical and pathologic variables were recorded for 236 institutional patients, and those patients in the SEER database with USC. Chi-square and Fisher exact t-tests were utilized and survival data generated via Kaplan Meier method; multivariate analysis was performed via cox-regression. RESULTS: The patients' mean age was 67.2years (range 40-91). Survival ranged from 0-184months (mean 42.8). We used a tumor size cut-off of 1cm and noted significant associations with myometrial invasion (p <0.0001), angiolymphatic invasion (p <0.0001), peritoneal washings (p=0.03), stage (p =0.015) and positive lymph nodes (p=0.05). Furthermore, recurrence was associated with larger tumors (p=0.03). In multivariate analysis, extra-uterine disease was the only factor associated with both recurrence and survival. Review of the SEER database noted association of larger tumors with lymph node involvement and a significant survival advantage with tumors <1cm in both univariate and multivariate analysis. Conclusions Treatment options for USC are often predicated on the surgical stage and therefore components of the staging are vitally important. The 1cm tumor-size cut-off should be studied prospectively as a prognostic indicator of survival and recurrence in USC and considered for inclusion in USC staging.
    Gynecologic Oncology 11/2012; · 3.93 Impact Factor
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    ABSTRACT: Benign breast disease (BBD) is an established risk factor for breast cancer among Caucasian women, but less is known about BBD in African American (AA) women. As AA women suffer from disproportionate mortality due to breast cancer, special focus on pathological characteristics that may influence disease risk is warranted. Benign breast biopsies from AA women were identified by the University Pathology Group in Detroit, Michigan. AA women age 20 to 84 who underwent a breast biopsy from 1997 to 2000 were eligible for the study. Subsequent breast cancers were identified through a linkage with the Detroit SEER program. The first biopsy was reviewed by the pathologist, and lesions were classified following Dupont and Page criteria along with involution and other histologic features. Logistic regression was used to estimate the risk of developing a subsequent breast cancer with the histologic characteristics of BBD. 1,406 BBD biopsies from AA women were included in this study with a median follow-up of 10.1 years. The majority (68%) showed non-proliferative disease, 29% had proliferative disease without atypia, and 3% had proliferative disease with atypia. Subsequent incident breast cancers occurred in 55 women (3.9%). Women whose biopsies showed proliferative disease with atypia were over three-fold more likely to develop breast cancer as women who had non-proliferative disease (RR 3.29, 95% C.I. 1.21-8.93). Better characterization of the risk of breast cancer among women with BBD, considering both ethnicity and detailed molecular findings, can lead to better surveillance, earlier diagnosis, and, potentially, improved survival.
    Cancer Prevention Research 10/2012; · 4.89 Impact Factor
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    ABSTRACT: To describe the pattern and frequency of oncogene mutations in white and African American women with endometrial cancer and to determine if racial differences in oncogene mutations exist among women with pathologically similar tumors. Patients with endometrial cancer from a large urban hospital were identified through medical records, and representative formalin-fixed paraffin-embedded tumor blocks were retrieved. The study sample included 150 patients (84 African Americans) who underwent total abdominal hysterectomy for endometrial cancer. The Sequenom MassARRAY system and the OncoCarta Assay version 1.0 (Sequenom) were used to test for 238 mutations in 19 common oncogenes. The χ test and the Fisher exact test were used to assess differences in distribution of variables by race and oncogene mutation status. There were 20 mutations identified in 2 oncogenes (PIK3CA and KRAS) in tumors from 19 women (12.7%). Most of the mutations were found in PIK3CA (16/20). Thirteen percent of endometrioid tumors harbored mutations (11 PIK3CA and 2 KRAS) as did 29% of the malignant mixed Mullerian tumors (3 PIK3CA and 1 KRAS). There were no observed mutations in serous, clear cell, or mucinous tumor types. Among low-grade endometrioid cancers, tumors from African American patients were significantly associated with harboring either a KRAS or PIK3CA mutation (P = 0.04), with 7 PIK3CA mutations and all 4 KRAS mutations identified in African American women. This study provides preliminary evidence that oncogene mutation frequency of some subtypes of histologically similar endometrial carcinoma differ by race. Additional studies are needed to further explore this phenomenon in patients with endometrial carcinoma.
    International Journal of Gynecological Cancer 10/2012; 22(8):1367-72. · 1.94 Impact Factor
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    ABSTRACT: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment. The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.
    European journal of cancer (Oxford, England: 1990) 03/2012; 48(13):1957-68. · 4.12 Impact Factor
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    ABSTRACT: Incidence of kidney cancer has been increasing over the past three decades, with more rapid increases and higher incidence rates among blacks than whites in the United States. An association between cigarette smoking and renal cell carcinoma (RCC), the most common form of kidney cancer, has been reported for whites, but the association in blacks is less clear. The association between smoking and RCC was examined in 1,217 incident cases and 1,235 population controls frequency-matched on age, race, gender, and study site in the Kidney Cancer Study in Detroit, MI, and Chicago, IL. In white individuals, increasing duration and number of pack-years of both were associated with increased risk of RCCs after adjusting for age, gender, education, study site, body mass index (BMI) and history of hypertension (P(trend) = 0.0002 and P(trend) = 0.002, respectively). Among black individuals, RCC risk increased with duration of smoking (P(trend) = 0.02) but not other measures. Compared with current smokers, RCC risk decreased with increasing years of smoking cessation among both whites and blacks (P(trend) = 0.01 and 0.02, respectively). When examining risk according to hypertension history, associations between smoking and RCC risk were observed only among individuals who reported never having been diagnosed with hypertension. Similarly, cigarette smoking was associated with increased risk of RCCs among nonobese individuals but not among those with BMI ≥ 30 kg/m(2). Our observation that smoking is associated with RCC only in nonobese individuals and those with no history of hypertension are novel findings. The complex relationships between RCCs, smoking, hypertension, and obesity require additional confirmation.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2012; 21(5):770-9. · 4.56 Impact Factor
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    ABSTRACT: Poorer survival from endometrial cancer in blacks than in whites is well documented. The aims of this study were to determine whether diabetes, hypertension, or other conditions influence survival and whether accounting for these conditions reduces this racial disparity. Using the SEER-Medicare database, we investigated the influence of diabetes, hypertension, and other comorbid conditions on survival in black and white women age ≥66 with endometrial cancer. We used Cox proportional hazards regression to evaluate the influence of comorbidities on survival for blacks and whites separately and to study survival differences between blacks and whites after adjustment for diabetes, hypertension, and other medical conditions, as well as for demographics, tumor characteristics, and treatment. In both racial subgroups, women with diabetes or other conditions had poorer overall survival, whereas hypertensive black women experienced better survival [HR, 0.74; 95% confidence interval (CI), 0.60-0.92]. For disease-specific survival, diabetes was associated with poorer survival in white women (HR, 1.19; 95% CI, 1.06-1.35) but not in blacks (HR, 0.97; 95% CI, 0.73-1.30); hypertension and other conditions were not significantly related to survival. After adjustment, black women had poorer survival than white women, with HRs of 1.16 (95% CI, 1.05-1.28) for overall and 1.27 (95% CI, 1.08-1.49) for disease-specific survival. Diabetes influences disease-specific survival in white women but not in blacks. The racial disparity in survival is not explained by the presence of other health conditions. Further research should focus on the unknown factors that lead to poorer survival in black women compared with whites.
    Cancer Epidemiology Biomarkers &amp Prevention 03/2012; 21(5):753-60. · 4.56 Impact Factor
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    ABSTRACT: We examined the association between HNF1B variants identified in a recent genome-wide association study and endometrial cancer in two large case-control studies nested in prospective cohorts: the Multiethnic Cohort Study (MEC) and the Women's Health Initiative (WHI) as part of the Population Architecture using Genomics and Epidemiology (PAGE) study. A total of 1,357 incident cases of invasive endometrial cancer and 7,609 controls were included in the analysis (MEC: 426 cases/3,854 controls; WHI: 931 cases/3,755 controls). The majority of women in the WHI were European American, while the MEC included sizable numbers of African Americans, Japanese and Latinos. We estimated the odds ratios (ORs) per allele and 95% confidence intervals (CIs) of each SNP using unconditional logistic regression adjusting for age, body mass index, and four principal components of ancestry informative markers. The combined ORs were estimated using fixed effect models. Rs4430796 and rs7501939 were associated with endometrial cancer risk in MEC and WHI with no heterogeneity observed across racial/ethnic groups (P ≥ 0.21) or between studies (P ≥ 0.70). The OR(per allele) was 0.82 (95% CI: 0.75, 0.89; P = 5.63 × 10(-6)) for rs4430796 (G allele) and 0.79 (95% CI: 0.73, 0.87; P = 3.77 × 10(-7)) for rs7501939 (A allele). The associations with the risk of Type I and Type II tumors were similar (P ≥ 0.19). Adjustment for additional endometrial cancer risk factors such as parity, oral contraceptive use, menopausal hormone use, and smoking status had little effect on the results. In conclusion, HNF1B SNPs are associated with risk of endometrial cancer and that the associated relative risks are similar for Type I and Type II tumors.
    PLoS ONE 01/2012; 7(1):e30390. · 3.53 Impact Factor
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    ABSTRACT: Pancreatic cancers are the fourth most-common cause of cancer-related deaths in the Western world, with >200,000 cases reported in 2010. Although up to 10% of these cases occur in familial patterns, the hereditary basis for predisposition in the vast majority of affected families is unknown. We used next-generation sequencing, including whole-genome and whole-exome analyses, and identified heterozygous, constitutional, ataxia telangiectasia mutated (ATM) gene mutations in 2 kindreds with familial pancreatic cancer. Mutations segregated with disease in both kindreds and tumor analysis demonstrated LOH of the wild-type allele. By using sequence analysis of an additional 166 familial pancreatic cancer probands, we identified 4 additional patients with deleterious mutations in the ATM gene, whereas we identified no deleterious mutations in 190 spouse controls (P = 0.046). When we considered only the mostly severely affected families with 3 or more pancreatic cancer cases, 4 deleterious mutations were found in 87 families (P = 0.009). Our results indicate that inherited ATM mutations play an important role in familial pancreatic cancer predisposition. SIGNIFICANCE: The genes responsible for the majority of cases of familial pancreatic ductal adenocarcinoma are unknown. We here identify ATM as a predisposition gene for pancreatic ductal adenocarcinoma. Our results have important implications for the management of patients in affected families and illustrate the power of genome-wide sequencing to identify the basis of familial cancer syndromes.
    Cancer Discovery 01/2012; 2(1):41-6. · 15.93 Impact Factor
  • Gynecologic Oncology - GYNECOL ONCOL. 01/2011; 120.
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    ABSTRACT: Three genome-wide association studies identified a region on chromosome 15q25.1 associated with lung cancer and measures of nicotine addiction. This region includes nicotinic acetylcholine receptor subunit genes CHRNA3 and CHRNA5. These studies were conducted in European or European American populations and do not provide risk estimates for African Americans. The goal of this study was to determine whether recently identified genetic variation in 3 SNPs (rs1051730, rs931794, rs8034191) on chromosome 15q25.1 contributes to risk of lung cancer in African Americans. Data were derived from three case-control studies. Participants included 1058 population-based non-small cell lung cancer cases selected from the Detroit area SEER registry and 1314 controls matched within study by age, race, and sex. Thirty-nine percent of participants were African American. Risk associated with rs1051730 (odds ratio 1.59; 95% confidence interval 1.16-2.19) and rs931794 (odds ratio 1.39; 95% confidence interval 1.09-1.78) increased in ever smoking African Americans adjusting for cigarettes smoked per day. Among white cases, the number of cigarettes smoked varied by genotype at all three SNPs, and when smoking quantity was included in the models, risk was not significantly associated with any of the three SNPs. These findings suggest that SNPs in the CHRNA3 and CHRNA5 region contribute to lung cancer risk, and while variant alleles are less frequent in African Americans, risk in this group may be greater than in whites and less likely to reflect an indirect effect on lung cancer risk through nicotine dependence.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 08/2009; 4(10):1195-201. · 4.55 Impact Factor
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    ABSTRACT: Although microstellite instability (MSI) is a prognostic marker in colorectal cancer, it's relation with prognosis in the endometrial cancer is controversial. The goal of this study is to identify the correlation between MSI and clinicopathologic markers along with survival in high grade endometrial carcinoma EC. Between 1995 and 2004, we identified 119 patients (57 type-I, and 62 type-II) diagnosed with high grade EC and underwent hysterectomy. Sections were immunostained using antibodies against MLH1, MSH2, and MSH6. Semi-quantitative scoring of immunoreactivity was based on percentage of tumor staining and staining intensity. Statistical analysis and survival were assessed using the Kaplan-Meier method and Cox regression. Tumors were considered microsatellite unstable (MSI) when at least 2/3 markers tested negative on IHC. Overall, there was no statistically significant difference in survival between patients with MSI tumors and those with microsatellite stable tumors (MSS) (p value=0.70). However, MSI tumors which tested negative for all three markers had markedly poor survival (median survival 3 months vs 71 months, p=0.04) when compared to MSS tumors. The risk of death was 13.2 times greater among women with MSI tumors (with 3 negative markers) compared to women with MSS tumors (OR=13.20 95% CI 3.50-49.76). Although this study has its limitation due to the small sample size, it raises the question of the prognostic significance of MSI in high grade endometrial carcinoma. It also points to the importance of evaluating three mismatch repair genes (MLH1, MSH2, and MSH6) as a prognostic indicator.
    Gynecologic Oncology 04/2009; 113(2):153-8. · 3.93 Impact Factor
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    ABSTRACT: The link between lung cancer and chronic obstructive lung diseases (COPD) has not been well studied in women even though lung cancer and COPD account for significant and growing morbidity and mortality among women. We evaluated the relationship between COPD and non-small cell lung cancer in a population-based case-control study of women and constructed a time course of chronic lung diseases in relation to onset of lung cancer. Five hundred sixty-two women aged 18 to 74, diagnosed with non-small cell lung cancer and 564 population-based controls matched on race and age participated. Multivariable unconditional logistic regression models were used to estimate risk associated with a history of COPD, chronic bronchitis, or emphysema. Lung cancer risk increased significantly for white women with a history of COPD (odds ratios [OR] = 1.85; 95% confidence intervals [CI]: 1.21-2.81), but this was not seen in African American women. Risk associated with a history of chronic bronchitis was strongest when diagnosed at age 25 or earlier (OR = 2.35, 95% CI: 1.17-4.72); emphysema diagnosed within 9 years of lung cancer was also associated with substantial risk (OR = 6.36, 95% CI: 2.36-17.13). Race, pack-years of smoking, exposure to environmental tobacco smoke as an adult, childhood asthma, and exposure to asbestos were associated with a history of COPD among lung cancer cases. In women, COPD is associated with risk of lung cancer differentially by race. Untangling whether COPD is in the causal pathway or simply shares risk factors will require future studies to focus on specific COPD features, while exploring underlying genetic susceptibility to these diseases.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2009; 4(3):291-9. · 4.55 Impact Factor
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    ABSTRACT: Polymorphisms in CYP1A1 and CYP1B1 genes in humans are associated with reduction of enzymatic activity towards several substrates, including those found 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 383 individuals diagnosed prior to 50 years of age identified from the metropolitan Detroit Surveillance, Epidemiology and End Results (SEER) program and 449 age, race and sex-matched controls ascertained through random digit dialing. Genotype frequencies varied significantly by race for CYP1A1 Ile(462)Val and CYP1B1 Leu(432)Val genotypes, so all analyses were stratified by race. No association was seen between lung cancer risk and polymorphisms in CYP1A1 Msp1 or CYP1B1 Leu(432)Val for Caucasians or African Americans, after adjusting for age at diagnosis, sex, pack years of smoking and family history of lung cancer. In Caucasians, those with the IIe/Val genotype at CYP1A1 Ile(462)Val locus were at decreased risk of having lung cancer compared to those with the lle/lle genotype, after adjusting for age at diagnosis, sex, pack years of smoking and family history of cancer (OR=0.41 95% Cl 0.19-0.90). These results were not replicated among the African American population, nor were they modified by amount of smoking.
    Lung Cancer 04/2007; 55(3):255-62. · 3.39 Impact Factor
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    ABSTRACT: Carcinoid tumors of the lung were first described in 1937, yet little is known about their etiology. The aim of the present investigation was to determine if there was excess risk of secondary cancers in a population-based sample after a lung carcinoid tumor diagnosis which may provide insight to the etiology. Subjects were 1882 cases diagnosed with carcinoid tumors of the lung between 1988 and 2000 whose information was obtained from the Surveillance, Epidemiology and End Results (SEER) Program database. Standardized incidence ratios were calculated by dividing the observed number of second primary cancers by the expected number of cancers. Excess risk of breast cancer was seen following diagnosis of a carcinoid tumor (SIR=1.80 95% CI 1.22-2.55). When stratified by time after diagnosis, excess risk of breast cancers in women was seen in the first 5 years after carcinoid diagnosis (SIR=1.68 95% CI 1.08-2.50) but fewer than expected breast cancers were diagnosed greater than 5 years after carcinoid diagnosis (SIR=0.29 95% CI 0.09-0.68). Prostate cancers also occurred 2.8 times more often than expected (95% CI 1.66-4.43), with risk being elevated only in the first 5 years post-carcinoid diagnosis. Development of lung carcinoids may be the result of genetic predisposition or environmental exposures, particularly those that are hormonally related. The role of genetics and sex hormones in lung carcinoid development, as well as the identification of other risk factors, should be explored.
    Lung Cancer 07/2006; 52(3):273-9. · 3.39 Impact Factor
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    ABSTRACT: The cytochrome P450 (CYP) superfamily of enzymes catalyse one of the first steps in the metabolism of carcinogens such as polycyclic aromatic hydrocarbons, nitroaromatics and arylamines. Polymorphisms within the CYP1A1 gene have been shown to be associated with lung cancer risk, predominantly among Asian populations. Despite functional evidence of a possible role of CYP1B1 in lung cancer susceptibility, only a few studies have evaluated polymorphisms in this gene in relation to lung cancer susceptibility. This population-based study evaluates polymorphisms in both of these CYP genes within never smokers, most of whom had environmental tobacco smoke (ETS) exposure. Cases (n = 160) were identified through the metropolitan Detroit Surveillance, Epidemiology and End Results program, and age, sex and race-matched population-based controls (n = 181) were identified using random digit dialing. Neither CYP1A1 MspI nor CYP1A1 Ile(462)Val was associated with lung cancer susceptibility among Caucasians or African-Americans. Among Caucasians, however, CYP1B1 Leu(432)Val was significantly associated with lung cancer susceptibility odds ratio (OR) for at least one valine allele = 2.87 [95% confidence interval (CI) 1.63-5.07]. Combinations of this Phase I enzyme polymorphism along with selected Phase II enzyme polymorphisms (GSTM1 null, GSTP1 Ile(105)Val and NQO1 C(609)T) were evaluated. The combination of CYP1B1 Leu(432)Val and NQO1 C(609)T appeared to be associated with the highest risk of lung cancer (OR = 4.14, 95% CI 1.60-10.74), although no combinations differed significantly from the risk associated with CYP1B1 Leu(432)Val alone. When individuals were stratified by household ETS exposure (yes/no), CYP1B1 Leu(432)Val alone and in combination with Phase II enzyme polymorphisms was more strongly associated with increased lung cancer susceptibility among those with at least some household ETS exposure. Additional studies will be required to further validate these findings among never smokers and to evaluate the effects of this polymorphism among smoking populations as well.
    Carcinogenesis 01/2006; 26(12):2207-12. · 5.64 Impact Factor
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    ABSTRACT: 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.
    Carcinogenesis 05/2005; 26(4):811-9. · 5.64 Impact Factor

Publication Stats

357 Citations
103.58 Total Impact Points

Institutions

  • 2005–2014
    • Karmanos Cancer Institute
      • Division of Hematology and Oncology
      Detroit, Michigan, United States
    • Wayne State University
      • • Division of Hematology and Oncology
      • • Department of Family Medicine and Public Health Sciences
      • • Department of Pathology
      Detroit, Michigan, United States