Metformin use and survival after non-small cell lung cancer: A cohort study in the US Military health system.

Research suggests that metformin may be associated with improved survival in cancer patients with type II diabetes. This study assessed whether metformin use after non-small cell lung cancer (NSCLC) diagnosis is associated with overall survival among type II diabetic patients with NSCLC in the U.S. military health system (MHS). The study included 636 diabetic patients with histologically confirmed NSCLC diagnosed between 2002 and 2007, identified from the linked database from the Department of Defense's Central Cancer Registry (CCR) and the Military Health System Data Repository (MDR). Time-dependent multivariate Cox proportional hazards models were used to assess the association between metformin use and overall survival during follow-up. Among the 636 patients, 411 died during the follow-up. The median follow-up time was 14.6 months. Increased post-diagnosis cumulative use (per 1 year of use) conferred a significant reduction in mortality (adjusted hazard ratio (HR) = 0.76; 95% CI = 0.65-0.88). Further analysis by duration of use revealed that compared to non-users, the lowest risk reduction occurred among patients with the longest duration of use (i.e. use for more than 2 years) (HR = 0.19; 95% CI = 0.09-0.40). Finally, the reduced mortality was particularly observed only among patients who also used metformin before lung cancer diagnosis and among patients at early stage of diagnosis. Prolonged duration of metformin use in the study population was associated with improved survival, especially among early stage patients. Future research with a larger number of patients is warranted.

Survival among Black and White patients with renal cell carcinoma in an equal-access health care system.

PURPOSE: Unequal access to health care may be a reason for shorter survival among Black patients with renal cell carcinoma (RCC) than among their White counterparts. No studies have investigated survival disparity among RCC patients in an equal-access health care delivery system. This study aimed to examine racial differences in survival among clear cell RCC patients in the Department of Defense's (DoD) Military Health System (MHS), which provides equal access to care to all persons. METHODS: The study used the DoD's Automated Central Tumor Registry to identify 2056 White patients and 370 Black patients diagnosed with clear cell RCC between 1988 and 2004. The subjects were followed through 2007 with a median follow-up time of 4.8 years. Kaplan-Meier survival curves were compared and a Cox model was used to estimate the hazard ratios (HRs) associated with survival by race. RESULTS: During follow-up, 1,027 White and 158 Black patients died. The Kaplan-Meier curves showed that Black patients had more favorable overall survival than did White patients (log rank p = 0.031). After adjustment for demographic, tumor, and treatment variables, the Cox model showed no statistically significant racial difference overall (adjusted HR 1.07, 95 % CI 0.90-1.28) or stratified by age, sex or tumor stage. However, among patients who did not undergo surgery, Black patients had poorer survival than White patients. CONCLUSIONS: The lack of racial difference in survival among RCC patients in the MHS may be related to equal access to health care. Improved access could reduce the survival disparity among RCC patients in the general population.

Colon cancer lymph node evaluation among military health system beneficiaries: an analysis by race/ethnicity.

BACKGROUND: The number of lymph nodes examined during colon cancer surgery falls below nationally recommended guidelines in the general population, with Blacks and Hispanics less likely to have adequate nodal evaluation in comparison to Whites. The Department of Defense's (DoD) Military Health System (MHS) provides equal access to medical care for its beneficiaries, regardless of racial/ethnic background. This study aimed to investigate whether racial/ethnic treatment differences exist in the MHS, an equal-access medical care system. METHODS: Linked data from the DoD cancer registry and administrative claims databases were used and included 2,155 colon cancer cases. Multivariate logistic regression assessed the association between race/ethnicity and the number of lymph nodes examined (<12 and ≥12) overall and for stratified analyses. RESULTS: No overall racial/ethnic differences in the number of lymph nodes examined was identified. Further stratified analyses yielded similar results, except potential racial/ethnic differences were found among persons with poorly differentiated tumors, where non-Hispanic Blacks tended to be less likely to have ≥12 lymph nodes dissected (odds ratio 0.34; 95 % confidence interval 0.14-0.80; p = 0.01) compared with non-Hispanic Whites. CONCLUSION: Racial/ethnic disparities in the number of lymph nodes evaluated among patients with colon cancer were not apparent in an equal-access healthcare system. However, among poorly differentiated tumors there might be racial/ethnic differences in nodal yield, suggesting the possible effects of factors other than access to healthcare.

Exposure-response relationships for select cancer and non-cancer health outcomes in a cohort of U.S. firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

OBJECTIVES: To examine exposure-response relationships between surrogates of firefighting exposure and select outcomes among previously studied US career firefighters. METHODS: Eight cancer and four non-cancer outcomes were examined using conditional logistic regression. Incidence density sampling was used to match each case to 200 controls on attained age. Days accrued in firefighting assignments (exposed-days), run totals (fire-runs) and run times (fire-hours) were used as exposure surrogates. HRs comparing 75th and 25th centiles of lagged cumulative exposures were calculated using loglinear, linear, log-quadratic, power and restricted cubic spline general relative risk models. Piecewise constant models were used to examine risk differences by time since exposure, age at exposure and calendar period. RESULTS: Among 19,309 male firefighters eligible for the study, there were 1333 cancer deaths and 2609 cancer incidence cases. Significant positive associations between fire-hours and lung cancer mortality and incidence were evident. A similar relation between leukaemia mortality and fire-runs was also found. The lung cancer associations were nearly linear in cumulative exposure, while the association with leukaemia mortality was attenuated at higher exposure levels and greater for recent exposures. Significant negative associations were evident for the exposure surrogates and colorectal and prostate cancers, suggesting a healthy worker survivor effect possibly enhanced by medical screening. CONCLUSIONS: Lung cancer and leukaemia mortality risks were modestly increasing with firefighter exposures. These findings add to evidence of a causal association between firefighting and cancer. Nevertheless, small effects merit cautious interpretation. We plan to continue to follow the occurrence of disease and injury in this cohort.

Breast reconstruction after mastectomy among Department of Defense beneficiaries by race.

BACKGROUND: Postmastectomy breast reconstruction increased approximately 20% between 1998 and 2008 in the United States and has been found to improve body image, self-esteem, and quality of life. These procedures, however, tend to be less common among minority women, which may be due to variations in health care access. The Department of Defense provides equal health care access, thereby affording an exceptional environment in which to assess whether racial variations persist when access to care is equal. METHODS: Linked Department of Defense cancer registry and medical claims data were used. The receipt of reconstruction was compared between white women (n = 2974) and black women (n = 708) who underwent mastectomies to treat incident histologically confirmed breast cancer diagnosed from 1998 through 2007. RESULTS: During the study period, postmastectomy reconstruction increased among both black (27.3% to 40.0%) and white (21.8% to 40.6%) female patients with breast cancer. Receipt of reconstruction did not vary significantly by race (odds ratio, 0.93; 95% confidence interval, 0.76-1.15). Reconstruction decreased significantly with increasing age, tumor stage, and receipt of radiotherapy and was significantly more common in more recent years and among active service women, TRICARE Prime (health maintenance organization) beneficiaries, and women whose sponsor was an officer. CONCLUSIONS: The receipt of breast reconstruction did not vary by race within this equal-access health system, indicating that the racial disparities reported in previous studies may have been due in part to variations in access to health care. Additional research to determine why a large percentage of patients with breast cancer do not undergo reconstruction might be beneficial, particularly because these procedures have been associated with noncosmetic benefits.

Colon cancer treatment: are there racial disparities in an equal-access healthcare system?

BACKGROUND: In the general US population, blacks and whites have been shown to undergo colon cancer treatment at disproportionate rates. Accessibility to medical care may be the most important factor influencing differences in colon cancer treatment rates among whites and blacks. OBJECTIVE: We assessed whether racial disparities in colon cancer surgery and chemotherapy existed in an equal-access health care system. In addition, we sought to examine whether racial differences varied according to demographic and tumor characteristics. DESIGN AND SETTING: Database research using the Department of Defense Military Health System. PATIENTS: Patients included 2560 non-Hispanic whites (NHW) and non-Hispanic blacks (NHB) with colon cancer diagnosed from 1998 to 2007. MAIN OUTCOME MEASURES: Logistic regression was used to assess the associations between race and the receipt of colon cancer surgery or chemotherapy while controlling for available potential confounders, both overall and stratified by age at diagnosis, sex, and tumor stage. RESULTS: After multivariate adjustment, the odds of receiving colon cancer surgery or chemotherapy for NHBs versus NHWs were similar (OR, 0.75 [95% CI, 0.37-1.53]; OR, 0.79 [95% CI, 0.59-1.04]). In addition, no effect modifications by age at diagnosis, sex, and tumor stage were observed. LIMITATIONS: Treatment data might not be complete for beneficiaries who also had non-Department of Defense health insurance. CONCLUSIONS: When access to medical care is equal, racial disparities in the provision of colon cancer surgery and chemotherapy were not apparent. Thus, it is possible that the inequalities in access to care play a major role in the racial disparities seen in colon cancer treatment in the general population.

Mortality and cancer incidence in a pooled cohort of US firefighters from San Francisco, Chicago and Philadelphia (1950-2009).

OBJECTIVES: To examine mortality patterns and cancer incidence in a pooled cohort of 29 993 US career firefighters employed since 1950 and followed through 2009. METHODS: Mortality and cancer incidence were evaluated by life table methods with the US population referent. Standardised mortality (SMR) and incidence (SIR) ratios were determined for 92 causes of death and 41 cancer incidence groupings. Analyses focused on 15 outcomes of a priori interest. Sensitivity analyses were conducted to examine the potential for significant bias. RESULTS: Person-years at risk totalled 858 938 and 403 152 for mortality and incidence analyses, respectively. All-cause mortality was at expectation (SMR=0.99, 95% CI 0.97 to 1.01, n=12 028). There was excess cancer mortality (SMR=1.14, 95% CI 1.10 to 1.18, n=3285) and incidence (SIR=1.09, 95% CI 1.06 to 1.12, n=4461) comprised mainly of digestive (SMR=1.26, 95% CI 1.18 to 1.34, n=928; SIR=1.17, 95% CI 1.10 to 1.25, n=930) and respiratory (SMR=1.10, 95% CI 1.04 to 1.17, n=1096; SIR=1.16, 95% CI 1.08 to 1.24, n=813) cancers. Consistent with previous reports, modest elevations were observed in several solid cancers; however, evidence of excess lymphatic or haematopoietic cancers was lacking. This study is the first to report excess malignant mesothelioma (SMR=2.00, 95% CI 1.03 to 3.49, n=12; SIR=2.29, 95% CI 1.60 to 3.19, n=35) among US firefighters. Results appeared robust under differing assumptions and analytic techniques. CONCLUSIONS: Our results provide evidence of a relation between firefighting and cancer. The new finding of excess malignant mesothelioma is noteworthy, given that asbestos exposure is a known hazard of firefighting.

GWAS of follicular lymphoma reveals allelic heterogeneity at 6p21.32 and suggests shared genetic susceptibility with diffuse large B-cell lymphoma.

Non-Hodgkin lymphoma (NHL) represents a diverse group of hematological malignancies, of which follicular lymphoma (FL) is a prevalent subtype. A previous genome-wide association study has established a marker, rs10484561 in the human leukocyte antigen (HLA) class II region on 6p21.32 associated with increased FL risk. Here, in a three-stage genome-wide association study, starting with a genome-wide scan of 379 FL cases and 791 controls followed by validation in 1,049 cases and 5,790 controls, we identified a second independent FL-associated locus on 6p21.32, rs2647012 (OR(combined)  = 0.64, P(combined)  = 2 × 10(-21)) located 962 bp away from rs10484561 (r(2)<0.1 in controls). After mutual adjustment, the associations at the two SNPs remained genome-wide significant (rs2647012:OR(adjusted)  = 0.70, P(adjusted)  =  4 × 10(-12); rs10484561:OR(adjusted)  = 1.64, P(adjusted)  = 5 × 10(-15)). Haplotype and coalescence analyses indicated that rs2647012 arose on an evolutionarily distinct haplotype from that of rs10484561 and tags a novel allele with an opposite (protective) effect on FL risk. Moreover, in a follow-up analysis of the top 6 FL-associated SNPs in 4,449 cases of other NHL subtypes, rs10484561 was associated with risk of diffuse large B-cell lymphoma (OR(combined)  = 1.36, P(combined)  =  1.4 × 10(-7)). Our results reveal the presence of allelic heterogeneity within the HLA class II region influencing FL susceptibility and indicate a possible shared genetic etiology with diffuse large B-cell lymphoma. These findings suggest that the HLA class II region plays a complex yet important role in NHL.

Surveillance mammography among female Department of Defense beneficiaries: a study by race and ethnicity.

BACKGROUND: Annual surveillance mammography is recommended after a diagnosis of breast cancer. Previous studies have suggested that surveillance mammography varies by demographics and initial tumor characteristics, which are related to an individual's access to health care. The Military Health System of the Department of Defense provides beneficiaries with equal access health care and thus offers an excellent opportunity to assess whether racial differences in surveillance mammography persist when access to care is equal. METHODS: Among female beneficiaries with a history of breast cancer, logistic regression was used to assess racial/ethnic variations in the use of surveillance mammography during 3 periods of 12 months each, beginning 1 year after diagnosis adjusting for demographic, tumor, and health characteristics. RESULTS: The rate of overall surveillance mammography decreased from 70% during the first year to 59% during the third year (P < .01). Although there was an overall tendency for surveillance mammography to be higher among minority women compared with non-Hispanic white women, after adjusting for covariates, the difference was found to be significant only during the first year among black women (odds ratio [OR], 1.46; 95% confidence interval [95% CI], 1.10-1.95) and the second year among Asian/Pacific Islander (OR, 2.29; 95%CI, 1.52-3.44) and Hispanic (OR, 1.92; 95%CI, 1.17-3.18) women. When stratified by age at diagnosis and type of breast cancer surgery performed, significant racial differences tended to be observed among younger women (aged < 50 years) and only among women who had undergone mastectomies. CONCLUSIONS: Minority women were equally or more likely than non-Hispanic white women to receive surveillance mammography within the Military Health System. The racial disparities in surveillance mammography reported in other studies were not observed in a system with equal access to health care.

Racial variation in tumor stage at diagnosis among Department of Defense beneficiaries.

BACKGROUND: Tumor stage at diagnosis often varies by racial/ethnic group, possibly because of inequitable health care access. Within the Department of Defense (DoD) Military Health System, beneficiaries have equal health care access. The objective of this study was to determine whether tumor stage differed between whites and blacks with breast, cervical, colorectal, and prostate cancers, which have effective screening regimens, based on data from the DoD Automated Cancer Tumor Registry from 1990 to 2003. METHODS: Distributions of tumor stage (localized vs nonlocalized) between whites and blacks in the military were compared stratified by sex, active duty status, and age at diagnosis. Logistic regression was used to further adjust for age, marital status, year of diagnosis, geographic region, military service branch, and tumor grade. Distributions of tumor stage were then compared between the military and general populations. RESULTS: Racial differences in the distribution of stage were significant only among nonactive duty beneficiaries. After adjusting for covariates, earlier stages of breast cancer after age 49 years and prostate cancer after age 64 years were significantly more common among white than black nonactive duty beneficiaries (P < .05), although the absolute difference was minimal for prostate cancer. Racial differences in stage for cervical and colorectal cancers were not significant after adjustment. Compared with the general population, racial differences in the military were similar or were slightly attenuated. CONCLUSIONS: Racial disparities in stage at diagnosis were apparent in the DoD equal-access health care system among older nonactive duty beneficiaries. Socioeconomic status, supplemental insurance, cultural beliefs, and biologic factors may be related to these results.

Racial variation in breast cancer treatment among Department of Defense beneficiaries.

BACKGROUND: Although the overall age-adjusted incidence rates for female breast cancer are higher among whites than blacks, mortality rates are higher among blacks. Many attribute this discrepancy to disparities in health care access and to blacks presenting with later stage disease. Within the Department of Defense (DoD) Military Health System, all beneficiaries have equal access to health care. The aim of this study was to determine whether female breast cancer treatment varied between white and black patients in the DoD system. METHODS: The study data were drawn from the DoD cancer registry and medical claims databases. Study subjects included 2308 white and 391 black women diagnosed with breast cancer between 1998 and 2000. Multivariate logistic regression analyses that controlled for demographic factors, tumor characteristics, and comorbidities were used to assess racial differences in the receipt of surgery, chemotherapy, and hormonal therapy. RESULTS: There was no significant difference in surgery type, particularly when mastectomy was compared with breast-conserving surgery plus radiation (blacks vs whites: odds ratio [OR], 1.1; 95% confidence interval [CI], 0.8-1.5). Among those with local stage tumors, blacks were as likely as whites to receive chemotherapy (OR, 1.2; 95% CI, 0.9-1.7) and hormonal therapy (OR, 1.0; 95% CI, 0.6-1.4). Among those with regional stage tumors, blacks were significantly less likely than whites to receive chemotherapy (OR, 0.4; 95% CI, 0.2-0.7) and hormonal therapy (OR, 0.5; 95% CI, 0.3-0.8). CONCLUSIONS: Even within an equal access health care system, stage-related racial variations in breast cancer treatment are evident. Studies that identify driving factors behind these within-stage racial disparities are warranted.

A pooled analysis of three studies evaluating genetic variation in innate immunity genes and non-Hodgkin lymphoma risk.

Genetic variation in immune-related genes may play a role in the development of non-Hodgkin lymphoma (NHL). To test the hypothesis that innate immunity polymorphisms may be associated with NHL risk, we genotyped 144 tag single nucleotide polymorphisms (tagSNPs) capturing common genetic variation within 12 innate immunity gene regions in three independent population-based case-control studies (1946 cases and 1808 controls). Gene-based analyses found IL1RN to be associated with NHL risk (minP = 0·03); specifically, IL1RN rs2637988 was associated with an increased risk of NHL (per-allele odds ratio = 1·15, 95% confidence interval = 1·05-1·27; P(trend) = 0·003), which was consistent across study, subtype, and gender. FCGR2A was also associated with a decreased risk of the follicular lymphoma NHL subtype (minP = 0·03). Our findings suggest that genetic variation in IL1RN and FCGR2A may play a role in lymphomagenesis. Given that conflicting results have been reported regarding the association between IL1RN SNPs and NHL risk, a larger number of innate immunity genes with sufficient genomic coverage should be evaluated systematically across many studies.

Genetic variation in Th1/Th2 pathway genes and risk of non-Hodgkin lymphoma: a pooled analysis of three population-based case-control studies.

The balance between T-helper 1 (Th1) and T-helper 2 (Th2) activity is critical in lymphoid cell development and differentiation. Immune dysfunction underlies lymphomagenesis, so an alteration in the regulation of key Th1/Th2 cytokines may lead to the development of non-Hodgkin lymphoma (NHL). To study the impact of polymorphisms in Th1/Th2 cytokines on NHL risk, we analyzed 145 tag single nucleotide polymorphisms (SNPs) in 17 Th1/Th2 cytokine and related genes in three population-based case-control studies (1946 cases and 1808 controls). Logistic regression was used to compute odds ratios (OR) for NHL and four major NHL subtypes in relation to tag SNP genotypes and haplotypes. A gene-based analysis adjusting for the number of tag SNPs genotyped in each gene showed significant associations with risk of NHL combined and one or more NHL subtypes for Th1 (IL12A and IL12RB1) and Th2 (IL4, IL10RB, and IL18) genes. The strongest association was for rs485497 in IL12A, which plays a central role in bridging the cellular and humoral pathways of innate resistance and antigen-specific adaptive immune responses (allele risk OR= 1·17; P(trend)= 0·00099). This SNP was also associated specifically with risk of follicular lymphoma (allele risk OR= 1·26; P(trend)= 0·0012). These findings suggest that genetic variation in Th1/Th2 cytokine genes may contribute to lymphomagenesis.

Genetic variation in caspase genes and risk of non-Hodgkin lymphoma: a pooled analysis of 3 population-based case-control studies.

Caspases play a critical role in regulation of apoptosis, cell differentiation, inflammation, and innate immunity, and several are mutated or have altered expression in non-Hodgkin lymphoma (NHL). To study the impact of genetic variation in caspases on NHL risk, we analyzed tag single nucleotide polymorphisms (SNPs) in 12 caspase and related genes in 3 population-based case-control studies (1946 cases and 1808 controls). Gene-based analysis, adjusting for the number of tagSNPs genotyped in each gene, showed significant associations for CASP8, CASP9, and CASP1. SNP-based analysis showed that CASP8 rs6736233 (odds ratio (OR) (CG) = 1.21; OR(CC) = 2.13; P trend = .011); CASP9 rs4661636 (OR(CT) = 0.89; OR(TT) = 0.77; P trend = .011); and CASP1 rs1785882 (OR(AT) = 1.12; OR(AA) = 1.30; P trend = .0054) were significantly associated with NHL risk and consistent across studies. It is noteworthy that genetic variants in CASP8 were associated with risk of all major NHL subtypes. Our findings suggest that genetic variation in caspases may play an important role in lymphomagenesis.

Variation in innate immunity genes and risk of multiple myeloma.

Multiple myeloma (MM) is a B-cell lymphoid malignancy suspected to be associated with immunologic factors. Given recent findings associating single-nucleotide polymorphisms (SNPs) in innate immunity genes with non-Hodgkin lymphoma, we conducted an investigation of innate immune gene variants using specimens from a population-based case-control study of MM conducted in Connecticut women. Tag SNPs (N = 1461) summarizing common variation in 149 gene regions were genotyped in non-Hispanic Caucasian subjects (103 cases, 475 controls). Odds ratios (OR) and 95% confidence intervals (CI) relating SNP associations with MM were computed using unconditional logistic regression, while the MinP test was used to investigate associations with MM at the gene level. We calculated permutation-adjusted P-values and false discovery rates (FDR) to account for the number of comparisons performed in SNP-level and gene-level tests, respectively. Three genes were associated with MM when controlling for a FDR of ≤10%: SERPINE1 (P(MinP) < 0.0001; FDR = 0.02), CCR7 (P(MinP) = 0.0006; FDR = 0.06) and HGF (P(MinP) = 0.001; FDR = 0.08). Two SNPs demonstrated robust associations: SERPINE1 rs2227667 (P = 2.1 × 10(-5) , P(permutation) = 0.03) and HGF rs17501108 (P = 5.0 × 10(-5) , P(permutation) = 0.07). Our findings suggest that genetic variants in SERPINE1 and HGF, and possibly CCR7, are associated with MM risk, and warrant further investigation in other studies.

Polymorphisms in DNA repair genes and risk of non-Hodgkin lymphoma in a pooled analysis of three studies.

Genetic variations in DNA repair genes are thought to play an important role in the pathogenesis and development of non-Hodgkin lymphoma (NHL). To further explore this hypothesis, we genotyped 319 tag single nucleotide polymorphisms (SNPs) in 27 DNA repair gene regions in 1946 cases and 1808 controls pooled from three population-based case-control studies of NHL in the US and Australia. Relative risks of NHL and NHL subtypes in relation to SNP genotypes were assessed using logistic regression. Associations of gene regions and pathways with NHL or NHL subtypes were explored using the minP and tail-strength statistics, respectively. Overall, genetic polymorphisms within the DNA repair pathway were associated with NHL (P = 0·005). Similar associations were seen with the double-strand break repair (P = 0·02) and nucleotide excision repair (P = 0·04) pathways. Five SNPs (BLM rs441399, RAD50 rs2237060, FAM82A2 rs2304583, ERCC3 rs4150506, and XRCC4 rs13178127) were particularly noteworthy because their gene regions were significantly associated with NHL or NHL subtypes (minP ≤ 0·05), or because of high level of statistical significance (P ≤ 0·005) and consistent findings across the three studies. These results support the hypothesis that common genetic polymorphisms in human DNA repair genes may modify the risk of NHL.

Genetic polymorphisms in nitric oxide synthase genes modify the relationship between vegetable and fruit intake and risk of non-Hodgkin lymphoma.

Oxidative damage caused by reactive oxygen species and other free radicals is involved in carcinogenesis. It has been suggested that high vegetable and fruit intake may reduce the risk of non-Hodgkin lymphoma (NHL) as vegetables and fruit are rich in antioxidants. The aim of this study is to evaluate the interaction of vegetable and fruit intake with genetic polymorphisms in oxidative stress pathway genes and NHL risk. This hypothesis was investigated in a population-based case-control study of NHL and NHL histologic subtypes in women from Connecticut, including 513 histologically confirmed incident cases and 591 randomly selected controls. Gene-vegetable/fruit joint effects were estimated using unconditional logistic regression model. The false discovery rate method was applied to adjust for multiple comparisons. Significant interactions with vegetable and fruit intake were mainly found for genetic polymorphisms on nitric oxide synthase (NOS) genes among those with diffuse large B-cell lymphoma and follicular lymphoma. Two single nucleotide polymorphisms in the NOS1 gene were found to significantly modify the association between total vegetable and fruit intake and risk of NHL overall, as well as the risk of follicular lymphoma. When vegetables, bean vegetables, cruciferous vegetables, green leafy vegetables, red vegetables, yellow/orange vegetables, fruit, and citrus fruits were examined separately, strong interaction effects were narrowed to vegetable intake among patients with diffuse large B-cell lymphoma. Our results suggest that genetic polymorphisms in oxidative stress pathway genes, especially in the NOS genes, modify the association between vegetable and fruit intake and risk of NHL.

Diabetes and Overall Survival among Breast Cancer Patients in the U.S. Military Health System.

Background: Although research suggests that type II diabetes mellitus (DM-2) is associated with overall and breast cancer-specific decreased survival, most prior studies of breast cancer survival investigated the effect of preexisting DM-2 without assessing the effect of DM-2 diagnosed at or after breast cancer diagnosis. This study examined the relationship between DM-2 diagnosed before and after breast cancer diagnosis and overall survival.Methods: This study uses linked Department of Defense cancer registry and medical claims data from 9,398 women diagnosed with breast cancer between 1998 and 2007. Cox proportional hazards models were used to assess the association between DM-2 and overall survival.Results: Our analyses showed that women with DM-2 diagnosed before breast cancer diagnosis tended to have a higher risk of mortality compared with women without diabetes [HR = 1.17; 95% confidence interval (CI), 0.95-1.44] after adjustment for potential confounders. Similarly, patients diagnosed with DM-2 at or after breast cancer diagnosis had increased mortality compared with women without DM-2 (HR = 1.39; 95% CI, 1.16-1.66). The similar tendency was also observed among most subgroups when results were stratified by race, menopausal status, obesity, tumor hormone receptor status, and stage.Conclusions: Using data from a health system that provides universal health care to its beneficiaries, this study showed an increased risk of death associated with DM-2, regardless of whether it was diagnosed before or at/after breast cancer diagnosis.Impact: These results suggest the potential effects of factors independent of the timing of DM-2 clinical diagnosis on the association of DM-2 with overall survival. Cancer Epidemiol Biomarkers Prev; 27(1); 50-57. ©2017 AACR.

Inferring past pesticide exposures: a matrix of individual active ingredients in home and garden pesticides used in past decades.

BACKGROUND: In retrospective studies of the health effects of home and garden pesticides, self-reported information typically forms the basis for exposure assessment. Study participants generally find it easier to remember the types of pests treated than the specific pesticides used. However, if the goal of the study is to assess disease risk from specific chemicals, the investigator must be able to link the pest type treated with specific chemicals or products. OBJECTIVES: Our goal was to develop a "pesticide-exposure matrix" that would list active ingredients on the market for treating different types of pests in past years, and provide an estimate of the probability that each active ingredient was used. METHODS: We used several different methods for deriving the active ingredient lists and estimating the probabilities. These methods are described in this article, along with a sample calculation and data sources for each. RESULTS: The pesticide-exposure matrix lists active ingredients and their probabilities of use for 96 distinct scenarios defined by year (1976, 1980, 1990, 2000), applicator type (consumer, professional), and pest type (12 categories). Calculations and data sources for all 96 scenarios are provided online. CONCLUSIONS: Although we are confident that the active ingredient lists are reasonably accurate for most scenarios, we acknowledge possible sources of error in the probability estimates. Despite these limitations, the pesticide-exposure matrix should provide valuable information to researchers interested in the chronic health effects of residential pesticide exposure.

Overall and recurrence-free survival among black and white bladder cancer patients in an equal-access health system.

BACKGROUND: While the incidence of bladder cancer is twice as high among whites than among blacks, mortality is higher among blacks than whites. Unequal access to medical care may be an important factor. Insufficient access to care could delay cancer detection and treatment, which can result in worse survival. The purpose of this study was to evaluate whether survival differed between black and white bladder cancer patients in the Department of Defense (DoD), which provides universal healthcare to all beneficiaries regardless of racial background. METHODS: This study was based on data from the U.S. DoD Automated Central Tumor Registry (ACTUR). White and black patients histologically diagnosed with bladder cancer between 1990 and 2004 were included in the study and followed to the end of 2007. The outcomes were all-cause mortality and recurrence. We assessed the relationship between race and outcomes of interest using Cox proportional hazard ratios (HRs) for all, non-muscle invasive (NMIBC), and muscle invasive (MIBC) bladder cancers, separately. RESULTS: The survival of black and white individuals did not differ statistically. No significant racial differences in survival (HR: 0.96, 95% CI: 0.76-1.22) or recurrence-free survival (HR: 0.94, 95% CI: 0.69-1.30) were observed after adjustment for demographic variables, tumor characteristics, and treatment. Similar findings were observed for NMIBC and MIBC patients, respectively. CONCLUSION: Black patients were more likely to present with MIBC than white patients. However, white and black patients with bladder cancer were not significantly different in overall and recurrence-free survival regardless of muscle invasion. Our study suggests the importance of equal access to healthcare in reducing racial disparities in bladder cancer survival.