Cruciferous Vegetable Consumption and Stomach Cancer: A Case-Control Study.

Objective: To investigate the association between regular cruciferous vegetable intake and stomach cancer.Methods: A hospital-based, case-control study was conducted at Roswell Park Comprehensive Cancer Center in Buffalo, NY, which included 292 stomach cancer patients and 1168 cancer-free controls recruited between 1992 and 1998 as part of the Patient Epidemiology Data System (PEDS). Dietary and other epidemiologic and confounding variables were collected by questionnaire. Multivariable logistic regression analyses were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between usual pre-diagnostic cruciferous vegetable intake and stomach cancer, with adjustment for other stomach cancer risk factors and dietary characteristics.Results: We observed strong inverse associations between stomach cancer and highest versus lowest intakes of total cruciferous vegetables (OR = 0.59, 95% CI: 0.42-0.83), raw cruciferous vegetables (OR = 0.53, 95% CI: 0.38-0.73), raw broccoli (OR = 0.61, 95% CI: 0.43-0.86), raw cauliflower (OR = 0.51, 95% CI: 0.35-0.73), and Brussels sprouts (OR = 0.66, 95% CI = 0.48-0.91).Conclusions: These data suggest that consuming raw cruciferous vegetables may be associated with a lower odds of stomach cancer, even after considering other dietary characteristics.

Usual Cruciferous Vegetable Consumption and Ovarian Cancer: A Case-Control Study.

Ovarian cancer is the fifth leading cause of cancer-related deaths among women, primarily due to diagnosis at late stages. Therefore, identification of modifiable risk factors for this disease is warranted. Using the Patient Epidemiology Data System (PEDS), collected from 1981 to 1998 at Roswell Park Cancer Institute, Buffalo, NY, we conducted a hospital-based, case-control analysis of self-reported cruciferous vegetable intake and ovarian cancer among 675 women with primary, incident ovarian cancer, and 1275 without cancer. Cruciferous vegetable intake was queried using a 44-item food frequency questionnaire (FFQ). Odds ratios (OR) and 95% confidence intervals (CI) were estimated with logistic regression, adjusting for age, body mass index (BMI), education, smoking status, parity, family history of ovarian cancer, total fruit consumption, total meat consumption, and total noncruciferous vegetable consumption. We observed a significant inverse association for women with highest vs. lowest intakes of total vegetables (OR = 0.65, 95% CI = 0.46-0.92), cooked cauliflower (OR = 0.82, 95% CI = 0.67-0.99), and cooked greens (OR = 0.63, 95% CI = 0.46-0.86) and an inverse, dose-dependent association between cooked cruciferous vegetables intake and ovarian cancer (for each additional ten servings per month, OR = 0.85, 95% CI = 0.76-0.96). These findings suggest that a diet that includes cruciferous vegetables could be an important modifiable risk factor for ovarian cancer.

The Association of Peripheral Blood Regulatory T-Cell Concentrations With Epithelial Ovarian Cancer: A Brief Report.

OBJECTIVE: There is a mounting body of evidence demonstrating higher percentages of regulatory T (Treg) cells in the peripheral blood of patients with cancer in comparison to healthy controls, but there is a paucity of epidemiological literature characterizing circulating Treg cells among patients with epithelial ovarian cancer (EOC). To investigate the role of peripheral Treg cells in ovarian neoplasms, we conducted a case-control study to characterize circulating concentrations of Treg cells among patients with EOC, women with benign ovarian conditions, and healthy controls without a history of cancer. MATERIALS AND METHODS: Participants were identified for inclusion due to their participation in the Data Bank and BioRepository program at Roswell Park Cancer Institute in Buffalo, NY. Patients included 71 women with a primary diagnosis of EOC and 195 women with a diagnosis of benign ovarian conditions. Controls included 101 age- and race-matched women without a history of cancer. Nonfasting, pretreatment peripheral blood levels of CD3+CD4+CD25+FOXP3+ Treg cells were measured using flow cytometric analyses and expressed as a percentage of total CD3+ cells and as a percentage of total CD3+CD4+ cells. RESULTS: Compared to healthy controls and women with benign ovarian conditions, patients with EOC had significantly higher frequency of Treg cells (P < 0.04). In multivariable logistic regression analyses using Treg frequency expressed as a percentage of CD+3 cells, we observed a significant positive association between Treg cell percentage and EOC risk, with each 1% increase associated with a 37% increased risk of EOC (odds ratio, 1.37; 95% confidence interval, 1.04-1.80). We observed a similar trend when Treg frequency was expressed as a percentage of CD3+CD+4 cells (odds ratio, 1.22; 95% confidence interval, 0.99-1.49). CONCLUSIONS: The current study provides support that peripheral Treg cell frequency is elevated in patients with EOC in comparison to women with benign ovarian conditions and healthy controls.

The association of lifetime physical inactivity with head and neck cancer: a hospital-based case-control analysis.

Despite mounting epidemiological evidence suggesting an inverse association between recreational physical activity and cancer risk, evidence associated with head and neck cancer is scant. We conducted a case-control analysis to examine the associations of lifetime physical inactivity with the risk of head and neck squamous cell carcinoma (HNSCC). We utilized data from the Patient Epidemiology Data System at Roswell Park Cancer Institute (RPCI). Participants included 246 patients with HNSCC and 504 cancer-free controls who received medical services at RPCI between 1990 and 1998. Participants were considered physically inactive if they did not participate in any regular, weekly recreational physical activity throughout their lifetime, prior to diagnosis. Multivariate logistic regression models were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) representing the association between lifetime physical inactivity and HNSCC risk. We observed a significant positive association between recreational physical inactivity and HNSCC risk (OR = 2.73, 95% CI 1.87-3.99, p < 0.001). In subgroup analyses by body mass index (BMI) (underweight/normal-weight: OR = 3.40, 95% CI 1.89-6.12, p < 0.001; overweight/obese: OR = 2.40, 95% CI 1.43-4.02, p < 0.001) and smoking status (former smoker: OR = 3.12, 95% CI 1.89-5.14, p < 0.001; never smoker: OR = 2.71, 95% CI 1.21-6.05, p = 0.020; current smoker: OR = 1.61, 95% CI 0.66-3.95, p = 0.300), significant positive associations were also observed. Results of the current analyses suggest that lifetime physical inactivity associates with HNSCC independent of BMI. In addition, physical inactivity may be a modifiable risk factor among never smokers. These data add to the growing body of evidence suggesting that physical inactivity may be an independent risk factor for cancer.

Recreational physical inactivity and mortality in women with invasive epithelial ovarian cancer: evidence from the Ovarian Cancer Association Consortium.

BACKGROUND: Little is known about modifiable behaviours that may be associated with epithelial ovarian cancer (EOC) survival. We conducted a pooled analysis of 12 studies from the Ovarian Cancer Association Consortium to investigate the association between pre-diagnostic physical inactivity and mortality. METHODS: Participants included 6806 women with a primary diagnosis of invasive EOC. In accordance with the Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. We utilised Cox proportional hazard models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) representing the associations of inactivity with mortality censored at 5 years. RESULTS: In multivariate analysis, inactive women had significantly higher mortality risks, with (HR=1.34, 95% CI: 1.18-1.52) and without (HR=1.22, 95% CI: 1.12-1.33) further adjustment for residual disease, respectively. CONCLUSION: In this large pooled analysis, lack of recreational physical activity was associated with increased mortality among women with invasive EOC.

Dietary risk factors for monoclonal gammopathy of undetermined significance in a racially diverse population.

ABSTRACT: Monoclonal gammopathy of undetermined significance (MGUS), a precursor of multiple myeloma, is associated with shorter lifespan and cardiac, renal, neurologic, and immune-related comorbidities. There is little known about modifiable risk factors for this condition. To determine whether the risk of MGUS is associated with dietary factors in a racially diverse population, we conducted a US population-based case-control study from the National Health and Nutrition Examination Survey (1988-2004), which included 373 individuals with MGUS and 1406 matched controls. Diet was characterized by one 24-hour dietary recall, with gram intake of individual foods and beverages aggregated into groups. Unconditional multivariable logistic regressions were used to model associations between intake of several food groups and MGUS, with odds ratios (ORs) and 95% confidence intervals (CIs) reported for the highest relative to the lowest quantile of intake. Daily gram intake of several food and beverage groups were significantly associated with MGUS. MGUS was inversely associated with whole-grain bread, oats, and rice (OR, 0.70; 95% CI, 0.48-1.00; P < .05), fruits (excluding juice) and vegetables (OR, 0.69; 95% CI, 0.52-0.93; P = .02), vegetables (OR, 0.75; 95% CI, 0.56-0.99; P < .05), tomatoes (OR, 0.72; 95% CI, 0.51-1.00; P < .05), and cruciferous vegetables (OR, 0.44; 95% CI, 0.26-0.74; P < .01). Direct associations were observed for sugar-sweetened beverages (OR, 1.34; 95% CI, 1.00-1.78; P < .05), sugar-sweetened soft drinks (OR, 1.41; 95% CI, 1.01-1.96; P = .04), and artificially sweetened soft drinks (OR, 1.55; 95% CI, 1.04-2.33; P = .03). Our study shows that diet is potentially a modifiable risk factor for MGUS.

Effects on the Physical Functioning of Two Exercise Interventions in Patients with Multiple Myeloma: A Pilot Feasibility Study.

Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway.

The association of body composition phenotypes before chemotherapy with epithelial ovarian cancer mortality.

BACKGROUND: The association of body composition with epithelial ovarian carcinoma (EOC) mortality is poorly understood. To date, evidence suggests high adiposity associates with decreased mortality (an obesity paradox), but the impact of muscle on this association has not been investigated. Herein, we define associations of muscle and adiposity joint-exposure body composition phenotypes with EOC mortality. METHODS: Body composition from 500 women in The Body Composition and Epithelial Ovarian Cancer Survival Study was dichotomized as normal/low skeletal muscle index (SMI), a proxy for sarcopenia and high/low adiposity. Four phenotypes were classified as fit/reference (normal SMI/low adiposity; 16.2%), overweight/obese (normal SMI/high adiposity; 51.2%), sarcopenia/overweight-obese (low SMI/high adiposity; 15.6%), and sarcopenia/cachexia (low SMI/low adiposity; 17%). We used multivariable Cox models to estimate associations of each phenotype with mortality for EOC overall and high-grade serous ovarian carcinoma (HGSOC). RESULTS: Overweight/obesity was associated with up to 51% and 104% increased mortality in EOC and HGSOC (HR = 1.51, 95% CI: 1.05-2.19 and HR = 2.04, 95% CI: 1.29-3.21). Sarcopenia/overweight-obesity was associated with up to 66% and 67% increased mortality in EOC and HGSOC (HR = 1.66, 95% CI: 1.13-2.45 and HR = 1.67, 95% CI: 1.05-2.68). Sarcopenia/cachexia was associated with up to 73% and 109% increased mortality in EOC and HGSOC (HR = 1.73, 95% CI: 1.14-2.63 and HR = 2.09, 95% CI: 1.25-3.50). CONCLUSIONS: Overweight/obesity, sarcopenia/overweight-obesity and sarcopenia/cachexia phenotypes were each associated with increased mortality in EOC and HGSOC. Exercise and dietary interventions could be leveraged as ancillary treatment strategies for improving outcomes in the most fatal gynecological malignancy with no previously established modifiable prognostic factors.

T Cell Exhaustion Markers in Multiple Myeloma Patients are Lower After Physical Activity Intervention.

PURPOSE: There is compelling evidence that CD4+ and CD8+T cells are dysfunctional in multiple myeloma, compromising their ability to control disease progression. Pre-clinical models suggest that exercise represents a non-pharmacologic means to reduce immune exhaustion, but no studies to date have examined the relationship between an exercise intervention and biomarkers of immune exhaustion in multiple myeloma patients. PATIENTS AND METHODS: The current study includes 24 multiple myeloma patients who participated in a six-month physical activity intervention, consisting of supervised strength training (n = 12) and unsupervised home-based walking arms (n = 12). Comprehensive flow cytometry was utilized to assess the frequency of CD4+ and CD8+T cells and subpopulations expressing the markers of exhaustion PD-1, TIGIT, TIM3 and/or LAG3. Ratios of exhausted to non-exhausted cell populations, and percentages of exhausted to total populations of the same lineage, were calculated for the baseline and final timepoints. RESULTS: Eighteen of 20 exhaustion measures were lower at the end of the intervention than at baseline, and several were significantly or borderline significantly reduced in the entire sample or in one of the arms. The entire sample saw improvements in the ratios of CD4+ TIGIT+ to non-exhausted CD4+ (0.7 [0.6] to 0.6 [0.4], P = .04) and CD8+ PD1+ to non-exhausted CD8+ (1.8 [2.6] to 1.5 [2.0], P = .06), and in total exhausted CD8+ as a percent of total CD8+ (72.9 [21.9] to 68.3 [19.6], P < .01). CONCLUSIONS: This pilot study suggests that physical activity induces changes in MM patients' immune systems, potentially rendering a less exhausted T cell state.

Physical Activity in Multiple Myeloma: A Review of the Current Literature.

One of the major issues patients with multiple myeloma (MM) suffer from is bone instability and the resulting difficulties that come along with it, such as pain and immobility. Few studies have been performed in this patient group to investigate the effects of physical exercise on outcomes such as muscle strength, quality of life, fatigue, and pain. A PubMed search was conducted by entering the search terms "multiple myeloma" and "exercise," and "multiple myeloma" and "physical activity" that yielded 178 and 218 manuscripts, respectively. Limiting the search results to clinical trials left 13 and 14 manuscripts, respectively, and 7 studies (1 retrospective chart review, 1 questionnaire study, and 5 prospective clinical trials). The majority of these studies (5) were published in the past decade. The outcomes of several studies of exercise in MM show that physical exercise is feasible for MM patients. Compared with the control groups, the most active participants show better outcomes, such as improvements in their blood counts and in quality-of-life parameters such as fatigue, pain, sleep, and mood. One trial found that MM patients were in much poorer condition than people in a normative standard group. Some of the reported outcomes of exercise in MM have been promising but need to be substantiated in a broader setting with more diverse participants, for a longer duration, and include more endpoints. Due to the disease-inherent risk of bone-related complications, an individualized, supervised training protocol could be a preferable tool.

Sugar Sweetened and Artificially Sweetened Beverage Consumption and Pancreatic Cancer: A Retrospective Study.

Pancreatic cancer (PanCa) is a highly fatal malignancy with few modifiable risk and prognostic factors. This study investigates the association between cola, diet cola, and non-cola soft drink consumption and PanCa risk and mortality. A retrospective study was conducted using data from the Patient Epidemiology Data System (1982-1998) at Roswell Park Comprehensive Cancer Center (Buffalo, NY, USA), including 213 PanCa patients and 852 cancer-free controls. Data were collected using a self-administered questionnaire, including a 46-item food frequency questionnaire (FFQ). Multivariable logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) of cola, diet cola, and non-cola soft drink consumption and PanCa risk. Cox proportional hazard regression was used to estimate hazard ratios (HR) and 95% CIs of cola, diet cola, and non-cola soft drink consumption and PanCa mortality. Stratified analyses were conducted by sex, body mass index (BMI), and smoking status. We observed significant 55% increased odds of PanCa among patients consuming ≥1 regular cola per day (OR: 1.55, 95% CI: 1.01-2.39). We also observed non-significant 38% increased hazard of mortality among patients consuming ≥1 regular cola per day (HR: 1.38, 95% CI: 0.91-2.07). We conclude that regular cola consumption is a modifiable lifestyle that may be associated with PanCa risk and mortality following diagnosis.

Physical Activity and Patient-Reported Outcomes in Monoclonal Plasma Cell Disorders.

INTRODUCTION: Plasma cell disorders (PCD) are a group of conditions characterized by disproportionate proliferation of a single clone of B lymphocytes. Multiple myeloma (MM) is a malignant type of plasma cell disorders. Improvements in MM survival have led patients and physicians to pursue strategies to improve quality of life for those living longer with this disease. Bone disease and instability associated with MM have made physicians reluctant to recommend physical activity (PA) to this patient population. The goal of this study was to examine the relationship between PA and physical and psychosocial patient-reported outcomes in patients with MM and precursor conditions. METHODS: We used a cross-sectional study design. Questionnaires on PA, demographics, fatigue, distress, and other aspects of quality of life were posted on the HealthTree® Cure Hub website, a patient portal through which individuals with MM and related disorders obtain support, track laboratories and other information about their diseases, and participate in research. RESULTS: A total of 794 individuals, including 664 with MM, are included in the current analysis. We observed potential inverse associations between PA and poor quality of life, including problems with sleep, fatigue, neuropathy, distress, and several psychosocial states. On average, patients reported that their PA levels have declined since diagnosis and that they would like to be even more active in the future than they were before their diagnosis. CONCLUSIONS: In our cross-sectional study, regular PA was associated with multiple quality-of-life indicators and other patient-reported outcomes, including better sleep and less fatigue, neuropathy, and distress. The findings of this study can help guide the design of prospective studies of the role of PA in MM survivorship.

Pre-Diagnosis Dietary Patterns and Risk of Multiple Myeloma in the NIH-AARP Diet and Health Study.

Background: Despite patient interest in knowing whether diet is linked to multiple myeloma (MM), there is limited research on dietary patterns and MM risk. Two studies have assessed this risk, albeit with a small number of MM cases. The EPIC-Oxford cohort and Oxford Vegetarian study (65 MM cases) showed that fish eaters, vegetarians and vegans had significantly reduced MM risk compared to meat eaters. The Nurses' Health Study and Health Professionals Follow-up Study (478 MM cases) showed a significantly increased MM risk in men with Empirical Dietary Inflammatory Pattern. Methods: The NIH-AARP Diet and Health study is a prospective cohort of 567,169 persons who completed a food frequency questionnaire in 1995-1996 and were followed until December 2011. Healthy Eating Index-2015 (HEI-2015), Healthy Diet Score (HDS), alternate Mediterranean Diet (aMED) and healthful Plant-based Diet Index (hPDI) scores were calculated using a priori defined methods and grouped into quartiles, with higher scores reflecting healthier eating patterns. We prospectively evaluated the association between pre-diagnosis dietary patterns and MM incidence in this cohort. Hazard ratios (HR) and 95% confidence intervals (95%CI) were estimated using multivariate Cox proportional hazards models adjusted for age at study entry, sex, race, body mass index, education, and total energy intake (by residual method). Sensitivity analysis was conducted to assess reverse causality by excluding MM cases diagnosed within one year of follow-up. Results: Among 392,589 participants (after exclusions), a total of 1,366 MM cases (59% males; 92% non-Hispanic whites) were identified during the follow-up period. Analysis revealed a significant association between hPDI scores and reduced MM risk (highest vs lowest quartile, HR 0.85; 95%CI 0.73-1.0; p=0.043) (Table). In sensitivity analysis (1,302 MM cases), the association was no longer significant (HR 0.87; 95%CI 0.74-1.03; p 0.09) but trended in the same direction. This may be due to small sample size, given MM is a rare disease. HEI-2015, HDS and aMED scores were not associated with MM risk. Conclusions: A healthful plant-based diet was associated with reduced MM risk in the NIH-AARP cohort. These results will help oncologists and patients make informed choices about their diet. To our knowledge, this is the largest epidemiologic study to date assessing pre-diagnosis dietary patterns and MM risk.

MCM3 is a novel proliferation marker associated with longer survival for patients with tubo-ovarian high-grade serous carcinoma.

Tubo-ovarian high-grade serous carcinomas (HGSC) are highly proliferative neoplasms that generally respond well to platinum/taxane chemotherapy. We recently identified minichromosome maintenance complex component 3 (MCM3), which is involved in the initiation of DNA replication and proliferation, as a favorable prognostic marker in HGSC. Our objective was to further validate whether MCM3 mRNA expression and possibly MCM3 protein levels are associated with survival in patients with HGSC. MCM3 mRNA expression was measured using NanoString expression profiling on formalin-fixed and paraffin-embedded tissue (N = 2355 HGSC) and MCM3 protein expression was assessed by immunohistochemistry (N = 522 HGSC) and compared with Ki-67. Kaplan-Meier curves and the Cox proportional hazards model were used to estimate associations with survival. Among chemotherapy-naïve HGSC, higher MCM3 mRNA expression (one standard deviation increase in the score) was associated with longer overall survival (HR = 0.87, 95% CI 0.81-0.92, p < 0.0001, N = 1840) in multivariable analysis. MCM3 mRNA expression was highest in the HGSC C5.PRO molecular subtype, although no interaction was observed between MCM3, survival and molecular subtypes. MCM3 and Ki-67 protein levels were significantly lower after exposure to neoadjuvant chemotherapy compared to chemotherapy-naïve tumors: 37.0% versus 46.4% and 22.9% versus 34.2%, respectively. Among chemotherapy-naïve HGSC, high MCM3 protein levels were also associated with significantly longer disease-specific survival (HR = 0.52, 95% CI 0.36-0.74, p = 0.0003, N = 392) compared to cases with low MCM3 protein levels in multivariable analysis. MCM3 immunohistochemistry is a promising surrogate marker of proliferation in HGSC.

Cruciferous vegetable consumption and pancreatic cancer: A case-control study.

BACKGROUND: Pancreatic cancer is a deadly malignancy with limited screening and few modifiable risk factors. The objective of this study was to investigate the association between a modifiable lifestyle behavior, cruciferous vegetable consumption, and pancreatic cancer, both overall and by subgroups based on non-modifiable, established risk factors. METHODS: We conducted a hospital-based, case-control study utilizing data from the Patient Epidemiology Data System (1982-1998) at Roswell Park Comprehensive Cancer Center (Buffalo, NY) which included 183 pancreatic cancer patients and 732 cancer-free controls. Data were collected using a self-administered questionnaire including a 52-item food frequency questionnaire and other epidemiologic data. Multivariable logistic regression, adjusted for age, body mass index (BMI), sex, smoking status, total meat, and family history of pancreatic cancer, was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations between cruciferous vegetable consumption and pancreatic cancer. Subgroup analyses were conducted by sex, smoking status, and BMI. RESULTS: We observed inverse associations between cruciferous vegetable intake and pancreatic cancer, with a significant 40% lower odds of pancreatic cancer among subjects consuming >1.5 servings per week (SPW) of raw cruciferous vegetables compared to those consuming less than 0.5 SPW (OR = 0.60, 95% CI: 0.39-0.93). Each additional SPW of total, raw, and cooked cruciferous vegetables was associated with a significant 7-15% lower odds of pancreatic cancer, with the strongest association seen in raw cruciferous vegetables (OR = 0.85, 95% CI: 0.75-0.95). We observed inverse associations between raw cruciferous vegetable intake and pancreatic cancer among people who were overweight, former smokers, and males, ranging from 50% to 59% lower odds. CONCLUSION: Consuming cruciferous vegetables, especially raw cruciferous vegetables, is a modifiable lifestyle behavior which may be inversely associated with pancreatic cancer, including among subgroups with other non- or not easily modifiable risk factors for this deadly malignancy.

Circulating CD14+ HLA-DRlo/- monocytic cells as a biomarker for epithelial ovarian cancer progression.

PROBLEM: Previous studies identified circulating CD14+ HLA-DRlo/- monocytic cells as an immune suppressive subset in solid malignancies, such as prostate, renal cell carcinoma, and pancreatic cancer. Such monocytic cells have been implicated not only in tumour progression but also as a potential barrier for immunotherapy. This study examined the relationship between the frequency of circulating monocytic cells and epithelial ovarian cancer (EOC) progression pre- and post-frontline chemotherapy, defined by disease stage, which is a leading prognostic factor for this malignancy. METHOD OF STUDY: Incident cases of 236 women with EOC were recruited and comprehensive flow cytometry was utilized to assess the frequency of peripheral blood CD33+ CD11b+ HLA-DR-/low CD14+ CD15- monocytic cells, henceforth termed CD14+ HLA-DRlo/- monocytic cells, prior to and after completion of frontline chemotherapy. Multivariable odds ratios (OR) were used to estimate the association between CD14+ HLA-DRlo/- monocytic cell percentages and disease stage. Wilcoxon signed-rank tests evaluated changes in these monocytic cell levels pre- and post-chemotherapy in a patient subset (n = 70). RESULTS: Patients with elevated frequencies of circulating CD14+ HLA-DRlo/- monocytic cells at diagnosis were at 3.33-fold greater odds of having advanced stage (III/IV) EOC (CI: 1.04-10.64), with a significant trend in increasing CD14+ HLA-DRlo/- monocytic cell levels (P = .04). There was a 2.02% median decrease of these monocytic cells post-chemotherapy among a subset of patients with advanced stage disease (P < .0001). CONCLUSION: These findings support the potential clinical relevance of CD14+ HLA-DRlo/- monocytic cells in EOC for prognosis and may indicate a non-invasive biomarker to measure disease progression.

Physical Inactivity and Pancreatic Cancer Mortality.

OBJECTIVE: To determine the association between pre-diagnostic recreational physical inactivity (RPI) and pancreatic cancer (PC) mortality. METHODS: This analysis included 107 patients seen at Roswell Park Comprehensive Cancer Center diagnosed with PC between 1989 and 1998. Cox proportional hazards models were used to determine hazard ratios (HR) and 95% confidence intervals (CI) for PC mortality associated with self-reported pre-diagnostic RPI. Models were adjusted for known prognostic factors, including age, sex, stage at diagnosis, smoking status, and body mass index (BMI). Results were also stratified by sex, BMI, smoking status, histology, and treatment status. RESULTS: We observed a significant association between RPI and PC mortality in all patients (HR = 1.72, 95% CI = 1.06-2.79), as well as among overweight or obese patients (HR = 2.74, 95% 95% CI = 1.42-5.29), females (HR = 2.63; 95% CI, 1.08-6.39), and non-smokers (HR = 1.72; 95% CI, 1.02-2.89). CONCLUSION: These results suggest that RPI prior to PC diagnosis is associated with a higher risk of death. Future studies with larger sample sizes are needed to explore whether this association varies across tumor histology.

Physical inactivity and head and neck cancer mortality.

BACKGROUND: This study was performed to examine the association between adulthood recreational physical inactivity (PIA) and mortality among patients with cancers of the head and neck. METHODS: Patients with head and neck cancer at Roswell Park between years 1990 to 1998 were included (N = 305). Multivariable Cox proportional hazard ratios (HR) with corresponding 95% confidence intervals (CI) were used to analyze the association between PIA and risk of dying. RESULTS: There was a 1.40-fold increase in risk of dying among PIA patients, when compared to active patients with head and neck cancers (HR = 1.40, CI: 1.03-1.91). This was observed greater in PIA women (HR = 2.40, CI: 1.28-4.52), patients who were overweight/obese (HR = 1.76, CI: 1.09-2.85), patients with pharynx as the primary site (HR = 1.85, CI: 1.01-3.38), and patients with distant metastasis (HR = 5.19, CI: 1.37-19.65). CONCLUSION: Physically inactive patients with head and neck cancers are at significantly greater risk of dying when compared to patients who are active.

Hereditary association between testicular cancer and familial ovarian cancer: A Familial Ovarian Cancer Registry study.

BACKGROUND: Although family history of testicular cancer is well-established as a risk factor for testicular cancer, it is unknown whether family history of ovarian cancer is associated with risk of testicular cancer. MATERIALS AND METHODS: Using data from the Familial Ovarian Cancer Registry on 2636 families with multiple cases of ovarian cancer, we systematically compared relative frequencies of ovarian cancer among relatives of men with testicular and non-testicular cancers. RESULTS: Thirty-one families with cases of both ovarian and testicular cancer were identified. We observed that, among men with cancer, those with testicular cancer were more likely to have a mother with ovarian cancer than those with non-testicular cancers (OR = 3.32, p = 0.004). Zero paternal grandmothers of men with testicular cancer had ovarian cancer. CONCLUSION: These observations provide compelling preliminary evidence for a familial association between ovarian and testicular cancers Future studies should be designed to further investigate this association and evaluate X-linkage.