Janine M. Joseph

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.

Lifetime physical inactivity is associated with lung cancer risk and mortality

INTRODUCTION Investigations of the independent associations of physical inactivity with cancer endpoints have been mounting in the epidemiological literature, in part due to the high prevalence of physical inactivity among cancer patients and to evidence that inactivity associates with carcinogenesis via pathways independent of obesity. Yet, physical inactivity is not currently recognized as a well-established risk or prognostic factor for lung cancer. As such, we examined the associations of lifetime physical inactivity with lung cancer risk and mortality in a hospital-based, case-control study. PRESENTATION OF CASE Materials and Methods: The analyses included data from 660 lung cancer patients and 1335 matched cancer-free controls. Multivariable logistic regression analyses were utilized to assess the association between lifetime physical inactivity and lung cancer risk, and Cox proportional hazards models were utilized to estimate the association between lifetime physical inactivity and mortality among lung cancer cases.Results: We observed a significant positive association between lifetime physical inactivity and lung cancer risk: [Odds ratio (OR)=2.23, 95% confidence interval (CI): 1.77-2.81]; the association remained significant among never smokers (OR=3.00, 95% CI:1.33-6.78) and non-smokers (OR=2.33, 95% CI: 1.79-3.02). We also observed a significant positive association between lifetime physical inactivity and lung cancer mortality [Hazard ratio (HR)=1.40, 95% CI: 1.14-1.71]; the association remained significant in non-smokers (HR=1.51, 95% CI: 1.16-1.95). DISCUSSION/CONCLUSION These data add to the body of evidence suggesting that physical inactivity is an independent risk and prognostic factor for cancer. Additional research utilizing prospectively collected data is needed to substantiate the current findings.

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.

No evidence that genetic variation in the myeloid-derived suppressor cell pathway influences ovarian cancer survival

Background: The precise mechanism by which the immune system is adversely affected in cancer patients remains poorly understood, but the accumulation of immunosuppressive/protumorigenic myeloid-derived suppressor cells (MDSCs) is thought to be a prominent mechanism contributing to immunologic tolerance of malignant cells in epithelial ovarian cancer (EOC). To this end, we hypothesized genetic variation in MDSC pathway genes would be associated with survival after EOC diagnoses. Methods: We measured the hazard of death due to EOC within 10 years of diagnosis, overall and by invasive subtype, attributable to SNPs in 24 genes relevant in the MDSC pathway in 10,751 women diagnosed with invasive EOC. Versatile Gene-based Association Study and the admixture likelihood method were used to test gene and pathway associations with survival. Results: We did not identify individual SNPs that were significantly associated with survival after correction for multiple testing (P < 3.5 × 10−5), nor did we identify significant associations between the MDSC pathway overall, or the 24 individual genes and EOC survival. Conclusions: In this well-powered analysis, we observed no evidence that inherited variations in MDSC-associated SNPs, individual genes, or the collective genetic pathway contributed to EOC survival outcomes. Impact: Common inherited variation in genes relevant to MDSCs was not associated with survival in women diagnosed with invasive EOC. Cancer Epidemiol Biomarkers Prev; 26(3); 420–4. ©2016 AACR.

The association of lifetime physical inactivity with bladder and renal cancer risk: A hospital-based case-control analysis

OBJECTIVES Recreational physical inactivity has been gaining recognition as an independent epidemiological exposure of interest in relation to cancer endpoints due to evidence suggesting that it may associate with cancer independent of obesity. In the current analyses, we examined the associations of lifetime recreational physical inactivity with renal and bladder cancer risk. METHODS In this hospital-based case-control study, we identified N=160 renal cancer patients, N=208 bladder cancer patients, and N=766 age frequency-matched controls without cancer. Participants self-reporting never participating in any regular/weekly recreational physical activity throughout their lifetime were classified as physically inactive. Utilizing unconditional multivariable logistic regression analyses, we estimated odds ratios and 95% confidence intervals to represent the associations between lifetime physical inactivity and renal and bladder cancer risk. RESULTS In multivariable logistic regression models, we observed significant positive associations between lifetime recreational physical inactivity and renal cancer and bladder cancer risk: odds ratio=1.77 (95% CI: 1.10-2.85) and odds ratio=1.73 (95% CI: 1.13-2.63), respectively. Similar associations also persisted among individuals who were not obese for both renal and bladder cancer: odds ratio=1.75 (95% CI: 1.03-2.98) and odds ratio=1.70 (95% CI: 1.08-2.69), respectively. CONCLUSIONS In this case-control study, we observed evidence of a positive association between renal and bladder cancer with lifetime recreational physical inactivity. These data add to the growing body of evidence suggesting that physical inactivity may be an important independent risk factor for cancer. However, additional studies using a larger sample and prospectively collected data are needed to substantiate the current findings.

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

ABSTRACT 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.

Lifetime physical inactivity is associated with increased risk for Hodgkin and non-Hodgkin lymphoma: A case-control study

BACKGROUND Although physical activity is a well-established risk factor for several cancer types, studies evaluating its association with lymphoma have yielded inconclusive results. In such cases where physical activity is not clearly associated with cancer risk in a dose-dependent manner, investigators have begun examining physical inactivity as an independent exposure of interest. METHODS Associations of self-reported, lifetime physical inactivity with risk of developing Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) were evaluated in a hospital-based case control study using data from the Patient Epidemiology Data System at Roswell Park Comprehensive Cancer Center. Participants included 87 patients with HL and 236 patients with NHL as well as 348 and 952 cancer-free controls, respectively. Multivariable-adjusted logistic regression models were fit to calculate odds ratios (OR) and 95% confidence intervals (CI) estimating the association between physical inactivity and lymphoma risk. RESULTS We observed significant, positive associations between lifetime recreational physical inactivity and risk of both HL (OR = 1.90, 95% CI: 1.15-3.15) and NHL (OR = 1.35, 95% CI: 1.01-1.82). CONCLUSIONS The current analysis provides evidence for a positive association between physical inactivity and risk of both HL and NHL. These results add to a growing body of research suggesting that lifetime physical inactivity may be an important independent, modifiable behavioral risk factor for 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.