Recreational physical activity and risk of epithelial ovarian cancer

Background

Physical activity may influence ovarian cancer risk through hormonal, inflammatory, or immune-mediated processes or by suppressing ovulation. In a population-based case–control study of epithelial ovarian cancer, we assessed risk associated with recreational physical activity with a focus on characterizing risk within histologic subtypes.

Methods

Information was collected during in-person interviews with 812 women with ovarian cancer diagnosed in western Washington State from 2002–2005 and 1,313 controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Exercise was assessed according to the average hours and metabolic equivalent (MET)-hours per week and the number of years in which regular recreational activity occurred.

Results

Relative to women who reported no regular exercise throughout adulthood, the overall risk of invasive, but not borderline, ovarian cancer was reduced among more active women. Reductions in risk of invasive disease were most evident among women with the greatest frequency of high-intensity activity during adulthood. For serous invasive cancer, women in the uppermost category of MET-hours per week of recreational activity in adulthood had 60% the risk of inactive women (95% CI 0.4–0.9), whereas this level of activity was associated with more than a doubling in risk of endometrioid and clear cell invasive tumors.

Conclusions

Our findings are compatible with an overall reduction in risk of invasive epithelial ovarian cancer associated with recreational activity but suggest that this association may differ in women with different histologic types of disease. Inconsistent findings across studies that have considered histologic type indicate that this issue is not yet resolved.     

Recreational physical activity and mammographic breast density characteristics.

Increased mammographic breast density is considered an intermediate marker of breast cancer risk. Physical activity is believed to reduce breast cancer risk; however, its effect on breast density is not well understood. We studied the association between recreational physical activity and mammographic characteristics of the breast among a population of premenopausal and postmenopausal women enrolled as controls (n = 728) in a case-control study of mammographic breast density and breast cancer. Women were enrolled shortly after obtaining their regular screening mammograms, and participants reported their current and lifetime recreational physical activity history using a self-administered, reliable questionnaire at study enrollment. Linear regression was used to determine associations between physical activity variables and the dense breast area, non-dense area, total breast area, and percent density. Age-adjusted analyses revealed significant inverse associations between physical activity variables and the non-dense area and total area and positive associations with percent breast density. These associations were attenuated and nonsignificant after adjustment for body mass index (BMI). Adjustment for additional factors did not substantially change the results. Physical activity was not associated with the dense breast area before or after adjustment for BMI. Self-reported recreational physical activity was not significantly associated with the mammographic characteristics of the breast after adjustment for BMI in this population. These results suggest that the mechanism by which physical activity reduces breast cancer risk may not involve breast density.     

Recreational physical activity and survival among young women with breast cancer

BACKGROUND: Most epidemiologic studies report a reduced risk of developing breast cancer associated with higher levels of recreational physical activity, but little is known regarding its effect on prognosis. METHODS: In this study, the authors investigated whether activity undertaken prior to diagnosis influenced breast cancer survival in a population-based cohort. A follow-up study was conducted among 1264 women ages 20 to 54 years who were diagnosed with invasive breast cancer between 1990 and 1992. Women in the study were interviewed within several months of diagnosis and were asked about their average frequency of moderate and vigorous activity at age 13 years, age 20 years, and during the year before diagnosis. With 8 to 10 years of follow-up, all-cause mortality status was determined by using the National Death Index (n = 290 deaths). RESULTS: A modest reduction in the hazards ratio (HR) was observed for the highest quartile of activity in the year before diagnosis compared with the lowest quartile (stage-adjusted and income-adjusted HR, 0.78; 95% confidence interval [95% CI], 0.56-1.08). High activity was associated with a reduced HR among women who were overweight or obese at the time of diagnosis (HR, 0.70; 95% CI, 0.49-0.99) but not among ideal weight or underweight women (HR, 1.08; 95% CI, 0.77-1.52). A reduced HR was not evident for activity at age 13 years or 20 years or for average activity across the 3 periods studied. CONCLUSIONS: The results of this study provided some suggestive evidence for a beneficial effect on survival of recreational physical activity undertaken in the year before diagnosis, particularly among women who are overweight or obese near the time of diagnosis.     

Recreational physical activity and survival in African-American women with ovarian cancer

Purpose

While recreational physical activity (RPA) has been associated with reduced mortality in breast, colorectal, and prostate cancers, evidence for epithelial ovarian cancer (EOC) is limited. Most EOC studies have been in predominantly white populations, although inactivity is more prevalent and survival is poorer among African-American (AA) women. We examined RPA before and after EOC diagnosis and associations with survival among AA women.

Methods

We analyzed data from 264 EOC survivors enrolled in a population-based, case–control study who completed surveys that included questions about pre- and post-diagnosis RPA. Data were collected on RPA frequency, intensity, and duration before diagnosis and approximately 1 year after the baseline interview. We calculated metabolic equivalent of task (MET)-hours/week for pre- and post-diagnosis RPA, and evaluated associations with risk of mortality using Cox proportional hazards models.

Results

RPA before diagnosis was not associated with mortality. Hazard ratios (HRs) for post-diagnosis RPA were <?1.0 but not statistically significant after adjustment for covariates; HRs were 0.94 (95% CI 0.58, 1.54) for >?0–9 MET-hours/week and 0.53 (95% CI 0.21, 1.35) for >?9 MET-hours/week.

Conclusions

Our results suggest that RPA may be inversely associated with mortality among AA women with ovarian cancer, although it is possible that the present study was underpowered to detect an association. There is a clear need for more studies of RPA after diagnosis in EOC survivors with attention to potential differences by race.

     

Recreational physical activity and ovarian cancer in a population-based case-control study

Results from epidemiologic studies of physical activity and ovarian cancer have been inconsistent, with 2 prospective studies reporting a modest positive association. We evaluated this relationship in a population-based case-control study conducted in Massachusetts and Wisconsin. Incident cases diagnosed between 1991 and 1994 were identified through statewide tumor registries. Community controls were selected randomly from lists of licensed drivers and Medicare recipients. Participation in moderate and vigorous recreational physical activity at age 12, age 20 and 5 years prior to diagnosis was assessed by telephone interview. Data were available for 327 cases and 3,129 controls. Results were adjusted for age, parity and other ovarian cancer risk factors. Total and vigorous physical activity were not associated with a substantial decrease in ovarian cancer risk at any age. The relative risk (RR) for women reporting > or = 7 vs. 0 hr/week of recent vigorous activity was 0.85 [95% confidence interval (CI) = 0.39-1.86; p for trend = 0.31]. When metabolic equivalent task (MET) hours of activity were estimated, only women in the highest category had any reduction in risk (RR for > 42 MET-hours/week at the reference age = 0.70; 95% CI = 0.36-1.35; p for trend = 0.41). Overall, our results provide only limited support for an inverse association between recreational physical activity and risk of ovarian cancer.     

Recreational physical activity and the risk of adult leukemia in Canada

Objective  

To examine the association between adult onset leukemia and recreational physical activity.     

Recreational physical activity and risk of papillary thyroid cancer (United States)

Objective: Exercise has been hypothesized to influence cancer risk through a variety of mechanisms including hormonal, metabolic and immunologic effects, yet its relation with the risk of thyroid cancer has not been examined. We conducted a population-based case–control study in women aged 18–64 in three counties of western Washington State to assess the relation of recreational physical activity with risk of papillary thyroid cancer. Methods: Of 558 women with thyroid cancer of the follicular epithelium diagnosed during 1988–1994 who were identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (n = 410). Controls (n = 574) were identified by random digit dialing, with a response proportion of 73.6%. Logistic regression was used to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with various aspects of recreational exercise. Results: Risk of thyroid cancer was reduced among women who reported that they engaged in regular recreational exercise during the 2 years before diagnosis relative to women who did not report exercise during that time period (OR = 0.76, 95% CI 0.59–0.98). A similar risk reduction was noted among women who reported having exercised regularly between ages 12 and 21 (OR = 0.83, 95% CI 0.64–1.1). However, no clear associations with aspects of recreational activity, including average hours exercised per week or weekly energy expenditure, were observed. Conclusions: These results provide some initial support for the hypothesis that physical activity may reduce risk of thyroid cancer.     

不同麻醉方法对老年颅内肿瘤患者术后不同时段认知功能的影响研究

目的 观察靶控静脉麻醉与静吸复合麻醉对老年颅内肿瘤患者术后不同时段认知功能的影响。方法临床纳入老年颅内肿瘤手术患者70例,根据术中麻醉方法的不同分为研究组与对照组,研究组实施丙泊酚复合瑞芬太尼靶控静脉麻醉,对照组实施静脉复合吸入异氟醚。观察两组患者术后恢复情况(呼吸恢复时间、睁眼时间、拔管时间、定向力恢复时间等)以及手术前后意识状态(OAAS)评分、认知功能(MMSE)评分等。结果 两组患者呼吸恢复时间、睁眼时间、拔管时间差异均无统计学意义(P＞0.05);研究组定向力恢复时间为(20.4±5.8)min,对照组为(23.2±4.3)min,差异有统计学意义(P＜0.05);研究组拔管即刻、离开手术室、拔管后1 h OAAS评分分别为(3.3±0.5)、(4.2±0.4)、(4.6±0.6),对照组分别为(2.3±0.2)、(3.3±0.4)、(3.9±0.3),差异均有统计学意义(P＜0.05);两组患者术前MMSE评分差异无显著性(P＞0.05);研究组术后24 h、48 h MMSE评分分别为(25.0±0.4)、(27.9±1.1),对照组分别为(23.2±0.9)、(25.8±1.3),差异有统计学意义(P＜0.05)。结论 对老年颅内肿瘤手术患者实施丙泊酚复合瑞芬太尼靶控静脉麻醉,诱导平稳且苏醒完全,对患者术后认知功能的影响相对较小。     

Recreational physical activity, leisure sitting time and risk of non-Hodgkin lymphoid neoplasms in the American Cancer Society Cancer Prevention Study II Cohort

Results of studies that examined the relationship between physical activity and non-Hodgkin lymphoid neoplasms (NHL) are inconsistent, and only one study to date examined time spent sitting in relation to NHL. We examined recreational physical activity and leisure-time sitting in relation to risk of NHL in the American Cancer Society Cancer Prevention Study II Nutrition Cohort. Between 1992 and 2007, 2,002 incident cases were identified among 146,850 participants who were cancer-free at enrollment. Cox proportional hazards regression was used to compute hazard ratios (HR) and 95% confidence intervals (CI) while adjusting for potential confounders. Women who sat for at least 6 hr/day were at 28% higher risk of NHL compared to women who sat for fewer than 3 hr/day. In analyses of specific subtypes, sitting time was associated with risk of multiple myeloma only (6+ vs. 3 hr/day sitting: HR = 2.40, 95% CI: 1.45-3.97). Women who engaged in any recreational physical activity had a nonsignificant 20%-30% lower risk of NHL (p-trend = 0.05) compared to women who reported no recreational physical activity. Neither leisure-time sitting nor recreational physical activity was associated with risk of NHL or major NHL subtype in men. There was no evidence of statistical interaction between physical activity and sitting time, or between body mass index and physical activity or sitting time. Further research is needed to confirm an association between sitting time and multiple myeloma and explore a possible association between physical activity and NHL.     

Recreational physical activity, body mass index, and survival in women with colorectal cancer

Background and purpose

Previous studies have shown that physical inactivity and obesity are risk factors for the development of colorectal cancer. However, controversy exists regarding the influence of these factors on survival in colorectal cancer patients. We evaluated the impact of recreational physical activity and body mass index (BMI) before and after colorectal cancer diagnosis on disease-specific mortality and all-cause mortality.

Patients and methods

This prospective cohort study included 1,339 women enrolled in the Women’s Health Initiative study who were diagnosed with colorectal cancer subsequent to study enrollment. BMI and recreational physical activity were measured before cancer diagnosis at study entry (pre-diagnostic) and after diagnosis at study follow-up interviews (post-diagnostic). We used Cox regression to estimate the association between pre- and post-diagnostic exposures and survival after colorectal cancer diagnosis.

Results

Among women diagnosed with colorectal cancer, 265 (13?%) deaths occurred during a median study follow-up of 11.9?years, of which 171 (65?%) were attributed to colorectal cancer. Compared with women reporting no pre-diagnostic recreational physical activity, those reporting activity levels of ≥18 MET-h/week had significantly lower colorectal cancer-specific mortality (hazard ratio (HR)?=?0.68; 95?% confidence interval (CI): 0.41–1.13) and all-cause mortality (HR?=?0.63; 95?% CI: 0.42–0.96). Similar inverse associations were seen for post-diagnostic recreational physical activity. Neither pre- nor post-diagnostic BMI were associated with mortality after colorectal cancer diagnosis.

Conclusion

Recreational physical activity before and after colorectal cancer diagnosis, but not BMI, is associated with more favorable survival.     

Recreational physical activity and risk of postmenopausal breast cancer in a large cohort of US women

Due to its potential effects on ovarian hormone production, physical activity has been proposed as a modifiable risk factor for breast cancer. The authors analyzed data from the American Cancer Society Cancer Prevention Study II (CPS-II) Nutrition Cohort to examine the association between various measures of physical activity and postmenopausal breast cancer risk. Information on physical activity was obtained in 1992 via a self-administered questionnaire for 72,608 postmenopausal female participants who were cancer-free. During the five year prospective follow-up, 1520 incident breast cancer cases were identified among these women. Cox proportional hazards modeling was used to compute hazard rate ratios (RR) and to adjust for potential confounding factors including mammography. Women who were most physically active (>42.0 MET-h/week) at baseline had 29% lower incidence rates than active women with the least activity (>0–7.0 MET-h/week) (95% CI, 0.49–1.02). The difference in risk was largest for localized breast cancer, and for women who did not use hormone replacement therapy (HRT) at enrollment. Our findings are consistent with other studies that show lower risk of postmenopausal breast cancer associated with regular physical activity.     

拟遗传学与DNA甲基化

人们将目光重新聚焦于拟遗传学，在对DNA甲基化进行深入研究的过程中，发现甲基化在转录抑制、细胞分化与衰老、基因组印记及肿瘤形成等过程中有重要作用。甲基化将可能应用于临床诊断与治疗。     

DNA甲基化与胶质瘤

表遗传学修饰的DNA甲基化在胶质瘤的发生发展中起重要作用。大量肿瘤抑制基因、细胞周期调控基因、DNA损伤修复基因、肿瘤侵袭相关基因等启动子区域CpG岛甲基化,与胶质瘤的发生发展密切相关。不同基因的甲基化发生频率与胶质瘤的组织类型和病理分级有关。某些基因的DNA甲基化可以为胶质瘤的早期诊断和预后评价提供分子生物学标记物,同时由于DNA甲基化具有可逆转性,也可为胶质瘤的基因治疗提供新的治疗靶点。     

DNA methylation and cancer

Tumor suppressor genes can be silenced by DNA methylation during cancer development. Aberrant DNA methylation is closely associated with histone deacetylases and histone methyltransferases that can modify histone amino-terminal lysines and develop specific histone codes, resulting in inactive chromatin formation. These processes change epigenetic information that builds up abnormal chromatin structure, and creates the unique features of cancer cells. It is well known that thousands of genes are deregulated in cancer cells. Epigenetic alterations involving aberrant DNA methylation is a possible mechanism that can explain the genome-wide abnormality of gene expression. The mechanism responsible for the aberrant DNA methylation is unclear now, however it seems that de novo DNA methyltransferases (DNMTs) play an important role in the process. DNMT3 A and DNMT3B are thought to be de novo DNMTs in human. A nucleoside analogue of cytidine induces demethylation of DNA in cancer cells by inhibiting the function of DNMTs. It is significant to elucidate precise mechanisms of aberrant DNA methylation and develop small molecules that can inhibit methylation.     

DNA methylation and cancer

There is tremendous ferment in the field of epigenetics as the relationships between chromatin structure and DNA methylation patterns become clearer. Central to this activity is the realization that the 'histone code', which involves the post-translational modification of histones and which has important ramifications for chromatin structure, may be linked to the DNA cytosine methylation pattern. New discoveries have suggested that histone lysine 9 methylation is implicated in the spread of heterochromatin in Drosophila and other organisms. Very recently it has been found that histone lysine 9 methylation is also necessary for some DNA methylation in Neurospora and plants. There is therefore the possibility that these two processes are closely linked, suggesting ways in which DNA methylation patterns may be established during normal development. Understanding these processes is fundamental to understanding what goes awry during the process of aging and carcinogenesis where DNA methylation patterns become substantially altered and contribute to the malignant phenotype.     

DNA methylation and cancer

The main thrusts of the arguments that aberrant DNA methylation is involved in the generation of tumor heterogeneity and progression can be summarized as follows. The methylation of specific cytosine residues in DNA is certainly an important component in multilevel gene control in eukaryotes. The discovery of CpG clusters in the flanking regions of genes and their under-methylation on housekeeping genes, except those located on inactive X-chromosomes, strongly suggests a controlling function for modification in these regions. Since methylation plays an important role in controlling normal cellular development, it follows that aberrations within this mechanism may be implicated in the abnormal gene control which characterizes cancer. Methylation patterns are not copied rigorously in rapidly dividing cells. This may be because there is normally a close coordination between DNA synthesis, DNA methylation, and DNA packaging, and changes in the timing of these processes could conceivably result in hypomethylation at some sites and de novo methylation at others. Since the greatest variability of methylation patterns is seen in nonexpressed genes, it is possible that there is a tendency for cells to activate genes when dividing in an inappropriate growth environment. The constant evolution and shuffling of methylation patterns which occur during division might play a role in the development of new phenotypes within cell populations. One might predict that selective pressures within the host would select for those cells with specific new methylation patterns allowing for the expression of genes necessary for survival in a particular environment. Many experiments have in fact shown that methylation levels and patterns and indeed methyltransferase levels (57) are altered in cancer cells. Thus, there is considerable heterogeneity within tumor populations with regard to this fundamental biological control mechanism. The fact that direct intervention by the use of 5-aza-Cyd can result in dramatic alterations in malignant potential allows this hypothesis to be tested more critically. Hopefully, the use of 5-aza-Cyd in defined systems will allow us to isolate genes which might become activated by drug treatment and which might contribute to metastatic potential. An understanding of the fundamental aspects of the enzymology and control of DNA methylation might therefore allow us to make significant inroads into understanding how heterogeneity is generated and what we might do about it.     

DNA甲基化与胶质瘤

表遗传学修饰的DNA甲基化在胶质瘤的发生发展中起重要作用。大量肿瘤抑制基因、细胞周期调控基因、DNA损伤修复基因、肿瘤侵袭相关基因等启动子区域CpG岛甲基化,与胶质瘤的发生发展密切相关。不同基因的甲基化发生频率与胶质瘤的组织类型和病理分级有关。某些基因的DNA甲基化可以为胶质瘤的早期诊断和预后评价提供分子生物学标记物,同时由于DNA甲基化具有可逆转性,也可为胶质瘤的基因治疗提供新的治疗靶点。     

Allelic losses and DNA methylation at DNA mismatch repair loci in sporadic colorectal cancer

Normal and tumor DNA samples of 35 patients with sporadic colorectal carcinoma were analyzed for microsatellite alterations at 12 markers linked to mismatch repair loci: hMLH1, hMSH2, hMSH3, hMSH6, hPMS1 and hPMS2. Remarkably, no correlation was observed between the replication error phenotype (RER+) and allelic losses at these loci. Hemizygous deletions, seen in 6/35 (17%) informative cases at hMLH1, 4/27 (15%) at hMSH2/hMSH6 and 6/34 (18%) at hMSH3, were rarely found in RER+ tumors. Since mismatch repair protein components act in molecular complexes of defined stoichiometry we propose that hemizygous deletion of the corresponding loci may be involved in colorectal tumorigenesis through defects in cellular functions other than replication error correction. The analysis of the methylation status of the promoter region of hMLH1 revealed that methylation might be an important mechanism of this locus inactivation in RER+ sporadic colorectal cancer.      

Recreational physical activity and epithelial ovarian cancer: a case-control study, systematic review, and meta-analysis.

It remains unclear whether physical activity is associated with epithelial ovarian cancer risk. We therefore examined the association between recreational physical activity and risk of ovarian cancer in a national population-based case-control study in Australia. We also systematically reviewed all the available evidence linking physical activity with ovarian cancer to provide the best summary estimate of the association. The case-control study included women ages 18 to 79 years with a new diagnosis of invasive (n=1,269) or borderline (n=311) epithelial ovarian cancer identified through a network of clinics, physicians, and state cancer registries throughout Australia. Controls (n=1,509) were randomly selected from the national electoral roll and were frequency matched to cases by age and state. For the systematic review, we identified eligible studies using Medline, the ISI Science Citation Index, and manual review of retrieved references, and included all case-control or cohort studies that permitted assessment of an association between physical activity (recreational/occupational/sedentary behavior) and histologically confirmed ovarian cancer. Meta-analysis was restricted to the subset of these studies that reported on recreational physical activity. In our case-control study, we observed weakly inverse or null associations between recreational physical activity and risk of epithelial ovarian cancer overall. There was no evidence that the effects varied by tumor behavior or histologic subtype. Twelve studies were included in the meta-analysis, which gave summary estimates of 0.79 (95% confidence interval, 0.70-0.85) for case-control studies and 0.81 (95% confidence interval, 0.57-1.17) for cohort studies for the risk of ovarian cancer associated with highest versus lowest levels of recreational physical activity. Thus, pooled results from observational studies suggest that a modest inverse association exists between level of recreational physical activity and the risk of ovarian cancer.