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No description available.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 5 uppsatser.

Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 105-114).

MPH / Department of Public Health / See the attached abstract below

Advancements in medicine and technology have led to an increasing number of cancer survivors. The development of a second primary cancer is one of the most severe sequelae of a cancer diagnosis, particularly for cancers that lack an effective screening tool as with ovarian cancer. Breast and ovarian cancer are major causes of morbidity and mortality in women; in the U.S., breast cancer has the highest incidence in women and ovarian cancer is the most fatal of gynecological cancers. Further, these two cancers have been found to co-occur. Along with possible treatment effects of the first cancer, shared risk factors, shared genetics, and interactions between these two have been hypothesized to contribute to their co-occurrence. Research on shared risk factors for second cancers is lacking and being able to identify potentially modifiable factors associated with second primary cancer could improve clinical recommendations for cancer survivors. Therefore, this dissertation examined risk factors for the development of double primary breast and ovarian cancer (DPBOC) in three parts 1) a comprehensive review of the literature to identify studies assessing risk factors for DPBOC, 2) a case-control study assessing the association between three potentially-modifiable risk factors (oral contraceptive (OC) use, parity, and breastfeeding), and risk of second primary ovarian cancer following breast cancer (BR-OV), second primary breast cancer following ovarian cancer (OV-BR), single primary ovarian cancer (OV), and single primary breast cancer (BR), and 3) a cohort study assessing OC use, parity, and breastfeeding and risk of BR-OV, OV, and BR. The comprehensive review identified few studies assessing epidemiologic risk factors for the development of DPBOC and most of the findings were not statistically significant. The majority of studies focused on treatment of breast cancer and risk of second primary ovarian cancer. While most of the findings on chemotherapy, radiotherapy, and Tamoxifen were heterogeneous and lacked statistical significance, hormone therapy for breast cancer may be associated with an increased risk of second primary ovarian cancer. The majority of studies on genetic risk factors for DPBOC looked at BRCA1/2 mutations or a crude measure of family history. Both BRCA1/2 and family history were consistently associated with risk of DPBOC, but studies varied on the extent of this risk due to differences in study design, exposure and outcome definition, and statistical power. No studies were identified examining DNA methylation and risk of DPBOC. The case-control study used data from the three clinic-based sites of the Breast Cancer Family Registry (BCFR) which consisted of women from breast and ovarian cancer families. We observed an inverse association with both OC use (OR=0.38, 95% CI: 0.22, 0.60) and breastfeeding (OR=0.52, 95% CI: 0.31, 0.87) and risk of DPBOC, but a positive association with parity (≥2 full-term pregnancies: OR=5.78, 95% CI: 2.82, 14.58), regardless of diagnosis order (BR-OV or OV-BR). We found similar associations for our OV and BR outcomes as well. When we examined differences between high and average risk women (using BRCA1/2 mutation status and predicted lifetime risk of breast or ovarian cancer), the inverse association with OC use only remained in women at average risk while the inverse association with breastfeeding only remained in women at high risk. As the positive association with parity and all of our outcomes disagreed with our hypothesis we conducted several sensitivity analyses to explore this finding. Survivor bias may have influenced our results as we observed differences in our findings between cases diagnosed ≤2 or ≤5 years before the baseline interview (pseudo-incident) and cases diagnosed >2 or >5 years before the baseline interview (prevalent). Specifically, the inverse association with OC use and all of our outcomes, and the positive association with parity and all of our outcomes were attenuated in the pseudo-incident group. To address concerns of selection and information bias in our case-control study, we conducted a cohort study using data from The Breast Cancer Prospective Family Study Cohort (ProF-SC). In contrast to our case-control findings, we observed a suggestive positive association between OC use and risk of BR-OV (HR=1.62, 95% CI: 0.91, 2.90) which became stronger in women at high risk, and an inverse association between having two or more full-term pregnancies compared to nulliparous and risk of BR-OV (HR=0.47, 95% CI: 0.22, 0.97) which did not vary by underlying risk of breast and ovarian cancer. However, our BR-OV results may have similarly been influenced by survivor bias as we observed differences in our results between our pseudo-incident and prevalent BR-OV cases; the association between OC use and BR-OV only remained in the prevalent cases. In summary, the results of this dissertation highlight the methodological challenges in the study of second primary cancers and the importance of considering survivor bias in a cohort of cancer survivors being followed for second cancers. Further, our results are suggestive of a discordant effect of OC use on first primary versus second primary ovarian cancer which should be explored in future studies.

Inflammation contributes to the etiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Therefore, it is of interest to investigate how diet relates to plasma inflammatory proteins, particularly whole grain and fibre intakes, as these factors have been associated with lower CVD and T2D risk. Only a limited number of observational studies have examined these relationships. The objective of this study was to investigate the cross-sectional relationships of whole and refined grain and dietary fibre intakes with plasma inflammatory proteins. There was a strong inverse relationship between whole grain intake and plasminogen activator inhibitor type 1 (PAI-1) (β =-0.102; SE=0.038; p=0.0077), and a positive relationship between refined grain intake and PAI-1 (β=0.076; SE=0.034; p=0.0251). Additionally, dietary fibre was related to lower concentrations of C-reactive protein (β=-0.034; SE=0.010; p=0.0008) and fibrinogen (β=-1.207; SE=0.505; p=0.0171). This research suggests that whole and refined grain and fibre intakes may influence inflammatory protein concentrations.

Inflammation contributes to the etiology of type 2 diabetes (T2D) and cardiovascular disease (CVD). Therefore, it is of interest to investigate how diet relates to plasma inflammatory proteins, particularly whole grain and fibre intakes, as these factors have been associated with lower CVD and T2D risk. Only a limited number of observational studies have examined these relationships. The objective of this study was to investigate the cross-sectional relationships of whole and refined grain and dietary fibre intakes with plasma inflammatory proteins. There was a strong inverse relationship between whole grain intake and plasminogen activator inhibitor type 1 (PAI-1) (β =-0.102; SE=0.038; p=0.0077), and a positive relationship between refined grain intake and PAI-1 (β=0.076; SE=0.034; p=0.0251). Additionally, dietary fibre was related to lower concentrations of C-reactive protein (β=-0.034; SE=0.010; p=0.0008) and fibrinogen (β=-1.207; SE=0.505; p=0.0171). This research suggests that whole and refined grain and fibre intakes may influence inflammatory protein concentrations.

Stress fractures represent one of the most common and serious overuse injuries in the military environment. The aim of this prospective study was to determine the incidence of stress fractures during 12 weeks of Basic Training (BT) by comparing the results of the intrinsic risk indicators obtained from a group of participants who suffered stress fractures, with the rest of the original group (controls) who did not suffer from any stress fractures, and to assess any changes in physical markers whilst following a progressive, scientifically designed, Physical Training (PT) Programme during the BT. The intrinsic risk factors investigated included sex, age, race (measured via questionnaire), foot morphology (wet test), Q angle, leg length discrepancy, bone density (dual-energy X-ray absorptiometry(DEXA), physical fitness (standardized military fitness test, isokinetic upper and lower leg strength, handgrip strength), flexibility (ankle plantarflexion and dorsiflexion, hip internal and external rotation), anthropometry (skinfold method and DEXA), female menstrual disturbances and lifestyle behaviours including smoking, female contraception use and medical history of previous injury (questionnaire). The cohort (n=183), also refered to as the Experimental Group (EG), was measured at the beginning and at the end of the BT period. The standardized physical fitness test was also completed in the fifth week of training. The latter’s results were compared to the results obtained by a Control Group (CG), who had undergone BT the year prior to this cohort. The size of the cohort, the intrinsic risk factor profile and the control of certain extrinsic risk factors may have contributed to zero incidences of stress fractures found. Within the intrinsic risk factor profile, sex, age, race, foot morphology, Q angle, hip external rotation and bone density were normal whilst the measured leg discrepancy and limited ankle dorsiflexion appeared to not have a sufficient risk for stress fracture development. The small sample of the cohort that reported having menstrual irregularities, smoked and had a history of previous fractures, did not place this cohort at risk for stress fracture development. The cohort did, however have lower isotonic, isokinetic and isometric strengths than the other cohorts who reported a relatively high stress fracture incidence. The BT period found statistically significant changes in bone density, flexibility, body composition, muscle strength and endurance. Female participants showed an increase in the T- and Z-scores of the left femur area, a deterioration in left ankle dorsiflexion and hip external rotation, whilst their plantarflexion increased. Their mesomorph component increased, and decreases in % body fat (BF) as well as in the ectomorph and endomorph component were also found. Male participants’ plantarflexion and hip external rotation decreased whilst their dorsiflexion increased. Lean body mass and mesomorph component increased whilst %BF, ectomorph and endomorph component decreased. The new cyclic-progressive PT programme controlled for risk of injury by allowing sufficient periods of recovery, by gradually increasing the duration, frequency, and intensity of training, by reducing repetitive weight-bearing activities and by including a variation of exercises. Running shoes, rather than combat boots, were also worn during PT. Marching on concrete was eliminated. Significant improvements were shown by both male and female participants in aerobic fitness and muscular endurance and muscular strength. Future research should include a larger size cohort, who developed stress fractures utilising BT groups from different corps and units in the South African Military environment. Other potential extrinsic risk factors, such as surface and equipment, should also be investigated. / Thesis (DPhil)--University of Pretoria, 2009. / Biokinetics, Sport and Leisure Sciences / unrestricted

Dementia is a devastating disorder that commonly affects people over the age of 65. Alzheimer's disease and vascular dementia are the most common forms of dementias. A number of studies have implicated cardiovascular risks as important factors in the development of dementia. These risks include high-risk behaviors such as smoking and risks related at least partially to health behaviors such as diet and exercise. This study examines a group of cardiovascular risk factors, as defined by the Framingham study, to ascertain if they are predictors of dementia. A retrospective chart review of 481consecutive patients seen in a geriatric medicine clinic produced a sample of 177 individuals diagnosed with dementia and 304 individuals without a dementia diagnosis. Relative risk ratio (RRR) results indicate that a history of hypertension (RRR= 1.80, p = .009) and a history of hypercholesterolemia (RRR = 1.85, p = .016) are significant predictors of Alzheimer's disease. A history of tobacco use (RRR = 2.18, p = .01) is a significant predictor of vascular dementia. Stepwise regression analyses indicate that hypercholesterolemia is an independent predictor of dementia (b = -.113, p = .009) and hypercholesterolemia (b = -.104, p = .018) and hypertension (b = -.094, p = .031) clustered together have an additive risk factor effect. These results are discussed in terms of the importance of specific health behaviors in the development and possible prevention of dementia.