<b>Background:</b> Anal, vulval and vaginal cancers predominantly affect postmenopausal women. Over 85% of registrations occur after the age of 50. Risk factors for these cancers, other than high-risk human papillomaviruses, are not well defined. <b>Methods:</b> 1.3 million UK women, mostly aged 50-65 at recruitment, were followed for incident anogenital cancer. Cox regression models with age as the underlying time variable were used to calculate adjusted relative risks associated with various lifetime exposures. <b>Results:</b> 570 anal, 898 vulval, and 170 vaginal cancers were registered over an average 13.8 years of follow-up. History of cervical intraepithelial neoplasia grade 3 (CIN 3) prior to recruitment was associated with a 4-fold increase in risk of anal cancer, a doubling of risk of vulval cancer, and a 7-fold increase in risk of vaginal cancer. Significant associations were also seen for past cervical cytological abnormalities, with an increase in risk of anal cancer for low-grade, and an increase in risk of all three cancers associated with high-grade abnormalities. Anal cancer risk was also associated with smoking, prior use of oral contraceptives, nulliparity, tubal ligation, and not living with a husband/partner. Risk of vulval cancer was increased in overweight, obese women, and those with a menopause prior to age 50. Risk of vaginal cancer was increased amongst women who were nulliparous, overweight or obese, who had a hysterectomy prior to recruitment, or who were not married or living with a partner. <b>Conclusions:</b> Despite anatomical proximity and histological similarities of the anogenital tissues, anal, vulval and vaginal cancers have heterogeneous associations with many lifetime exposures, suggesting differences in aetiology. Past high-grade cervical abnormalities are a marker of increased risk of subsequent anogenital cancer, but only a small proportion of women with such a history go on to develop anal, vulval or vaginal cancer later in life.

No description available.

Evidence from international comparisons and migrant studies suggest that environmental factors, such as a Western diet, may be important in prostate cancer development, possibly through effects on hormone and growth factor secretion and metabolism. However, despite considerable research, convincing associations between diet and risk for prostate cancer have not been established. Random and systematic measurement error in dietary assessment using traditional survey methods may contribute to inconsistent findings, particularly as they may not capture adequately specific nutritional constituents of the diet that may be associated with risk, such as fatty acids or vitamins. Validated biomarkers of nutritional factors and hormonal activity, as used in this thesis, provide more precise, objective and integrated measures of exposure, with the capacity to clarify potential mechanisms in the causal pathway of prostate cancer development. Nutritional and hormonal biomarkers investigated for their potential role in the development of prostate cancer include: folate and vitamin B₁₂, which are essential for DNA methylation, repair and synthesis; phytanic acid, obtained predominantly from ruminant fat intake and associated with an enzyme (α-Methylacyl-Coenzyme A Racemase (AMACR)) that is consistently over-expressed in prostate cancer tissue; and insulin-like growth factor (IGF-I), a growth factor influenced by diet and involved in the regulation of cell proliferation, differentiation, and apoptosis. All work presented in this thesis is from the European Prospective Investigation into Cancer and Nutrition (EPIC) study of 500,000 European men and women, using prospectively collected diet and lifestyle data and biological samples. The large number of prostate cancer cases diagnosed during long-term follow-up of EPIC participants enabled investigation of heterogeneity in risk for prostate cancer by time from recruitment to diagnosis (of particular importance for a disease with a long pre-clinical phase) and cancer characteristics such as disease grade and stage. Plasma phytanic acid concentration was highly correlated with dietary intake of fat from dairy products (r = 0.46) and beef (r = 0.30); capturing differences between countries in consumption of fat from these foods. Although phytanic acid is a useful biomarker of ruminant fat consumption, there was little evidence to support the hypothesis that the association between dairy products and prostate cancer risk (as suggested by previous work in EPIC and other studies) is mediated by phytanic acid (OR for doubling in concentration 1.05; 95%CI 0.91 – 1.21; P _trend = 0.53). There was strong evidence for an association between higher circulating IGF-I concentration and risk for prostate cancer (OR for highest versus lowest fourth 1.69; 95% CI: 1.35, 2.13; P _trend = 0.0002). Furthermore, the positive association observed among men diagnosed with advanced stage disease and among men diagnosed more than seven years after blood collection, supports the hypothesis that high IGF-I concentration is associated with clinically significant prostate cancer many years before diagnosis. There was no evidence of an association between prostate cancer risk and dietary folate or vitamin B₁₂ intake, or between circulating levels of folate (OR for doubling in concentration 1.05; 95%CI 0.95 – 1.15; <en>P _trend = 0.33) or vitamin B₁₂ (1.05; 95%CI 0.92 – 1.21; P _trend = 0.47) and only limited evidence for an increased risk associated with elevated vitamin B₁₂ in a meta-analysis of six prospective studies, that included the present study. All of these analyses were based on a blood sample taken at one point in time, with the assumption that this reflects the ‘true’ underlying concentration over the long-term. The poor to modest reliability estimates (intra-class correlation coefficients ranging from 0.18 to 0.48) for circulating concentrations of folate, IGF-I, phytanic acid and vitamin B₁₂ taken in samples approximately six years apart in a sub-sample of participants from EPIC Oxford, show that estimates of usual concentrations based on a single blood measurement weaken the ability to detect associations with disease risk. Where small effect sizes are anticipated, this may bias associations toward the null. In conclusion, there is convincing evidence that IGF-I is an important and potentially modifiable risk factor for prostate cancer many years before diagnosis. However, there is little evidence for an association between biomarkers of folate, vitamin B₁₂ and phytanic acid concentrations and risk for prostate cancer. Future studies should, where possible, incorporate multiple blood samples taken several years apart to better characterise long term relationships between biomarkers of nutritional and hormonal exposure and disease risk and pool individual participant data from multiple prospective studies to strengthen the power to detect modest associations.

published_or_final_version / Medicine / Master / Master of Research in Medicine

Metastasis is the most fearsome aspect of breast cancer (BC) a common disease in women, because it drives mortality. Although BC can invade almost any organ, it is most often found to invade the bone (31-79%), the brain (3-12%), the liver (8-18%) and the lung (11-13%). The site of distant metastasis is often associated with cause of death and length of survival. This dissertation examines whether the presence of select lifestyle and clinical factors can predict metastatic spread to the lung and/or the liver for a particular woman with advanced breast cancer. A systematic review of the literature identified tobacco use as a risk factor for lung metastasis in women with BC and suggested that obesity, hormone replacement therapy prior to BC diagnosis, hormonal therapy post diagnosis, and post-mastectomy radiation therapy may have an impact on this association. The review also uncovered that liver disease (i.e. hepatic steatosis, chronic hepatitis B infection, cirrhosis) is associated with the occurrence of liver metastasis in patients with colorectal cancer and that hyperglycemic and oxidative stress conditions as well as alcohol consumption were found to be associated with liver metastasis in colorectal or BC patients. We conducted a retrospective hospital-based case-control study of the association of select lifestyle and clinical factors with metastases detected in the lung and the liver among women diagnosed with stages II-IV BC and seen at the Columbia University Medical Center from 2008 to 2013. Select relevant clinical variables were extracted from the hospital patient charts and lifestyle factors from patients’ responses to a questionnaire developed for the purposes of this research. We examined whether smoking and / or post-mastectomy radiation therapy to the breast and/or the chest area were associated with an increased risk of 1st site lung metastasis in our sample of women with metastatic BC. We found that lifestyle factors such as smoking history or BMI at diagnosis did not affect the likelihood of 1st site lung metastasis in our sample of women. We also investigated whether a history of alcohol intake or chronic liver disease was associated with risk of developing a 1st site liver metastasis. Our analyses suggested that lifestyle factors such as alcohol intake or obesity might not affect the likelihood of 1st site liver metastasis in women with metastatic BC. We also report that a history of chronic liver disease significantly increased the odds of 1st site liver metastasis. Given our findings around adjuvant post mastectomy radiation therapy and chronic liver disease, we suggest collecting adjuvant treatment or relevant comorbid information in larger cohort studies. A better understanding of the relationship between these factors and the sites of metastasis has the potential to increase our understanding of the metastatic process. If we can find ways to identify women at high risk of metastatic disease, or develop preventive or therapeutic measures against lung or liver metastasis, we can hope to reduce mortality from metastases.

<p>Oral cancer is characterised by marked geographical differences in frequency and site preference as reported by various studies. In South Africa, a few studies have been reported on the patterns and aetiology of oral cancer, and age standardised incidence rates (ASIR). Studies in several countries have shown an increase in oral cancer incidence among younger people. Title:&nbsp / Epidemiology of oral cancer in South Africa 1996-2002.&nbsp / Aim and Objective: The aim of this study was to determine the age standardised incidence rates (ASIR) of oral cancer by age, gender, race&nbsp / and site in South Africa for a consecutive period of seven years. Method: Pathology case records of oral cancer diagnosed over a seven-year period from 1996 to 2002 and reported to the National&nbsp / Cancer Registry (NCR) were analysed for age, sex, race, and date of diagnosis, basis of diagnosis, topography and tumour type. The data was tabulated and categorised using Microsoft Excel. The South African population size for each year of the study was estimated by linear extrapolation using the 1996 and 2001 census results. Age standardisation incidence rates against the world&nbsp / population were calculated by the standard direct method. Results: The total number of oral squamous cell carcinoma cases over the 7-year period was 9702. The majority of cases (34%) were&nbsp / on the tongue. The male to female ratio was 1:3. The age standardized incidence rates in this study was lower among African women / (0.640 per 100000 per year) and the highest was 13.40 new cases per 100000 per year (coloured males). Lip cancer was highest among both males and females of the white population. The cumulative rate of developing oral cancer was 1:83 and 1:32 for males and females respectively.</p>

<p>Oral cancer is characterised by marked geographical differences in frequency and site preference as reported by various studies. In South Africa, a few studies have been reported on the patterns and aetiology of oral cancer, and age standardised incidence rates (ASIR). Studies in several countries have shown an increase in oral cancer incidence among younger people. Title:&nbsp / Epidemiology of oral cancer in South Africa 1996-2002.&nbsp / Aim and Objective: The aim of this study was to determine the age standardised incidence rates (ASIR) of oral cancer by age, gender, race&nbsp / and site in South Africa for a consecutive period of seven years. Method: Pathology case records of oral cancer diagnosed over a seven-year period from 1996 to 2002 and reported to the National&nbsp / Cancer Registry (NCR) were analysed for age, sex, race, and date of diagnosis, basis of diagnosis, topography and tumour type. The data was tabulated and categorised using Microsoft Excel. The South African population size for each year of the study was estimated by linear extrapolation using the 1996 and 2001 census results. Age standardisation incidence rates against the world&nbsp / population were calculated by the standard direct method. Results: The total number of oral squamous cell carcinoma cases over the 7-year period was 9702. The majority of cases (34%) were&nbsp / on the tongue. The male to female ratio was 1:3. The age standardized incidence rates in this study was lower among African women / (0.640 per 100000 per year) and the highest was 13.40 new cases per 100000 per year (coloured males). Lip cancer was highest among both males and females of the white population. The cumulative rate of developing oral cancer was 1:83 and 1:32 for males and females respectively.</p>

published_or_final_version / abstract / toc / Medicine / Master / Doctor of Medicine

Background: Estrogen receptor (ER)- and progesterone receptor (PR)-negative (ER-PR-) breast cancer is associated with higher grade and poorer prognosis compared with other breast cancer subtypes. High parity, coupled with lack of breastfeeding, has been associated with an increased risk of ER-PR- cancer. The mechanism of this etiology is unclear, and may be obfuscated by ER and PR correlation with each other as well as other prognostic tumor characteristics. Methods: Using population-based and clinic-based ascertained cases and controls from the Breast Cancer Family Registry, I examined reproductive risk factors, including parity, breastfeeding, and oral contraceptive (OC) use, in relation to ER and PR status, using polytomous logistic regression (for the population-based data) and the method of generalized estimating equations (GEE) (for the clinic-based data) as well as the pseudo-conditional likelihood approach, which accounts for correlated outcome variables. Results: High parity (≥ 3 live births) combined with lack of breastfeeding, was positively associated with ER-PR- tumors (odds ratio [OR]=1.57, 95% confidence interval [CI] 1.10-2.24, population-based cases vs. controls) relative to nulliparity. There was no association with ER-PR- tumors and parity in women who breastfed (OR=0.93, 95%CI 0.71-1.22) relative to nulliparous women. Associations with ER-PR- cancer were higher across all races/ethnicities among women who did not breastfeed compared with women who did. Population-based and clinic-based data were generally in agreement (OR=2.07, 95% CI 1.09-3.91, clinic-based cases vs. controls, relative to nulliparity). When adjusted for the correlation of PR-status and grade, to ER-status, the association between high parity +lack of breastfeeding and ER- status, was maintained. OC use before year 1975 was associated with an increased risk of ER-PR- tumors (OR=1.32, 95% CI 1.04-1.67, population-based data, cases vs. controls) relative to never use of OCs. For women who began OC use in 1975 or later there was no increased risk. Analysis of OC use in clinic-based data agreed with the findings of the population-based data. Conclusions: My findings support that there are modifiable factors for ER-PR- breast cancer, and that breastfeeding in particular may mitigate the increased risk of ER-PR-cancers seen from multiparity. The mechanism of both risk and risk mitigation may operate primarily through the estrogen, rather than progesterone, pathway.

Little is known about the receipt of cancer screening for new primary cancers among Canadian cancer survivors. The objectives of this thesis are to i) synthesize evidence comparing receipt cancer screening between cancer survivors and non-cancer controls; and ii) analyze breast and cervical cancer screening receipt among Nova Scotian colorectal cancer (CRC) survivors. This thesis consists of a systematic review and meta-analysis, and a population-based cohort study of Nova Scotian CRC survivors. We found that while cancer survivors were more likely to receive cancer screening than the general population, a significant proportion of cancer survivors were not screened. We observed significant heterogeneity between studies, most of which remained unexplained after subgroup and sensitivity analyses. 30.1% and 47.9% of Nova Scotian CRC survivors never received a breast and cervical cancer screen after their CRC diagnosis. Receipt of pre-CRC diagnosis screening was strongly predictive of receiving screening post-diagnosis.