Background Night shift work is inevitable for maintaining continuous services in different sectors e.g. healthcare, financial, transport and service sectors. Night shift work increases exposure of light at night. Exposure of light at night suppresses production of a neurohormone melatonin. Melatonin has shown potential cancer protective action in animal experiments. Melatonin deficiency is suggested to be related to the development of various cancer especially breast cancer. Breast cancer incidence in Hong Kong is rising. Particular concern about association between night shift work and breast cancer is raised. Objective To collect evidence from studies of other countries with study populations of different professions and to evaluate the relationship between night shift work and breast cancer Method MEDLINE was searched to identify publications, limited to English articles, from 1973 to May 2011. Search terms include (circadian rhythm or night work or night shift or shift work or work schedule tolerance) and (cancer or neoplasm or neoplasia) and (risk or rate or incidence). No restriction was set to the publication type. Results Altogether 343 titles retrieved from MEDLINE search. Finally, 8 primary observational studies that met inclusion criteria were identified for this review. Of these, two were prospective cohort studies, one was retrospective cohort study, two were nested case-control studies and three were case-control studies. Most of the study had crude exposure assessment of night shift work, in which four studies relied on group level of exposure probability instead of individual exposure information. Six of eight studies showed positive results on the association of night shift work and breast cancer in women. Three studies found that risk of breast cancer was increased significantly for those who had engaged in night shift work in a long duration i.e. more than 20-30 years, but they were all conducted in populations of same occupational group i.e. nurse and only a moderate increase of breast cancer risk was found. The results were subject to confounding and bias. No consistent results were found for effect of shorter duration of night shift work on risk of breast cancer. Conclusion Based on the studies included, there is suggestive evidence of an association of night shift work and breast cancer. Further studies on this are needed. Involvement of population of different occupational groups, controlling confounder of hormone use and conducting exposure assessment with high reliability using individual information instead of that from group are suggested. / published_or_final_version / Community Medicine / Master / Master of Public Health

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ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

ABSTRACT Background Oesophageal cancer has a high mortality; it is the 6th most common cause of death due to cancer worldwide. Of the common subtypes of oesophageal cancer, it is the adenocarcinomas that have been rising rapidly in incidence throughout the western world. The incidence of adenocarcinomas now exceeds the previously common squamous cell carcinoma. These recent changes in the incidence patterns of oesophageal cancer suggests that the environmental risk factors associated with these subtypes differ, and that changes in the prevalence of these exposures over time are the most likely explanation for the observed shifts in the incidence. However, due to its low incidence until a few decades ago, the adenocarcinoma subtype has been less studied compared to squamous cell carcinoma, and the environmental factors associated with this cancer have not been so clearly defined. Smoking and alcohol have been the strongest environmental risk factors reported for oesophageal squamous cell carcinoma (OSCC) whereas for oesophageal adenocarcinoma (OAC), the effect of smoking appears to be weaker, and the evidence for an effect of alcohol is scant and inconsistent. However, epidemiologic studies consistently identify people with frequent symptoms of gastro-oesophageal reflux (GOR) as having the highest risk of OAC, but the effect of GOR on OSCC has been negligible. Furthermore, it has been argued that adenocarcinoma occurring at the gastro-oesophageal junction (GOJAC) may have different aetiology again. Together, these reports suggest the three subtypes of oesophageal cancers (OAC, GOJAC and OSCC) may arise through different mechanisms with different strengths in the impact of risk factors. This thesis investigated the independent associations of smoking, alcohol and gastro-oesophageal reflux on cancers of the oesophagus by considering the possibility of variation in the risks due to differences in the dose effect patterns of various measures such as smoking, alcohol and GOR. Method Data from a population-based case-control study of oesophageal and ovarian cancers in Australia were used. Study participants comprised histologically confirmed cases of OSCC (n=308), OAC (n=367) and GOJAC (n=426) who were frequency matched to 1580 controls from the general population. Exposure history for both cases and controls were derived from health and lifestyle questionnaires. Unconditional multivariate logistic regression was used to calculate the odds ratios and 95% confidence intervals for the risk factors analysed. In addition, generalised additive model with a logit link was also used to explore and present the non-linearity in the dose effect pattern for continuous exposures adjusting for other confounding factors. The effects of two exposures combined on these cancers were assessed by obtaining synergy index. Results Smokers were at significantly higher risk of all three subtypes of oesophageal cancer with the risk greatest for OSCC. The effect of smoking was greater for adenocarcinoma occurring at the gastro-oesophageal junction compared to that of the oesophagus. Of the various measures of smoking, duration was significantly associated with all three subtypes of cancer whereas intensity was associated with only OSCC and GOJAC and the dose effect was non-linear. Time since quitting was associated with a steady decline in risk of all three cancers emphasising the health benefits of quitting among smokers. Alcohol was not associated with OAC or GOJAC but was significantly associated with OSCC among those drinking in excess of 170g/week. The association between alcohol and OSCC was modified by smoking; the association with alcohol was significantly greater among current smokers with effect. Low to moderate wine consumption was associated with significant risk reduction for all three cancers compared to non-drinkers. Increased frequency of GOR symptoms was associated with increased risks of OAC and GOJAC, although the risk of OSCC was constrained to frequent GOR symptoms only. The effect of GOR symptoms were exacerbated by smoking whereas it was weakened by regular NSAID use. Lastly, the sensitivity analysis that assessed the effect of non-participation among controls in the estimated effect of smoking and BMI (the two risk factors most likely to be affected by non-participation) showed a slight overestimation of effect of smoking assuming higher exposure rate among non-participants but not BMI while the effect remained strong and statistically significant. Conclusion Smoking, alcohol and GOR symptoms were the environmental factors strongly associated with all subtypes of oesophageal cancers. However, the dose effect patterns of these exposures varied by cancer subtypes. Smoking and alcohol were the larger contributing factors for OSCC whereas smoking and GOR symptoms had greater impact on OAC and GOJAC. Low to moderate wine consumption and regular NSAID use reduced the risk of all three subtypes significantly. While selection bias may have led to mildly inflated risks for smoking, the effects persisted even when modelled under extreme scenarios of biased participation amongst controls, and there was no evidence that selection bias materially affected the other associations.

One of the most common types of cancer among women is breast cancer. It represents one of the diseases leading to a high number of mortalities among women. On the other hand, prostate cancer is the second most frequent malignancy in men worldwide. The early detection of prostate cancer is fundamental to reduce mortality and increase the survival rate. A comparison between six types of machine learning models as Logistic Regression, Decision Tree, Random Forest, Gradient Boosting, k Nearest Neighbors, and Naïve Bayes has been performed. This research aims to identify the most efficient machine learning algorithms for identifying the most significant risk factors of prostate and breast cancers. For this reason, National Health Interview Survey (NHIS) and Prostate, Lung, Colorectal, and Ovarian (PLCO) datasets are used. A comprehensive comparison of risk factors leading to these two crucial cancers can significantly impact early detection and progressive improvement in survival. / Includes bibliography. / Thesis (P.S.M.)--Florida Atlantic University, 2021. / FAU Electronic Theses and Dissertations Collection

This follows an earlier study of the same data set, which, through its findings, presented new questions that are investigated in this study. Both studies used a prospective controlled design, wherein women receiving genetic counseling for breast cancer risk were randomized into two groups. Subjects receiving an audiotaped recording of their genetic consultation (tape group) were compared to subjects who also had a genetic consultation but did not receive an audiotaped recording of it (no-tape group). Participants were drawn from attendees at the genetic clinics of two London hospitals and included 115 women with a family history of breast cancer. Cancer worry and psychological distress were assessed before genetic consultation (baseline), and at one- and six-month follow-ups by post. Objective risk was estimated by the geneticist during the consultation, and subjective risk was assessed at one month follow-up. The goals of the current study were to investigate relationships between cancer worry, psychological distress, and recall of genetic risk for breast cancer in a sample of women receiving genetic counseling for breast cancer risk, and to investigate the role sociodemographic variables on cancer worry, psychological distress, or risk recall for these women. Results for this sample of women with a family history of breast cancer found that there were consistent relationships between cancer worry, psychological distress, objective risk, and subjective risk before and after genetic consultation. This suggests that women=s psychological responses are appropriate to their level of cancer risk. There were no differences found between the tape and no-tape groups for objective or subjective risk, or for nearness of recall accuracy or degree of under-/over-estimation. Provision of an audiotaped recording of the genetic consultation did not appear to enhance recall of risk information. The role of sociodemographic variables on the psychological and risk variables assessed in this study was very minor. Age was mildly correlated with cancer worry, and employment was predictive of cancer worry only at baseline.

Ovarian cancer is the fifth most common cause of cancer death in females and the most lethal gynecologic cancer. Globally, an estimated 240,000 people are diagnosed with ovarian cancer each year, with 22,530 new cases in the United States in 2019. Parity, oral contraceptive use, and lactation are protective, while early menarche, late menopause, and nulliparity have opposite effects. The “incessant ovulation” theory has thus emerged, in which a higher number of ovulations may be a cause of epithelial ovarian cancer (EOC). However, the mechanisms of this theory are unknown; one possibility is that the chance of acquiring a cancer-initiating pathogenic variant increases with each ovulatory cycle because of a microenvironment that promotes DNA damage. In this dissertation, we aimed to leverage genetic epidemiologic data to test this potential mechanism by evaluating the presence of gene-environment interaction between DNA repair capacity (measured through the presence of pathogenic variants in DNA repair genes) and lifetime ovulatory years (LOY). In the first aim of this dissertation, we conducted a systematic review and meta-analysis, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, to formally evaluate the strength of evidence and to generate summary point estimates for the association between LOY and EOC. We then executed two analytic aims to evaluate if the presence of pathogenic variants in DNA repair genes exacerbated the increase in ovarian cancer risk associated with LOY. In Aim 2, we evaluated interaction on the additive scale in the United Kingdom (UK) Biobank through use of a novel DNA repair capacity score developed in this dissertation, measured by quantifying the number of pathogenic variants present per individual from a list of 163 DNA repair genes, using whole exome sequencing (WES) data. In Aim 3, we evaluated the presence of interaction between pathogenic BRCA1/2 status and LOY in the Breast Cancer Family Registry (BCFR), a cohort enriched for familial risk. In both empirical aims, we assessed the presence of interaction on the additive scale using the relative excess risk due to interaction (RERI) formula. We compared results across the two empirical aims. We found the relationship between lifetime ovulations and ovarian cancer risk to be consistent and replicable in the published literature. In pooled estimates from 22 published studies, a one-year increase in LOYs was associated with a 4% (3-6%) increased risk of ovarian cancer and those with a high number of ovulations (compared to low LOYs) had a 2.15-fold (95% CI 1.82, 2.54) increased risk of ovarian cancer. We also confirmed the positive association between increasing LOYs and ovarian cancer risk in the UK Biobank and the BCFR cohorts. Although interaction on the additive scale was not detected, there were strong positive associations between pathogenic variants in DNA repair genes and ovarian cancer risk. In the UK Biobank, the presence of at least one pathogenic variant in a DNA repair gene was associated with a significant 27% increased risk of epithelial ovarian cancer (EOC) (95% CI 5-55%). Among women at high risk of ovarian cancer due to family history of breast and/or ovarian cancer, there was a strong relationship between BRCA1/2 pathogenic variants and ovarian cancer, regardless of the number of ovulations experienced. The association between LOY and ovarian cancer was found to be consistent and replicable, despite differences in study design, covariates, and measurement. We also detected robust evidence that increasing lifetime ovulations and pathogenic DNA repair variants were associated with ovarian cancer risk. Such variants were exceedingly rare in both cohorts, which limited power to detect interaction in an already rare cancer. Despite such associations, there was no evidence of synergy between LOY and impaired DNA repair capacity, but rather, high LOY and impaired DNA repair capacity may be independent risk factors of ovarian cancer. Each exposure may describe a separate class of women at increased risk of ovarian cancer that should be targeted for future prevention and screening strategies.

No description available.

published_or_final_version / Diagnostic Radiology / Master / Master of Philosophy