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  • 1.
    Lu, Sai San Moon
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Antibiotic use and risk of colorectal cancer: A population-based register study2019Självständigt arbete på avancerad nivå (masterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
  • 2.
    Lu, Sai San Moon
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Antibiotics use in relation to colorectal cancer risk, survival and postoperative complications2024Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Growing evidence suggests that antibiotic-induced dysbiosis of gut microbiota potentially contributes to colorectal cancer development and oncological outcomes. However, the role of antibiotics in colorectal cancer incidence, survival and postoperative outcomes at a population level remains incompletely understood.

    Aims: The overall aim of the thesis is to investigate prescription antibiotics use in relation to colorectal cancer risk, survival and postoperative complications, particularly surgical site infections including anastomotic leakage.

    Methods: The thesis work includes matched case-control and cohort studies, leveraging complete population-based data from Swedish national registers. Paper I is a matched case-control study that consists of 40 545 colorectal cancer cases and 202 720 matched controls, aiming to investigate antibiotics use and risk of incident colorectal cancer. Multivariable conditional logistic regression was used. Paper II is a cohort study, including 47 303 colorectal cancer cases, investigating antibiotics use in relation to cancer-specific survival. Stratified Cox proportional-hazards regression was used. Paper III includes 38 839 colorectal cancer cases who had undergone abdominal tumour-resection surgery and assesses antibiotics use in relation to surgical site infections, including anastomotic leakage, within 30 days after surgery. Logistic regression with multi-level mixed-effects models was used.

    Results: In paper I, a dose-response association between antibiotics use and a higher risk of proximal colon cancer was found, whereas a slight inverse association with rectal cancer was observed, mainly in women. A null association was found between methenamine hippurate, assessed as a negative control due to no known effect on gut microbiome, and the risk of colorectal cancer. In paper II, the findings did not support any substantial negative effect of antibiotics on cancer-specific survival, except for very high cumulative exposure (>180 days) in stage I-III diseases. In stage IV colorectal cancer, modest inverse relationships between antibiotics use and survival were noted. In paper III, prescription antibiotics use up to 4.5 years before surgery was associated with a higher risk of surgical site infections, including anastomotic leakage, after colon cancer surgery but not rectal cancer surgery. A null association was observed between methanamine hippurate and the risk of surgical site infections. For cardiovascular and/or neurological complications, also considered as a negative control due to expected negligible or null effects of gut microbiome on these outcomes after surgery, associations were null in both colon and rectal cancer.

    Conclusion: These studies provided further support for antibiotics use as a modifiable risk factor for proximal colon cancer and identified antibiotics taken long before surgery as a novel risk factor for surgical site infections, including anastomotic leakage, after colon cancer surgery. In contrast, we did not find any substantial negative impact of antibiotics on cancer-specific survival. Taken together, the findings described in this thesis provide etiological insights and may contribute to strategies to prevent colon cancer and improve postoperative outcomes through prudent use of antibiotics, thereby aiding in the reduction of colorectal cancer incidence and mortality.

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  • 3.
    Lu, Sai San Moon
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Inequalities in early childhood mortality in Myanmar: Association between parents’ socioeconomic status and early childhood mortality2018Självständigt arbete på avancerad nivå (magisterexamen), 10 poäng / 15 hpStudentuppsats (Examensarbete)
    Abstract [en]

    Introduction: Despite substantial global achievements in reducing early childhood mortality, disparitiesremain across and within countries and regions. Reducing these inequalities is important forimproving population health and attaining the Sustainable Development Goals adopted bythe United Nations General Assembly in 2015. There have been some empirical studies ofinequalities in early childhood mortality conducted in developing countries yet very little isknown about these issues in Myanmar. This study aims to fill this knowledge gap byinvestigating association between socioeconomic status and early childhood mortality acrossa ten-year period in Myanmar.

    Method: Using cross-sectional data obtained from the Myanmar Demographic Heath Survey (2015-2016), univariate and multivariate logistic regressions were performed to investigateassociations between parents’ education and household wealth, and four age specific earlychildhood mortality outcomes being: under-five (0-4 years); neonatal (0-28 days); postneonatal (1-11 months) and child (1-4 years). Data for 10,081 children born to 4,737 marriedwomen (aged 15-49 years) were analyzed.

    Results: Mortality during the first five years of age was associated with household wealth status, andthe association remained robust after adjusting for confounders. Under-five children fromthe richest families had 67% (95% CI 44 to 80%) lower odds of dying compared with childrenin the poorest families after adjusting for individual proximate factors (mothers’ age at birth,mothers’ use of cigarettes or tobacco, birth interval, birth order and sex of the child). Theassociation between mortality and household wealth was strongest for post neonatal deaths.Both mother’s and father’s education were important for early childhood mortality; thehighest benefit from parents’ education was with respect to child mortality in the one to fouryear age bracket. For example, children born to highly educated mothers had 83% (95% CI23 to 96%) lower odds of death in this age group, compared with children born to motherswith primary schooling as their highest educational attainment, after adjusting for individualproximate factors. Similarly in the multivariate analysis, among fathers with highereducation, the odds of child mortality between one and four years of age, were 88% (95% CI16 to 98%) lower than that for fathers for whom the highest educational attainment was atthe primary level.

    Conclusion: Socioeconomic indicators, such as household wealth status, mother’s and father’s education,are important for child survival before five years of age. The association between householdwealth and childhood mortality is stronger after the neonatal period, with the benefits ofparents’ education strongest for child mortality in the one to four year age group. Thesefindings provide much needed evidence about association between socioeconomic factorsand age stratified early childhood mortality in Myanmar. Health policy aimed at reducingearly childhood mortality must take socioeconomic determinants into account in order toaddress socioeconomic disparities. This work provides a platform for further empiricalstudies using advanced statistical methods to unpack these and other socially determinedinequalities.

  • 4.
    Lu, Sai San Moon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Mohammed, Zahraa
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Häggström, Christel
    Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
    Myte, Robin
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Lindquist, Elisabeth
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS). Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR).
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi. Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Antibiotics Use and Subsequent Risk of Colorectal Cancer: A Swedish Nationwide Population-Based Study2022Ingår i: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 114, nr 1, s. 38-46Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antibiotics use may increase colorectal cancer (CRC) risk by altering the gut microbiota, with suggestive evidence reported. Our study aims to investigate antibiotics use in relation to subsequent CRC risk.

    METHODS: This is a nationwide, population-based study with a matched case-control design (first primary CRC cases and 5 matched, cancer-free controls). Complete-population data, extracted from Swedish national registers for the period 2005-2016, were used to calculate odds ratios and 95% confidence intervals.

    RESULTS: We included 40 545 CRC cases and 202 720 controls. Using the full dataset, we found a positive association between more frequent antibiotics use and CRC, excluding antibiotics prescribed within 2 years of diagnosis attenuated results toward the null. In site-specific analyses, excluding the 2-year washout, the positive association was confined to the proximal colon (adjusted odds ratio for very high use vs no use = 1.17, 95% confidence interval = 1.05 to 1.31). For rectal cancer, an inverse association, which appears to be driven by women, was observed. Quinolones and sulfonamides and/or trimethoprims were positively associated with proximal colon cancer, whereas a more general inverse association, across antibiotics classes, was observed for rectal cancer. We found no association between methenamine hippurate, a urinary tract antiseptic not affecting the gut microbiota, and CRC risk.

    CONCLUSIONS: This register-based study covering the entire population of Sweden found a robust association between antibiotics use and higher risk of proximal colon cancer and an inverse association with rectal cancer in women. This study strengthens the evidence from previous investigations and adds important insight into site-specific colorectal carcinogenesis.

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  • 5.
    Lu, Sai San Moon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap.
    Ahmed, Maghfoor
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi. Umeå universitet, Medicinska fakulteten, Umeå Centre for Microbial Research (UCMR). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Wallenberg centrum för molekylär medicin vid Umeå universitet (WCMM). Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Prediagnostic prescription antibiotics use and survival in patients with colorectal cancer: a swedish national register-based study2023Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 32, nr 10, s. 1391-1401Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Antibiotics use is associated with higher colorectal cancer risk, but little is known regarding any potential effects on survival.

    METHODS: We conducted a nationwide cohort study, using complete-population data from Swedish national registers between 2005 and 2020, to investigate prediagnostic prescription antibiotics use in relation to survival in colorectal cancer patients.

    RESULTS: We identified 36,061 stage I-III and 11,242 stage IV colorectal cancer cases diagnosed between 2010 and 2019. For stage I-III, any antibiotics use (binary yes/no variable) was not associated with overall or cancer-specific survival. Compared with no use, moderate antibiotics use (total 11-60 days) was associated with slightly better cancer-specific survival [adjusted HR (aHR) = 0.93; 95% confidence interval (CI), 0.86-0.99)], whereas very high use (>180 days) was associated with worse survival [overall survival (OS) aHR = 1.42; 95% CI, 1.26-1.60, cancer-specific survival aHR = 1.31; 95% CI, 1.10-1.55]. In analyses by different antibiotic types, although not statistically significant, worse survival outcomes were generally observed across several antibiotics, particularly macrolides and/or lincosamides. In stage IV colorectal cancer, inverse relationships between antibiotics use and survival were noted.

    CONCLUSIONS: Overall, our findings do not support any substantial detrimental effects of prediagnostic prescription antibiotics use on cancer-specific survival after colorectal cancer diagnosis, with the possible exception of very high use in stage I-III colorectal cancer. Further investigation is warranted to confirm and understand these results.

    IMPACT: Although the study findings require confirmation, physicians probably do not need to factor in prediagnostic prescription antibiotics use in prognosticating patients with colorectal cancer.

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  • 6.
    Lu, Sai San Moon
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Rutegård, Martin
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Häggström, Christel
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Gylfe, Åsa
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk mikrobiologi.
    Harlid, Sophia
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    van Guelpen, Bethany
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Antibiotics use up to 4.5 years before colorectal cancer surgery is associated with an elevated risk of surgical site infections, including anastomotic leakage, particularly in colon cancer: a Swedish nationwide studyManuskript (preprint) (Övrigt vetenskapligt)
  • 7.
    Pham, Thu Thi
    et al.
    Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Berlin, Germany.
    Nimptsch, Katharina
    Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
    Aleksandrova, Krasimira
    Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology—BIPS, Bremen, Germany; Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany.
    Jenab, Mazda
    Nutrition and Metabolism Branch, International Agency for Research on Cancer (IARC-WHO), World Health Organization, Lyon, France.
    Fedirko, Veronika
    Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, TX, Houston, United States; Department of Epidemiology, Rollins School of Public Health, Emory University, GA, Atlanta, United States.
    Wu, Kana
    Department of Nutrition, Harvard T.H. Chan School of Public Health, MA, Boston, United States.
    Eriksen, Anne Kirstine
    Danish Cancer Society Research Center, Copenhagen, Denmark.
    Tjønneland, Anne
    Danish Cancer Society Research Center, Copenhagen, Denmark; Department of Public Health, University of Copenhagen, Copenhagen, Denmark.
    Severi, Gianluca
    Université Paris-Saclay, UVSQ, Inserm “Exposome and Heredity” Team, Villejuif, France.
    Rothwell, Joseph
    Université Paris-Saclay, UVSQ, Inserm “Exposome and Heredity” Team, Villejuif, France.
    Kaaks, Rudolf
    Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Katzke, Verena
    Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Catalano, Alberto
    Centre for Biostatistics, Epidemiology, and Public Health, Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.
    Agnoli, Claudia
    Epidemiology and Prevention Unit, Department of Epidemiology and Data Science, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
    Masala, Giovanna
    Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
    De Magistris, Maria Santucci
    Azienda Ospedaliera Universitaria (AOU) Federico II, Naples, Italy.
    Tumino, Rosario
    Hyblean Association for Epidemiological Research, AIRE ONLUS, Ragusa, Italy.
    Vermeulen, Roel
    Institute of Risk Assessment Sciences, Utrecht University, Utrecht, Netherlands.
    Aizpurua, Amaia
    Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain.
    Trobajo-Sanmartín, Camino
    Instituto de Salud Pública y Laboral de Navarra, Pamplona, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarre Institute for Health Research (IdiSNA), Pamplona, Spain.
    Chirlaque, María-Dolores
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Department of Epidemiology, Regional Health Council, IMIB-Arrixaca, Murcia University, Murcia, Spain.
    Sánchez, Maria-Jose
    Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), Granada, Spain; Instituto de Investigación Biosanitaria ibs.GRANADA, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.
    Lu, Sai San Moon
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
    Cross, Amanda J.
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
    Christakoudi, Sofia
    Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom; Department of Inflammation Biology, School of Immunology and Microbial Sciences, King's College London, London, United Kingdom.
    Weiderpass, Elisabete
    International Agency for Research on Cancer, World Health Organization, Lyon, France.
    Pischon, Tobias
    Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Hum-boldt-Universität zu Berlin, Berlin, Germany; Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany; Core Facility Biobank, Berlin Institute of Health, Charité-Universitätsmedizin Berlin, Berlin, Germany.
    Pre-diagnostic circulating resistin concentrations and mortality among individuals with colorectal cancer: results from the european prospective investigation into cancer and nutrition study2024Ingår i: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Resistin is a protein involved in inflammation and angiogenesis processes and may play a role in the progression of colorectal cancer (CRC). However, it remains unclear whether resistin is associated with increased mortality after CRC diagnosis. We examined pre-diagnostic serum resistin concentrations in relation to CRC-specific and all-cause mortality among 1343 incident CRC cases from the European Prospective Investigation into Cancer and Nutrition cohort. For CRC-specific mortality as the primary outcome, hazard ratios (HRs) and 95% confidence intervals (95% CI) were estimated from competing risk analyses based on cause-specific Cox proportional hazards models and further in sensitivity analyses using Fine–Gray proportional subdistribution hazards models. For all-cause mortality as the secondary outcome, Cox proportional hazards models were used. Subgroup analyses were performed by sex, tumor subsite, tumor stage, body mass index and time to CRC diagnosis. Resistin was measured on a median of 4.8 years before CRC diagnosis. During a median follow-up of 8.2 years, 474 deaths from CRC and 147 deaths from other causes were observed. Resistin concentrations were not associated with CRC-specific mortality (HRQ4vsQ1 = 0.95, 95% CI: 0.73–1.23; Ptrend =.97; and HRper doubling of resistin concentration = 1.00; 95% CI: 0.84–1.19; P =.98) or all-cause mortality. Results from competing risk (sensitivity) analysis were similar. No associations were found in any subgroup analyses. These findings suggest no association between pre-diagnostic circulating resistin concentrations and CRC-specific or all-cause mortality among persons with CRC, and the potential insignificance of resistin in CRC progression.

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