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Vitamin D/Calcium and Lung Cancer group presentation

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    J E S S I C A G R A T I G N Y

    S I L A S H A R N E S S

    L I N D S E Y O W N B Y

    M O L L Y C H A F F I N

    J E N N I F E R B A I L E Y

    Cancer

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    Cancer Today

    Cancer can be described as uncontrolled growth ofabnormal body cells. Cancer occurs when cellularDNA is damaged, but the cell does not repair itself or

    die but continues to reproduce unneeded cells.

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    Cancer Today

    Cancer is the 2nd leading cause of death in the USA

    Accounts for nearly 1 in 4 deaths

    Lung cancer Greatest risk factor is cigarette use and other tobacco-related

    products

    Accounts for about 14% of cancer diagnosises

    Largest percentage of cancer-related deaths (~27%) Death rates have decreased since the early 1990s

    American Cancer Society http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf

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    Methods of Cancer Prevention

    Healthy lifestyle

    Diet

    Variation and moderation

    Lifestyle

    Decreased alcohol consumption and tobacco use

    Physical activity

    Each year, more than 572,000 Americans die ofcancer; about one-third of these deaths are linked topoor diet, physical inactivity, and carrying too much

    weight.

    American Cancer Society http://www.cancer.org/acs/groups/content/@epidemiologysurveilance/documents/document/acspc-036845.pdf

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    Current Methods of Cancer Treatment

    Surgery

    Chemotherapy

    Radiation

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    Vitamin D and Cancer Overview

    1,25-dihydroxyvitamin D has been shown to decreasetumor invasion, metastasis, and angiogenesis inmany cancer models of tobacco-related cancer

    Tobacco smoke chemicals may influence vitamin Dmetabolism and function, and conversely vitamin Dmay modify the carcinogenicity of tobacco smokechemicals

    Reduced concentrations of vitamin D are associatedwith increased proliferation, decreased apoptosis,and inhibited differentiation in cells

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    Calcium and Cancer Overview

    Although the exact mechanism is unclear, Calciumsupplementaion has been shown to decrease the riskof cancer.

    According to the National Cancer Institute, Calciummay indirectly reduce cell proliferation and improvecell signaling, causing cancer cells to differentiateand/or die.

    http://www.cancer.gov/cancertopics/factsheet/prevention/calcium

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    Introduction of Tobacco-Related Study

    Study design

    Population

    n=

    Duration Follow-up method/time

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    Objective for Tobacco-Related Cancer Study

    Tobacco smoke chemicals may influence vitamin Dmetabolism and function, and conversely vitamin Dmay modify the carcinogenicity of tobacco smokechemicals

    Hypothesis: lower plasma 25-hydroxyvitamin D[25(OH)D] is associated with a higher risk oftobacco-related cancer in the general population

    The endpoint of this study was incident tobacco-

    related cancer Ascertain information on other cancers

    The most common cancer associated with smoking is lung

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    Maybe insert Table 1 from the study here?

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    Method for Tobacco-Related Study

    Method of selection

    Plasma sample collection method

    Questionnaires

    Tobacco consumption Alcohol consumption

    Lifestyle

    BMI

    Statistical analyses Cox proportional hazards regression (95% CI)

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    Results from Tobacco-Related Study

    Associations with low 25(OH)D

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    Insert Table 2?

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    Possible Limitations

    Participant bias

    Degree of sun exposure Seasonal variation

    Delay in measurement Residual confounding Observational shows no causality, only associations

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    Strengths of the Study

    Homogenous population

    28 year follow up

    Detailed smoking history

    Strong statistical power

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    Significant Findings of Tobacco-Related Study

    Lower concentrations of 25(OH)D were associatedwith a higher risk of tobacco-related cancer but notother cancers

    Biologic plausibility Smoking is associated with reduced 25(OH)D

    concentrations Reduced concentrations of vitamin D are associated with

    increased proliferation, decreased apoptosis, and inhibiteddifferentiation in both normal and neoplastic cells

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    Introduction of CaD RCT

    Study design

    Population

    n=

    Duration Follow-up method/time

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    Objective for CaD RCT

    Associations have been established for high calciumintake and reduced cancer risk. Luminal effect of high calcium intake provided a plausible

    mechanism

    Determine the efficacy of calcium alone and calciumplus vitamin D in reducing incident cancer risk of alltypes Null hypothesis was that there would be no difference in all

    cancer incidence between the 3 calcium and vitamin D txgroups

    The primary outcome was fracture incidence and theprincipal secondary outcome was cancer incidence

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    Method for CaD RCT

    Recruited on a population-based sample

    Random telephone dialing of all listed numbers in the counties

    Inclusion criteria

    Subjects were randomly assigned to receive 1,400-1,500 mg supplemental calcium/D alone (Ca-only),supplemental calcium plus 1,100 IU vitamin D3/d(Ca + D), or placebo

    Serum samples taken Primary designed endpoints of the study concerned

    skeletal status and the calcium economy

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    Methods of CaD RCT

    Statistical analyses

    Survival analysis used to plot and evaluate differences incancer incidence

    Various logistic regression models were developed to estimate

    relative risk of being in the cancer group at conclusion of thetrial and to explore the determinants of observed rates ofcancer incidence

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    Results of CaD RCT

    50 women developed nonskin cancer during thecourse of the study 13 in first year

    37 thereafter

    Table 1 While the findings for the effect of vitamin D are not

    considered a chance association, it is uncertainwhether the marginal calcium effect represents a

    chance occurrence Few other calcium trials have cancer outcome as the endpoint

    Explain the possible method of calcium on cancer tx

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    Significant Findings of CaD RCT

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    Strengths of CaD RCT

    Population based

    Low drop out rate

    High level of tx adherence (compliance)

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    Weaknesses of CaD RCT

    Cancer was not the principal outcome variable

    Mechanisms are not well known at this time

    Several of the effects of vitamin D in cancer model

    systems require concentrations of of calcitriolsubstantially higher than can be achievedphysiologically in intact humans aw3

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    Conclusion from Studies

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    Unsolved Problems in Cancer Research

    No cure

    Tx is hard on patients

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    Future Research Needed

    Understand tx mechanisms

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    Take Home Message

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    Sources

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