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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 of abnormal 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 1990’s 

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 of cancer; 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 associated with 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 risk of 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 of tobacco-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 associated with 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 of cancer 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 uncertain whether 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