University of North Carolina at Chapel Hill
School of Public Health
Department of Epidemiology

Fundamentals of Epidemiology (EPID 168)

Final Examination, Fall 1997

The following exam questions relate to the article: Freudenheim J et al. Exposure to breastmilk in infancy and the risk of breast cancer. Epidemiology 1994;5:324-331. You may refer to this article du ring the examination.

NOTE:

    • Write all answers on the answer sheets provided.
    • You may keep the examination questions.
    • Write the last five digits of your student id number in the upper right-hand corner of each page of your answer sheets.
    • This examination is closed book. However, you may use a calculator, English, foreign language, or medical dictionary.
    • When you finish please sign your name on the sign-out sheet under the pledge:

"I have neither given nor received help from others in completing this examination."

    • Good luck and happy holidays.

______________________________________________________________________________________

 

  1. Which of the following best characterizes the present study as presented in the article (2 pts):

    1. Analytic study to investigate the hypothesized relationship in an available dataset
    2. Descriptive study using available data
    3. Analytic study of data collected to investigate the hypothesized relationship
    4. A post-hoc analysis of data collected primarily for another study (i.e., of secondary data)

 

  1. Find an example from the paper for each of the following (give the page number and quote enough of the words to identify the point or passage; the same point or phrase cannot be used more than once) (2 pts each)

    1. A finding from a migrant study or studies;
    2. A finding from descriptive epidemiology;
    3. An association from an ecologic study.

 

  1. Several previous studies of exposure to breastmilk and risk of breast cancer in adulthood reported little association in crude analyses (p. 324). The authors suggest that the absence of an association could have resulted from a fai lure to adjust for age. Which of the following best explains why failure to adjust for age could have obscured an underlying true association. (Choose one best answer.) (2 pts)

    1. Age is causally related to breast cancer risk and an infantís age is related to her exposure to breastmilk.
    2. Age is causally related to breast cancer risk and infant feeding practices have changed over time.
    3. Age is causally related to breast cancer risk but not associated with breast feeding purchases.
    4. Age is causally related to breast cancer risk but is causally related to breast feeding practices.

 

  1. The authors describe their study as a case-control study of dietary and reproductive factors for breast cancer (p. 324). Which of the following best describes the type of situation for which case-control studies are most advantageo us compared to other designs. (choose one best answer). ( 2 pts)

    1. rare exposure, common endemic disease.
    2. rare exposure, rare endemic disease.
    3. common exposure, common endemic disease
    4. common exposure, rare endemic disease

 

  1. The authors used the term "cohort effects" in regard to results from previously reported studies. Which of the following best describes what is meant by cohort effects in this context? (choose one best answer). (2 pts)

    1. Breast cancer cases are heterogeneous with respect to known factors.
    2. Secular changes in infant feeding practices result in an association between age and exposure to breastmilk.
    3. Breast cancer and control subjects come from nonoverlapping birth cohorts.
    4. Recall accuracy of breastmilk exposure may differ by birth cohort.

 

  1. Cases in this study were incident cases of conformed cancer of the breast (p. 325). Which of the following best describes the advantage of selecting incident cases over prevalent cases (choose one best answer) (2 pts)

    1. selecting from a pool of prevalent cases would make separation of factors associated with risk and those with survival more difficult.
    2. selecting from a pool of prevalent cases would make exposure assessment more difficult because of pre-existing disease status.
    3. selecting from a pool of incident cases creates a more homogenous case group with regard to unknown confounding factors.
    4. selecting from a pool of incident cases reduces misclassification bias.

 

  1. The authors characterize this study as a case-control study of primary and histologically confirmed cancer of the breast in women. For each of the two key terms in this phrase, briefly explain its meaning and significance for the s tudy: (2 pts each)

    1. primary
    2. histologically-confirmed

 

  1. In this study, controls were selected by a random process from residents of the two counties and were frequency age matched to cases (p. 325). Which of the following best describes a reason for preferring community controls over ho spital-based controls for this study? (choose one best answer). (2 pts)

    1. the random selection of controls from the community usually produces groups of cases and controls that are similar in known and unknown confounding variables.
    2. the random selection of controls from the community provides a better estimate of breastmilk exposure among the source population.
    3. the random selection of controls from the community ensures that the subsequent odds ratio is not an overestimation of the association of breast feeding and adult breast cancer.
    4. The random selection of controls from the community reduces the likelihood of differential misclassification of exposure in cases and controls.

 

  1. Information on breastmilk exposure was based on subject's self-report (p. 325). If exposure information could also be obtained from an independent source (such as physician records, or reports from parents), then the agreement betw een these two methods could be compared. Which of the following measures would be most appropriate to quantify the reliability between the two methods? (choose one best answer). (2 pts)

    1. kappa coefficient
    2. correlation coefficient of reproducibility
    3. intraclass correlation coefficient
    4. product-moment correlation
    5. A or B
    6. A, B, or C

 

  1. In a hypothetical validation study of self-report of being breastfed as an infant, the presence of a newly discovered antibody that could serve as a "gold standard" indicator of being breast fed as an infant was compared to self-re port. Testing for the presence of this new antibody is very expensive and was done only on the 204 cases age 40-50 (see table 1). The following data from the validation study were compiled. Calculate the (a) sensitivity, (b) specificity, (c) positive pre dictive value, and (d) predictive value of a negative test. Construct an appropriate 2x2 table and show your work (6 pts)

Data from validation study:

    1. the breastfed antibody was found in 73.5% cases.
    2. 80 self-reports were false negative

 

  1. From the data presented in Table 1 answer the following:

    1. For premenopausal women with greater than a high school education, compute and interpret the odds ratio for having breastfed as an infant and breast cancer as an adult. (2 pts)
    2. Referring to your analysis in part (a), assume now that 20% of controls who gave a positive history of having been breastfed had not in fact been breastfed, but that all other data were correct. Compute and interpret the odds ratio for having breastfed as an infant and breast cancer as an adult under this assumption. (2 pts)
    3. Which of the following best describes the type of misclassification illustrated in part (b) above. (2 pts)

    1. differential misclassification of disease and exposure status
    2. differential misclassification of exposure
    3. nondifferential misclassification of exposure
    4. nondifferential misclassification of disease and exposure status
    5. none of the above

 

  1. For each of the following statements, indicate if it is TRUE OR FALSE: (1 pt each)

    1. By matching the controls to the cases on age, the authors have ensured that age will not be a confounder .
    2. The procedure for identifying cases is essentially one of active surveillance.
    3. The difference between the proportion of cases interviewed and the proportion of controls interviewed will cause selection bias.
    4. The fact that premenopausal controls who had been breastfed were somewhat older than controls who had not (page 325, bottom of col. 2) indicates frequency matching by age did not "work.
    5. The absence of an association between age and breast cancer in tables 1 and 2 is likely to be a reflection of selection bias from the low response rates for cases and controls.
    6. In postmenopausal women there appears to be a "dose response" relationship between body mass index and the association between having been breastfed.
    7. A case-control study design is often the design of choice in outbreak investigations.
    8. For a factor under study to be considered an effect modifier it must be an independent risk factor for the outcome of interest

 

  1. A list of control variables for use in the logistic regression models appears on page 325, middle of column 2. These variables have been chosen because they (choose one best answer): (2 pts)

    1. are likely to be associated with breast cancer risk in the bottle-fed women.
    2. are known or suspected risk factors for breast cancer, or at least proxies for such factors
    3. are likely to be associated with infant feeding history in the controls
    4. are likely to be associated with infant feeding history in the cases

 

  1. The presentation of data in Table 2 can be used to examine a number of relationships. Using these data give a numerical example of each of the following (show your work and in one sentence explain what the number means): (2 pts eac h)

    1. An association between breast cancer risk and having zero pregnancies. Use > 3 pregnancies as a reference.
    2. An association between having been breastfed and being over 165 cm in height. Use <160 cm as a reference.
    3. An association between breast cancer and having been breastfed, overall.

 

  1. On page 326, 2nd column, the authors state "As shown in Table 3, the risk of breast cancer associated with having been breastfed, was about 0.7 for both pre- and postmenopausal women." In this context, to which of the following epi demiologic measures does the term "risk" refer? Choose one best answer. (2 pts)

    1. Cumulative incidence
    2. Incidence density
    3. Attributable risk
    4. Odds ratio

 

  1. Using the data in Table 3, estimate AND state the meaning of the following measures (for this question you may ignore the possibility of selection bias in cases and controls):

    1. Attributable Risk Proportion (ARP) for NOT having been breastfed for all breast cancer (both premenopausal and postmenopausal breast cancer, combined). Note that an ARP is also known as the etiologic fraction in the e xposed. (3 pts)
    2. Population Attributable Risk Proportion (PARP) for NOT having been breastfed for premenopausal and for postmenopausal breast cancer, separately (i.e., 2 PARP's). Note that the PARP is also known as the etiologic fract ion. (4 pts)
    3. Why would you or would you not expect the PARP to be different for premenopausal breast cancer compared to the PARP for postmenopausal breast cancer case in this investigation (part b)? (2 pts)

 

  1. In the multiple logistic model referred to as Model 2 in Table 3, what was the coefficient for the variable not-having-been-breastfed among all breast cancer cases? (2 pts)

    Which of the following assumptions is involved in that model? Indicate True or False for each assumption. (1 pt each)

    1. The odds of breast cancer vary as the product of the odds for age and the odds for education.
    2. The odds of breast cancer vary as the sum of the odds for age and the odds for education.
    3. Age, education, and not having been breastfed were independent of (i.e., uncorrelated with) each other.
    4. Breast cancer is a rare disease.

 

  1. Suppose that cases who refused to participate in this study were less likely to have been breastfed as infants than those who participated in the study. Which of the following best describes what this fact would imply for the obser ved relative risk associated with being breastfed compared with what would have been observed had all persons participated I the study? (choose one best answer). (2 pts)

    1. the observed relative risk would be biased away from the null.
    2. the observed relative risk would be subject to selection bias and the direction of the bias can not be estimated.
    3. the observed relative risk would be biased toward the null.
    4. the observed relative risk would be subject to misclassification bias and the direction of the bias can not be estimated.

 

  1. In table 3, the confidence intervals for the OR's for all women do not include the value 1.0, whereas all but one of the OR's for premenopausal breast cancer and postmenopausal breast cancer do. Mathematically, what does this patte rn reflect? (2 pts)

 

  1. On page 324, 2nd column, the authors offer a possible explanation of why two previous studies of breastfeeding and breast cancer found little crude association, observing that the result may have been "confounded by a fa ilure to adjust for age, because of cohort effects with regard to breastfeeding frequency". The following stratified analysis has been constructed to illustrate a situation where cohort effects with regard to breastfeeding completely obscure a true prote ctive association seen when age is controlled.
  2.  

    Age < 60

     

    Age > 60

     

    Total

     

    Breastfed

    Bottlefed

     

    Breastfed

    Bottlefed

     

    Breastfed

    Bottlefed

    Cases

    24

    40

     

    256

    100

     

    280

    140

    Controls

    79

    86

     

    204

    54

     

    280

    140

    OR

    0.653

     

    0.678

     

    1.0

    Based on these hypothetical data:

    a. demonstrate that there is a cohort effect for breastfeeding, (2 pts)

     

    b. briefly explain (1-2 sentences referring to specific numbers or calculations for these tables) how failure to adjust for age interferes with finding a protective effect of breastfeeding. (2 pts)

     

  3. An epidemiology graduate student finds evidence in the literature that childhood sunlight exposure may affect adult breast cancer risk. To explore this hypothesis, she obtains from the authors the palace of birth for all of the sub jects in the present study and constructs a sunlight exposure variable ('high" or "low") based on geologic and meteorologic data for the years of the subject's childhood. Her data show that 56.2% of the 219 premenopausal women who were not breastfed as i nfants grew up with "high" sunlight exposure. Based on this fact and the partially-completed tables below, (a) calculate the odds ratio of breast cancer with respect to breastmilk exposure within each of the two sunlight exposure strata, and (b) briefly describe the relationship of the sunlight exposure variable to the association between breast cancer and breastmilk exposure (i.e. in relation to confounding and effect modification. (4 pts)
  4.  

    High sunlight

     

    Low sunlight

     

    Cases

    Controls

    Total

     

    Cases

    Controls

    Total

    Breastfed

     

    24

     

     

    67

     

     

    Bottlefed

    81

     

     

     

    36

     

     

    Total

     

     

    191

     

     

     

    284

     

  5. Use the data from Table 2 (Distribution of Characteristics of Postmenopausal Cases and Controls) to draw separate 2 x 2 tables for women who have had : 0 pregnancies, 1-2 pregnancies, and >=3 pregnancies. (5 pts)

    1. calculate odds ratios for each of these three categories.
    2. Assuming no effects of confounding, interpret your findngs in part (a).

  

  1. A hypothetical cross-sectional ancillary study to this report was conducted. In that study a survey of breast cancer annual incidence rates in geographically distinct areas was completed. Region A in the upper Midwest were breast c ancer mortality is high, and Region B the Southeast where mortality from breast cancer is low. The following data were obtained.

 

Region A

 

Region B

 

Age

No. of cases

Population

Rate/1,000

No. of cases

Population

Rate/1,000

< High School Education

40-50

10

7,000

1.4

10

15,000

0.7

51-60

15

10,000

1.5

20

5,000

4.0

61-65

30

3,000

10

600

55,000

10.9

Total

55

20,000

630

75,000

>= High School Education

40-50

5

1,000

5.0

6

2,000

3.0

51-60

5

2,000

2.5

10

15,000

0.7

61-65

4

500

8.0

4

1,000

4.0

Total

14

3,500

20

18,000

 

Grand total

69

23,500

 

 

650

93,000

 

Crude

 

 

2.9

 

 

 

Compute the following (for adjusted rates use the direct method and the total population as a standard):

    1. the overall region B crude event rate. (1 pt)
    2. Age and educational achievement adjusted rate for Region B: (2 pts)
    3. Age and educational achievement adjusted rate for Region B: (2 pts)
    4. Compare the overall crude rates with the age and educational achievement adjusted rates. Briefly explain your findings. (2 pts)

 

  1. Write a brief statement for or against a causal relationship between breastfeeding in infancy and risk of breast cancer as an adult. Comment specifically on at least two of Bradford Hill's criteri for causal inference. Include in y our comments data or statements from the article. (5 pts)
  2.  

  3. Assuming that this relationship is causal, why might a similar study, 50 years from now, fail to find as strong a relationship? (2 pts)

 

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Format 8/4/2000 vs