University of North Carolina at Chapel Hill
School of Public Health
Department of Epidemiology
Fundamentals of Epidemiology (EPID 168)
Final Examination, Fall 1997
Answer Guide
1. C. Analytic study of data collected to investigate the
hypothesized relationship
2. a. A finding from a migrant study or studies: "Studies of
migrants provide some evidence; for example, migrants to the
United States from Japan experienced a rate of breast cancer
intermediate between the lower rate in Japan and the higher
rate in the U.S."
b. A finding from descriptive epidemiology: *Many possibilities,
including either of these sentences:
"This finding implies a possible connection between the
trend toward increasing bottlefeeding in the postwar
period and current trends toward increasing incidence of
breast cancer. Furthermore, it offers a partial
explanation of the international variation in breast
cancer rates, with rates considerably lower in less
developed than in developed nations."
c. An association from an ecologic study: *"Micozzi found mean
adult height and breast cancer incidence in 30 countries to be
highly correlated (r=0.8)."
3. B. Age is causally related to breast cancer risk and infant feeding
practices have changed over time.
4. D. Common exposure, rare endemic disease.
5. B. Secular changes in infant feeding practices result in an association
between age and exposure to breastmilk.
6. A. selecting from a pool of prevalent cases would make separation of
factors associated with risk and those with survival more difficult.
7. a. Primary -- Primary breast cancer is a tumor that originates in the
breast, rather than a tumor in the breast that is the result of
metastasis from a tumor that originated in another location or
tissue. In general, tumors originating in the same organ and
tissue are more likely to have similar etiologies than are
tumors that originate in different organs.
b. Histologically-confirmed -- histological confirmation
refers to the verification of the diagnosis (of breast cancer)
through laboratory examination of tumor tissue. Microscopic
examination of tumor cells establishes the existence and type
of tumor with a greater degree of certainty than does a
clinical diagnosis alone. Counting only histological-confirmed
cases reduces the potential for false positive breast cancer
diagnoses and the misclassification bias will cause.
8. B. The random selection of controls from the community provides a
better estimate of breastmilk exposure among the source population.
9. A. Kappa coefficient
10. Table:
Biomarker validation of women's self-report of having been breastfed
Breastfeeding biomarker found
Yes No Total
S r --------------------------------------------
e e Breastfed 70 26 96
l p
f o Not breastfed 80 28 108
r --------------------------------------------
t Total 150 54 204
Derivation: 204 cases tested (overall total), 73.5% (=150) have
the marker (so 54=204-150 do not), 80 are false negatives by
self-report (so 80 = "yes" biomarker, "no" self-report), and the
remaining cells and marginals are obtained from these numbers.
a. Sensitivity = 70 / 150 = 47% (Answers the question, "Of women
who truly were breastfred, as demonstrated by the presence of the
biomarker for having been breastfed, what % were correctly
classified by self-report?"))
b. Specificity = 28 / 54 = 52% (Answers the question, "Of women
who were not breastfed, as demonstrated by the absence of the
biomarker, what % were correctly classified by self-report?")
c. Positive predictive value (PPV) = 70 / 96 = 73% (Answers the
question, "Of women classified, on the basis of their self-report,
as 'having been breastfed', what % were correctly classified?")
d. Negative predictive value (NPV) = 28 / 108 = 26% (Answers the
question, "Of women classified, on the basis of their self-report,
as 'not having been breastfed', what % were correctly classified?")
11. a. Table:
Adult breast cancer by having been breastfed as an infant,
among premenopausal women with education beyond high school
Case Control Total
------------------------
Breastfed 61 93 154
Not breastfed 69 61 130
-------------------------
Total 130 154 284
OR = (61 x 61) / (93 x 69) = 0.58.
Interpretation: having been breastfed appears to be protective
against female adult breast cancer, with a reduction in risk of
approximately 40%.
b. Table:
Adult breast cancer by having been breastfed as an infant,
among premenopausal women with education beyond high school,
assuming that 20% of controls who reported having been
breastfed had in fact not been
Cases Controls Total
-------------------------
Breastfed 61 74 135
Not breastfed 69 80 149
-------------------------
Total 130 154 284
Derivation: 20% of the 93 controls who reported having been
breastfed had not been, so 20% of 93 (=18.6->19) are switched from
"Breastfed" to "Not breastfed", being added to the 61 who reported
not having been breastfed. The remaining 80% of 93 (=74.4->74)
remain in the upper row.
OR = (61 x 80) / (74 x 69) = 1.0, i.e. no association.
c. B. differential misclassification of exposure
12. TRUE or FALSE
a. False - matching controls to cases does not prevent the
matching variable (age) from being associated with the exposure
(having been breastfed), so the matching cannot prevent
confounding. (See also d. and e.)
b. True - The nurse telephoned hospitals on a frequent, regular
basis, to identify all breast cancer cases.
c. False - The difference in the proportions interviewed among
cases and among controls provides a great deal of potential for
selection bias, but if nonparticipation was not related to having
been breastfed then selection bias will not occur.
d. False - The matching caused cases and controls to have the same
age distribution, so it did "work"; matching would not be expected
to eliminate an association between age and the exposure, since
exposure status was not known when controls were being selected and
in any case would not have been used in the matching procedure.
e. False - The matching procedure prevented an association.
f. False - The association between body mass index and breast
cancer can be assessed by estimating odds ratios from Table 2. To
avoid confounding infant feeding history we should preferably
assess the association separately in breastfed women and in women
who have not been breastfed (omitting the complexities from
considering body mass to be an intervening variable in the effect
of infant feeding history). To avoid being misled by a possible
"synergism" involving infant feeding and body mass, ideally we
would look in the "unexposed" group. However, although this study
focuses on breastfeeding, one can also consider "formula feeding"
as an exposure that might be "synergistic" with body mass. So we
can choose either exposure group (or both).
Here are the computations:
From Table 2:
Cases Controls
------------------------- -------------------------
Breastfed Not breastfed Breastfed Not breastfed
Body mass ---------- -------------- --------- -------------
index (kg/mz)
16-22 48 15 89 19
23-27 103 26 125 16
>27 90 17 91 16
To show the details, here is a table for estimating OR's for body mass index and breast cancer:
Breastfed Not breastfed Total
Body mass --------------- --------------- ---------------
index (kg/m sq) Cases Controls Cases Controls Cases Controls
16-22 48 89 15 19 63 108
23-27 103 125 26 16 129 141
>27 90 91 17 16 107 107
and the resulting OR's are [e.g., (90 * 89) / (48 * 91) = 1.83]:
Breastfed Not breastfed Total
Body mass --------- ------------- ---------
index (kg/m sq)
16-22 (ref. level) 1.0 1.0 1.0
23-27 1.83 2.06 1.57
>27 1.83 1.34 1.71
The OR's in the total column are shown to illustrate that in this
case there is some confounding by breastfeeding history, at body
mass index level 23-27 kg/m sq. Within either breastfed or not
breastfed group there is no "dose-response" relationship.
g. True - Generally, generally an outbreak investigation begins
after the outbreak has begun and the investigation seeks to
determine what characteristics of cases might have been responsible
for their disease. If the cases happened to be part of an existing
cohort for which the requisite exposure information was already
available in some form, then a retrospective cohort study would be
another possibility. If cases are still occurring a prospective
cohort study might be initiated, but the better an idea the
investigators have about which exposures to assess, the more they
should intervene to minimize the occurrence of additional cases.
h. False - for a factor to be considered a confounder, it must be
an independent risk factor for the outcome, but this requirement
does not pertain to effect modification. For example, genital
ulcers cannot cause HIV by themselves, but in conjunction with a
sex partner who is HIV infected, genital ulcers can increase
(modify) the risk of HIV infection.
13. Potential confounders are factors that are known or suspected risk
factors for breast cancer or its detection, or at least proxies for
such factors.
14. a. Breast cancer risk and no previous pregnancies
Cases Controls Total
-------------------------------
No pregnancies 50 38 88
>= 3 pregnancies 167 216 383
-------------------------------
Total 217 254 471
OR = (50 x 216) / (38 x 167) = 1.7 (for zero vs. >= 3 pregnancies)
Interpretation: having never been pregnant was associated with an
increased breast cancer rate, with an apparent 70% greater rate
among nulligravidae (women who have never been pregnant).
Other choices of a reference level produce the same result, e.g.,
1-2 pregnancies as the reference level:
OR = (50 x 102) / (38 x 82) = 1.6.
If both groups, 1-2 pregnancies and 3+ pregnancies are combined
and used as the reference group, then:
OR = (50 x 318) / (38 x 249) = 1.7
b. Height above 165 centimeters and having been breastfed
Height > 165 cm < 160 cm Total
-----------------------------------
Breastfed 148 183 331
Not breastfed 41 25 66
----------------------------------
Total 189 208 397
OR = (148 x 25) / (183 x 41) = 0.49.
Interpretation: Women who were breastfed were less likely
to be over 165 cm. tall.
Other possible OR's --
> 165 vs. 160-165: OR = (148 x 43) / (213 x 41) = 0.73
> 165 vs. all others: OR = (148 x 68) / (396 x 41) = 0.62
c. Breast cancer and having been breastfed (crude)
Cases Controls Total
----------------------------------
Breastfed 241 305 546
Not breastfed 58 51 109
----------------------------------
Total 299 356 655
OR = (241 x 51) / (305 x 58) = 0.69
Interpretation: having been breastfed was associated with lower
risk of breast cancer
15. D. The statement refers to the (relative) risk of breast cancer
between women who were and were not breastfed, estimated using
the odds ratio.
16. a. Estimate RR for Not breastfed as 1/OR for Breastfed: 1 / 0.69 = 1.45
ARP = (RR - 1) / RR = (1.45 - 1) / 1.45 = 0.45/1.45 = 0.31
Interpretation: Some 31% of breast cancer in women who were not
breastfed was attributable to their having not been breastfed.
b. If know the formula (or can derive it from the diagram and the
"grand synthesis"):
P(E|D) (RR-1)
PARP = --------------- and since breast cancer is rare, use OR.
RR
(117)
----------- (1.47-1)
(117+112) (0.51) (0.47)
Premenopausal: ----------------------- = --------------- = 0.16
1.47 1.47
AND
(58)
-------------- (1.45-1)
(58+241) (0.19) (0.45)
Postmenopausal: ------------------------- = --------------- = 0.06
1.45 1.45
Meaning: In women who wre not breastfed, some 16% of premenopausal
breast cancer and some 6% of postmenopausal breast cancer were
attributable to their having not been breastfed.
OR, reason as follows:
Proportion of exposed (Not breastfed) cases that are atttributable to not having been breastfed is:
ARP = (RR-1)/RR
Since breast cancer is rare, we can estimate with
(OR-1)/OR = (1.47-1) / 1.47 = 0.3197 for postmenopausal.
However, this proportion applies only to cases who are exposed
(because ARP is "proportion of exposed cases . . ."). So estimate
proportion of all cases who are exposed:
= Pr(Exposed|Case) = 117 / (117+112) = 0.51 for postmenopausal
Muliplying 1. by 2., 0.51 x 0.3197 = 16% for postmenopausal
c. The PARP for premenopausal breast cancer is expected to be
greater due to the secular decrease in breastfeeding during the
decades when these women were infants. Thus, the proportion
exposed to not having been breastfed is substantially greater for
the premenopausal breast cancer cases. Hence, their PARP is
greater.
17. Logistic model coefficients for risk factor variables are natural
logarithms of odds ratios per one unit change in the variable.
So the coefficient was ln(0.70) = -0.3567
Assumptions:
a. True - The odds of breast cancer vary as the product of the odds
for age and the odds for education.
b. False - Only in a few special cases will the product of two odds
equal their sum (e.g., both odds equal zero or both odds equal two).
The logistic model is additive in the logit (logarithm of odds),
multiplicative in the odds.
c. False - One of the reasons for using mathematical modeling is
that the risk factors (exposures and potential confounders) ARE
associated (i.e., not independently distributed)
d. True - Breast cancer is a rare disease.
18. C. The observed relative risk would be biased toward the null.
19. Smaller sample sizes produce wider confidence intervals, so if the
point estimates for the crude and stratum-specific measures are about
the same, then the confidence intervals for the latter will be wider.
20.
AGE < 60 AGE > 60 TOTAL
----------------------------------------------------
Breast Bottle Breast Bottle Breast Bottle
------ ------ ------ ------ ------ ------
Cases 24 40 256 100 280 140
Controls 79 86 204 54 280 140
----------------------------------------------------
OR 0.653 0.678 1.0
a. Control women in older stratum are more likely to have been
breastfed than control women in the younger stratum, e.g., odds of
having been breastfed are 0.9 (79/86) among younger women and 3.8
for AGE > 60.
b. Age is a strong risk factor for breast cancer, so if breastfed
women were older than bottle-fed women, than a possible protective
effect of breastfeeding could have been offset by the greater risk
associated with older age.
21. 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 place of
birth for all of the subjects 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=B9s childhood. Her data
show that 56.2% of the 219 premenopausal women who were NOT breastfed
as infants 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)
High Sunlight Cases Controls Total
Breastfed Yes 44 24 68
Breastfed No 81 *42 123
Total 125 66 191
Low Sunlight Cases Controls Total
Breastfed Yes 67 *120 187
Breastfed No 36 *61 97
Total 103 181 284
* crude from Table 1 or Table 3 = 0.68
High sunlight OR = (44x42)/(24x81) = 0.95
Low sunlight OR = (67x61)/(120x36) = 0.95.
Sunlight is a confounder of the protective effect of breastfeeding
as an infant. It is not an effect modifier.
22. 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: a. 0 pregnancies, b. 1-2 pregnancies, c. >=3
pregnancies. Be sure to include appropriate labels. (5 pts)
0 pregnancies 1-2 pregnancies 3 pregnancies
Cases Controls Cases Controls Cases Controls
Breast 34 35 71 90 136 180
Bottle 16 3 11 12 31 36
Total 50 38 82 102 167 216
a) Calculate odds ratios for each of these three categories.
0 pregnancies: OR = (34 x 3) / (16 x 35) = 0.18
1-2 pregnancies: OR = (71 x 12) / (11 x 90) = 0.86
>=3 pregnancies: OR = (136 x 36) / (31 x 180) = 0.88
b) Assuming no effects of confounding, interpret your findings in
part (a).
There is effect modification. The magnitude of the protective
effect of having been breast-fed on development of breast cancer
is dependent on pregnancy history. Having been breast-fed is a
stronger protective factor for those women who never had a pregnancy.
23. 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 where breast cancer mortality is high, and Region B the
Southeast where mortality from breast cancer is low. The following
data were obtained.
Region A Region B
Cases Population Rate/1000 Cases Population Rate/1000
< High School Education
Age
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
Age
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
a. Compute the overall Region B crude event rate: (1 pt) = 7.0/1000
Using the total population as a standard compute the following by the
direct method of adjustment:
b. Age and educational achievement adjusted rate for Region A (2 pts)
= 6.0/1000
c. Age and educational achievement adjusted rate for Region B (2 pts)
= 6.3/1000
d. Comparison of the overall crude rates with the age and educational
achievement adjusted rates.
Briefly explain your findings. (2 pts): Much of the difference
between the crude rates of the two regions is due to the different
distributions of age and educational achievement.
24. Causal relationship - Comment specifically on at least two of Bradford
Hill's criteria for causal inference. Include in your comments data or
statements from the article. (5 pts)
25. Assuming that this relationship is causal, why might a similar study,
50 years from now, fail to find as strong a relationship? (2 pts)
Formula changes (less fat), overfeeding reduced reflecting recent trends.
_____________________________________________
Schoenbach, \ epid168 \ exams 1997 Final exam - answer guide;
12/10/1998, 12/12/1998