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Nov 30, 2013 (3 years and 6 months ago)

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Health Sciences Library



Statistical Approaches

for Cancer Family Studies

with

Times to Event Data

Dr.
Yun
-
Hee Choi

(
Epidemiology & Biostatistics
, Western University
)

Tues
day

January
15
, 201
3


The following citations are provided for your interest by the LRCP library. They are not necessarily
endorsed by today’s presenter. For more resources on this or other topics, contact the LRCP
library x55209 or email
gabriel.boldt@lhsc.on.ca



1.


Yun
-
Hee Choi
.

(2012)
A Frailty
-
Model
-
Based Method for Estimating
Age
-
Dependent Penetrance

from
Family Data
.

Journal of Biometrics and Biostatistics, doi: 10.4172/2155
-
6180


Abstract
:


In this paper, we propose a
general frailty model
-
based approach to accommodate
this

design, where the frailty random effect accounts for shared risk among family members not
due to the observed risk

factors.

Available:
Open access provided by the Journal of Biometrics and Biostatis
tics.

2.


Choi, Y.
-
H.
and Briollais, L.

(2011) An
EM Composite Likelihood Approach for Multistage Sampling of Family Data
with
Missing Genetic Covariates.


Statistica Sinica 21, 231
-
253
.



Abstract
:


We propose here a statistical approach based on the composite likelihood framework.
The composite likelihood is a weighted product of individual likelihoods corresponding to the
sampling strata, where the weights are the inverse sampling probabilities of t
he families in each
stratum.

Available: Online through Western Libraries.

3.


Choi, Y.
-
H.
, Kopciuk, K. and Briollais, L.

(2008)

Estimating the Lifetime Risk Associated with Mutated Genes Involve
d in Complex
Diseases.

Human He
redity, 66, 238
-
251.


Abstract
:

This work gives a general methodological framework for analyzing family
-
based
designs in gene characterization studies and provides more rationale for the choice of an
efficient design and an appropriate likelihood method to estimate the risk as
sociated with an

inher
ited gene mutation.

Available: Online through Western Libraries.

Previous Oncology Grand Round bibliographies are available on the Health Sciences Library
website:
http://wohkn.ca/content.php?pid=240142&sid=2096720

4.


Choi, Y.
-
H.
, and D.E. Matthews

(2005)

Accelerated Life Regression Modelling of Dependent Bivariate Time
-
to
-
Event Data.
Canadian Journal of Statistics, 33, 449
-
464.


Abstract
:


To analyze bivariate
time
-
to
-
event data from matched or naturally paired study
designs, researchers frequently use a random effect called frailty to model the dependence
between within
-
pair response measurements. The authors propose a computational framework
for fitting depend
ent bivariate time
-
to
-
event data that combines frailty distributions and
accelerated life regression models. In this framework users can choose from several parametric
options for frailties, as well as the conditional distributions for within
-
pair response
s. The authors
illustrate the flexibility that their framework represents using paired data from a study of laser
photocoagulation therapy for retinopathy in diabetic patients.

Available: Online through Western Libraries.

5.


Choi,Y.-H.
, Cotterchio, M., McKeown
-
Eyssen, G.,
et al.

Penetrance of Colorectal Cancer among MLH1/MSH2 Carriers Participating in the Colorectal
Canc
er Familial Registry in Ontario.


Hered Cancer Clin Pract. 2009 Aug 23;7(1):14.


PMID: 19698169
.


Results
:


The risks

of developing CRC by age 70 were 60% and 47% among men and women
carriers of any MMR mutation, respectively. Among MLH1 mutation carriers, males had
significantly higher risks than females at all ages (67% vs. 35% by age 70, p
-
value = 0.02), while
the ris
ks were similar in MSH2 carriers (about 54%). The relative risk associated with MLH1 was
almost constant with age (hazard ratio (HR) varied between 5.5
-
5.1 over age 30
-
70), while the
HR for MSH2 decreased with age (from 13.1 at age 30 to 5.4 at age 70).

Av
ailable: Free Full Text in PubMed Central.

6
.


Kopciuk KA,
Choi YH
, Parkhomenko E,

et al.

Penetrance of HNPCC
-
related cancers in a retrolective cohort of 12 large Newfoundland
families carrying a MSH2 founder mutation: an evaluation using modified segregation
models.

Hered Cancer Clin Pract. 2009 Oct 28;7(1):16.


PMID: 19863818
.


Results
:


Lifetime (age 70) risk estimates for male and female carriers were similar for
developing any HNPCC cancer (Males = 98.2%, 95% Confidence Interval (CI) = (93.8%,
99.9%); Females = 92.8%, 95% CI = (82.4%, 99.1%)) but female carriers experienced
substantiall
y reduced lifetime risk for developing CRC compared to male carriers (Females =
38.9%, 95% CI = (24.2%, 62.1%); Males = 84.5%, 95% CI = (67.3%, 91.3%)). Female non
-
carriers had very low lifetime risk for these two outcomes while male non
-
carriers had lifet
ime
risks intermediate to the female carriers and non
-
carriers. Female carriers had a lifetime risk of
developing EC of 82.4%. Relative risks for developing any HNPCC cancer (carriers relative to
non
-
carriers) were substantially greater for females compare
d to their male counterparts
(Females = 54.8, 95%CI = (4.4, 379.8); Males = 9.7, 95% CI = (0.3, 23.8)). Relative risks for
developing CRC at age 70 were substantially greater for females compared to their male
counterparts (Females = 23.7, 95%CI = (5.6, 13
7.9); Males = 6.8%, 95% CI = (2.3, 66.2)).
However, the risk of developing CRC decreased with age among both genders.

Available: Free Full Text in PubMed Central.