Nicotine Dependence and Lung Cancer Genetics in African Americans
Phase: NA
Conditions: Lung Cancer
Sponsor: Temple University

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 1 of 15
Protocol Title
Nicotine Dependence and Lung Cancer Genetics in African Americans
Principal Investigators
FCCC: Camille Ragin, PhD, MPH
CUNY Hunter: Joel Erblich, PhD, MPH
Co-Investigator(s):
Claudia Henschke, MD, Icahn School of Medicine at Mount Sinai
Participating/Collaborating Institutions:
CUNY Hunter College 
695 Park Ave, NY, NY 10065
Icahn School of Medicine at Mount Sinai
One Gustave L. Levy Place, Box 1081, New York, NY 10029
Statistician:
Karthik Devarajan
Funding Source:
National Cancer Institute 
Initial Version Date: 11/20/2018

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 2 of 15
Table of Contents
Section
Page
1.0
Introduction…………………………………………………………………………….    3
2.0 
Objectives………………........................................................................................   3
3.0
Background…………………………………………………………………………..   3-4
4.0
Study Design…………………………………………………………………………… 4-7
4.1 ………………………………………………………………………………
5-7
4.2 ………………………………………………………………………………
7
5.0
Risk to Participants………………………………………………………………….
7
6.0
Potential Benefits to Participants…………………………………………………
6
7.0
Provisions to Maintain the Confidentiality of Data……………………………..
6
8.0
Costs to Participants………………………………………………………………    
7
9.0
Consent Process………………………………………………………………………
7
10.0   Off-Study Criteria…………………………………………………………………….    7
11.0
Drugs and Devices……………………………………………………………………
7
12.0
Multi-Site Research Study…………………………………………………….
7-8
13.0
Statistical Analysis…………………………………………………………………
8-9
14.0
Data Safety Monitoring Plan………………………………………………………
9
15.0
Adverse Event Reporting……………………………………………………….
10
16.0
Quality Assurance Procedures and Participant Confidentiality……………
10
17.0
Participant Informed Consent………………………………………………………. 10
18.0
References…………………………………………………………………………….
11-14

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 3 of 15
1.0 Introduction
Racial differences in the burden of lung cancer persist despite significant nationwide efforts to 
promote smoking cessation. A higher incidence of lung cancer is notable among African 
American (AA) in comparison to Whites, and this has not changed for more than a decade.1 
Despite the fact that AAs smoke fewer cigarettes per day than Whites,2,3 they are less likely to 
stop smoking and are more likely to engage in deeper and longer inhalations.4-7  Although 
access to health care and other systemic and socio-economic barriers contribute substantially to 
these problems, biological factors continue to be a critical contributor to lung cancer disparities.8 
In particular, research by the study investigators and others 9-11 (see also preliminary work 
section) have raised the intriguing possibility that  differences between AA and Whites may be 
attributable to genetic factors that may be contribute to poorer  metabolism of tobacco-related 
carcinogens and increased risk of addiction.12-14 
2.0 Objectives
Aim 1: Identify ancestry-informative variants in tobacco metabolism and detoxification pathway 
genes that correlate with metabolic/detoxification capacity in AA smokers.  
Aim 2: Identify ancestry-informative variants in tobacco addiction pathway genes that correlate 
with measures of nicotine dependence in AA smokers.
Aim 3: Explore the possibility that genetic feedback about increased lung cancer risk associated 
with African American ancestry may influence perceived risk, cancer worry, acute psychological 
distress, and motivation to quit.
3.0 Background/Rationale
Genetics, race, tobacco-related carcinogen metabolism, and addiction. Two prominent groups 
of potent tobacco carcinogens are benzo[a]pyrene and tobacco-specific nitrosamines such as 
N'-nitrosonornicotine (NNN) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). NNK is 
reduced in the body to NNAL and activated by Phase I enzymes to a reactive metabolite that 
alkylates DNA or is further detoxified by Phase II enzymes in the UGT pathway to NNAL – 
glucuronide (NNAL-Gluc). Phase III enzymes (ABC transporters) are known to efflux Phase II 
conjugates from cells to enable excretion from the body. NNAL is a potent carcinogen in 
rats.15,16 Studies demonstrate that urinary NNAL-Gluc:NNAL ratio, a measure of an individual’s 
metabolism and detoxification capacity, is higher in Whites compared to AA,13,14 suggesting 
racial differences in metabolic activation/detoxification of tobacco smoke carcinogens. Genetic 
polymorphisms have been described for a number of Phase I, II/III enzymes involved in the 
metabolism of tobacco and efflux of carcinogens. Many of these polymorphisms have been 
linked to phenotypic differences in protein activity or expression and are likely to be a major 
source of inter-individual variation in susceptibility to tobacco carcinogenesis and thus increased 
lung cancer risk.17-23 Levels of urinary NNAL metabolites can be influenced by polymorphisms in 
the Phase I and II genes,24,25 highlighting the importance of genetic variants in tobacco 
metabolism and carcinogenesis. 
Interestingly, the association of genetic variants in Phase I/II/III genes with the metabolism and 
efflux of tobacco smoke carcinogens from cells may prove to be dependent on race, because 
the frequency of these polymorphisms varies among racial/ethnic groups.26 Our preliminary data 
presented below also provides further support by demonstrating that in Phase I/II/III genes, 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 4 of 15
polymorphisms with varied frequencies between AA and Whites (i.e., Ancestry Informative 
Markers [AIMs]) are predicted to be biologically important and could influence the expression 
and function of these genes. Less well studied are ancestry informative polymorphisms related 
to addiction.  Although a number of studies have identified associations between a variety of 
genetic polymorphisms and addiction and smoking-related outcomes,11, 27,28 no study to date 
has specifically investigated effects of ancestry-informative markers on addiction and smoking 
behavior in AA smokers.
Clinical relevance of genetic risk information.  One potentially important clinical application of 
genetic testing for lung cancer risk is the provision of test feedback to smokers in the hopes of 
encouraging cessation. Accumulating research in this area has yielded mixed results, with 
recent meta-analyses suggesting that genetic feedback about increased lung cancer risk can 
result in significant short-term improvements in smoking cessation, but no long-term changes.29 
These findings are perhaps not surprising, given the poor long-term smoking cessation success 
rates, even with available treatments. Experimental studies that systematically manipulate risk 
information and assess immediate outcomes that are relevant to behaviour change (e.g., worry, 
perceived risk, motivation to quit) might provide a clearer and more accurate picture of the utility 
of genetic testing feedback in presenting a “teachable moment” in which to intervene to 
encourage behaviour change. Consistent with this possibility, Consultant Lipkus and 
colleagues30 conducted an experimental study in which hypothetical lung cancer genetic risk 
information was manipulated, and they found that high-risk information caused immediate 
increases in motivation to quit smoking. Our pilot data from AA current smokers also confirms 
this. Similarly, other experimental studies using hypothetical risk information as a model found 
that genetic risk feedback resulted in immediate increases in worry and perceived risk.31, 32 
Overall, the literature suggests that experimental studies of hypothetical risk can be a useful tool 
in understanding the short-term effects of receiving genetic risk information. What has not yet 
been examined is the possibility that adding personally relevant information to the feedback can 
enhance effects. Feedback regarding genetic ancestry may thus also have a significant impact 
on perceived risk, worry, and motivation to quit. Based on empirical and theoretical models of 
heath literacy and numeracy advanced by Consultant Lipkus and others,33, 34 the proposed 
study will explore the potentially important contribution of personally relevant quantitative 
information to key motivational outcomes related to behaviour change. For example, AA 
smokers who are informed that their genetic ancestry is in fact highly concordant with AA 
heritage may be particularly concerned about genetic risks that have been shown to be 
overrepresented in AAs. Conversely, those who learn that they have low levels of genetic 
concordance with AA heritage may then self-identify less strongly as AA, resulting in lower 
concern for genetic risks that are overrepresented in AA smokers. To date, no study has 
investigated this intriguing possibility.
4.0 Study Design
This is a multi-centered study being conducted at the following centers:
Fox Chase Cancer Center (FCCC) by the lead investigator, Camille Ragin, PhD, MPH.  FCCC 
will serve as the coordinating center for this study.
CUNY Hunter College under the direction of  Joel Erblich, PhD, MPH will conduct community 
based research initiatives and recruit study participants from the community. 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 5 of 15
Icahn School of Medicine at Mount Sinai with Claudia Henschke, MD will obtain IRB approval, 
recruit subjects and execute the protocol at Mount Sinai.
We will enroll 360 AA smokers, 180 from clinic-based settings in Philadelphia and NYC that 
serve smokers and 180 from the general community in Philadelphia and NYC. This recruitment 
strategy will provide a regionally-diverse sample with an increased range of smoking and 
dependence levels, which will enhance generalizability, as well as power to detect hypothesized 
genetic effects. To ensure that the demographics of both clinic and community-based samples 
are balanced, both subgroups will be matched on age and gender. 
Subjects that had participated in protocol 14-814, PI Ragin’s cohort of cancer-free individuals 
and indicated they would like to be contacted for possible participation in future research will be 
offered an opportunity to enroll in this study. These participants will complete the intervention 
aspect of the study and we anticipate they will help us to reach our recruitment goals. This 
protocol enrolled subjects in NYC and Philadelphia. It also allowed those enrolled to be notified 
of other cancer related studies led by Ragin and/or her collaborators.  
Recruitment and study setting: Philadelphia and NYC are racially diverse, with AAs comprising 
a large portion of the general populations. This proposed study will leverage on our existing 
cohort (CAP3) infrastructure, as well as the considerable resources of the Mount Sinai Health 
System, with which we have partnered to enhance recruitment.
4.1 Subject Recruitment and Data Collection
Face-to-face: As previously described in IRB 11-880, study subjects will be recruited 
from various locations throughout the metropolitan area of the aforementioned study 
cities (for example, stores, shops, community centers, senior centers, health fairs etc.). 
Based on results from protocol 11-880, we have determined that “on-site” (face-to-face) 
recruitment from various locations throughout the Philadelphia metropolitan area works 
best for control recruitment; subsequently, we will use this method as the primary 
recruitment method for this study. Primary care and specialty clinics within TUHS (e.g. 
ENT and Pulmonary clinics) to identify current smokers. We will also utilize study flyers 
(attached in recruitment section) throughout the TUHS with the contact information for 
study staff. If the individual calls in we will answer any questions and schedule their 
enrollment during their next appointment at a TUHS clinic.
After informed consent is obtained Mouthwash/Saliva samples will be collected at 
the completion of the study questionnaire. Participants will be supplied with a 50 mL 
falcon tube containing 10ml of scope. Participants will be instructed to gargle while tilting 
to the back of the throat for 30-60 seconds before spitting it back into a separate tube. 
Participants will be required to have refrained from eating and drinking at least 30 
minutes prior to performing the mouthwash rinses. All mouthwash samples will be 
transported at 4 degrees Celsius (on ice packs) to the laboratory where they will be 
processed. All samples will be labeled with a unique ID number corresponding to the 
questionnaire but without personal identifiers. For urine collection, study staff will instruct 
the participant on how to conduct a clean catch urine sample and the participant will self-
collect in nearest rest room. 
All participants with a history of cancer screening (e.g. Pap test, breast 
mammography [females], PSA and/or DRE [males], oral or skin cancer screening, etc.) 
within the past 12 months will be asked to sign an authorization to request information 
from another facility. We will use the standard authorization form used by Fox Chase 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 6 of 15
Cancer Center (FCCC) (attached), which authorizes the research study staff to request 
cancer screening results from another health care facility/medical provider. The signed 
authorization form will be sent along with a memo outlining the specific cancer screening 
result that would be requested.  All reports will be de-identified upon receipt and labeled 
with the participants study ID number. The cancer screening results will be collected in 
order to confirm self-reported cancer status. 
All study materials will be labeled with a unique ID and no PHI. Maintenance of 
participant confidentiality is discussed in detail within the “Risk to Participants” section of 
this document.
For Aim 3: Participants recruited through Aims 1 and 2 at each of the two study sites will 
be randomly assigned to one of four conditions, in a 2 x 2 fully-crossed between-groups 
factorial design. In one group (“High Risk, High Ancestry [HRHA]”), participants will be 
asked to consider a hypothetical scenario in which genetic test results reveal that: 1) 
they carry genotypes that place AA smokers at a particularly high (~50%-80%) risk for 
the development of lung cancer, and 2) their profile of AIMs reflects a particularly high 
concordance with AA heritage (~90%). In a second group (“Low Risk, Low Ancestry 
[LRLA]”), participants will be asked to consider a scenario in which genetic test results 
reveal that: 1) they are at normal (~7%-10%) risk for the development of lung cancer, 
and 2) their profile of AIMs reflects a particularly low concordance with AA heritage 
(~10%). The final two groups will receive “High Risk, Low Ancestry (HRLA)” and “Low 
Risk, High Ancestry (LRHA)” hypotheticals, respectively. Participants will be block 
randomized by age and gender to one of four groups following the 2 (Risk) x 2 
(Ancestry) design. To increase feasibility, randomization will be conducted independently 
at all sites. Following randomization, participants will be presented with a brochure 
describing the nature of two hypothetical genetic tests, one which assesses lifetime risk 
for the development of lung cancer in AA smokers, and one which characterizes the 
degree of a participant’s genetic concordance with AA ancestry. The brochure will be 
explained in a standardized fashion to the participants by the graduate student trainees.  
Participants will then be given the hypothetical feedback according to their randomized 
condition (HRHA, HRLA, LRHA, LRLA), followed immediately by the post-feedback 
assessments (see Measures). Participants will then be debriefed, offered a $30 gift card, 
and thanked for their participation.
Intervention Administration: The intervention will be administered by graduate student 
trainees.  They will be trained to administer the brochure and feedback in a standardized 
fashion. Dr. Erblich will train the graduate students in the administration of the 
hypothetical genetic feedback and the collection of questionnaire data during the post-
feedback assessment. The trainees will practice with each other until they achieve 
proficiency. Dr. Erblich will also personally observe the first five participant interactions in 
both NYC and Philadelphia, as well as a random selection of later interactions (n=10) to 
ensure intervention fidelity.  Additional training will be conducted as necessary to ensure 
fidelity to the intervention.  
To address Aim 3, we will administer the following well-established questionnaires, all of 
which have excellent psychometric properties. The questionnaires are brief, so as not to 
create undue participant burden. Numeracy, an important predictor of response to risk 
information, will be assessed using the 7-item Subjective Numeracy scale (SNS), 
developed by Fagerlin and colleagues. Self-perception of Ancestry Scale (a personal 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 7 of 15
estimation of the genetic proportion of African ancestors) will be assessed using a 
measure described and validated by Ruiz-Linares et al. 
Post-Feedback Assessment: Motivation to quit will be assessed using the Motivation to 
Quit Smoking Scale (MTSS), which has been found to be a strong predictor of quit 
attempts.74,75 Perceived risk of lung cancer will be assessed using an established face-
valid perceived risk scale developed and used by PI Erblich in previous work. Cancer 
worry will be assessed using the well-established 4-item Cancer Worry Scale. 
Psychological distress will be measured using the BSI-18. For all assessments, 
participants will be instructed to respond based on how they believe they would feel if 
they actually received the genetic information that was presented to them. 
Projected Recruitment: The number of participants that will be enrolled into this study will 
be 180 for 3 years (approximately 60 patients per year, per site). 
Number of 
subjects per year 
projected at 
FCCC
Total number of 
subjects at 
FCCC
Number of subjects 
nationally or 
internationally (if 
applicable
Number of 
subjects at 
collaborating 
institutions (if 
applicable)
Up to: 60
Up to:180
360
180
4.2 Inclusion and exclusion criteria
Key Inclusion Criteria:
1.
Men and women age 18 years and older and able to speak and read English 
2.
Must be in good health and not knowingly have a cancer at the time of study 
inclusion
Key Exclusion Criteria:
1.
Head and Neck cancer diagnosis at the time of the oral cancer screening
2.
Low DNA quantity found in mouthwash/saliva sample
3.
Incomplete questionnaire data
4.
Cancer diagnosis within the last 2 years
5.0 Risks to Participants
Risk to the subject is breach of confidentiality. In order to minimize this risk, all information 
obtained from or for this research study will be kept as confidential as possible. Identification of 
questionnaire data and saliva specimens will be assigned a coded study number and files will 
be kept secure.
6.0 Potential Benefits to Participants 
No direct benefit will be gained by subjects, except for the satisfaction they might experience by 
participating in a medical research study. Benefits to society will be those associated with a 
better understanding of the effects of ancestry on motivation to quit smoking and screen for lung 
cancer. 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 8 of 15
7.0 Provisions to Maintain the Confidentiality of Data 
All specimens and associated data (questionnaire, cancer screening results, urine specimen, as 
well as mouthwash samples) will be stored with a unique ID only and not with subject identifiers. 
Identifiable information will never be placed on specimens or associated data (laboratory or 
questionnaire data). 
8.0 Costs to Participants
Not Applicable 
9.0 Consent Process
On-Site Recruitment: Local Information tables will be set up in various locations such as senior 
centers, community recreation centers, churches, community health fairs and neighborhood 
block meetings. The information table will be manned by research staff who will explain the 
research studies conducted in the Ragin Lab and the purpose of the participant recruitment. 
Recruitment initiated by Phone-Call: Research staff will call participants that enrolled in 14-814 
and indicated their interest in future research opportunities and briefly describe the study 
objectives and rationale. The research staff will answer all questions asked by the potential 
participant and an invitation will be extended to participate in this study. If he/she agrees to 
enroll in this study, they will sign an informed consent document, questionnaires will be 
administered, and biological samples will be collected by trained research staff. 
As part of the informed consent process, all participants recruited in this study that have not 
been enrolled in 14-814 will be given an opportunity to join the 14-814 registry study.  On-Site 
Recruitment as described in section 9.0 of that protocol will be followed. 
10.0
Off-Study Criteria
Participants will only be removed from the study if a cancer diagnosis is made at the time of the 
oral cancer screening or if the participant is re-contacted for other research opportunities within 
the Ragin Lab and they had a cancer diagnosis subsequent to joining the study.
11.0
Drugs and Devices
Not Applicable
12.0
Multi-Site Research Study
This study will be conducted at sites across the northeastern region of the country. Survey data 
and biological specimens collected from NYC and Philadelphia, will be housed at FCCC. 
In an effort to minimize a breach in participant confidentiality, all site-PIs and their respective 
team members will: provide current Human Subjects Training and be given access to both 
Presage Lite and REDCap, where they will securely enter patient information and complete 
study related questionnaires. Paper copies are also available for back up if needed.  Scanned 
copies of signed consent forms will be emailed to the study coordinator at FCCC using HIPAA 
compliant networks and stored in a password protected file on FCCC stored on a HIPAA 
compliant institutional network drive. Only coded bio-specimens will be sent to FCCC where all 
laboratory procedures will take place. 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 9 of 15
Adverse events that take place at an external site will first be reported to the respective site’s 
IRB followed by FCCC’s IRB. All study findings will be reported under the blanket of the African 
Caribbean Cancer Consortium, a collaborative research group where Dr. Ragin is the PI.
13.0
Statistical Analysis
Aim 1: Variance stabilizing and normalizing transformations will be applied when appropriate. 
Descriptive statistics for demographic variables will be presented. The range and mean 
concentrations of free (NNAL), conjugated (NNAL-Gluc) and total (NNAL+NNAL-Gluc) 
biomarkers will be summarized by genotype. These concentrations as well as the ratio of NNAL-
Gluc:NNAL concentrations will be correlated with each AIM after adjusting for smoking dose 
(pack-years), age and recruitment setting (clinic vs. community) using analysis of variance. A 
similar analysis will be done by correlating these variables with each haplotype block. In 
addition, multiple linear regression will be used to correlate NNAL concentration with proportion 
of African ancestry after adjusting for smoking dose, age and recruitment setting. To account for 
multiple testing, the Benjamini-Hochberg (BH) method will be used to control the false discovery 
rate (FDR). All tests will be two-sided and tests with FDR ≤ 10% will be considered to be 
statistically significant.35 
Sample Size and Power: With 360 samples split in a 1:3 ratio between the minor and major 
allele groups, we will have 80% power to detect an effect size of 0.45 in mean NNAL 
concentration (total) between the groups using a two-sided test at a significance level of 0.005. 
This computation is based on a standard deviation of 1 for NNAL concentrations (on the log2-
scale) from pilot studies. An effect size of 0.45 corresponds to a 1.37-fold change in NNAL 
concentration between groups. Similarly, with 360 samples split in a 1:3 ratio between the minor 
and major allele groups, we will have 80% power to detect an effect size of 1.09 in mean NNAL 
concentration ratio between the groups using a two-sided test at a significance level of 0.005. 
This computation is based on a standard deviation of 2.44 for NNAL concentration ratios (on the 
log2-scale) from pilot studies. An effect size of 1.09 corresponds to a 2.13-fold change in NNAL 
expression between groups. A significance level of 0.005 results in 1 false discovery per 200 
non-differentially expressed SNPs.
Aim 2: For each SNP, nicotine dependence (as determined by high-very high FTND scores: 6-
10) will be modeled using genotype after adjusting for smoking dose (pack-years), age and 
recruitment setting using logistic regression (LR). Sensitivity, specificity and prediction accuracy 
(along with 95% confidence bounds) will be used to characterize the precision of binary 
predictions from LR. Multiple linear regression will be used to correlate the proportion of African 
ancestry with FTND score (low vs. high) after adjusting for smoking dose, age and recruitment 
setting. All tests will be two-sided and the Benjamini-Hochberg method will be used to account 
for multiple testing.35 Secondary outcomes will include cigarettes per day, age at initiation, and 
intention to quit. To account for the potentially large number of SNPs resulting from this 
univariate analysis, penalized logistic regression (PLR) will be used to develop a prediction 
model for nicotine dependence using these SNPs.36 PLR has been demonstrated to have 
excellent power to identify covariate effects as well as superior prediction accuracy compared to 
competing methods like Classification and Regression Trees and Multifactor Dimensionality 
Reduction.37-40 Sensitivity, specificity and prediction accuracy (along with 95% confidence 
bounds) will be used to characterize the precision of binary predictions from PLR. AUC curves 
(along with 95% confidence bounds) will be used to characterize the predictive value of models 
from these methods. A participant whose predictive probability is > 0.5 will be classified as 
having high nicotine dependence; however, alternative thresholds will also be evaluated in this 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 10 of 15
analysis. In addition, the performance of each model will be evaluated using leave-one-out 
cross validation. All computations will be performed using R statistical language and 
environment.41 
Sample Size and Power: With 180 subjects each in the low-medium (scores 0-5) and high-very 
high (scores 6-10) nicotine dependence groups, we will have 80% power to detect a difference 
in the range of 0.14-0.19 (in minor allele frequency between groups in SNPs of interest) at the 
0.005 significance level. This calculation assumes a 10-40% minor allele frequency in the low 
nicotine dependence group.
Aim 3: Variance stabilizing and normalizing transformations will be applied to the data as 
appropriate. Analysis of variance will be used to identify the individual and interaction effects of 
factors on each outcome measure. The Benjamini-Hochberg FDR method56 will be used to 
adjust for multiple tests involving each factor or interaction across the various outcome 
measures, and each test with an FDR ≤ 10% will be considered significant. The primary study 
analyses will be a 2 (Risk) x 2 (Ancestry) factorial ANOVA.  With this statistical approach, we 
will be able to test for main effects of Risk and Ancestry, as well as Risk x Ancestry interactions.  
The primary outcome measure will be motivation to quit; perceived risk, cancer worry, and 
psychological distress will serve as secondary outcomes.  In addition to this primary analysis, 
we will also consider including covariates (e.g., demographics, numeracy, FTND, study site, 
gender, age) to control for external sources of variation.  Finally, we will be able to explore 
possible moderating effects of these covariates. Although of course, the proposed study is not 
powered to detect such effects, such exploratory findings may be important when deciding next 
steps in formally utilizing the results to develop interventions aimed at increasing knowledge of 
genetic lung cancer risk.
Sample size and power: Power computations for this aim are based on the 2 x 2 factorial design 
described above. With 90 participants per experimental condition (combination of genetic risk 
and ancestry), we would be able to detect an effect size of 0.685 due to genetic risk or ancestry 
at a significance level of 0.0125 with 80% power. Similarly, we would be able to detect an effect 
size of 0.895 due to an interaction between genetic risk and ancestry at a significance level of 
0.0125 with 80% power.42 A significance level of 0.0125 has been used to account for the four 
outcome measures of interest in this aim and the calculations are based on a standard deviation 
of 1.37 for motivation to quit smoking from the literature.43 
14.0
Data Safety Monitoring Plan
The PIs and Co-Is have the responsibility to oversee data handling, safety and issues of 
confidentiality, and has the responsibility to train research team members in procedures for 
safeguarding the well-being of human subjects and the confidentiality and correct handling of 
data as well as data storage. The PIs are responsible for monitoring protocol conduct and 
reporting to the Institutions’ Data & Safety Monitoring Board (DSMB) any adverse events related 
to study procedures. The PIs will also be responsible for reviewing and completing the adverse 
event assessment.
15.0
Adverse Events
In accordance with FCCC guidelines, this protocol will employ the following mechanisms for 
adverse event reporting: 1) alert the FCCC review committees of any and all reports of adverse 
events; 2) inform all members of the study team of any all reports of adverse events.  If 3 or 

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 11 of 15
more adverse events are reported, the study team will assess potential causes of the adverse 
events and, if events are clearly linked to study participation, discontinue the study. 
16.0
Quality Assurance Procedures and Participant Confidentiality
Information about study subjects will be kept confidential and managed according to the 
requirements of the Health Insurance Portability and Accountability Act of 1996 (HIPAA). Those 
regulations required a signed subject authorization informing the subject of the following: The 
protected health information (PHI) that will be collected from patient; who will have access to 
that information and why; who will use or disclose that information; the rights of a research 
subject to revoke their authorization or use their PHI. In the event that a participant revokes 
authorization to collect or use PHI, the investigator, by regulation, retains the ability to use all 
information prior to the revocation of subject authorization.  To ensure confidentiality identifier 
will be recorded and used with electronic data collected and all records will be secured in a 
locked location. 
All participants will be screened for eligibility using a checklist created for this study and the 
Principal Investigator will regularly audit accrual to ensure that participants meet eligibility 
criteria. In addition, the Principal Investigator will regularly audit the study files to ensure that 
questionnaires completed by participants contain all study items. Lastly, in order to protect 
confidentiality, all data will be numerically coded and will contain no other identifying factors. 
Information linking the numeric codes to the participant’s name will be kept in a secured file 
cabinet in a secured office. In addition, computer data files will be stored on password-protected 
computers.
17.0
Participant Informed Consent
See separate Informed consent document

FCCC Principal Investigator: Camille Ragin
CUNY Hunter: Joel Erblich
Abbreviated Title: Nicotine Dependence and LCa Genetics in AAs
IRB # 18-8004
Page 12 of 15
18.0
References
1.
Howlader N, Noone AM, Krapcho M, Miller D, Bishop K, Altekruse SF, Kosary CL, Yu M, 
Ruhl J, Tatalovich Z, et al. (ed). SEER Cancer Statistics Review, 1975-2013, National 
Cancer Institute, Bethesda, MD, based on November 2015 SEER data submission, 
posted to the SEER web site, April 2016
2.
Haiman CA, Stram DO, Wilkens LR, Pike MC, Kolonel LN, Henderson BE, Le ML. Ethnic 
and racial differences in the smoking-related risk of lung cancer. N.Engl.J Med 2006 Jan 
26;354(4):333-42
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