Jan T. Lowery

Small cell lung cancer in women: risk associated with smoking, prior respiratory disease, and occupation

Small cell carcinoma of the lung (SCLC) occurs most frequently in heavy smokers, yet exhibits a lesser predominance among men than other smoking-associated lung cancers. Incidence rates have increased more rapidly in women than men and at a faster rate among women than other cell types. To investigate the importance of smoking and other risk factors, a case-control study of SCLC in women was conducted. A total of 98 women with primary SCLC and 204 healthy controls, identified by random-digit dialing and frequency matched for age, completed telephone interviews. Data collected include demographics, medical history, family cancer history, residence history, and lifetime smoking habits. Odds ratios (ORs) and 95% confidence intervals (95% CI) were calculated using logistic regression analysis. Risk for small cell carcinoma in women is strongly associated with current use of cigarettes. Ninety-seven of 98 cases had smoked cigarettes; 79% of cases were current smokers and 20% were former smokers at the time of diagnosis compared to 13% current and 34% former smokers among controls. The ORs associated with smoking are 108.7 (95% CI 14.8-801) for ever-use of cigarettes, 278.9 (95% CI 37.0-2102) for current smoking, and 31.5 (95% CI 4. 1-241) for former smoking. Risk increases steeply with pack-years of smoking and decreases with duration of smoking cessation. After adjusting for age, education, and lifetime smoking history, medical history of physician-diagnosed respiratory disease including chronic bronchitis, emphysema, pneumonia, tuberculosis, asthma, and hay fever is not associated with a significant increase in lung cancer risk. Employment in blue collar, service, or other high risk occupations is associated with a two to three-fold non-significant increase in risk for small cell carcinoma after adjusting for smoking.

Common familial colorectal cancer linked to chromosome 7q31: a genome-wide analysis.

Present investigations suggest that approximately 30% of colorectal cancer cases arise on the basis of inherited factors. We hypothesize that the majority of inherited factors are moderately penetrant genes, common in the population. We use an affected sibling pair approach to identify genetic regions that are coinherited by siblings with colorectal cancer. Individuals from families with at least two siblings diagnosed with colorectal adenocarcinoma or high-grade dysplasia were enrolled. Known familial colorectal cancer syndromes were excluded. A genome-wide scan on 151 DNA samples from 70 kindreds was completed using deCODE 1100 short tandem repeat marker set at an average 4-cM density. Fine mapping on a total of 184 DNAs from 83 kindreds was done in regions suggesting linkage. Linkage analysis was accomplished with Merlin analysis package. Nonparametric linkage analysis revealed three genetic regions with logarithm of the odds (LOD) scores >or=2.0: Ch. 3q29, LOD 2.61 (P = 0.0003); Ch. 4q31.3, LOD 2.13 (P = 0.0009); and Ch. 7q31.31, LOD 3.08 (P = 0.00008). Affected siblings with increased sharing at the 7q31 locus have a 3.8-year (+/- 3.5) earlier age of colorectal cancer onset although this is not statistically significant (P = 0.11). No significant linkage was found near genes causing known syndromes or regions previously reported (8q24, 9q22, and 11q23). The chromosome 3q21-q24 region reported to be linked in colorectal cancer relative pairs is supported by our study, albeit a minor peak (LOD 0.9; P = 0.02). No known familial cancer genes reside in the 7q31 locus, and thus the identified region may contain a novel susceptibility gene responsible for common familial colorectal cancer.

Ethnic Disparities in Breast Tumor Phenotypic Subtypes in Hispanic and Non-Hispanic White Women

AIMS Hispanic women are at a lower risk of getting breast cancer than non-Hispanic white (NHW) women, yet they experience a higher risk of mortality after diagnosis. There is some evidence to suggest differences in tumor pathology; however, very limited research has been published on Hispanic women. This represents one of the first studies to evaluate the prevalence of tumor markers and phenotypic subtypes that are associated with poorer prognosis (human epidermal growth factor receptor 2 [HER2], triple negative and basal-like tumors) among Hispanic women. METHODS We reviewed pathology reports, obtained paraffin blocks of breast cancer tissue, and established tissue microarrays from NHW (n=119) and Hispanic women (n=69) who were Colorado participants in the 4-Corners Breast Cancer Study. We evaluated ethnic differences in the prevalence of tumor markers and phenotypic subtypes and assessed the contribution of risk factors in explaining the observed differences. RESULTS Consistent with other studies, Hispanic women had a higher prevalence of estrogen receptor-negative tumors compared with NHWs (36.2% vs. 22.7%, p=0.05). Hispanics also had an unexpectedly higher proportion of HER2-positive tumors compared with NHWs (31.9% vs. 14.3%, p<0.01). Independent of other prognostic factors, Hispanics were 2.8 times more likely to have a HER2-positive tumor (95% confidence interval [CI] 0.98-7.86). Hispanics were less likely to have the more favorable luminal A subtype, but no significant differences were observed for the less favorable basal-like or triple negative subtypes. However, there were suggestive differences when considering menopausal status. CONCLUSIONS These findings provide evidence that breast cancers among Hispanic women comprise a distinct spectrum of tumor subtypes when compared with NHW women.

Clinically Relevant Changes in Family History of Cancer Over Time

CONTEXT Knowledge of family cancer history is important for assessing cancer risk and guiding screening recommendations. OBJECTIVE To quantify how often throughout adulthood clinically significant changes occur in cancer family history that would result in recommendations for earlier or intense screening. DESIGN AND SETTING Descriptive study examining baseline and follow-up family history data from participants in the Cancer Genetics Network (CGN), a US national population-based cancer registry, between 1999 and 2009. PARTICIPANTS Adults with a personal history, family history, or both of cancer enrolled in the CGN through population-based cancer registries. Retrospective colorectal, breast, and prostate cancer screening-specific analyses included 9861, 2547, and 1817 participants, respectively; prospective analyses included 1533, 617, and 163 participants, respectively. Median follow-up was 8 years (range, 0-11 years). Screening-specific analyses excluded participants with the cancer of interest. MAIN OUTCOME MEASURES Percentage of individuals with clinically significant family histories and rate of change over 2 periods: (1) retrospectively, from birth until CGN enrollment and (2) prospectively, from enrollment to last follow-up. RESULTS Retrospective analysis revealed that the percentages of participants who met criteria for high-risk screening based on family history at ages 30 and 50 years, respectively, were as follows: for colorectal cancer, 2.1% (95% confidence interval [CI], 1.8%-2.4%) and 7.1% (95% CI, 6.5%-7.6%); for breast cancer, 7.2% (95% CI, 6.1%-8.4%) and 11.4% (95% CI, 10.0%-12.8%); and for prostate cancer, 0.9% (95% CI, 0.5%-1.4%) and 2.0% (95% CI, 1.4%-2.7%). In prospective analysis, the numbers of participants who newly met criteria for high-risk screening based on family history per 100 persons followed up for 20 years were 2 (95% CI, 0-7) for colorectal cancer, 6 (95% CI, 2-13) for breast cancer, and 8 (95% CI, 3-16) for prostate cancer. The rate of change in cancer family history was similar for colorectal and breast cancer between the 2 analyses. CONCLUSION Clinically relevant family history of colorectal, breast, and prostate cancer that would result in recommendations for earlier or intense cancer screening increases between ages 30 and 50 years, although the absolute rate is low for prostate cancer.

Telehealth Personalized Cancer Risk Communication to Motivate Colonoscopy in Relatives of Patients With Colorectal Cancer: The Family CARE Randomized Controlled Trial

PURPOSE The rate of adherence to regular colonoscopy screening in individuals at increased familial risk of colorectal cancer (CRC) is suboptimal, especially among rural and other geographically underserved populations. Remote interventions may overcome geographic and system-level barriers. We compared the efficacy of a telehealth-based personalized risk assessment and communication intervention with a mailed educational brochure for improving colonoscopy screening among at-risk relatives of patients with CRC. METHODS Eligible individuals age 30 to 74 years who were not up-to-date with risk-appropriate screening and were not candidates for genetic testing were recruited after contacting patients with CRC or their next of kin in five states. Enrollees were randomly assigned as family units to either an active, personalized intervention that incorporated evidence-based risk communication and behavior change techniques, or a mailed educational brochure. The primary outcome was medically verified colonoscopy within 9 months of the intervention. RESULTS Of the 481 eligible and randomly assigned at-risk relatives, 79.8% completed the outcome assessments within 9 months; 35.4% of those in the personalized intervention group and 15.7% of those in the comparison group obtained a colonoscopy. In an intent-to-treat analysis, the telehealth group was almost three times as likely to get screened as the low-intensity comparison group (odds ratio, 2.83; 95% CI, 1.87 to 4.28; P < .001). Persons residing in rural areas and those with lower incomes benefitted at the same level as did urban residents. CONCLUSION Remote personalized interventions that consider family history and incorporate evidence-based risk communication and behavior change strategies may promote risk-appropriate screening in close relatives of patients with CRC.

A randomized trial to increase colonoscopy screening in members of high-risk families in the colorectal cancer family registry and cancer genetics network.

Background: Individuals with a strong family history of colorectal cancer have significant risk for colorectal cancer, although adherence to colonoscopy screening in these groups remains low. This study assessed whether a tailored telephone counseling intervention can increase adherence to colonoscopy in members of high-risk families in a randomized, controlled trial. Methods: Eligible participants were recruited from two national cancer registries if they had a first-degree relative with colorectal cancer under age 60 or multiple affected family members, which included families that met the Amsterdam criteria for hereditary non-polyposis colon cancer (HNPCC), and if they were due for colonoscopy within 24 months. Participants were randomized to receive a tailored telephone intervention grounded in behavioral theory or a mailed packet with general information about screening. Colonoscopy status was assessed through follow-up surveys and endoscopy reports. Cox proportional hazards models were used to assess intervention effect. Results: Of the 632 participants (ages 25–80), 60% were female, the majority were White, non-Hispanic, educated, and had health insurance. Colonoscopy adherence increased 11 percentage points in the tailored telephone intervention group, compared with no significant change in the mailed group. The telephone intervention was associated with a 32% increase in screening adherence compared with the mailed intervention (HR, 1.32; P = 0.01). Conclusions: A tailored telephone intervention can effectively increase colonoscopy adherence in high-risk persons. This intervention has the potential for broad dissemination to healthcare organizations or other high-risk populations. Impact: Increasing adherence to colonoscopy among persons with increased colorectal cancer risk could effectively reduce incidence and mortality from this disease. Cancer Epidemiol Biomarkers Prev; 23(4); 601–10. ©2014 AACR.

Awareness and Preferences Regarding BRCA1/2 Genetic Counseling and Testing Among Latinas and Non-Latina White Women at Increased Risk for Hereditary Breast and Ovarian Cancer

This study was an investigation of awareness, cognitions, and psychosocial and educational needs related to genetic counseling and testing among Latinas and non-Latina whites at increased risk for having a BRCA1/2 mutation. Sixty-three Latina and eighty-four non-Latina white women completed telephone surveys employing a mixture of quantitative and qualitative questions assessing awareness, benefits, risks, barriers, and genetic counseling communication preferences regarding BRCA1/2 testing. Among participants who had not previously had genetic counseling/testing, 56.9% of Latinas (29/51) and 34.8% of non-Latina white participants (24/69) were unaware of the availability of BRCA1/2 testing. In multivariate logistic regression analysis, Latina ethnicity was the only statistically significant independent factor associated with lack of awareness (OR = 0.42; 95% CI = 0.19–0.35). No appreciable differences were noted between ethnic groups regarding perceived benefits of BRCA1/2 testing or desired genetic counseling topics. These findings underscore the importance of increasing awareness of cancer genetic counseling and genetic testing among both Latina and non-Latina white populations.

Understanding the contribution of family history to colorectal cancer risk and its clinical implications: A state‐of‐the‐science review

Persons with a family history (FH) of colorectal cancer (CRC) or adenomas that are not due to known hereditary syndromes have an increased risk for CRC. An understanding of these risks, screening recommendations, and screening behaviors can inform strategies for reducing the CRC burden in these families. A comprehensive review of the literature published within the past 10 years has been performed to assess what is known about cancer risk, screening guidelines, adherence and barriers to screening, and effective interventions in persons with an FH of CRC and to identify FH tools used to identify these individuals and inform care. Existing data show that having 1 affected first‐degree relative (FDR) increases the CRC risk 2‐fold, and the risk increases with multiple affected FDRs and a younger age at diagnosis. There is variability in screening recommendations across consensus guidelines. Screening adherence is <50% and is lower in persons under the age of 50 years. A providers recommendation, multiple affected relatives, and family encouragement facilitate screening; insufficient collection of FH, low knowledge of guidelines, and poor family communication are important barriers. Effective interventions incorporate strategies for overcoming barriers, but these have not been broadly tested in clinical settings. Four strategies for reducing CRC in persons with familial risk are suggested: 1) improving the collection and utilization of the FH of cancer, 2) establishing a consensus for screening guidelines by FH, 3) enhancing provider‐patient knowledge of guidelines and communication about CRC risk, and 4) encouraging survivors to promote screening within their families and partnering with existing screening programs to expand their reach to high‐risk groups. Cancer 2016.

Contractor safety practices and injury rates in construction of the Denver International Airport

BACKGROUND We sought to explain the variation in injury rates found for categories of companies and contracts involved in the construction of the Denver International Airport (DIA) by surveying contractors about company and contract-level safety practices. METHODS We conducted 213 telephone interviews (83% response) with representatives of contracts with payrolls of more than

The impact of direct-to-consumer marketing of cancer genetic testing on women according to their genetic risk

250,000. We investigated the bivariate relationship between safety actions reported in the survey and injury occurrence by calculating the aggregate injury rates (lost work-time (LWT) rates and non-LWT rates) for the group of respondent contracts reporting always taking the action and for the group not always taking the action. Using Poisson regression, we examined the association between contract injury rates and contract safety practices while controlling for variables previously shown to affect contract-level injury rates. RESULTS In Poisson regression, two actions, 1) disciplinary action always resulting when safety rules were violated and 2) always considering experience modification ratings when selecting subcontractors, were associated with lower LWT injury rates. Three actions or contract characteristics resulted in lower non-LWT rates: management always establishing goals for safety for supervisors, conducting drug testing at times other than badging or after an accident, and completing the DIA contract on budget, rather than over budget. Reportedly consistent use of a number of accepted safety practices was associated with significantly higher injury rates in bivariate and multivariate analyses. CONCLUSIONS The pattern of counterintuitive results found in this study suggests that questions reflecting agreed-upon safety practices, when asked of the person responsible for all on-site construction activities, are likely to elicit normative responses. Objective validation of reported safety practices is critical to evaluating their efficacy in reducing injury rates, along with measures of both time at risk and outcome and control for prevailing risk of the work performed.