Deirdre A. Hill

Etiologic heterogeneity among non-Hodgkin lymphoma subtypes.

Understanding patterns of etiologic commonality and heterogeneity for non-Hodgkin lymphomas may illuminate lymphomagenesis. We present the first systematic comparison of risks by lymphoma subtype for a broad range of putative risk factors in a population-based case-control study, including diffuse large B-cell (DLBCL; N = 416), follicular (N = 318), and marginal zone lymphomas (N = 106), and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL; N = 133). We required at least 2 of 3 analyses to support differences in risk: (1) polytomous logistic regression, (2) homogeneity tests, or (3) dichotomous logistic regression, analyzing all 7 possible pairwise comparisons among the subtypes, corresponding to various groupings by clinical behavior, genetic features, and differentiation. Late birth order and high body mass index (>/= 35) kg/m(2)) increased risk for DLBCL alone. Autoimmune conditions increased risk for marginal zone lymphoma alone. The tumor necrosis factor G-308A polymorphism (rs1800629) increased risks for both DLBCL and marginal zone lymphoma. Exposure to certain dietary heterocyclic amines from meat consumption increased risk for CLL/SLL alone. We observed no significant risk factors for follicular lymphoma alone. These data clearly support both etiologic commonality and heterogeneity for lymphoma subtypes, suggesting that immune dysfunction is of greater etiologic importance for DLBCL and marginal zone lymphoma than for CLL/SLL and follicular lymphoma.

Serum concentrations of IGF-I, IGFBP-3 and c-peptide and risk of hyperplasia and cancer of the breast in postmenopausal women.

Experimental evidence suggests that insulin and insulin‐related growth factors may play a role in breast pathology through their mitogenic and anti‐apoptotic effects on breast cells. Our objective was to assess the relationship between serum concentrations of insulin‐like growth factor‐I (IGF‐I), its major binding protein (IGFBP‐3), the ratio IGF‐I:IGFBP‐3, c‐peptide (a marker of insulin secretion) and the ratio c‐peptide:fructosamine (a marker of insulin resistance) and the risk of epithelial hyperplasia (an established breast cancer risk factor) and localized breast cancer among postmenopausal women. Study subjects were patients who provided serum before breast biopsy or mastectomy in 3 hospitals in Grand Rapids, MI between 1977 and 1987. Two case groups, 186 subjects with epithelial hyperplasia of the breast and 185 subjects with localized breast cancer, were compared to 159 subjects with nonproliferative breast changes that have not been associated with increased breast cancer risk. Serum concentrations of IGF‐I, IGFBP‐3 and the ratio IGF‐I:IGFBP‐3 were not related to risk of either hyperplasia or breast cancer. For women in the highest quartile of c‐peptide or of c‐peptide:fructosamine compared to those in the lowest quartile, the odds ratios (ORs) for hyperplasia were 3.0 (95% confidence interval [CI] 1.4–6.5) and 3.3 (95% CI 1.5–7.3), respectively (p trend = 0.02 and 0.02, respectively). The corresponding ORs for breast cancer were 1.5 (95% CI 0.7–3.0) and 1.6 (95% CI 0.8–3.2), respectively (p trend = 0.35 and 0.25, respectively). Our results suggest that insulin and insulin resistance may play a role in breast pathology in postmenopausal women.

Serum concentrations of estrogens, sex hormone-binding globulin, and androgens and risk of breast cancer in postmenopausal women.

We assessed the relationship between serum concentrations of estrogens, androgens, and sex hormone‐binding globulin and risk of breast cancer among postmenopausal women. Study participants provided serum prior to breast biopsy or mastectomy in 3 hospitals in Grand Rapids, Michigan between 1977 and 1987. A total of 179 subjects with localized breast cancer were compared to 152 subjects with nonproliferative breast changes that have not been associated with elevated breast cancer risk. Increasing serum concentrations of estrone and estrone sulfate were associated with increases in breast cancer risk; the odds ratios (ORs) in the fourth quartiles compared to the first were 2.3 (95% confidence interval (CI) 1.1–4.6) for both (p‐trend = 0.02 and 0.03, respectively). Estradiol and bioavailable estradiol concentrations were associated with nonstatistically significant increases in risk. Androstenediol levels were associated with risk (p‐trend = 0.01); the OR in the fourth compared to the first quartile was 2.2 (95% CI 1.0–4.6). Testosterone, dehydroepiandrosterone and androstenedione levels were not associated with increased risk. Sex hormone‐binding globulin was associated with a nonsignificant decrease in risk. Associations with estrone and estrone sulfate persisted after adjustment for androstenediol (ORs for fourth compared to first quartiles were 2.0 (95% CI 0.9–4.5) and 2.2 (95% CI 1.0–4.6), respectively (p‐trend = 0.16 for both). The association with androstenediol was attenuated after adjustment for estrone (OR for fourth compared to first quartile was 1.6 (95% CI 0.7–3.6); p‐trend = 0.13). Higher serum concentrations of estrogens were associated with increased breast cancer risk in postmenopausal women. Androgen levels were not independently associated with substantially increased risk.

Clinically Relevant Changes in Family History of Cancer Over Time

CONTEXTnKnowledge of family cancer history is important for assessing cancer risk and guiding screening recommendations.nnnOBJECTIVEnTo quantify how often throughout adulthood clinically significant changes occur in cancer family history that would result in recommendations for earlier or intense screening.nnnDESIGN AND SETTINGnDescriptive 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.nnnPARTICIPANTSnAdults 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.nnnMAIN OUTCOME MEASURESnPercentage 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.nnnRESULTSnRetrospective 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.nnnCONCLUSIONnClinically 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

PURPOSEnThe 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.nnnMETHODSnEligible 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.nnnRESULTSnOf 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.nnnCONCLUSIONnRemote 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 (ORu2009=u20090.42; 95% CIu2009=u20090.19–0.35). 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.

Is the closest facility the one actually used? An assessment of travel time estimation based on mammography facilities.

AbstractBackgroundCharacterizing geographic access depends on a broad range of methods available to researchers and the healthcare context to which the method is applied. Globally, travel time is one frequently used measure of geographic access with known limitations associated with data availability. Specifically, due to lack of available utilization data, many travel time studies assume that patients use the closest facility. To examine this assumption, an example using mammography screening data, which is considered a geographically abundant health care service in the United States, is explored. This work makes an important methodological contribution to measuring access—which is a critical component of health care planning and equity almost everywhere.nMethodWe analyzed one mammogram from each of 646,553 women participating in the US based Breast Cancer Surveillance Consortium for years 2005–2012. We geocoded each record to street level address data in order to calculate travel time to the closest and to the actually used mammography facility. Travel time between the closest and the actual facility used was explored by woman-level and facility characteristics.ResultsOnly 35xa0% of women in the study population used their closest facility, but nearly three-quarters of women not using their closest facility used a facility within 5xa0min of the closest facility. Individuals that by-passed the closest facility tended to live in an urban core, within higher income neighborhoods, or in areas where the average travel times to work was longer. Those living in small towns or isolated rural areas had longer closer and actual median drive times.ConclusionSince the majority of US women accessed a facility within a few minutes of their closest facility this suggests that distance to the closest facility may serve as an adequate proxy for utilization studies of geographically abundant services like mammography in areas where the transportation networks are well established.

Geographic Access to Breast Imaging for US Women

PURPOSEnThe breast imaging modalities of mammography, ultrasound, and MRI are widely used for screening, diagnosis, treatment, and surveillance of breast cancer. Geographic access to breast imaging services in various modalities is not known at a national level overall or for population subgroups.nnnMETHODSnA retrospective study of 2004-2008 Medicare claims data was conducted to identify ZIP codes in which breast imaging occurred, and data were mapped. Estimated travel times were made for each modality for 215,798 census block groups in the contiguous United States. Using Census 2010 data, travel times were characterized by sociodemographic factors for 92,788,909 women aged ≥30 years, overall, and by subgroups of age, race/ethnicity, rurality, education, and median income.nnnRESULTSnOverall, 85% of women had travel times of ≤20 minutes to nearest mammography or ultrasound services, and 70% had travel times of ≤20 minutes for MRI with little variation by age. Native American women had median travel times 2-3 times longer for all 3 modalities, compared to women of other racial/ethnic groups. For rural women, median travel times to breast imaging services were 4-8-fold longer than they were for urban women. Black and Asian women had the shortest median travel times to services for all 3xa0modalities.nnnCONCLUSIONSnTravel times to mammography and ultrasound breast imaging facilities are short for most women, but for breast MRI, travel times are notably longer. Native American and rural women are disadvantaged in geographic access based on travel times to breast imaging services. This work informs potential interventions to reduce inequities in access and utilization.

Method of Detection and Breast Cancer Survival Disparities in Hispanic Women

Background: Hispanic women in New Mexico (NM) are more likely than non-Hispanic women to die of breast cancer–related causes. We determined whether survival differences between Hispanic and non-Hispanic women might be attributable to the method of detection, an independent breast cancer prognostic factor in previous studies. Methods: White women diagnosed with invasive breast cancer from 1995 through 2004 were identified from NM Surveillance Epidemiology End Results (SEER) files (n = 5,067) and matched to NM Mammography Project records. Method of cancer detection was categorized as “symptomatic” or “screen-detected.” The proportion of Hispanic survival disparity accounted for by included variables was assessed using Cox models. Results: In the median follow-up of 87 months, 490 breast cancer deaths occurred. Symptomatic versus screen-detection was classifiable for 3,891 women (76.8%), and was independently related to breast cancer-specific survival [hazard ratio (HR), 1.6; 95% confidence interval (95% CI), 1.3-2.0]. Hispanic women had a 1.5-fold increased risk of breast cancer–related death, relative to non-Hispanic women (95% CI, 1.2-1.8). After adjustment for detection method, the Hispanic HR declined from 1.50 to 1.45 (10%), but after inclusion of other prognostic indicators the Hispanic HR equaled 1.23 (95% CI, 1.01-1.48). Conclusions: Although the Hispanic HR declined 50% after adjustment, the decrease was largely due to adverse tumor prognostic characteristics. Impact: Reduction of disparate survival in Hispanic women may rely not only on increased detection of tumors when asymptomatic but on the development of greater understanding of biological factors that predispose to poor prognosis tumors. Cancer Epidemiol Biomarkers Prev; 19(10); 2453–60. ©2010 AACR.