Lifetime personal cigarette smoking and risk of young-onset breast cancer by subtype among non-Hispanic Black and White women in the Young Women's Health History Study.

PURPOSE: To evaluate the association between lifetime personal cigarette smoking and young-onset breast cancer (YOBC; diagnosed <50 years of age) risk overall and by breast cancer (BC) subtype, and whether risk varies by race or socioeconomic position (SEP). METHODS: Data are from the Young Women's Health History Study (YWHHS), a population-based case-control study of non-Hispanic Black (NHB) and White (NHW) women, ages 20-49 years (n = 1812 cases, n = 1381 controls) in the Los Angeles County and Metropolitan Detroit Surveillance, Epidemiology, and End Results (SEER) registry areas, 2010-2015. Lifetime personal cigarette smoking characteristics and YOBC risk by subtype were examined using sample-weighted, multivariable-adjusted polytomous logistic regression. RESULTS: YOBC risk associated with ever versus never smoking differed by subtype (Pheterogeneity = 0.01) with risk significantly increased for Luminal A (adjusted odds ratio [aOR] 1.34; 95% confidence interval [CI] 1.06-1.68) and HER2-type (aOR 1.97; 95% CI 1.23-3.16), and no association with Luminal B or Triple Negative subtypes. Additionally, ≥30 years since smoking initiation (versus never) was statistically significantly associated with an increased risk of Luminal A (aOR 1.55; 95% CI 1.07-2.26) and HER2-type YOBC (aOR 2.77; 95% CI 1.32-5.79), but not other subtypes. In addition, among parous women, smoking initiated before first full-term pregnancy (versus never) was significantly associated with an increased risk of Luminal A YOBC (aOR 1.45; 95% CI 1.11-1.89). We observed little evidence for interactions by race and SEP. CONCLUSION: Findings confirm prior reports of a positive association between cigarette smoking and Luminal A YOBC and identify a novel association between smoking and HER2-type YOBC.

A Review of Research on Disparities in the Care of Black and White Patients With Cancer in Detroit.

Racial disparities in cancer incidence and outcomes are well-documented in the US, with Black people having higher incidence rates and worse outcomes than White people. In this review, we present a summary of almost 30 years of research conducted by investigators at the Karmanos Cancer Institute's (KCI's) Population Studies and Disparities Research (PSDR) Program focusing on Black-White disparities in cancer incidence, care, and outcomes. The studies in the review focus on individuals diagnosed with cancer from the Detroit Metropolitan area, but also includes individuals included in national databases. Using an organizational framework of three generations of studies on racial disparities, this review describes racial disparities by primary cancer site, disparities associated with the presence or absence of comorbid medical conditions, disparities in treatment, and disparities in physician-patient communication, all of which contribute to poorer outcomes for Black cancer patients. While socio-demographic and clinical differences account for some of the noted disparities, further work is needed to unravel the influence of systemic effects of racism against Black people, which is argued to be the major contributor to disparate outcomes between Black and White patients with cancer. This review highlights evidence-based strategies that have the potential to help mitigate disparities, improve care for vulnerable populations, and build an equitable healthcare system. Lessons learned can also inform a more equitable response to other health conditions and crises.

Urologists' Perceptions of Active Surveillance and Their Recommendations for Low-risk Prostate Cancer Patients.

OBJECTIVE: To assess practicing urologists' attitudes and perceptions of active surveillance (AS) and other treatment options for low-risk prostate cancer. METHODS: This was a cross-sectional survey of urologists practicing in Michigan and Georgia. Urologists were asked about perceptions and practices pertaining to AS. RESULTS: Overall, 225 urologists completed the survey; 147 (65%) were from Michigan and 78 (35%) were from Georgia. Most urologists reported they provided (99%), discussed (97%), and offered (61%) AS to all of their low-risk patients. Most believed AS is effective (97%) and underused (90%), while 80% agreed that curative therapy (surgery, radiation) is overused in the United States. Although most (79%) endorse that Black men are more likely to have aggressive low-risk disease, 89% reported feeling comfortable recommending AS to Black men. In multivariable analysis, significant provider-related predictors of AS recommendation were practice location, number of years in practice, beliefs pertaining to survival benefit of prostatectomy and effectiveness of AS, and expectation that patients are not interested in AS. The patient characteristics of race, age, life expectancy, fear of cancer progression, and fear of treatment side effects were also significant predictors of AS recommendations. CONCLUSION: Most urologists surveyed stated that AS is effective and underused for low-risk prostate cancer . Overall, urologists are much less likely to recommend AS to younger men and slightly less to Black men. AS recommendations varied by practice location and by years in practice. These findings indicate targeted educational efforts in the US are needed to influence urologists toward greater acceptance of AS.

Physical activity and quality of life in African American cancer survivors: The Detroit Research on Cancer Survivors study.

BACKGROUND: The benefit of regular exercise in improving cancer outcomes is well established. The American Cancer Society (ACS) released a recommendation that cancer survivors should engage in at least 150 minutes of moderate to vigorous physical activity (PA) per week; however, few report meeting this recommendation. This study examined the patterns and correlates of meeting ACS PA recommendations in the Detroit Research on Cancer Survivors (ROCS) cohort of African American cancer survivors. METHODS: Detroit ROCS participants completed baseline and yearly follow-up surveys to update their health and health behaviors, including PA. This study examined participation in PA by select characteristics and reported health-related quality of life (HRQOL) as measured with the Functional Assessment of Cancer Therapy and Patient-Reported Outcomes Measurement Information System instruments. RESULTS: Among the first 1500 ROCS participants, 60% reported participating in regular PA, with 24% reporting ≥150 min/wk. Although there were no differences by sex, prostate cancer survivors were the most likely to report participating in regular PA, whereas lung cancer survivors were the least likely (P = .022). Survivors who reported participating in regular PA reported higher HRQOL (P < .001) and lower depression (P = .040). CONCLUSIONS: Just 24% of African American cancer survivors reported meeting the ACS guidelines for PA at the baseline, but it was encouraging to see increases in activity over time. Because of the established benefits of regular exercise observed in this study and others, identifying and reducing barriers to regular PA among African American cancer survivors are critical for improving outcomes and minimizing disparities.

The Epidemiology of Cancer Among Homeless Adults in Metropolitan Detroit.

BACKGROUND: Homeless individuals suffer and die disproportionately from chronic diseases and disorders. We describe the epidemiology of cancer among homeless persons in metropolitan Detroit. METHODS: A retrospective cohort study was performed using 1973-2014 data from the Metropolitan Detroit Cancer Surveillance System, a population-based cancer registry and member of the National Institutes of Health-National Cancer Institute's Surveillance, Epidemiology, and End Results program. Homeless adults were identified through address at diagnosis listed as a homeless shelter, hospital, or supplemental field indicating homelessness. Age-adjusted, sex-specific proportional incidence ratios (PIR) compared cancer incidence proportions by primary tumor site of homeless patients to the nonhomeless referent population. Kaplan-Meier curves depicted unadjusted survival differences in a propensity score matched sample. Differences in 10-year survival were assessed using the score test with a sandwich estimator accounting for matched cluster effects. Statistical tests were two-sided. RESULTS: A total of 388 individuals experienced homelessness at first primary invasive cancer diagnosis. Statistically significantly higher proportions of respiratory system (PIR = 1.51; 95% confidence interval = 1.28 to 1.79) and female genital system (PIR = 1.83; 95% confidence interval = 1.31 to 2.55) cancers were observed among homeless men and women, respectively. Homeless persons had poorer overall and cancer-reported survival compared with a propensity score matched referent population (median: overall survival, 20.0 vs 38.0 months, respectively, P < .001; cancer-reported survival, 38.0 vs 64.0 months, respectively, P < .001). CONCLUSION: Disparities in disease burden exist between adults who are experiencing homelessness compared with the nonhomeless population at cancer diagnosis. These findings provide clinically relevant information to understand the cancer burden in this medically underserved population and suggest an urgent need to develop cancer prevention and intervention programs to reduce disparities and improve the health of homeless persons.

The Detroit Research on Cancer Survivors (ROCS) Pilot Study: A Focus on Outcomes after Cancer in a Racially Diverse Patient Population.

BACKGROUND: African Americans are often diagnosed with advanced stage cancer and experience higher mortality compared with whites in the United States. Contributing factors, like differences in access to medical care and the prevalence of comorbidities, do not entirely explain racial differences in outcomes. METHODS: The Detroit Research on Cancer Survivors (ROCS) pilot study was conducted to investigate factors related to short- and long-term outcomes among patients with cancer. Participants completed web-based surveys, and mailed saliva specimens were collected for future genetic studies. RESULTS: We recruited 1,000 participants with an overall response rate of 68%. Thirty-one percent completed the survey without any interviewer support and the remaining participated in an interviewer-administered survey. Seventy-four percent provided a saliva specimen and 64% consented for tumor tissue retrieval. African American survivors required more interviewer support (P < 0.001); however, their response rate (69.6%) was higher than non-Hispanic whites (65.4%). African Americans reported poorer overall cancer-related quality of life compared with non-Hispanic whites, measured by FACT-G score (P < 0.001), however, this relationship was reversed after controlling for socioeconomic factors, marital status, and the presence of comorbidities. CONCLUSIONS: In this pilot study, we demonstrated that a web-based survey supplemented with telephone interviews and mailed saliva kits are cost-effective methods to collect patient-reported data and DNA for large studies of cancer survivors with a high proportion of minority patients. The preliminary data collected reinforces differences by race in factors affecting cancer outcomes. Our efforts continue as we expand this unique cohort to include more than 5,000 African American cancer survivors. IMPACT: Formal investigation of factors influencing adverse outcomes among African American cancer survivors will be critical in closing the racial gap in morbidity and mortality.

Attitudes towards health research participation: a qualitative study of US Arabs and Chaldeans.

BACKGROUND: The Arab Muslim and Chaldean Christian American community is unified by language but culturally diverse. Researchers are challenged to engage the Arab/Chaldean community to meet immigrant health needs. Arabs/Chaldeans are identified as white in clinical data sets making it difficult to identify health behaviours and patterns unique to the community. OBJECTIVES: To explore the views of members of the Arab/Chaldean community, including researchers and the lay public, regarding health research participation and the role of clinicians, researchers and community leaders in the research process. METHODS: A qualitative study of Arab and Chaldean adults and researchers conducted in a US community with a large Arab/Chaldean population. Five semi-structured focus group discussions were triangulated with five in-depth semi-structured interviews with Arab or Chaldean primary care researchers. Responses were audio-recorded and transcribed verbatim. Transcripts were coded and thematically analysed, and findings confirmed with community representatives. RESULTS: Three themes were identified: (i) research expectations: risks and benefits; (ii) health care environment: clinicians as recruiters and (iii) research participations: risks and benefits. Themes captured concerns with social relationships, reputation or trust and the cost and benefit of research participation. In the Arab/Chaldean community, institutional and political fears and distrust are amplified. Respect for physicians, teachers and faith leaders connected with or recruiting for studies enhances likelihood of research participation. CONCLUSION: Clinical researchers should address the cultural and immigration histories of Arab/Chaldean research participants. Studies that maximize trust will minimize participation bias and lay the groundwork for improved health. Institutional, sociocultural and personal factors require a pre-study phase to engage and educate participants.

Renal cell carcinoma risk associated with lower intake of micronutrients.

Kidney cancer incidence in African Americans (AA) is higher than among European Americans (EA); reasons for this disparity are not fully known. Dietary micronutrients may have a protective effect on renal cell carcinoma (RCC) development by inhibiting oxidative DNA damage and tumor growth. We evaluated whether any micronutrient associations differed by race in the US Kidney Cancer Study. 1142 EA and AA RCC cases and 1154 frequency-matched controls were enrolled in a population-based case-control study between 2002 and 2007. Dietary micronutrient intake was derived from an interviewer-administered diet history questionnaire. RCC risk associated with micronutrient intake was estimated using adjusted odds ratios from logistic regression comparing lower to highest quartiles of intake and sample weighting. Inverse associations with RCC risk were observed for α-carotene, ß-carotene, lutein zeaxanthin, lycopene, vitamin A, folate, thiamin, vitamin C, α-tocopherol, ß-tocopherol, γ-tocopherol, and selenium. A trend for ß-cryptoxanthin was suggested among EA but not AA or the total sample (P-interaction = .04). Otherwise, findings did not differ by race, gender, age, or smoking status. The increase in RCC risk associated with lower micronutrient intake is similar within AA and EA populations. A diet rich in sources of micronutrients found in fruits, vegetables, and nuts may help to reduce the overall risk of RCC.

Clinical and economic burden associated with stage III to IV triple-negative breast cancer: A SEER-Medicare historical cohort study in elderly women in the United States.

BACKGROUND: The current study was performed to describe patient characteristics, treatment patterns, survival, health care resource use (HRU), and costs among older women in the United States with advanced (American Joint Committee on Cancer stage III/IV) triple-negative breast cancer (TNBC) in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. METHODS: Women who were aged ≥66 years at the time of diagnosis and diagnosed with advanced TNBC between January 1, 2007, and January 1, 2011, in the SEER-Medicare database and who were followed for survival through December 31, 2013, were eligible. Patient demographic and clinical characteristics at the time of diagnosis, subsequent treatment patterns, and survival outcomes were analyzed. HRU and costs for the first 3 months after diagnosis, the last 3 months of life, and the time in between are summarized. All analyses were stratified by American Joint Committee on Cancer stage of disease. RESULTS: There were 1244 patients newly diagnosed with advanced TNBC; the majority were aged ≥75 years (61% with stage III disease and 57.4% with stage IV disease) and white (>70% of patients in both disease stage groups). The most common treatment approaches were surgery combined with chemotherapy for patients for stage III disease (50.6%) and chemotherapy alone or with radiotherapy for patients with stage IV disease (31.3%). Diverse chemotherapy regimens were administered for each line of therapy; nevertheless, the medications used were consistent with national guidelines. Patients with stage III and stage IV disease were found to have a similar mean number of hospitalizations and outpatient visits, but mean monthly costs were greater for patients with stage IV disease at all 3 time points. The mean cost per patient-month (in 2013 US dollars) was $4810 for patients with stage III disease and $9159 for patients with stage IV disease. CONCLUSIONS: Among older women with advanced TNBC, significant treatment variations and considerable HRU and costs exist. Further research is needed to find effective treatments with which to reduce the clinical and economic burden of this disease. Cancer 2018;124:2104-14. © 2018 American Cancer Society.

Discordance between original and central laboratories in ER and HER2 results in a diverse, population-based sample.

PURPOSE: To investigate the discordance between original and central laboratories in estrogen receptor (ER) status, in tumors originally deemed to be ER-negative, and in HER2 status in a diverse population-based sample. METHODS: In a follow-up study of 1785 women with Stage I-III breast cancer diagnosed between 2005 and 2007 in the Detroit and Los Angeles County SEER registry catchment areas, participants were asked to consent to reassessment of ER (in tumors originally deemed to be ER-negative) and HER2 status on archival tumor samples approximately four years after diagnosis. Blocks were centrally prepared and analyzed for ER and HER2 using standardized methods and the guidelines of the American Society of Clinical Oncology and the College of American Pathologists. Analyses determined the discordance between original and central laboratories. RESULTS: 132 (31%) of those eligible for ER reassessment and 367 (21%) eligible for HER2 reassessment had archival blocks reassessed centrally. ER discordance was only 6%. HER2 discordance by immunohistochemistry (IHC) was 26%, but final HER2 results-employing FISH in tumors that were IHC 2+ at the central laboratory-were discordant in only 6%. Half of the original laboratories did not perform their own assays. CONCLUSIONS: Discordance between original and central laboratories in two large metropolitan areas was low in this population-based sample compared to previously reported patient samples. Centralization of testing for key pathology variables appears to be occurring in many hospitals. In addition, quality improvement efforts may have preceded the publication and dissemination of specialty society guidelines.

Patients' Survival Expectations With and Without Their Chosen Treatment for Prostate Cancer.

PURPOSE: Overtreatment of screen-detected localized prostate cancer (LPC) is an important public health concern, since the survival benefit of aggressive treatment (surgery or radiation) has not been well established. We investigated the survival expectations of patients who had LPC with and without their chosen treatment. METHODS: A population-based sample of 260 men (132 black, 128 white) 75 years old or younger with newly diagnosed LPC completed a self-administered survey. How long the patients expected to live with their chosen treatment, how long they would expect to live with no treatment, and factors associated with the difference in perceived life expectancy were assessed using multivariable analysis. RESULTS: Without any treatment, 33% of patients expected that they would live less than 5 years, 41% 5 to 10 years, 21% 10 to 20 years, and 5% more than 20 years. With their chosen treatment, 3% of patients expected to live less than 5 years, 9% 5 to 10 years, 33% 10 to 20 years, and 55% more than 20 years. Treatment chosen, age, general health perception, and perceived cancer seriousness predicted the differences in perceived life expectancy, while race and actual tumor risk did not. After adjustment for other covariates, men who choose surgery or radiation expected greater gain in survival than men who chose watchful waiting or active surveillance. CONCLUSIONS: Most patients with LPC underestimated their life expectancy without treatment and overestimated the gain in life expectancy with surgery or radiation. These unrealistic expectations may compromise patients' ability to make informed treatment decisions and may contribute to overtreatment of LPC. Primary care physicians, when included in the decision process, should focus on helping patients develop realistic expectations and choices that support their treatment goals.

Racial Differences in Treatment Decision-Making for Men with Clinically Localized Prostate Cancer: a Population-Based Study.

PURPOSE: Racial differences in prostate cancer treatment patterns have motivated concerns about over- and undertreatment. We surveyed black and white patients with localized prostate cancer (LPC) regarding their treatment decision-making processes to gain a better perspective on factors associated with LPC treatment choice. METHODS: We conducted a population-based, cross-sectional survey of 260 men (132 black, 128 white) aged ≤75 years, with newly diagnosed LPC. Our primary outcome was treatment choice (either surgery, radiation, or watchful waiting/active surveillance (WW/AS)), and our primary predictors were race and tumor risk level. RESULTS: Overall, treatment choice did not differ by race. As cancer risk increased, both black and white patients were more likely to undergo surgery and less likely to receive radiation. However, the pattern of WW/AS was different between white and black men. White men were less likely to select WW/AS as cancer risk increased, while risk level was unrelated to black men undergoing WW/AS. Urologist's recommendation had the greatest impact on men's treatment choice, followed by tumor risk level, age, and personal preferences. CONCLUSIONS: Although there were no overall racial differences in treatment choice, when stratified by tumor risk level, the pattern of WW/AS was different between white and black patients, suggesting that over- and undertreatment is a larger concern for black than white men. A risk-stratified approach to understand racial disparities in LPC treatment and better strategies to aid black men in their treatment decision-making are needed to reduce racial disparities in prostate cancer outcomes.

A genome-wide association study of renal cell carcinoma among African Americans.

Genome-wide association studies (GWAS) of renal cell carcinoma (RCC) in populations of European ancestry have identified four susceptibility loci. No GWAS has been conducted among African Americans (AA), who experience a higher incidence of RCC. We conducted a GWAS in which we analyzed 1,136,723 common single-nucleotide polymorphisms (SNP) among 255 cases and 375 controls of African ancestry, and further investigated 16 SNPs in a replication set (140 cases and 543 controls). The 12p11.23 variant rs10771279, located 77 kb from the European-ancestry RCC marker rs718314, was associated with RCC risk in the GWAS (P = 1.2 × 10(-7)) but did not replicate (P = 0.99). Consistent with European-ancestry findings, the A allele of rs7105934 on 11q13.3 was associated with decreased risk [OR, 0.76, 95% confidence interval (CI), 0.64-0.91; P = 0.0022]. The frequency of this allele was higher than that observed in the European-ancestry GWAS (0.56 and 0.07, respectively, among controls). The rs7105934 association was stronger for clear cell RCC (ccRCC: OR, 0.56; P = 7.4 × 10(-7)) and absent for cases of other or unknown histology (OR, 1.02; P = 0.86). Analyses of rs7105934 by subtype among European-ancestry participants from these studies yielded similar findings (ORs 0.69 and 0.92, respectively). This study provides, to our knowledge, the first evidence that rs7105934 is an RCC susceptibility locus among AAs. Our finding that the association with this SNP may be specific to clear-cell RCC is novel and requires additional investigation. Additional investigation of rs10771279 and other suggestive GWAS findings is also needed.

Estimating health literacy in family medicine clinics in metropolitan Detroit: a MetroNet study.

OBJECTIVE: Assessing health literacy during the clinical encounter is difficult. Many established instruments are lengthy and not practical for use in a busy practice setting. Our objective was to compare the performance of 3 health literacy screening questions against the Short Test of Functional Health Literacy for Adults (S-TOFHLA) in an urban, ethnically diverse primary care practice-based research network. METHODS: A convenience sample of patients in clinics in the Detroit area were recruited to complete a questionnaire that included the S-TOFHLA and 3 items similar to the Chew screening questions. Area under the receiver operating characteristic (AUROC) curves compared the test characteristics of the screening questions to the S-TOFHLA. RESULTS: The participation rate was 92% (N = 599). Most participants were women (65%) and African American (51%); 51.8% had a household annual income of <$20,000. Almost all (96.7%) had an adequate score on the S-TOFHLA. The screening question with the largest AUROC (0.83; 95% CI, 0.70-0.95) was "How often do you have someone help you read instructions, pamphlets or other written materials from your doctor or pharmacy?"; the AUROC for all 3 questions was 0.90 (95% CI, 0.85-0.95). CONCLUSIONS: Self-administration of the 3 screening questions demonstrated high performance compared with the 36-item S-TOFHLA interview instrument. These screening questions should help providers identify patients who may need extra support to follow health prescriptions.

An investigation of risk factors for renal cell carcinoma by histologic subtype in two case-control studies.

To investigate whether renal cell carcinoma (RCC) histologic subtypes possess different etiologies, we conducted analyses of established RCC risk factors by subtype (clear cell, papillary and chromophobe) in two case-control studies conducted in the United States (1,217 cases, 1,235 controls) and Europe (1,097 cases, 1,476 controls). Histology was ascertained for 706 U.S. cases (58% of total) and 917 European cases (84%) through a central slide review conducted by a single pathologist. For the remaining cases, histology was abstracted from the original diagnostic pathology report. Case-only analyses were performed to compute odds ratios (ORs) and 95% confidence intervals (CI) summarizing subtype differences by age, sex and race. Case-control analyses were performed to compute subtype-specific ORs for other risk factors using polytomous regression. In case-only analyses, papillary cases (N = 237) were older (OR = 1.2, 95% CI = 1.1-1.4 per 10-year increase), less likely to be female (OR = 0.5, 95% CI = 0.4-0.8) and more likely to be black (OR = 2.6, 95% CI = 1.8-3.9) as compared to clear cell cases (N = 1,524). In case-control analyses, BMI was associated with clear cell (OR = 1.2, 95% CI = 1.1-1.3 per 5 kg/m(2) increase) and chromophobe RCC (N = 80; OR = 1.2, 95% CI = 1.1-1.4), but not papillary RCC (OR = 1.1, 95% CI = 1.0-1.2; test versus clear cell, p = 0.006). No subtype differences were observed for associations with smoking, hypertension or family history of kidney cancer. Our findings support the existence of distinct age, sex and racial distributions for RCC subtypes, and suggest that the obesity-RCC association differs by histology.

Patient perspective on watchful waiting/active surveillance for localized prostate cancer.

OBJECTIVE: To describe prostate cancer treatment decision making, focusing on knowledge and attitudes toward observation, known as watchful waiting (WW) or active surveillance (AS), and reasons for not choosing WW/AS. METHODS: Semistructured in-person interviews were conducted with 21 men (14 black; 7 white) with recently diagnosed localized prostate cancer. RESULTS: All cancers were detected by prostate-specific antigen screening; 14 men had low-risk disease. Nineteen chose surgery or radiation treatment. The majority wanted to "get rid of" or "cure" the cancer by undergoing aggressive therapy, even with awareness of the potential for significant side effects. Most men seemed unaware of the uncertainty/controversies that aggressive treatment may not cure their cancer or improve their survival. Limited knowledge about WW/AS was common, and few remembered WW/AS being presented as a viable option. Rather, many men perceived it as "doing nothing." Some men, who initially were inclined toward WW/AS, yielded to pressure from family, physicians, or both to choose aggressive treatment. Lack of physician support was a significant barrier to WW/AS. CONCLUSIONS: The observational strategy (WW/AS) was not viewed as a reasonable approach, even for those with low-risk cancer. The desire for aggressive therapy may reflect the complex psychology associated with receiving a diagnosis of cancer and the limited supportive counseling received. Further efforts to better understand and educate patients and physicians may help men make informed and appropriate treatment decisions to maximize quality of life without compromising survival.

A case-control study of peripheral blood mitochondrial DNA copy number and risk of renal cell carcinoma.

BACKGROUND: Low mitochondrial DNA (mtDNA) copy number is a common feature of renal cell carcinoma (RCC), and may influence tumor development. Results from a recent case-control study suggest that low mtDNA copy number in peripheral blood may be a marker for increased RCC risk. In an attempt to replicate that finding, we measured mtDNA copy number in peripheral blood DNA from a U.S. population-based case-control study of RCC. METHODOLOGY/PRINCIPAL FINDINGS: Relative mtDNA copy number was measured in triplicate by a quantitative real-time PCR assay using DNA extracted from peripheral whole blood. Cases (n = 603) had significantly lower mtDNA copy number than controls (n = 603; medians 0.85, 0.91 respectively; P = 0.0001). In multiple logistic regression analyses, the lowest quartile of mtDNA copy number was associated with a 60% increase in RCC risk relative to the highest quartile (OR = 1.6, 95% CI = 1.1-2.2; P(trend) = 0.009). This association remained in analyses restricted to cases treated by surgery alone (OR (Q1) = 1.4, 95% CI = 1.0-2.1) and to localized tumors (2.0, 1.3-2.8). CONCLUSIONS/SIGNIFICANCE: Our findings from this investigation, to our knowledge the largest of its kind, offer important confirmatory evidence that low mtDNA copy number is associated with increased RCC risk. Additional research is needed to assess whether the association is replicable in prospective studies.

Body mass index and renal cell cancer: the influence of race and sex.

BACKGROUND: Obesity is a risk factor for renal cell (or renal) cancer. The increasing prevalence of obesity may be contributing to the rising incidence of this cancer over the past several decades. The effects of early-age obesity and change in body mass index (BMI) on renal cancer have been studied less thoroughly, and the influence of race has never been formally investigated. METHODS: Using data gathered as part of a large case-control study of renal cancer (1214 cases and 1234 controls), we investigated associations with BMI at several time points, as well as with height. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were computed using logistic regression modeling. Race- and sex-stratified analyses were conducted to evaluate subgroup differences. RESULTS: Obesity (BMI ≥ 30 kg/m) early in adulthood (OR = 1.6 [95% CI = 1.1 to 2.4]) and 5 years before diagnosis (1.6 [1.1 to 2.2]) was associated with renal cancer. The association with early-adult obesity was stronger among whites than blacks (test for interaction, P = 0.006), whereas the association with obesity near diagnosis was marginally stronger in women than men (test for interaction, P = 0.08). The strongest association with renal cancer was observed for obese whites both in early adulthood and before interview (2.6 [1.5 to 4.4]); this association was not present among blacks. Estimates of the annual excess rate of renal cancer (per 100,000 persons) attributed to both overweight and obesity (BMI > 25 kg/m) ranged from 9.9 among black men to 5.6 among white women. CONCLUSION: Obesity, both early and later in life, is associated with an increased risk of renal cancer. The association with early obesity seems to be stronger among whites than blacks.

Cigarette smoking and renal cell carcinoma risk among black and white Americans: effect modification by hypertension and obesity.

BACKGROUND: Incidence of kidney cancer has been increasing over the past three decades, with more rapid increases and higher incidence rates among blacks than whites in the United States. An association between cigarette smoking and renal cell carcinoma (RCC), the most common form of kidney cancer, has been reported for whites, but the association in blacks is less clear. METHODS: The association between smoking and RCC was examined in 1,217 incident cases and 1,235 population controls frequency-matched on age, race, gender, and study site in the Kidney Cancer Study in Detroit, MI, and Chicago, IL. RESULTS: In white individuals, increasing duration and number of pack-years of both were associated with increased risk of RCCs after adjusting for age, gender, education, study site, body mass index (BMI) and history of hypertension (P(trend) = 0.0002 and P(trend) = 0.002, respectively). Among black individuals, RCC risk increased with duration of smoking (P(trend) = 0.02) but not other measures. Compared with current smokers, RCC risk decreased with increasing years of smoking cessation among both whites and blacks (P(trend) = 0.01 and 0.02, respectively). When examining risk according to hypertension history, associations between smoking and RCC risk were observed only among individuals who reported never having been diagnosed with hypertension. Similarly, cigarette smoking was associated with increased risk of RCCs among nonobese individuals but not among those with BMI ≥ 30 kg/m(2). CONCLUSION: Our observation that smoking is associated with RCC only in nonobese individuals and those with no history of hypertension are novel findings. IMPACT: The complex relationships between RCCs, smoking, hypertension, and obesity require additional confirmation.

Timing of androgen deprivation therapy use and fracture risk among elderly men with prostate cancer in the United States.

PURPOSE: Fractures are a recognized consequence of androgen deprivation therapy (ADT); however, less is known about the incidence of fracture in relation to the timing of ADT use or the impact of fracture on mortality in men with prostate cancer. METHODS: Using data from the Surveillance, Epidemiology, and End Results-Medicare linked database, we estimated adjusted hazard ratios (aHRs) using time-dependent Cox regression for fracture incidence related to the recency of exposure and dose among prostate cancer patients on gonadotropin-releasing hormone (GnRH) agonists, as well as mortality associated with fractures. RESULTS: In our cohort of 80 844 patients, ADT was associated with an increased rate of fracture in both non-metastatic patients (aHR = 1.34; 95% confidence interval [CI] = 1.29-1.39) and metastatic patients (aHR = 1.51; 95%CI = 1.36-1.67). Fracture rates increased with increasing cumulative GnRH dose but decreased with increasing number of months since last use in each dose category. The mortality rate doubled for men experiencing a fracture after their diagnosis compared with that for men who did not experience a fracture (aHR = 2.05; 95%CI = 1.98-2.12). CONCLUSIONS: ADT in elderly men with prostate cancer increased the incidence of fractures, and the effect appears to diminish with increasing time since the last dose of a GnRH agonist. Experiencing a fracture after the diagnosis of prostate cancer was associated with decreased survival.