Advances in human genetics have led to epidemiological investigations not only of the effects of genes alone but also of gene–environment (G–E) interaction. A widely accepted design strategy in the study of how G–E relate to disease risks is the population-based case–control study (PBCCS). For simple random samples, semiparametric methods for testing G–E have been developed by Chatterjee and Carroll in 2005. The use of complex sampling in PBCCS that involve differential probabilities of sample selection of cases and controls and possibly cluster sampling is becoming more common. Two complexities, weighting for selection probabilities and intracluster correlation of observations, are induced by the complex sampling. We develop pseudo-semiparametric maximum likelihood estimators (pseudo-SPMLE) that apply to PBCCS with complex sampling. We study the finite sample performance of the pseudo-SPMLE using simulations and illustrate the pseudo-SPMLE with a US case–control study of kidney cancer.
Hardy–Weinberg equilibrium; Population weights; Selection probability; Stratified multistage cluster sampling; Taylor linearization
Hepatocellular carcinoma (HCC) has a poor prognosis and, unlike most cancers, HCC incidence and mortality rates are increasing in the United States. While risk is known to vary among different racial and ethnic groups, less is known about the variability of risk within these groups by neighborhood socioeconomic status (SES).
HCC cases diagnosed in the Surveillance, Epidemiology and End Results (SEER) 11 cancer registries between 1996 and 2007, and the population of the SEER 11 catchment areas was studied. Analyses were conducted to compare census tract area family poverty, educational attainment, and unemployment by race and ethnicity. A multiple linear regression model, weighted by the number of cases and the number of individuals in each census tract, with adjustment for registry, was used to calculate mean differences in area-level attributes between HCC cases and the population.
HCC cases in most racial/ethnic groups had lower mean neighborhood-level measures of SES than their referent population. An exception was seen among Hispanics. Comparing white cases with cases of other racial groups and to Hispanics, white cases lived in neighborhoods with less family poverty, fewer high-school dropouts, and lower unemployment. Compared with white cases, Asian and Pacific Islander and Hispanic cases lived in neighborhoods with a higher percentage of foreign-born population.
Low neighborhood-level SES and immigrant status may be associated with greater risk of HCC within specific racial and ethnic groups.
These findings could help to focus control resources for HCC toward the most affected communities.
No previous prospective US study has examined if the incidence of colorectal cancer (CRC) is disproportionately high in low socioeconomic status (SES) populations of both men and women. This study examined the relationship between both individual and area-level SES and CRC incidence, overall and by tumor location.
Data were obtained from the ongoing prospective NIH-AARP Diet and Health Study of persons (50–71 years old) who resided in 6 US states and 2 metropolitan areas at baseline in 1995–1996. Incident CRCs were ascertained from tumor registries through December 2006. SES was measured by self-reported education and census-tract socioeconomic deprivation. Baseline and follow-up questionnaires collected detailed information on individual-level CRC risk factors including family history and health behaviors.
Among 506,488 participants analyzed, 7,676 were diagnosed with primary invasive colorectal adenocarcinomas: 46.6% in the right colon, 26.7% in the left colon and 25.9% in the rectum. The overall incidence of CRC was significantly higher among people who had low-educational level or lived in low-SES neighborhoods, relative to respective highest-SES groups, even after accounting for other risk factors. These associations were stronger in the rectum than in left or right colon. In the right colon, there were no significant SES differences by either SES measure after accounting for covariates.
SES, assessed by either individual-level education or neighborhood measures, was associated with risk of CRC even after accounting for other risk factors. The relationship between SES and CRC was strongest in the rectum and weakest in the right colon.
colorectal cancer; socioeconomic status; risk factors; health behavior; poverty
Sexual function among testicular cancer survivors is a concern because affected men are of reproductive age when diagnosed. We conducted a case-control study among United States military men to examine whether testicular cancer survivors experienced impaired sexual function.
A total of 246 testicular cancer cases and 236 ethnicity and age matched controls were enrolled in the study in 2008-2009. The Brief Male Sexual Function Inventory (BMSFI) was used to assess sexual function.
Compared to controls, cases scored significantly lower on sex drive (5.77 vs. 5.18), erection (9.40 vs. 8.63), ejaculation (10.83 vs. 9.90), and problem assessment (10.55 vs. 9.54). Cases were significantly more likely to have impaired erection (OR 1.72; 95% CI 1.11-2.64), ejaculation (OR 2.27; 95% CI 1.32-3.91), and problem assessment (OR 2.36; 95% CI 1.43-3.90). In histology and treatment analysis, nonseminoma, chemotherapy and radiation treated cases risk of erectile dysfunction, delayed ejaculation, and/or problem assessment were greater when compared to controls.
This study provides evidence that testicular cancer survivors are more likely to have impaired sexual functioning compared to demographically matched controls. The observed impaired sexual functioning appeared to vary by treatment regimen and histologic subtype.
Testicular cancer; sexual function; military men
The purpose of this study was to separately examine the impact of neighborhood socioeconomic deprivation and availability of healthcare resources on prostate cancer risk among African-American and Caucasian men.
In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995–1996) data from adult men, ages 50–71 years. Incident prostate cancer cases (n=22,523; 1,089 among African Americans) were identified through December 2006. Life-style and health risk information was ascertained by questionnaires administered at baseline. Area-level socioeconomic indicators were ascertained by linkage to the US Census and the Area Resource File. Multilevel Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
A differential effect among African Americans and Caucasians was observed for neighborhood deprivation (P-interaction = 0.04), percent uninsured (P-interaction = 0.02), and urologist density (P-interaction = 0.01). Compared to men living in counties with the highest density of urologists, those with fewer had a substantially increased risk of developing advanced prostate cancer (HR=2.68, 95% CI=1.31, 5.47) among African-American.
Certain socioeconomic indicators were associated with an increased risk of prostate cancer among African-American men compared to Caucasians. Minimizing differences in health care availability may be a potentially important pathway to minimizing disparities in prostate cancer risk.
cohort; prostate cancer; multilevel; neighborhood; socioeconomic deprivation; healthcare availability; Census
Meat mutagens, including heterocyclic amines (HCAs), polycyclic aromatic hydrocarbons (PAHs) and N-nitroso compounds (NOCs), may be involved in colorectal carcinogenesis depending on their activation or detoxification by phase I and II xenobiotic metabolizing enzymes (XME). Using unconditional logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), we examined the intake of five meat mutagens and >300 single nucleotide polymorphisms (SNPs) in 18 XME genes in relation to advanced colorectal adenoma (1205 cases and 1387 controls) and colorectal cancer (370 cases and 401 controls) within the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Dietary intake of meat mutagens was assessed using a food frequency questionnaire with a detailed meat-cooking module. An interaction was observed between 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) intake and the NAT1 polymorphism rs6586714 in the adenoma study (P
interaction = 0.001). Among individuals carrying a GG genotype, high MeIQx intake was associated with a 43% increased risk of adenoma (95% CI 1.11–1.85, P
trend = 0.07), whereas the reverse was observed among carriers of the A variant (OR = 0.50, 95% CI 0.30–0.84, P
trend = 0.01). In addition, we observed some suggestive (P < 0.05) modifying effects for SNPs in other XME genes (UGT1A, CYP2E1, EPHX1, AHR and GSTM3), but these were not significant after adjustment for multiple testing. This large and comprehensive study of XME genes, meat mutagens and the risk of colorectal tumours found that a NAT1 polymorphism modified the association between MeIQx intake and colorectal adenoma risk.
Guidelines from the American Cancer Society recommend annual breast MRI screening for women with a projected lifetime risk of ≥20% based on risk models that use family history. Since MRI screening is costly and has limited specificity, estimates of the numbers of U.S. women with breast cancer risk ≥20% would be useful.
We used data from the 2000 and 2005 National Health Interview Survey and the National Cancer Institute’s (NCI) Breast Cancer Risk Assessment Tool (i.e. Gail Model 2 with a revision for African Americans) to calculate estimates of U.S. women by age and race/ethnicity categories with a lifetime absolute breast cancer risk of ≥20%. Distributions of 5-year and lifetime absolute risk of breast cancer are compared across demographic groups.
We estimated that 1.09% (95% CI = 0.95% to 1.24%) of women aged 30–84 years have a lifetime absolute breast cancer risk of ≥20%, which translates to 880,063 U.S. women eligible for MRI screening. The 5-year risks are highest for White non-Hispanics and lowest for Hispanics. The lifetime risks decrease with age and are generally highest for White non-Hispanics, lower for African American non-Hispanic and lowest for Hispanics.
We provide national estimates of the number of U.S. women who would be eligible for MRI breast screening and distributions of 5-year and lifetime risks of breast cancer using the NCI Breast Cancer Risk Assessment Tool.
These estimates inform the potential resources and public health demand for MRI screening and chemo-preventive interventions that might be required for U.S. women.
It has been hypothesized that the risk of testicular germ cell tumors (TGCT) is associated with maternal hormone levels. To examine the hypothesis, some studies have used perinatal factors as surrogates for hormone levels. To determine the validity of this assumption, hormone-perinatal factor relationships were examined in the Collaborative Perinatal Project.
Maternal estradiol, estriol and testosterone levels in first and third trimester serum samples were correlated with perinatal factors among 300 mothers representative of populations at high (white Americans) or low (black Americans) risk of TGCT.
Among white participants, testosterone levels, were negatively associated with maternal height (p<0.01) and age (p=0.02), and positively associated with maternal weight (p=0.02) and BMI (p<0.01), while estradiol levels were negatively associated with height (p=0.03) and positively associated with son’s birthweight (p=0.04). Among black participants, estriol levels were negatively associated with maternal weight (p=0.01), BMI (p=0.02) and gestational age p<0.01), and positively associated with son’s birthweight (p<0.01), length (p=0.04) and head circumference (p=0.03).
These findings indicate that the use of perinatal characteristics as surrogates for hormone levels should be limited to a specific ethnic group. Among white men, previously reported associations of TGCT with maternal weight and age may be due to lower maternal testosterone levels.
testicular cancer; maternal hormones; perinatal factors
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.
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.
In white individuals, increasing duration and number of pack years of were both associated with increased risk of RCC 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 to 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 RCC among non-obese individuals, but not among those with BMI≥30 kg/m2.
Our observation that smoking is associated with RCC only in non-obese individuals and those with no history of hypertension are novel findings
The complex relationships between RCC, smoking, hypertension and obesity require additional confirmation.
Renal Cell Carcinoma; Cigarette Smoking; Hypertension; Body Mass Index; Race/Ethnicity
This study examined whether the risk of premature mortality associated with living in socioeconomically deprived neighborhoods varies according to health status of individuals, accounting for individual-level socioeconomic and health-risk factors.
566,402 community-dwelling adults (50–71 years of age) in six US states and two metropolitan areas participated in the ongoing prospective NIH-AARP Diet and Health Study, which began in 1995. This analysis included 565,679 eligible subjects. Data were obtained on dietary, lifestyle, self-rated health status, and medical history on baseline mailed questionnaires. Participants were linked to 2000 census data for an index of census-tract socioeconomic deprivation. The main outcome was all-cause mortality ascertained through 2006.
In adjusted survival analyses of persons in good-to-excellent health at baseline, risk of mortality increased with increasing levels of census-tract socioeconomic deprivation. In comparison, neighborhood socioeconomic mortality disparities among persons in fair-to-poor health were not statistically significant after adjustment for demographic characteristics, educational achievement, lifestyle factors and medical conditions of participants.
Neighborhood socioeconomic inequalities lead to large disparities in risk of premature mortality among healthy US adults, but not for persons who were already in poor health.
Kaposi sarcoma-associated herpesvirus (KSHV) seropositivity is associated with sexual, environmental, and socioeconomic exposures. Whether these characteristics are independent risk factors is uncertain because of reliance on selected high-risk or hospital-based populations and incomplete adjustment for confounding. Therefore, we evaluated risk factors for KSHV seropositivity in a population-based study in Uganda using principal components analysis (PCA).
The study population comprised 2,681 individuals randomly selected from a nationally-representative population-based HIV/AIDS sero-behavioral survey conducted in 2004/05. Questionnaire and laboratory data (97 variables) were transformed into a smaller set of uncorrelated variables using PCA. Multivariable logistic regression models were fitted to estimate odds ratios and 95% confidence intervals for the association between components and KSHV seropositivity.
Data were reduced to three principal components (PCs) labeled as Sexual behavioral, Socioeconomic, and Knowledge PCs. In crude analysis, KSHV seropositivity was associated with the Knowledge (ptrend = 0.012) and Socioeconomic components (ptrend = 0.0001), but not with the Sexual-behavioral component (ptrend = 0.066). KSHV seropositivity was associated with the Socioeconomic PC (ptrend = 0.037), but not with the Sexual-behavioral and Knowledge PCs, in the models including PCs, age, gender and geographic region.
Our results fit with the view that in Uganda socioeconomic characteristic may influence KSHV seropositivity. Conversely, the results fit with the interpretation that in Uganda sexual-behavioral characteristics, if relevant, contribute minimally.
Kaposi sarcoma-associated herpesvirus; Uganda; Kaposi sarcoma; Socioeconomic; Principal Components Analysis; Human herpesvirus 8
The Global Enteric Multicenter Study (GEMS) is an investigation of the burden (number of cases and incidence) of moderate-to-severe diarrhea (MSD) in children <60 months of age at 7 sites in sub-Saharan Africa and South Asia. The population attributable fraction for a putative pathogen, either unadjusted or adjusted for other pathogens, is estimated using the proportion of MSD cases from whom the pathogen was isolated and the odds ratio for MSD and the pathogen from conditional logistic regression modeling. The adjusted attributable fraction, proportion of MSD cases taken to a sentinel health center (SHC), number of cases presenting to an SHC, and the site's population are used to estimate the annual number of MSD cases and MSD incidence rate attributable to a pathogen or group of pathogens. Associations with death and nutritional outcomes, ascertained at follow-up visits to case and control households, are evaluated both in MSD cases and in the population.
Given the large racial differences in prostate cancer risk, further investigation of diet and prostate cancer is warranted among high-risk groups. The purpose of this study was to examine the association between type of meat intake and prostate cancer risk among African-American men.
In the large, prospective NIH-AARP Diet and Health Study, we analyzed baseline (1995–1996) data from African-American participants, ages 50–71 years. Incident prostate cancer cases (n=1,089) were identified through 2006. Dietary and risk factor data were ascertained by questionnaires administered at baseline. Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) within intake quantiles.
Neither white nor processed meat intake was associated with prostate cancer, regardless of meat cooking method. Red meats cooked at high temperatures were associated with an increased risk of prostate cancer (HR=1.18, 95%CI=1.00–1.38 and HR=1.22, 95%CI=1.03–1.44, for the upper two intake tertiles). Intake of the heterocyclic amine (HCA), 2-amino-3,4,8-trimethylimidazo[4,5-f] quinoxaline (DiMeIQx) was positively associated with prostate cancer (HR=1.30; 95% CI= 1.05–1.61, P=0.02). No associations were observed for intake of other HCAs.
Red meats cooked at high temperatures were positively associated with prostate cancer risk among African-American men. Further studies are needed to replicate these findings.
incidence; prostate; cancer; diet; meat consumption; race; African-American
Previous studies have not examined potential interactions between meat intake and characteristics of the local environment on the risk of mortality. This study examined the impact of area socioeconomic deprivation on the association between meat intake and all-cause and cause-specific mortality after accounting for individual-level risk factors.
In the prospective NIH-AARP Diet and Health Study, we analyzed data from adults, ages 50–71 years at baseline (1995–1996). Individual-level dietary intake and health risk information was linked to the demographic and socioeconomic context of participants’ local environment based on census tract data. Deaths (n=33,831) were identified through December 2005. Multilevel Cox models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for quintiles of area deprivation scores.
Associations of red and processed meats with mortality were consistent across deprivation quintiles. Men residing in least-deprived neighborhoods had a stronger protective effect for white meat consumption. No differences by deprivation index were observed for women.
Red and processed meat intake increases mortality risk regardless of level of deprivation within a given neighborhood suggesting biological mechanisms rather than neighborhood contextual factors may underlie these meat-mortality associations. The effect of white meat intake on cancer mortality was modified by area deprivation among men.
meat consumption; mortality; census; socioeconomic; clustered survival data
Other than male sex, family history, advanced age, and race, risk factors for chronic lymphocytic leukemia and small lymphocytic lymphoma (CLL/SLL) are unknown. Very few studies have investigated diet in relation to these leukemias, and no consistent associations are known.
Using two large prospective population-based studies, we evaluated the relationship between diet and CLL/SLL risk. Among 525,982 men and women free of cancer at enrollment, we identified 1,129 incident CLL/SLL cases during 11.2 years of follow-up.
We found no associations between total fat, saturated fat, fiber, red meat, processed meat, fruit or vegetable intake and risk of CLL/SLL. We noted a suggestive positive association between body mass index (BMI) and CLL/SLL (hazard ratio =1.30; 95% confidence interval= 0.99-1.36).
We did not find any associations between foods or nutrients and CLL/SLL.
Our large prospective study indicates that diet may not play a role in CLL/SLL development.
diet; chronic lymphocytic leukemia; body mass index; cohort study
Smoking, alcohol use, diet, body mass index (BMI), and physical activity have been studied independently in relation to pancreatic cancer. We generated a healthy lifestyle score to investigate their joint effect on pancreatic cancer risk.
In the prospective National Institutes of Health-AARP Diet and Health Study, a total of 450,416 participants aged 50–71 years completed the baseline food frequency questionnaire (1995–1996) eliciting diet and lifestyle information and were followed up through December 2003. We identified 1,057 eligible incident pancreatic cancer cases. Participants were scored for five modifiable lifestyle factors as “unhealthy” (0 points) or “healthy” (1 point) based on current epidemiologic evidence. Participants received 1 point for each respective lifestyle factor: nonsmoking, limited alcohol use, adherence to the Mediterranean dietary pattern, 18 ≤ BMI <25 kg/m2, or regular physical activity. A combined score (0–5 points) was calculated by summing the scores from the five factors. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for pancreatic cancer.
Compared to the lowest combined score (0 points), the highest score (5 points) was associated with a 58% reduction in risk of developing pancreatic cancer in all participants (RR, 0.42; 95% CI, 0.26–0.66, P trend < .001). Scores of less than 5 points explained 27% of pancreatic cancer cases in our population.
This large study suggests that having a high, as opposed to a low, score on an index combining five modifiable lifestyle factors substantially reduces one’s risk of pancreatic cancer.
Many epidemiologic studies have examined the association between CRP and risk of cancer with inconsistent results.
We conducted two nested, case-control studies in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study and Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Trial to test whether pre-diagnostic circulating CRP concentrations were associated with pancreatic adenocarcinoma. Between 1985 and 2004, 311 cases occurred in ATBC and between 1994 and 2006, 182 cases occurred in PLCO. Controls (n=510 in ATBC, n=374 in PLCO) were alive at the time the case was diagnosed and were matched by age, date of blood draw, sex, and race. We used conditional logistic regression adjusted for smoking to calculate odds ratios (OR) and 95% confidence intervals (CI) for pancreatic cancer.
CRP concentrations (ng/ml) tended to be inversely or not associated with pancreatic cancer risk in ATBC, PLCO, and combined analyses (per standardized quintile increase in CRP, continuous OR= 0.94, 95% CI 0.89, 0.99; OR=0.99, 95% CI 0.95, 1.04; OR=0.98, 95% CI 0.95, 1.01, respectively). In combined analyses, we observed a significant interaction (p-interaction=0.02) such that inverse associations were suggestive in younger (OR=0.95; 95% CI, 0.90–1.01), but not older participants.
Our results do not support the hypothesis that higher CRP concentrations are associated with incident pancreatic cancer.
Our results highlight the importance of investigating more specific biomarkers for inflammation that may reflect the biological mechanisms underlying pancreatic cancer in prospective cohort studies.
CRP; ATBC; PLCO; Pancreatic; Case-Control
Dietary guidelines advise consumers to limit intake of red meat and choose lean protein sources, such as poultry and fish. Poultry consumption has been steadily increasing in the U.S., but the effect on cancer risk remains unclear. In a large U.S. cohort, we prospectively investigated poultry and fish intake and cancer risk across a range of malignancies in men and women. Diet was assessed at baseline (1995–1996) with a food frequency questionnaire in 492,186 participants of the National Institutes of Health-AARP Diet and Health Study. Over a mean follow-up of 9 years, we identified 74,418 incident cancer cases. In multivariate Cox proportional hazards regression models, we estimated the substitution and addition effects of white meat (poultry and fish) intake in relation to cancer risk. In substitution models with total meat intake held constant, a 10 gram (per 1,000 kilocalories) increase in white meat intake offset by an equal decrease in red meat intake was associated with a statistically significant reduced (3–20%) risk of cancers of the esophagus, liver, colon, rectum, anus, lung, and pleura. In addition models with red meat intake held constant, poultry intake remained inversely associated with esophageal squamous cell carcinoma, liver cancer, and lung cancer, but we observed mixed findings for fish intake. As the dietary recommendations intend, the inverse association observed between white meat intake and cancer risk may be largely due to the substitution of red meat. Simply increasing fish or poultry intake, without reducing red meat intake, may be less beneficial for cancer prevention.
poultry; fish; canned tuna; cancer; cohort
Prospective associations between quantity and frequency of alcohol consumption and cancer-specific mortality were studied using a nationally representative sample with pooled data from the 1988, 1990, 1991, and 1997–2004 administrations of the National Health Interview Survey (n = 323,354). By 2006, 8,362 participants had died of cancer. Cox proportional hazards regression was used to estimate relative risks. Among current alcohol drinkers, for all-site cancer mortality, higher-quantity drinking (≥3 drinks on drinking days vs. 1 drink on drinking days) was associated with increased risk among men (relative risk (RR) = 1.24, 95% confidence interval (CI): 1.09, 1.41; P for linear trend = 0.001); higher-frequency drinking (≥3 days/week vs. <1 day/week) was associated with increased risk among women (RR = 1.32, 95% CI: 1.13, 1.55; P-trend < 0.001). Lung cancer mortality results were similar, but among never smokers, results were null. For colorectal cancer mortality, higher-quantity drinking was associated with increased risk among women (RR = 1.93, 95% CI: 1.17, 3.18; P-trend = 0.03). Higher-frequency drinking was associated with increased risk of prostate cancer (RR = 1.55, 95% CI: 1.01, 2.38; P for quadratic effect = 0.03) and tended to be associated with increased risk of breast cancer (RR = 1.44, 95% CI: 0.96, 2.17; P-trend = 0.06). Epidemiologic studies of alcohol and cancer mortality should consider the independent effects of quantity and frequency.
alcohol drinking; cohort studies; diet; food habits; mortality; neoplasms; risk factors
Adverse socioeconomic conditions, at both the individual and the neighborhood level, increase the risk of colorectal cancer (CRC) death, but little is known regarding whether CRC survival varies geographically and the extent to which area-level socioeconomic deprivation affects this geographic variation. Using data from the National Institutes of Health (NIH)-AARP Diet and Health Study, the authors examined geographic variation and the role of area-level socioeconomic deprivation in CRC survival. CRC cases (n = 7,024), identified during 1995–2003, were followed for their CRC-specific vital status through 2005 and overall vital status through 2006. Bayesian multilevel survival models showed that there was significant geographic variation in overall (variance = 0.2, 95% confidence interval (CI): 0.1, 0.2) and CRC-specific (variance = 0.3, 95% CI: 0.1, 0.4) risk of death. More socioeconomically deprived neighborhoods had a higher overall risk of death (most deprived quartile vs. least deprived: hazard ratio = 1.2, 95% CI: 1.1, 1.4) and a higher CRC-specific risk of death (most deprived quartile vs. least deprived: hazard ratio = 1.2, 95% CI: 1.1, 1.5). However, neighborhood socioeconomic deprivation did not account for the geographic variation in overall and CRC-specific risks of death. In future studies, investigators should evaluate other neighborhood characteristics to help explain geographic heterogeneity in CRC survival. Such research could facilitate interventions for reducing geographic disparity in CRC survival.
cohort studies; colorectal neoplasms; geography; multilevel analysis; residence characteristics; socioeconomic factors; survival
Advanced glycation end-products (AGEs) accumulate in human tissue proteins during aging, particularly under hyperglycemia conditions. AGEs induce oxidative stress and inflammation via the receptor for AGEs (RAGE) and soluble RAGE (sRAGE) can neutralize the effects mediated by RAGE/ligand engagement.
We examined the association between Nε-(carboxymethyl)lysine (CML), a prominent AGEs, and sRAGE and colorectal cancer risk in a prospective case-cohort study nested within a cancer prevention trial among 29,133 Finnish male smokers. Among study subjects who were alive without cancer five years after baseline (1985–1988), we identified 483 incident colorectal cancer cases and randomly sampled 485 subcohort participants as the comparison group with the follow-up to April 2006. Baseline serum levels of CML-AGE, sRAGE, glucose and insulin were determined. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% confidence intervals (CI).
Comparing highest with lowest quintile of sRAGE, the RR for incident colorectal cancer was 0.65 (95% CI: 0.39, 1.07; P value for trend = 0.03), adjusting for age, years of smoking, body mass index, and CML-AGE. Further adjustment for serum glucose strengthened the association (RR: 0.52; 95% CI: 0.30, 0.89; P value for trend = 0.009). Highest quintile of CML-AGE was not associated with an increased risk of colorectal cancer (multivariate RR: 1.20; 95% CI: 0.64, 2.26).
Higher prediagnostic levels of serum sRAGE were associated with lower risk of colorectal cancer in male smokers.
This is the first epidemiologic study to implicate the receptor for advanced glycation end-products in colorectal cancer development.
advanced glycation end-products; soluble receptor for advanced glycation end-products; colorectal cancer; risk; case-cohort; inflammation
The Study of Tamoxifen and Raloxifene (STAR) demonstrated that raloxifene was as effective as tamoxifen in reducing the risk of invasive breast cancer (IBC) in postmenopausal women and had lower risks of thromboembolic events, endometrial cancer, and cataracts but had a nonstatistically significant higher risk of noninvasive breast cancer. There is a need to summarize the risks and benefits of these agents.
Patients and Methods
Baseline incidence rates of IBC and other health outcomes, absent raloxifene and tamoxifen, were estimated from breast cancer chemoprevention trials; the Surveillance, Epidemiology and End Results Program; and the Women's Health Initiative. Effects of raloxifene and tamoxifen were estimated from STAR and the Breast Cancer Prevention Trial. We assigned weights to health outcomes to calculate the net benefit from raloxifene compared with placebo and tamoxifen compared with placebo.
Risks and benefits of treatment with raloxifene or tamoxifen depend on age, race, breast cancer risk, and history of hysterectomy. Over a 5-year period, postmenopausal women with an intact uterus had a better benefit/risk index for raloxifene than for tamoxifen. For postmenopausal women without a uterus, the benefit/risk ratio was similar. The benefits and risks of raloxifene and tamoxifen are described in tables that can help identify groups of women for whom the benefits outweigh the risks.
We developed a benefit/risk index to quantify benefits from chemoprevention with tamoxifen or raloxifene. This index can complement clinical evaluation in deciding whether to initiate chemoprevention and in comparing the benefits and risks of raloxifene versus tamoxifen.
Background Previously, we have shown that increasing adult height is associated with increased risk of testicular germ-cell tumor (TGCT). Recently, a number of single nucleotide polymorphisms (SNPs) have been found to be related to height. We examined whether these SNPs were associated with TGCT and whether they explained the relationship between height and TGCT.
Methods We genotyped 15 height-related SNPs in the US Servicemen’s Testicular Tumor Environmental and Endocrine Determinants (STEED) case–control study. DNA was extracted from buccal cell samples and Taqman assays were used to type the selected SNPs. We used logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (95%CIs).
Results There were 561 cases and 676 controls for analysis. Two SNPs were found to be associated with risk of TGCT, rs6060373 (CC vs TT, OR = 1.51, 95% CI: 1.06–2.15) and rs143384 (CC vs TT, OR = 1.53, 95% CI: 1.09–2.15). rs6060373 is an intronic polymorphism of ubiquinol-cytochrome c reductase complex chaperone (UQCC), and rs143384 is a 5′UTR polymorphism of growth differentiation factor 5 (GDF5). No individual SNP attenuated the association between height and TGCT. Adjustment for all SNPs previously associated with adult height reduced the associations between adult height and TGCT by ~8.5%, although the P-value indicated only weak evidence that this difference was important (P = 0.26).
Conclusions This novel analysis provides tentative evidence that SNPs which are associated with adult height may also share an association with risk of TGCT.
Body height; case–control studies; epidemiology; polymorphism; single nucleotide; testicular neoplasms
Knowledge of family cancer history is essential for estimating an individual’s cancer risk and making clinical recommendations regarding screening and referral to a specialty cancer genetics clinic. However, it is not clear if reported family cancer history is sufficiently accurate for this purpose.
In the population-based 2001 Connecticut Family Health Study, 1019 participants reported on 20 578 first-degree relatives (FDR) and second-degree relatives (SDR). Of those, 2605 relatives were sampled for confirmation of cancer reports on breast, colorectal, prostate, and lung cancer. Confirmation sources included state cancer registries, Medicare databases, the National Death Index, death certificates, and health-care facility records. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated for reports on lung, colorectal, breast, and prostate cancer and after stratification by sex, age, education, and degree of relatedness and used to estimate report accuracy. Pairwise t tests were used to evaluate differences between the two strata in each stratified analysis. All statistical tests were two-sided.
Overall, sensitivity and positive predictive value were low to moderate and varied by cancer type: 60.2% and 40.0%, respectively, for lung cancer reports, 27.3% and 53.5% for colorectal cancer reports, 61.1% and 61.3% for breast cancer reports, and 32.0% and 53.4% for prostate cancer reports. Specificity and negative predictive value were more than 95% for all four cancer types. Cancer history reports on FDR were more accurate than reports on SDR, with reports on FDR having statistically significantly higher sensitivity for prostate cancer than reports on SDR (58.9% vs 21.5%, P = .002) and higher positive predictive value for lung (78.1% vs 31.7%, P < .001), colorectal (85.8% vs 43.5%, P = .004), and breast cancer (79.9% vs 53.6%, P = .02).
General population reports on family history for the four major adult cancers were not highly accurate. Efforts to improve accuracy are needed in primary care and other health-care settings in which family history is collected to ensure appropriate risk assessment and clinical care recommendations.
Cigarette smoking, obesity, type 2 diabetes, and to a less extent, meat cooked at high temperatures are associated with pancreatic cancer. Cigarette smoke and foods cooked at higher temperatures are major environmental sources of advanced glycation end-products (AGEs). AGEs accumulate during hyperglycemia and elicit oxidative stress and inflammation through interaction with the receptor for AGEs (RAGE). Soluble RAGE (sRAGE) acts as an anti-inflammatory factor to neutralize AGEs and block the effects mediated by RAGE. In this study, we investigated the associations of prediagnostic measures of Nε-(carboxymethyl)-lysine (CML)-AGE and sRAGE with pancreatic cancer in a case-cohort study within a cohort of 29,133 Finnish male smokers. Serum samples and exposure information were collected at baseline (1985-1988). We measured CML-AGE, sRAGE, glucose and insulin concentrations in fasting serum from 255 incident pancreatic cancer cases that arose through April 2005 and from 485 randomly sampled subcohort participants. Weighted Cox proportional hazard regression models were used to calculate relative risks (RR) and 95% confidence intervals (CI), adjusted for age, years of smoking and body mass index. CML-AGE and sRAGE were mutually adjusted. CML-AGE levels were not associated with pancreatic cancer (fifth compared with first quintile, RR (95% CI): 0.68 (0.38-1.22), Ptrend = 0.27). In contrast, sRAGE levels were inversely associated with pancreatic cancer (fifth compared with first quintile, RR (95% CI): 0.46 (0.23-0.73), Ptrend = 0.002). Further adjustment for glucose or insulin levels did not change the observed associations. Our findings suggest that sRAGE is inversely associated with pancreatic cancer risk among Finnish male smokers.
advanced glycation end-products; soluble receptor for advanced glycation end-products; pancreatic cancer; risk; prospective