Background

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.

Methods

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.

Results

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.

Conclusion

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.

Impact

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.

Background

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).

Methods

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.

Results

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.

Conclusions

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.

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Objective

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.

Methods

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.

Results

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.

Conclusion

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.

Background

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.

Methods

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.

Results

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).

Conclusion

We did not find any associations between foods or nutrients and CLL/SLL.

Impact

Our large prospective study indicates that diet may not play a role in CLL/SLL development.

Background

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.

Methods

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.

Results

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.

Conclusion

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.

Background

Many epidemiologic studies have examined the association between CRP and risk of cancer with inconsistent results.

Methods

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.

Results

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.

Conclusion

Our results do not support the hypothesis that higher CRP concentrations are associated with incident pancreatic cancer.

Impact

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.

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.

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.

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.

Background

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.

Methods

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).

Results

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).

Conclusion

Higher prediagnostic levels of serum sRAGE were associated with lower risk of colorectal cancer in male smokers.

Impact

This is the first epidemiologic study to implicate the receptor for advanced glycation end-products in colorectal cancer development.

Purpose

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.

Results

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.

Conclusion

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.

Background

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.

Methods

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.

Results

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).

Conclusions

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.

BACKGROUND

Renal cell carcinoma and hypertension (a well-established renal cancer risk factor) are both more frequent among blacks than whites in the U.S. The association between hypertension and renal cell carcinoma has not been examined in black Americans. We investigated the hypertension–renal cancer association by race, and we assessed the role of hypertension in the racial disparity of renal cancer incidence.

METHODS

Participants were enrolled in a population-based case-control study in Detroit and Chicago during 2002–2007 (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519 blacks). Participants reported their history of hypertension and antihypertensive drug use. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic characteristics, smoking, body mass index, and family history of cancer.

RESULTS

Hypertension doubled renal cancer risk (OR=2.0 [CI=1.7–2.5]) overall. For whites the OR was 1.9 (CI=1.5–2.4), while for blacks it was 2.8 (2.1–3.8) (p for interaction=0.11). ORs increased with time after hypertension diagnosis (p for trend <0.001), reaching 4.1 (CI=2.3–7.4) for blacks and 2.6 (CI=1.7–4.1) for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI=2.3–8.8) for blacks and 2.1 (CI=1.2–3.8) for whites. If these estimates correctly represent causal effects and if, hypothetically, hypertension could be prevented entirely among persons aged 50–79 years, the black/white disparity in renal cancer could be reversed among women and reduced by two-thirds among men.

CONCLUSIONS

Hypertension is a risk factor for renal cancer among both blacks and whites, and might explain a substantial portion of the racial disparity in renal cancer incidence. Preventing and controlling hypertension might reduce renal cancer incidence, adding to the known benefits of blood pressure control for heart disease and stroke reduction, particularly among blacks.

Vitamin D has been hypothesized to protect against cancer. We followed 16,819 participants in NHANES III from 1988 through 2006, expanding upon an earlier NHANES III study (1988–2000). Using Cox proportional hazard regression models, we examined risk related to baseline serum 25-hydroxyvitamin D (25(OH)D) for total cancer mortality, in both sexes, and by racial/ethnic groups, as well as for site-specific cancers. Because serum was collected in the south in cooler months and the north in warmer months, we examined associations by collection season (“summer/higher latitude” and “winter/lower latitude”). We identified 884 cancer deaths during 225,212 person-years. Overall cancer mortality risks were unrelated to baseline 25(OH)D status in both season/latitude groups, and in non-Hispanic whites, non-Hispanic blacks, and Mexican-Americans. In men, risks were elevated at higher levels (e.g., for ≥100 nmol/L, RR=1.85 (95% CI=1.02–3.35) compared to <37.5 nmol/L). Athough risks were unrelated to 25(OH)D in all women combined, risks significantly decreased with increasing 25(OH)D in the summer/higher latitude group (for ≥100 nmol/L, RR= 0.52 (95% CI=0.25–1.15) compared to <37.5 nmol/L, P-trend=0.03, based on continuous values). We also observed a suggestion of an inverse association with colorectal cancer mortality(P-trend=0.09) and a positive association with lung cancer mortality among males (P-trend=0.03). Our results do not support a the hypothesis that 25(OH)D is associated with reduced cancer mortality. Although cancer mortality in females was inversely associated with 25(OH)D in the summer/higher latitude group, cancer mortality at some sites was increased among men with higher 25(OH)D. These findings argue for caution before increasing 25(OH)D levels to prevent cancer.

Background

This paper examines the prevalence of cancer screening use as reported in 2005 among U.S. adults, focusing on differences among historically underserved subgroups. We also examine trends from 1992 through 2005 to determine if differences in screening use are increasing, staying the same, or decreasing.

Methods

Data from the National Health Interview Surveys between 1992 and 2005 were analyzed to describe patterns and trends in cancer screening practices, including Pap test, mammography, prostate-specific antigen (PSA), and colorectal screening. Logistic regression was used to report 2005 data for population subgroups defined by a number of demographic and socioeconomic characteristics.

Results

Rates of use for cancer tests are rising only for colorectal cancer, due largely to the increase in colorectal endoscopy screening. Use of all the modalities was strongly influenced by contact with a physician and by having health insurance coverage.

Conclusions

There remain large gaps in use for all screening modalities by education, income, usual source of care, health insurance, and recent physician contact. These specific populations would benefit from interventions to overcome these barriers to screening.

Obesity is a well-established risk factor for postmenopausal breast cancer, but mechanisms underlying the association are unclear. Adipocyte-derived, cytokine-like adipokines have been suggested as contributory factors. To evaluate their association with breast cancer risk factors and breast cancer risk, we conducted a nested case-control study of 234 postmenopausal breast cancer cases and 234 controls in a cohort of U.S. women with prospectively-collected serum samples obtained in the mid 1970’s and followed for up to 25 years. Adiponectin, absolute plasminogen activator inhibitor-1 (aPAI-1), and resistin were measured by a multiplex immunoassay. Sex hormones were available for 67 cases and 67 controls. Among controls, we found that lower levels of adiponectin and higher levels of aPAI-1 were correlated with increasing levels of estradiol (Spearman r=−0.26, p-value=0.033; r=0.42, p=0.0003), decreasing levels of sex hormone binding globulin (r=0.38, p=0.0013; r=−0.32, p=0.0076), and increasing body mass index (BMI) (r=−0.31, p=<0.0001; r=0.39, p=<0.0001). Hormones were not associated with resistin. Among the relatively small percentage of women using postmenopausal hormones at the time of blood collection (13.7%), aPAI-1 levels were higher than in nonusers (p=0.0054). Breast cancer risk was not associated with circulating levels of adiponectin (age-adjusted p for linear trend=0.43), aPAI-1 (p=0.78), or resistin (p=0.91). The association was not confounded by BMI, parity, age at first full-term birth, age at menopause, current postmenopausal hormone use, and circulating sex steroid hormones. Furthermore, adipokine associations were not modified by BMI (p>0.05). The lack of association with risk may be due to measurement error of the laboratory assays. In conclusion, lower levels of adiponectin and higher levels of aPAI-1 measured in prospectively-collected serum from postmenopausal women were associated with increasing BMI but not breast cancer risk.

Objectives

Use of non-steroidal anti-inflammatory drugs (NSAIDs) has been inversely associated with colorectal cancer; however, the association within colorectal subsites or among higher risk individuals is understudied. We investigated NSAID use and colorectal adenocarcinoma by subsite, and among individuals with a family history of colon cancer in the National Institutes of Health-AARP Diet and Health Study.

Methods

Using Cox proportional hazards regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for colorectal cancer incidence among 301,240 men and women (mean age 62.8 y); including 26,994 individuals with a first degree relative with a history of colon cancer. We accrued 3,894 colorectal cancer cases during 10 years of follow-up; 372 cases had a first degree relative with colon cancer.

Results

Both aspirin and non-aspirin NSAID use reduced colorectal cancer risk (HR for users compared to non-users=0.91, 95% CI: 0.85, 0.98; HR=0.82, 95% CI: 0.77, 0.87, respectively). Daily aspirin use reduced the risk of cancer in the distal colon (HR=0.84, 95% CI: 0.71, 0.99) and rectum (HR=0.76, 95% CI: 0.64, 0.90); daily non-aspirin NSAID use reduced the risk of both proximal (HR=0.65, 95% CI: 0.54, 0.78) and distal colon cancer (HR=0.69, 95% CI: 0.55, 0.87), but not rectal cancer. Among participants with a first degree relative with colon cancer, daily use of aspirin was associated with a decreased risk of rectal cancer (HR= 0.38, 95% CI: 0.19, 0.78), and daily use of non-aspirin NSAIDs was associated with a decreased risk of colon cancer (HR= 0.49, 95% CI: 0.29, 0.82). No protective benefit for daily aspirin use and colon cancer or daily non-aspirin NSAID use and rectal cancer was observed in this higher risk subgroup, although power was limited by small case numbers.

Conclusions

NSAID use was associated with a reduced colorectal cancer risk; the magnitude of this association differed between aspirin and non-aspirin NSAIDs. Daily aspirin and non-aspirin NSAID use by individuals with a family history of colon cancer significantly reduced the risk of rectal and colon cancer, respectively.

Background

Meat could be involved in bladder carcinogenesis via multiple potentially carcinogenic meat-related compounds related to cooking and processing, including nitrate, nitrite, heterocyclic amines (HCAs), and polycyclic aromatic hydrocarbons. We comprehensively investigated the association between meat and meat components and bladder cancer.

Methods

During 7 years of follow-up, 854 transitional cell bladder cancer cases were identified among 300,933 men and women who completed a validated food frequency questionnaire in the large prospective NIH-AARP Diet and Health Study. We estimated intake of nitrate and nitrite from processed meat and HCAs and PAHs from cooked meat using quantitative databases of measured values. We calculated total dietary nitrate and nitrite based on literature values.

Results

The hazard ratios (HR) and 95% confidence intervals (CI) for red meat (HR for fifth compared to first quintile=1.22, 95% CI=0.96–1.54, p-trend=0.07) and the HCA 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) (HR=1.19, 95% CI=0.95–1.48, p-trend=0.06) conferred a borderline statistically significant increased risk of bladder cancer. We observed positive associations in the top quintile for total dietary nitrite (HR=1.28, 95% CI=1.02–1.61, p-trend= 0.06) and nitrate plus nitrite intake from processed meat (HR=1.29 95% CI=1.00–1.67, p-trend= 0.11).

Conclusions

These findings provide modest support for a role for total dietary nitrite and nitrate plus nitrite from processed meat in bladder cancer. Our results also suggest a positive association between red meat and PhIP and bladder carcinogenesis.

It has been hypothesized that the increased prevalence of testicular germ cell tumors (TGCT) may be attributable to endocrine disrupting chemicals, such as persistent organic pollutants (POPs); these may be modulated by hormone-metabolizing enzymes. Using data from 568 cases and 698 controls enrolled in the U.S. Servicemen’s Testicular Tumor Environmental and Endocrine Determinants Study, we examined associations between TGCT and POPs, including p,p′-DDE, chlordane-related compounds, and polychlorinated biphenyls (PCBs), modified by polymorphisms in 5 hormone-metabolizing genes (CYP17A1, CYP1A1, HSD17B1, HSD17B4, and AR). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models that stratified associations of POP exposure and TGCT risk by genotype. Two polymorphisms in CYP1A1, rs1456432 and rs7495708, modified the association between trans-nonachlor and total chlordanes and TGCT risk. Among men with a minor allele for rs1456432, those with the highest quartiles had an increased risk of TGCT (OR=1.90, 95% CI, 1.01–3.56) compare to those with the lowest; there were no increased risk among men with the homozygous major allele genotype (p-interaction=0.024). Similar results were seen for rs7495708. HSD17B4 rs384346 modified the associations between TGCT risk and PCB-118 and PCB-138 concentrations: the 45–55% reductions in TGCT risk for men with the highest quartiles compared to the lowest quartiles were only present in those who had a major homozygous allele genotype (p-interactions<0.04). Thus, there are suggestions that certain CYP1A1 and HSD17B4 polymorphisms may modify the associations between POPs and TGCT risk. With false discovery rate values >0.2, however, caution is advisable when interpreting the findings of this study.

Background

Although family history of cancer is widely ascertained in research and clinical care, little is known about assessment methods, accuracy, or other quality measures. Given its widespread use in cancer screening and surveillance, better information is needed regarding the clarity and accuracy of family history information reported in the general population.

Methods

This telephone survey in Connecticut examined coherence and completeness of reports from 1,019 respondents about 20,504 biological relatives.

Results

Of 2,657 cancer reports, 97.7% were judged consistent with malignancy (vs. benign or indeterminate conditions); 79% were site-specific, 10.8% had unspecified cancer sites and 8.6% had “ill-defined” sites. Only 6.1% of relatives had unknown histories. Unknown histories and ambiguous sites were significantly higher for second-degree relatives. The adjusted percentage of first-degree relative reports with ambiguous sites increased with decreasing education and African-American race of survey respondents, and with deceased vital status of relatives. Ambiguous second-degree relative reports were also associated with deceased vital status, and with male gender of respondents.

Conclusions

These findings suggest that family history of cancer reports from the general population are generally complete and coherent.

Impact

Strategies are needed to improve site specificity and thus maximize the utility of such information in primary care settings.