Jane C. Schroeder

Circulating levels of inflammatory cytokines and risk of colorectal adenomas

The association between obesity and colorectal neoplasia may be mediated by inflammation. Circulating levels of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) are elevated in the obese. Adipose tissue can produce and release the inflammatory cytokines that are potentially procarcinogenic. We examined circulating levels of CRP, IL-6, and TNF-alpha in relation to risk factors and the prevalence of colorectal adenomas. Plasma levels of CRP, IL-6, and TNF-alpha were quantified in 873 participants (242 colorectal adenoma cases and 631 controls) in a colonoscopy-based cross-sectional study conducted between 1998 and 2002. Multivariable logistic regression was used to estimate associations between known risk factors for colorectal neoplasia and circulating levels of inflammatory cytokines and associations between inflammatory cytokines and colorectal adenomas. Several known risk factors for colorectal neoplasia were associated with higher levels of inflammatory cytokines, including older age, current smoking, and increasing adiposity. The prevalence of colorectal adenomas was associated with higher concentrations of IL-6 and TNF-alpha and, to a lesser degree, with CRP. For IL-6, adjusted odds ratios (OR) for colorectal adenomas were 1.79 [95% confidence interval (CI), 1.19-2.69] for the second highest plasma level and 1.85 (95% CI, 1.24-2.75) for the highest level compared with the reference level. A similar association was found with TNF-alpha, with adjusted ORs of 1.56 (95% CI, 1.03-2.36) and 1.66 (95% CI, 1.10-2.52), respectively. Our findings indicate that systemic inflammation might be involved in the early development of colorectal neoplasia.

Agricultural risk factors for t(14;18) subtypes of non-Hodgkin's lymphoma.

The t(14;18) translocation is a common somatic mutation in non-Hodgkin’s lymphoma (NHL) that is associated with bcl-2 activation and inhibition of apoptosis. We hypothesized that some risk factors might act specifically along t(14;18)-dependent pathways, leading to stronger associations with t(14;18)-positive than t(14;18)-negative non-Hodgkin’s lymphoma. Archival biopsies from 182 non-Hodgkin’s lymphoma cases included in a case-control study of men in Iowa and Minnesota (the Factors Affecting Rural Men, or FARM study) were assayed for t(14;18) using polymerase chain reaction amplification; 68 (37%) were t(14;18)-positive. We estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) for various agricultural risk factors and t(14;18)-positive and -negative cases of non-Hodgkin’s lymphoma, based on polytomous logistic regression models fit using the expectation-maximization (EM) algorithm. T(14;18)-positive non-Hodgkin’s lymphoma was associated with farming (OR 1.4, 95% CI = 0.9–2.3), dieldrin (OR 3.7, 95% CI = 1.9–7.0), toxaphene (OR 3.0, 95% CI = 1.5–6.1), lindane (OR 2.3, 95% CI = 1.3–3.9), atrazine (OR 1.7, 95% CI = 1.0–2.8), and fungicides (OR 1.8, 95% CI = 0.9–3.6), in marked contrast to null or negative associations for the same self-reported exposures and t(14;18)-negative non-Hodgkin’s lymphoma. Causal relations between agricultural exposures and t(14;18)-positive non-Hodgkin’s lymphoma are plausible, but associations should be confirmed in a larger study. Results suggest that non-Hodgkin’s lymphoma classification based on the t(14;18) translocation is of value in etiologic research.

Ionizing Radiation and Chronic Lymphocytic Leukemia

The U.S. government recently implemented rules for awarding compensation to individuals with cancer who were exposed to ionizing radiation while working in the nuclear weapons complex. Under these rules, chronic lymphocytic leukemia (CLL) is considered to be a nonradiogenic form of cancer. In other words, workers who develop CLL automatically have their compensation claim rejected because the compensation rules hold that the risk of radiation-induced CLL is zero. In this article we review molecular, clinical, and epidemiologic evidence regarding the radiogenicity of CLL. We note that current understanding of radiation-induced tumorigenesis and the etiology of lymphatic neoplasia provides a strong mechanistic basis for expecting that ionizing radiation exposure increases CLL risk. The clinical characteristics of CLL, including prolonged latency and morbidity periods and a low case fatality rate, make it relatively difficult to evaluate associations between ionizing radiation and CLL risk via epidemiologic methods. The epidemiologic evidence of association between external exposure to ionizing radiation and CLL is weak. However, epidemiologic findings are consistent with a hypothesis of elevated CLL mortality risk after a latency and morbidity period that spans several decades. Our findings in this review suggest that there is not a persuasive basis for the conclusion that CLL is a nonradiogenic form of cancer.

Time to clearance of human papillomavirus infection by type and human immunodeficiency virus serostatus.

Persistent infection with high‐risk human papillomavirus (HPV) is central to cervical carcinogenesis. Certain high‐risk types, such as HPV16, may be more persistent than other HPV types, and type‐specific HPV persistence may differ by HIV serostatus. This study evaluated the association between HPV type and clearance of HPV infections in 522 HIV‐seropositive and 279 HIV‐seronegative participants in the HIV Epidemiology Research Study (HERS, United States, 1993–2000). Type‐specific HPV infections were detected using MY09/MY11/HMB01‐based PCR and 26 HPV type‐specific probes. The estimated duration of type‐specific infections was measured from the first HPV‐positive visit to the first of two consecutive negative visits. Hazard ratios (HRs) and 95% confidence intervals (CIs) for HPV clearance were calculated using Cox models adjusted for study site and risk behavior (sexual or injection drugs). A total of 1,800 HPV infections were detected in 801 women with 4.4 years median follow‐up. HRs for clearance of HPV16 and related types versus low‐risk HPV types were 0.79 (95% CI: 0.64–0.97) in HIV‐positive women and 0.86 (95% CI: 0.59–1.27) in HIV‐negative women. HRs for HPV18 versus low‐risk types were 0.80 (95% CI: 0.56–1.16) and 0.57 (95% CI: 0.22–1.45) for HIV‐positive and ‐negative women, respectively. HPV types within the high‐risk category had low estimated clearance rates relative to low‐risk types, but HRs were not substantially modified by HIV serostatus.

Dietary Flavonoid Intake and Breast Cancer Survival among Women on Long Island

Background: Laboratory research and a growing number of epidemiologic studies have provided evidence for a reduced risk of breast cancer associated with dietary intake of certain classes of flavonoids. However, the effects of flavonoids on survival are not known. In a population-based cohort of breast cancer patients, we investigated whether dietary flavonoid intake before diagnosis is associated with subsequent survival. Methods: Women ages 25 to 98 years who were newly diagnosed with a first primary invasive breast cancer between August 1, 1996, and July 31, 1997, and participated in a population-based, case-control study (n = 1,210) were followed for vital status through December 31, 2002. At the case-control interview conducted shortly after diagnosis, respondents completed a FFQ that assessed dietary intake in the previous 12 months. All-cause mortality (n = 173 deaths) and breast cancer–specific mortality (n = 113 deaths) were determined through the National Death Index. Results: Reduced hazard ratios [age- and energy-adjusted hazard ratio (95% confidence interval)] for all-cause mortality were observed among premenopausal and postmenopausal women for the highest quintile of intake, compared with the lowest, for flavones [0.63 (0.41-0.96)], isoflavones [0.52 (0.33-0.82)], and anthocyanidins [0.64 (0.42-0.98)]. No significant trends in risk were observed. Results were similar for breast cancer–specific mortality only. Conclusion: Mortality may be reduced in association with high levels of dietary flavones and isoflavones among postmenopausal U.S. breast cancer patients. Larger studies are needed to confirm our findings. (Cancer Epidemiol Biomarkers Prev 2007;16(11):2285–92)

DNA Repair Polymorphisms XRCC1 and MGMT and Risk of Adult Gliomas

X-ray cross complementing group 1 (XRCC1) and O6-methylguanine-DNA methyltransferase (MGMT) are pivotal repair genes focused on repairing lesions due to ionizing radiation, alkylating agents, and oxidative DNA damage, risk factors previously linked to gliomas. Using the population based San Francisco Adult Glioma study, we evaluated associations between XRCC1 Arg399Gln, MGMT Leu84Phe, and MGMT Ile143Val polymorphisms with glioma risk among white cases (n = 441 to 453) and controls (n = 487 to 526). We found no evidence of an association between XRCC1 genotypes and glioma. We observed a weak positive association for the MGMT Leu84Phe polymorphism (Leu or Phe/Phe versus Leu/Leu: adjusted OR = 1.26; CI 0.90–1.75) and the MGMT Ile143Val polymorphism (Ile or Val/Val versus Ile/Ile: adjusted OR = 1.20; CI 0.85–1.71).

GSTM1 and GSTT1 Polymorphisms, Cigarette Smoking, and Risk of Colon Cancer: A Population-based Case-control Study in North Carolina (United States)

Cigarette smoke is a risk factor for colon cancer, but the importance of dose and interaction with genetic susceptibility remain poorly understood. We used data from a population-based case control study, to examine the association between cigarette smoking and colon cancer in African Americans and whites, and colon cancer and polymorphisms in GSTM1 and GSTT1. A total of 554 cases of primary colon cancer and 874 controls were included in this analysis. We found no association between cigarette smoking (ever versus never) and colon cancer in African Americans (odds ratio (OR)=0.93, 95% confidence interval (CI)=0.65–1.33). In contrast, there was an increased risk of cigarette smoking in whites (OR=1.43, CI=1.05–1.94). There was a small increased risk of colon cancer for individuals with GSTM1 null (African Americans, OR=1.43, CI, 0.98–2.09; whites, OR=1.19, CI, 0.90–1.58) and a decreased risk of colon cancer for individuals with GSTT1 null (African Americans, OR=0.59, CI: 0.40–0.86; whites, OR=0.72, CI: 0.53–1.00). There were weak interactions between GSTT1 null and cigarette smoking in whites, and GSTM1 null genotype and cigarette smoking in African Americans. GSTT1 and GSTM1 polymorphisms may be weakly related to colon cancer risk and there may be racial differences in gene-smoking interactions.

Associations of Antioxidant Nutrients and Oxidative DNA Damage in Healthy African-American and White Adults

High antioxidant intake has been shown to reduce cancer risk and may also mitigate the effects of oxidative DNA damage, which is hypothesized to be causally linked to carcinogenesis. This study examined potential racial differences in (a) dietary intakes and plasma concentrations of vitamin C, vitamin E, and carotenoids and oxidative DNA damage and (b) associations between plasma antioxidants and oxidative DNA damage. Data were from a cross-sectional study of 164 generally healthy nonsmoking African-Americans and Whites in North Carolina, ages 20 to 45 years, equally distributed by race and sex. Participants completed a demographic and health questionnaire, four 24-h dietary recalls, and a dietary supplement inventory; had height and weight measured; and provided a semifasting blood sample. African-Americans had statistically significantly lower plasma concentrations of vitamin E, α-carotene, β-carotene, and lutein + zeaxanthin than Whites, as well as lower self-reported intake of most antioxidants. Levels of oxidative DNA damage, measured using the alkaline comet assay, were lower in African-Americans than Whites. An inverse association between lycopene and oxidative DNA damage (r = −0.20; P = 0.03) was found in the combined study population after adjusting for sex, age, body mass index, passive smoke exposure, physical activity, education, income, and alcohol intake. There was also a positive association of vitamin E with oxidative DNA damage in the total population (r = 0.21; P = 0.02) and in African-American men (r = 0.63; P = 0.01) after adjusting for covariates. This study is among the first to examine these associations in a sample of healthy adults with an adequate representation of African-Americans. (Cancer Epidemiol Biomarkers Prev 2007;16(7):1428–36)

Obesity and Prostate Cancer Aggressiveness among African and Caucasian Americans in a Population-based Study

Background: This study evaluated obesity and prostate cancer aggressiveness relationship in a population-based incident prostate cancer study. Methods: The North Carolina–Louisiana Prostate Cancer Project includes medical records data for classification of prostate cancer aggressiveness at diagnosis by using clinical criteria for 1,049 African American (AA) and 1,083 Caucasian American (CA) participants. An association between prostate cancer aggressiveness and obesity, measured using body mass indices (BMI) and waist-to-hip ratio (WHR), was assessed using ORs and 95% CIs adjusted for confounders. Results: A significantly positive association was found between prostate cancer aggressiveness and obesity. The ORs for high aggressive prostate cancer among prediagnosis obese and severely obese were 1.48 (95% CI = 1.02–2.16) and 1.98 (95% CI = 1.31–2.97), respectively, compared with normal weight research subjects. Race-stratified results suggested the association is stronger among CAs. Interaction model showed that normal weight AAs had more aggressive prostate cancer than normal weight CAs (OR = 2.69, 95% CI = 1.36–5.30); severe obesity was associated with aggressive disease in AAs (OR = 3.90, 95% CI = 1.97–7.75). WHR > 0.98 among all research subjects adjusted for race was significantly associated with high aggressive prostate cancer (OR = 1.42, 95% CI = 1.00–2.00) when compared with WHR < 0.90. The stratified result is less clear among AAs. Conclusions: This study shows a positive association between obesity and aggressive prostate cancer. AAs have more aggressive prostate cancer in general than CAs even at normal weight. Therefore, the association between obesity and aggressiveness is not as evident in AAs as in CAs. Impact: This study provides a unique opportunity to examine impact of race on obesity and high aggressive prostate cancer relationship. Cancer Epidemiol Biomarkers Prev; 20(5); 844–53. ©2011 AACR.

Consumption of trans-Fatty Acid and Its Association with Colorectal Adenomas

trans-Fatty acid consumption is known to have detrimental effects on cardiovascular health, but little is known about its role in digestive tract neoplasia. To investigate the association between colorectal adenomas and trans-fatty acid consumption, the authors utilized data from a cross-sectional study of 622 individuals who underwent complete colonoscopy between 2001 and 2002 at the University of North Carolina Hospitals. Participants were interviewed about demographic, lifestyle, and dietary factors thought to be related to colorectal cancer. trans-Fatty acid consumption, energy adjusted by the residual method, was categorized into quartiles based on its distribution in controls. Compared with participants in the lowest quartile of consumption, those in the highest quartile had an increased prevalence of colorectal adenomas, with an adjusted prevalence odds ratio of 1.86 (95% confidence interval: 1.04, 3.33). The authors further investigated the relation between trans-fatty acid consumption and colorectal neoplasia by examining the adenoma characteristics, with the adjusted prevalence odds ratios showing little or no difference by adenoma location, size, or number. These results suggest that consumption of high amounts of trans-fatty acid may increase the risk of colorectal neoplasia, and they provide additional support to recommendations to limit trans-fatty acid consumption.