Search

Animal studies suggest that lymphomagenesis can be induced by exposure to carcinogenic aromatic and heterocyclic amines found in diet, cigarette smoke and the environment, but human epidemiologic investigations of these exogenous exposures have yielded conflicting results. As part of our evaluation of the role of aromatic and heterocyclic amines, which are metabolized by N-acetyltransferase (NAT) enzymes, in the etiology of non-Hodgkin lymphoma (NHL), we examined NHL risk in relation to genetic variation in NAT1 and NAT2 and exposure to cigarette smoke and dietary heterocyclic amines and mutagens. We genotyped 10 common single nucleotide polymorphisms (SNPs) in NAT1 and NAT2 among 1136 cases and 922 controls from a population-based case-control study in four geographical areas of the USA. Relative risk of NHL for NAT1 and NAT2 genotypes, NAT2 acetylation phenotype, and exposure to cigarette smoke and dietary heterocyclic amines and mutagens was estimated using odds ratios (ORs) and 95% confidence intervals (CIs) derived from unconditional logistic regression models. We observed increased risk of NHL among individuals with the NAT1*10/*10 genotype compared with individuals with other NAT1 genotypes (OR = 1.60, 95% CI = 1.04-2.46, P = 0.03). We also observed increased NHL risk in a dose-dependent model among NAT2 intermediate- and rapid-acetylators compared with slow-acetylators, although only the trend was statistically significant (intermediate: OR = 1.18, 95% CI = 0.97-1.44, P = 0.1; rapid: OR = 1.43, 95% CI = 0.97-2.14, P = 0.07; P for linear trend = 0.03). Compared with non-smokers, NHL risk estimates for current cigarette smoking were increased only among NAT2 intermediate/rapid-acetylators (OR = 2.44, 95% CI = 1.15-5.20, P = 0.02). Our data provide evidence that NAT1 and NAT2 genotypes are associated with NHL risk and support a contributory role for carcinogenic aromatic and/or heterocyclic amines in the multi-factorial etiology of NHL.

Background: Few studies have examined obesity and risk for multiple myeloma, and the results are inconsistent. Laboratory evidence suggests mechanisms through which obesity could influence carcinogenesis of this hematopoietic malignancy. Methods: We examined the association between anthropometric characteristics and incident multiple myeloma in a prospective, population-based sample of 37,083 postmenopausal women. In 1986, the women completed a mailed questionnaire that included self-report of height and weight, and friend measurement of waist and hip circumferences. During 16 years of follow up, 95 cases of multiple myeloma were identified through linkage to the Iowa Cancer Registry. Results: In an age-adjusted model, women in the highest category of several anthropometric measurements compared with the lowest category were at increased risk of developing multiple myeloma. For body mass index (kg/m2), the rate ratio (95% confidence interval) was 1.5 (0.92–2.6); for weight, 1.9 (1.1–3.4); for waist circumference, 2.0 (1.1–3.5); and for hip circumference, 1.8 (1.0–3.0). Conclusion: Greater adiposity may increase the risk of multiple myeloma.

The incidence of non-Hodgkin lymphoma (NHL) has risen over the past several decades. Reasons for this increase are largely unexplained.In this population-based case-control study, we examined NHL risk and exposure to organochlorine compounds using concentrations in carpet dust as an exposure indicator. We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among women and men ages 20-74 years in Iowa, Los Angeles County, and the Detroit and Seattle metropolitan areas. Controls were selected using random-digit-dialing or Medicare files. Organochlorine concentrations were measured in vacuum bag dust from 603 white cases and 443 white controls who had owned most of their carpets for at least 5 years.NHL risk was elevated if any of the polychlorinated biphenyl (PCB) congeners (PCBs 105, 138, 153, 170, or 180) was detected (odds ratio = 1.5; 95% confidence interval = 1.2-2.0). Risk was elevated in the top tertile of PCB 180 (1.7; 1.1-2.6) and in the top 2 tertiles of total PCBs (middle tertile, 1.6 [1.1-2.4]; top tertile 1.5 [1.0-2.2]). There was a positive trend in risk with increasing PCB 180 levels (P trend = 0.03). NHL risk was elevated if dichlorodiphenyldichloroethylene (DDE) was detected (1.3; 1.0-1.7), but only among men. A positive, but not monotonic, dose-response relationship was observed for DDE (P trend = 0.02).Our findings suggest an increased risk of NHL associated with exposure to PCBs, with evidence of greater effects for PCB 180. There is also some evidence of an association with DDE.

Although parity is associated with a decreased risk of ovarian cancer in the general population, this association among women with a family history is less clear. We examined this question in a prospective cohort of 31,377 Iowa women 55-69 years of age at baseline. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated through Cox regression. We identified 181 incident epithelial ovarian cancers through 13 years of follow-up. At baseline, 14% of the women reported breast or ovarian cancer in a first-degree relative, and an additional 12% reported a family history in a second-degree relative. Among women without a family history of breast or ovarian cancer in a first-degree relative, nulliparous women were at slightly increased risk of ovarian cancer (RR = 1.4, 95% CI = 0.9-2.4) compared with parous women, whereas among women with a family history, nulliparous women were at a much higher risk (RR = 2.7, 95% CI = 1.1-6.6) than parous women. Similar results were seen when family history included first- or second-degree relatives with breast or ovarian cancer or a first- or second-degree relative with ovarian cancer only. Nulliparity may be more strongly associated with an increased risk of ovarian cancer among women with a family history of breast or ovarian cancer, compared with women who do not have a family history of those cancers.

Low B-vitamin intake may increase risk of breast cancer through decreased DNA repair capacity. Alcohol intake increases risk for breast cancer, with evidence from prospective studies of an interaction between alcohol and folate. We explored dietary intake of folate and other B vitamins with risk of breast cancer in a cohort study of 34,387 postmenopausal women. To measure diet, we mailed a food frequency questionnaire; we estimated nutrient intakes and categorized them into four levels:10th, 11th-30th, 31st-50th, and50th percentiles. Through 12 years of follow-up, we identified 1,586 cases of breast cancer in the cohort at risk. We estimated relative risks (RRs) and 95% confidence intervals (CIs) through Cox regression models adjusted for age, energy, and other risk factors. Women in the lowest 10th percentile of folate intake from diet alone were at modestly increased risk of breast cancer relative to those above the 50th percentile: RR = 1.21 (95% CI = 0.91--1.61). We examined the joint association of folate intake and alcohol use on risk of breast cancer, with the reference group defined as women with high folate (50th percentile) and no alcohol use. The RRs of breast cancer associated with low dietary folate intake were 1.08 (95% CI = 0.78--1.49) among nondrinkers, 1.33 (95% CI = 0.86--2.05) among drinkers ofor = 4 gm per day, and 1.59 (95% CI = 1.05--2.41) among drinkers of4 gm per day. These results suggest that the risks of postmenopausal breast cancer may be increased among women with low intakes of folate if they consume alcohol-containing beverages.

Although farming has been linked to prostate cancer mortality, few investigations have addressed its association with prostate cancer incidence. We followed a population-based cohort of 1,177 cancer-free men for up to 9 years and identified 81 incident prostate cancers. Men whose usual occupation was farmer were at an increased risk of prostate cancer after adjustment for age, smoking, alcohol, and dietary factors (RR = 1.7; 95% CI = 1.0-2.7). Exclusion of well-differentiated, localized tumors slightly strengthened the association (RR = 2.0; 95% CI = 1.1-3.6). Risk was confined to older (age 70+ years) farmers (RR = 2.2; 95% CI = 1.1-4.3); we found no evidence of an effect among younger farmers (RR = 1.0; 95% CI = 0.4-2.1).

Prior studies assessing social ties and mortality risk in older persons have not considered the dynamic nature of social ties, health, and functional status in this age group. We evaluated the association between change in social ties (assessed in 1982 and 1985) and subsequent mortality through 1993 in a population-based cohort of 2,575 rural persons ages 65-102 years. The same summary measure of social ties was constructed for both interviews and included marital status, number of close friends and relatives, church attendance, and membership in a group. Compared with persons reporting higher levels of social ties at both interviews, a decrease to a low level of social ties was associated with an increased mortality risk for both men [hazard ratio (HR) = 1.8; 95% confidence interval (CI) = 1.2-2.7] and women (HR = 2.1; 95% CI = 1.5-3.0). Lower levels of social ties at both interviews were also associated with greater mortality risk in men (HR = 2.2: 95% CI = 1.5-3.1) and women (HR = 2.2; 95% CI = 1.6-2.9), whereas an increase to a higher level of social ties was not associated with subsequent mortality risk. Adjustment for age, education, smoking status, cognitive function, onset of a major illness, change in physical function, change in self-perceived health status, and change in depressive symptoms eliminated the association between loss of social ties and survival, but both men (HR = 2.3; 95% CI = 1.5-3.5) and women (HR = 1.8; 95% CI = 1.2-2.6) reporting low levels of social ties at both interviews remained at elevated risk. The lack of an association between loss of social ties and mortality risk after adjusting for demographic, health, and functional status variables indicates that these are either confounding or intervening variables in a social ties and mortality association. In contrast, sustained low levels of social ties appear to influence mortality risk independent of these same variables and imply that continued social isolation may be a more important determinant of mortality risk than recent changes in social ties.