Calcium plus vitamin D supplementation and the risk of colorectal cancer.

BACKGROUND: Higher intake of calcium and vitamin D has been associated with a reduced risk of colorectal cancer in epidemiologic studies and polyp recurrence in polyp-prevention trials. However, randomized-trial evidence that calcium with vitamin D supplementation is beneficial in the primary prevention of colorectal cancer is lacking. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 36,282 postmenopausal women from 40 Women's Health Initiative centers: 18,176 women received 500 mg of elemental calcium as calcium carbonate with 200 IU of vitamin D3 [corrected] twice daily (1000 mg of elemental calcium and 400 IU of vitamin D3) and 18,106 received a matching placebo for an average of 7.0 years. The incidence of pathologically confirmed colorectal cancer was the designated secondary outcome. Baseline levels of serum 25-hydroxyvitamin D were assessed in a nested case-control study. RESULTS: The incidence of invasive colorectal cancer did not differ significantly between women assigned to calcium plus vitamin D supplementation and those assigned to placebo (168 and 154 cases; hazard ratio, 1.08; 95 percent confidence interval, 0.86 to 1.34; P=0.51), and the tumor characteristics were similar in the two groups. The frequency of colorectal-cancer screening and abdominal symptoms was similar in the two groups. There were no significant treatment interactions with baseline characteristics. CONCLUSIONS: Daily supplementation of calcium with vitamin D for seven years had no effect on the incidence of colorectal cancer among postmenopausal women. The long latency associated with the development of colorectal cancer, along with the seven-year duration of the trial, may have contributed to this null finding. Ongoing follow-up will assess the longer-term effect of this intervention. (ClinicalTrials.gov number, NCT00000611.).

Thyroid Cancer after Childhood Exposure to External Radiation: An Updated Pooled Analysis of 12 Studies.

Studies have causally linked external thyroid radiation exposure in childhood with thyroid cancer. In 1995, investigators conducted relative risk analyses of pooled data from seven epidemiologic studies. Doses were mostly <10 Gy, although childhood cancer therapies can result in thyroid doses >50 Gy. We pooled data from 12 studies of thyroid cancer patients who were exposed to radiation in childhood (ages <20 years), more than doubling the data, including 1,070 (927 exposed) thyroid cancers and 5.3 million (3.4 million exposed) person-years. Relative risks increased supralinearly through 2-4 Gy, leveled off between 10-30 Gy and declined thereafter, remaining significantly elevated above 50 Gy. There was a significant relative risk trend for doses <0.10 Gy (P < 0.01), with no departure from linearity (P = 0.36). We observed radiogenic effects for both papillary and nonpapillary tumors. Estimates of excess relative risk per Gy (ERR/Gy) were homogeneous by sex (P = 0.35) and number of radiation treatments (P = 0.84) and increased with decreasing age at the time of exposure. The ERR/Gy estimate was significant within ten years of radiation exposure, 2.76 (95% CI, 0.94-4.98), based on 42 exposed cases, and remained elevated 50 years and more after exposure. Finally, exposure to chemotherapy was significantly associated with thyroid cancer, with results supporting a nonsynergistic (additive) association with radiation.

Occupation, pesticide exposure and risk of multiple myeloma.

OBJECTIVES: This population-based case-control study examined the relationship between occupation, living or working on a farm, pesticide exposure, and the risk of multiple myeloma. METHODS: The study included 573 persons newly diagnosed with myeloma and 2131 controls. Information was obtained on sociodemographic factors, occupational history, and history of living and working on a farm. Occupational and industrial titles were coded by standardized classification systems. A job-exposure matrix was developed for occupational pesticide exposure. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression. RESULTS: Farmers and farm workers had odds ratios of 1.9 (95% CI 0.8-4.6) and 1.4 (95% CI 0.8-2.3), respectively. An odds ratio of 1.7 (95% CI 1.0-2.7) was observed for sheep farm residents or workers, whereas no increased risks were found for cattle, beef, pig, or chicken farm residents or workers. A modestly increased risk was observed for pesticides (OR 1.3, 95% CI 0.9-1.8). Significantly increased risks were found for pharmacists, dieticians and therapists (OR 6.1, 95% CI 1.7-22.5), service occupations (OR 1.3, 95% CI 1.02-1.7), roofers (OR 3.3, 95% CI 1.1-9.8), precision printing occupations (OR 10.1, 95% CI 1.03-99.8), heating equipment operators (OR 4.7, 95% CI 1.4-15.8), and hand molders and casters (OR 3.0, 95% CI 1.0-8.4). CONCLUSIONS: A modest increased risk of multiple myeloma is suggested for occupational pesticide exposure. The increased risk for sheep farm residents or workers indicates that certain animal viruses may be involved in myeloma risk.

A pooled analysis of thyroid cancer incidence following radiotherapy for childhood cancer.

Childhood cancer five-year survival now exceeds 70-80%. Childhood exposure to radiation is a known thyroid carcinogen; however, data are limited for the evaluation of radiation dose-response at high doses, modifiers of the dose-response relationship and joint effects of radiotherapy and chemotherapy. To address these issues, we pooled two cohort and two nested case-control studies of childhood cancer survivors including 16,757 patients, with 187 developing primary thyroid cancer. Relative risks (RR) with 95% confidence intervals (CI) for thyroid cancer by treatment with alkylating agents, anthracyclines or bleomycin were 3.25 (0.9-14.9), 4.5 (1.4-17.8) and 3.2 (0.8-10.4), respectively, in patients without radiotherapy, and declined with greater radiation dose (RR trends, P = 0.02, 0.12 and 0.01, respectively). Radiation dose-related RRs increased approximately linearly for <10 Gy, leveled off at 10-15-fold for 10-30 Gy and then declined, but remained elevated for doses >50 Gy. The fitted RR at 10 Gy was 13.7 (95% CI: 8.0-24.0). Dose-related excess RRs increased with decreasing age at exposure (P < 0.01), but did not vary with attained age or time-since-exposure, remaining elevated 25+ years after exposure. Gender and number of treatments did not modify radiation effects. Thyroid cancer risks remained elevated many decades following radiotherapy, highlighting the need for continued follow up of childhood cancer survivors.

Evaluation of concurrent personal measurements of acrylonitrile using different sampling techniques.

In a retrospective assessment of employee exposure to acrylonitrile (AN) for an epidemiological study, investigators from the National Cancer Institute (NCI) and the National Institute for Occupational Safety and Health (NIOSH) evaluated the feasibility of using historic acrylonitrile air samples without modification. The evaluation discussed here was to determine whether the air sampling results across plants were comparable. During site visits to each plant conducted between 1984 and 1986, study investigators collected personal air samples for four days on approximately ten jobs per day. During these visits, IHs at seven of the eight plants also collected personal samples to compare their sample values to the study-collected sample values. Each plant's IH collected these concurrent measurements for their own use and independent of the IHs at the other plants. The plant IHs had no common sampling protocol but, rather, used professional judgment in deciding sampling logistics for their concurrent measurement. In addition, each plant IH used a different laboratory to analyze samples (the study industrial hygienists used one laboratory). Three sampling methods were used by plant industrial hygienists to collect concurrent measurements: charcoal tubes, passive monitors, and porous polymer tubes. The study investigators only used charcoal tubes. Two hundred and sixty four (264) pairs of concurrent measurements were collected. To assess the +/- comparability of the data sets, paired-observation tests were used. The two sets of charcoal tubes were found to compare favorably with each other. The study's charcoal tubes were 1.2 times higher than results from plant passive monitors. No correlation was found between the study's charcoal tube results and plant porous polymer tube results, although the means for 34 pairs of samples were equivalent. As a result of this evaluation, the investigators decided that no adjustments would be made to the plant measurements. This type of evaluation should be considered when using measurement data in multisite epidemiological studies.

Why do Black Americans have a higher risk of pancreatic cancer than White Americans?

BACKGROUND: For several decades, the incidence of pancreatic cancer has been 50% to 90% higher among blacks than among whites in the United States. The purpose of this study was to identify risk factors that may contribute to this racial disparity. METHODS: We conducted a population-based case-control study of pancreatic cancer diagnosed in Atlanta (GA), Detroit (MI), and 10 New Jersey counties from August 1986 through April 1989. In-person interviews were exclusively with subjects (526 cases and 2153 population controls), rather than with next of kin. RESULTS: The determinants of the higher incidence of pancreatic cancer among blacks than among whites differed by sex. Among men, established risk factors (, cigarette smoking, long-term diabetes mellitus, family history of pancreatic cancer) account for 46% of the disease in blacks and 37% in whites, potentially explaining all but 6% of the excess risk among blacks. Among women, however, other factors appear to contribute to the racial disparity, notably moderate/heavy alcohol consumption (>7 drinks per week) and elevated body mass index (above the first quartile). When these less accepted risk factors were combined with the established risk factors, 88% of the disease in black women and 47% in white women were explained, potentially accounting for all of the excess risk among blacks in our female study population. CONCLUSIONS: Among men, the established risk factors (mainly cigarette smoking and diabetes mellitus) explain almost the entire black/white disparity in incidence. Among women, however, other factors appear to contribute to the racial disparity, notably moderate/heavy alcohol consumption and elevated body mass index. In the absence of these factors, pancreatic cancer incidence rates among blacks probably would not exceed those among whites of either sex.