Loraine D. Marrett

An application of capture-recapture methods to the estimation of completeness of cancer registration

Completeness of cancer registration has not been consistently ascertained across different registries. This report describes how capture-recapture methods have been used to estimate completeness at the Ontario Cancer Registry. The method was applied in two fashions; first, using three data sources in a modeling approach: and second, using two data sources and standard, simple capture-recapture methods. The modeling approach is more flexible, since several variables that influence cancer registration can be considered and can be used to identify reporting patterns of different data sources. In the present analysis, estimates of completeness of the registry as a whole were remarkably similar using either two or three data sources, and site-specific comparisons differed by at most 7%. Because of the advantages of capture-recapture methods-estimation of level of completeness, possible comparability of estimates across different registries, and versatility to consider other determinants of cancer registration-a plea for greater use of these methods in cancer registration is made.

Case-control study of bladder cancer and chlorination by-products in treated water (Ontario, Canada)

Chlorine is by far the most commonly used chemical for the disinfection of water supplies in North America. However, chlorine reacts with organic material in the raw water producing a number of halogenated hydrocarbon by-products. This population-based case-control study in Ontario, Canada examined the relationship between bladder cancer and exposure to chlorination by-products in public water supplies. Residence and water source histories and data from municipal water supplies were used to estimate individual exposure according to water source, chlorination status, and by-product levels (represented by trihalomethane [THM] concentration). Exposures were estimated for the 40-year period prior to the interview, using 696 cases diagnosed with bladder cancer between 1 September 1992 and 1 May 1994 and 1,545 controls with at least 30 years of exposure information. Odds ratios (OR) adjusted for potential confounders were used to estimate relative risk. Those exposed to chlorinated surface water for 35 or more years had an increased risk of bladder cancer compared with those exposed for less than 10 years (OR=1.41, 95 percent confidence interval [CI]=1.10–1.81). Those exposed to an estimated THM level≥50 μg/liter for 35 or more years had 1.63 times the risk of those exposed for less than 10 years (CI=1.08–2.46). These results indicate that the risk of bladder cancer increases with both duration and concentration of exposure to chlorination by-products, with population attributable risks of about 14 to 16 percent. Chlorination by-products represent a potentially important risk factor for bladder cancer.

Pre-natal and peri-natal exposures and risk of testicular germ-cell cancer

The present case‐control study was undertaken to investigate the association between exposure to maternal hormones and risk of testicular germ‐cell cancer by histologic subgroups. Cases were males, aged 16 to 59 years, diagnosed with testicular germ‐cell cancer in Ontario between 1987 and 1989. Histologic review was performed on all eligible cases for the purpose of categorizing cases as seminoma or non‐seminoma (the latter classified 2 ways, with and without tumors containing seminoma). Risk factor data were collected on 502 cases, 346 case mothers, 975 age‐matched controls, and 522 control mothers. Exogenous hormone exposure was associated with elevated risk (OR = 4.9, 95% CI 1.7–13.9). Several additional risk factors were associated with risk of testicular cancer: bleeding and threatened miscarriage (OR = 0.6, 95% CI 0.3–1.0), maternal cigarette smoking (12+ cigarettes/day OR = 0.6, 95% CI 0.4–1.0). pre‐term birth (OR = 1.6, 95% CI 1.0–2.5), and treatment for undescended testicle (OR = 8.0, 95% CI 3.2–20.0). First births were associated with elevated risk (OR = 1.7, 95% CI 1.0–2.8) among mothers below the age of 24 years at conception. There was little evidence that risk factors differed by histologic subgroup. We found evidence that exposure to maternal hormones, particularly estrogens, is associated with testicular germ‐cell cancer risk. Not only does exposure to elevated levels (exogenous hormone use, pre‐term birth, and first births among young mothers) increase risk but also exposure to relatively lower levels (heavy cigarette consumption and, perhaps, bleeding and threatened miscarriage) may decrease cancer risk. Int. J. Cancer 87:438–443, 2000.

Risk factors for renal cell carcinoma: results of a population-based case-control study

For a case-control study of risk factors for renal cell carcinoma, a mailed questionnaire was used to collect data on 518 cases and 1,381 population-based controls in Ontario, Canada. Active cigarette smoking increased risk twofold among males (odds ratio estimate [OR]=2.0, 95 percent confidence interval (CI)=1.4–2.8) and females (OR=1.9, CI=1.3–2.6). Passive smoking appeared to increase risk somewhat among nonsmokers (males: OR=1.6, CI=0.5–4.7; females: OR=1.7, CI=0.8–3.4). A high Quetelet index (QI) was associated with a twofold increase in risk in both sexes, although this was based on reported weight at age 25 years for males (OR=1.9, CI=1.2–3.1) and five years prior to data collection for females (OR=2.5, CI=1.4–4.6). Diuretic use was associated with significantly increased risk among females, but not among males. Phenacetin use increased risk, while acetaminophen use was not associated with altered risk, although few subjects used either compound. Multiple urinary tract infections increased risk, but only significantly in females (OR=1.9, CI=1.2–2.9). Our data indicate the need for further exploration of passive smoking and diuretics as risk factors, as well as elucidation of mechanisms by which high lifetime QI and frequent urinary-tract infections might increase risk of this cancer.

Trends in the incidence of cutaneous malignant melanoma in New South Wales, 1983–1996

The incidence of cutaneous malignant melanoma (CMM) has been rising in fair‐skinned populations throughout the world for decades. The upward trend may, however, finally be slowing in some of these populations. Recent (1983–1996) CMM incidence trends for a high incidence area (New South Wales, Australia) have been examined according to gender, age group, body site and tumour thickness. Despite continuing upward trends in older age groups, particularly among men (e.g., 7.20% increase per year in men aged 75+), incidence for younger ages is stabilizing (in men) or declining (in women): average annual percentage changes of −3.03 and −0.88 were observed for women aged 15–34 and 35–54, respectively. Patterns suggest a birth‐cohort effect, with those born since 1945 or 1950 having lower (females) or similar (males) rates to those born earlier. For each gender, all‐ages incidence rose by a similar amount for each of the main body sites except the leg in women, where incidence fell by 0.49% per year. In men, the incidence of both thin (≤75 mm) and thick (>75 mm) melanomas increased (significantly, by 2.63% per year and non‐significantly, by 0.93% per year, respectively) between 1989 and 1996. In women, incidence remained stable for both thickness subgroups. These data are consistent with a stabilization or reduction in either total sun exposure or intermittency of exposure among New South Wales cohorts born since about 1950. Because incidence rates are still much higher than they were a few decades ago, however, efforts to reduce sun exposure, particularly in children and youth, must continue.

Pregnancy outcomes in females after treatment for childhood cancer.

This Ontario province-wide cohort study was conducted to compare the risk of adverse pregnancy outcomes in female childhood cancer survivors who received abdominal-pelvic radiation and/or chemotherapy with alkylating agents with the risk among those who were treated by non-sterilizing alkylating agents with the risk among those who were treated by non-sterilizing surgery only. Females in Ontario, Canada, diagnosed in 1964-1988 before age 20 with a histologically confirmed malignancy and who had survived for at least 5 years, attained age 18, and were alive at the time of study, were identified through the Ontario Cancer Registry. We ascertained pregnancy outcomes by a telephone-administered questionnaire. Treatment data were abstracted from medical records for 830 subjects 18-49 years of age, the analysis comprised 340 survivors who had one or more pregnancies after treatment. There was no evidence of an increased risk of having a spontaneous abortion or an infant with a birth defect. Survivors receiving abdominal-pelvic radiation were more likely to have a low birth weight infant (odds ratio estimate [OR] = 3.64; 95% confidence interval [CI] = 1.33-9.96), a premature low birth weight infant (OR = 3.29; 95% CI = 0.97-11.1), or an infant who died in the perinatal period (OR = 2.41; 95% CI = 0.50-11.5), compared with those receiving surgery. Risks of perinatal death and having a low birth weight infant increased with dose of radiotherapy directed to the abdomen.

Ambient UV, personal sun exposure and risk of multiple primary melanomas

ObjectiveSun exposure is the main cause of melanoma in populations of European origin. No previous study has examined the effect of sun exposure on risk of multiple primary melanomas compared with people who have one melanoma.MethodsWe identified and enrolled 2,023 people with a first primary melanoma (controls) and 1,125 with multiple primary melanomas (cases) in seven centers in four countries, recorded their residential history to assign ambient UV and interviewed them about their sun exposure.ResultsRisk of multiple primary melanomas increased significantly (P < 0.05) to OR = 2.10 for the highest exposure quarter of ambient UV irradiance at birth and 10 years of age, to OR = 1.38 for lifetime recreational sun exposure, to OR = 1.85 for beach and waterside activities, to OR = 1.57 for vacations in a sunnier climate, to OR = 1.50 for sunburns. Occupational sun exposure did not increase risk (OR = 1.03 for highest exposure). Recreational exposure at any age increased risk and appeared to add to risk from ambient UV in early life.ConclusionsPeople who have had a melanoma can expect to reduce their risk of a further melanoma by reducing recreational sun exposure whatever their age. The same is probably true for a person who has never had a melanoma.

The Prevalence of CDKN2A Germ-Line Mutations and Relative Risk for Cutaneous Malignant Melanoma: An International Population-Based Study

Germ-line mutations of CDKN2A have been identified as strong risk factors for melanoma in studies of multiple-case families. However, an assessment of their relative risk for melanoma in the general population has been difficult because they occur infrequently. We addressed this issue using a novel population-based case-control study design in which “cases” have incident second- or higher-order melanomas [multiple primary melanoma (MPM)] and “controls” have incident first primary melanoma [single primary melanoma (SPM)]. Participants were ascertained from nine geographic regions in Australia, Canada, Italy, and United States. In the 1,189 MPM cases and 2,424 SPM controls who were eligible and available for analysis, the relative risk of a subsequent melanoma among patients with functional mutations who have an existing diagnosis of melanoma, after adjustments for age, sex, center, and known phenotypic risk factors, is estimated to be 4.3 (95% confidence interval, 2.3-7.7). The odds ratio varied significantly depending on the type of mutation involved. The results suggest that the relative risk of mutation carriers in the population may be lower than currently believed and that different mutations on the CDKN2A gene may confer substantially different risks of melanoma. (Cancer Epidemiol Biomarkers Prev 2006;15(8)1520–5)

Cancer incidence and mortality in Ontario First Nations, 1968-1991 (Canada).

Objective: To determine cancer incidence and mortality rates in Ontario First Nations (FN) people (native Indians) during 1968–1991 and to compare these with rates in the Ontario population. Methods: A cohort of 141,290 Ontario FN was created from registration files maintained by the Canadian government. Cancers and deaths were ascertained by linkage to the provincial cancer registry and mortality file, which also provided general population comparison data. Results: Cancer incidence was significantly lower in FN compared to the general population for all cancer (rate ratio (RR) = 0.72 for females; 0.62 for males), breast cancer (RR = 0.54), lung cancer in men (RR = 0.68), prostate cancer (RR = 0.57) and colorectal cancer (RR = 0.58 and 0.57 in men and women, respectively). Rates were significantly higher in FN for cervical cancer (RR = 1.73) and gallbladder cancer (2.05 and 2.20 in men and women, respectively). Incidence rates increased significantly in FN people between 1968–1975 and 1984–1991 for all cancer and for the major cancers (breast, lung, prostate and colorectal). Colorectal cancer rate ratios were significantly higher in 1984–1991 than in 1968–1975, indicating converging incidence rates. Patterns of cancer mortality were similar. Conclusions: These trends are compatible with a population in epidemiologic transition to the Euro-American disease pattern which is dominated by chronic diseases.

Congenital abnormalities and childhood cancer

The examination of specific characteristics of neoplasms diagnosed in children have suggested that a significant proportion can be attributed to a genetic mutation or genetic predisposition. Although the study of a genetic predisposition to cancer in children remains in the early stages, congenital abnormalities could provide essential information for mapping predisposing lesions in children with cancer.