Case-control studies of fatal cancers often rely on proxy respondents. Therefore, it is important to determine the completeness and accuracy of proxy-reported information. We evaluated proxy reports using the Ontario Familial Colon Cancer Registry epidemiology questionnaire. A proxy questionnaire was completed by spouses or relatives identified by a sample of participating cases. Item non-response and percentage agreement (between case and proxy reports) were assessed. More than 30% of proxies were unable to report on physical activity, gynecological surgery, alcohol intake, weight 20 years ago, and oral contraceptive use. Proxy reports of medical history and bowel screening varied, the percentage missing ranging from 5% for diabetes to 44% for familial polyposis in the case of medical history, and from 4% for colonoscopy to 27% for hemoccult tests in the case of screening. Agreement between case and proxy report was good to excellent for colonic screening, most medical history, and for reproductive, medication and vitamin use variables (74% to 100%). It is useful to collect proxy information on such variables as medical history, parity, colonic screening and vitamin use, whereas oral contraceptive use and previous weight are not well reported.
Pancreatic adenocarcinoma is one of the deadliest cancers with mortality rates almost equaling incidence rates. Each year, approximately 3,500 Canadians are diagnosed with this disease. Although somewhat inconsistent, epidemiological studies have found that allergies are associated with a reduced pancreas cancer risk while there appears to be no association with asthma. These associations were evaluated in a population-based case-control study conducted in Ontario. Incident cases of pancreatic adenocarcinoma, identified through the Ontario Cancer Registry (OCR), and diagnosed April 1, 2003 to June 1, 2006, were recruited by the Ontario Pancreas Cancer Study (OPCS). Controls were recruited from the Ontario Familial Colorectal Cancer Registry (OFCCR). Data on 276 cases and 378 controls were available for the current study. Multivariable logistic regression analysis was used to obtain age-adjusted odds ratio (AOR) estimates. Ever having allergies or hayfever was associated with reduced pancreas cancer risk (OR = 0.43, 95% confidence interval (CI): 0.29-0.63). There was no association observed between a history of asthma and pancreas cancer risk. Findings are of great importance to understanding the biological mechanisms involved in pancreas cancer development.
Animal and human studies have reported an association between antidepressant (AD) medication use and breast cancer risk. A population-based case-control study was designed specifically to examine this association among women in Ontario, Canada.
The Ontario Cancer Registry (OCR) identified women diagnosed with primary breast cancer. Controls, randomly sampled from the female population of Ontario, were frequency matched by 5-year age groups. A mailed self-administered questionnaire included questions about lifetime use of AD and potential confounders. Multivariate logistic regression yielded odds ratio estimates.
'Ever' use of AD was reported by 14% (441/3077) cases versus 12% (372/2994) controls. The age-adjusted odds ratio (AOR) for 'ever' use was 1.17, (95% CI: 1.01, 1.36). An increased risk was also observed for selective serotonin reuptake inhibitors = 1.33 (95% CI: 1.07, 1.66), Sertraline = 1.58 (95% CI: 1.03, 2.41), and Paroxetine = 1.55 (95% CI: 1.00, 2.40). None of the 30 variables assessed for confounding altered the risk estimate by more than 10%. Multivariate adjustment including all possible breast cancer risk factors yielded an unchanged, but not significant, point estimate (MVOR = 1.2, 95% CI: 0.96, 1.51). No relationship was observed for duration or timing of AD use.
A modest association between 'ever' use of AD and breast cancer was found using the most parsimonious multivariate model. OR estimates did not change, but CI were widened and statistical significance lost, after adjustment for factors associated with breast cancer risk.
Comment In: Int J Epidemiol. 2003 Dec;32(6):966-714681257
Animal and human studies have suggested that antidepressant medications may be associated with several cancers. The authors evaluated the association between antidepressant medication use and the risk of non-Hodgkin's lymphoma using a Canadian population-based case-control study, the National Enhanced Cancer Surveillance Study. Non-Hodgkin's lymphoma cases (n=638) diagnosed in 1995-1996 were identified using the Ontario Cancer Registry, and controls (n=1,930) were identified from the Ontario Ministry of Finance Property Assessment Database. Antidepressant medication use was ascertained using a self-administered questionnaire. Multivariate logistic regression was used to estimate odds ratios. "Ever" use of antidepressant medications was not associated with non-Hodgkin's lymphoma risk. The odds ratio for non-Hodgkin's lymphoma with 25 or more months of tricyclic antidepressant medication use was 1.6; however, this was nonsignificant. Duration or history of use or individual types of antidepressant medications were not associated with non-Hodgkin's lymphoma risk. These findings do not support an increased risk of non-Hodgkin's lymphoma with antidepressant medication use.
Antihistamines are structurally similar to DPPE, a tamoxifen derivative known to promote tumor growth, and to antidepressants. Animal experiments have linked certain antihistamines and antidepressants with enhanced tumor growth in mice. The few epidemiologic studies examining antihistamine use have not indicated an increased risk. In light of suggestive animal data, structural similarities between antihistamines and DPPE, the widespread use of antihistamines, and the lack of epidemiologic investigation into their use and breast cancer risk, it is important to examine this issue. Female cases aged 25-74 years, diagnosed 1996 to 1998, were identified through the Ontario Cancer Registry. Controls were a random, age-matched sample of women. Cases (n=3,133) and controls (n=3,062) completed a mailed questionnaire that included questions about antihistamines used regularly (undefined), type and duration. Age-adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were obtained using logistic regression. Antihistamine users were at no increased risk for breast cancer (OR=0.93, 95% CI: 0.81, 1.06), and no trend in risk was observed for age starting or duration of use. Antihistamine users were at no increased risk. No confounding or effect modification was identified in multivariate modeling. Our findings do not support the hypothesis that women who use antihistamines are at a greater breast cancer risk than those who do not.
To investigate the association between allergies, asthma, and breast cancer risk in a large, population-based case-control study.
Breast cancer cases (n = 3,101) were identified using the Ontario Cancer Registry and population controls (n = 3,471) through random digit dialing. Self-reported histories of allergies, hay fever, and asthma were collected by questionnaire. Logistic regression was used to assess associations between breast cancer risk and history of allergy/hay fever and asthma, with 16 possible confounders examined. Analyses were stratified by menopausal status.
A history of allergies or hay fever was associated with a small reduction in breast cancer risk [age-adjusted odds ratio (AOR) = 0.86, 95 % confidence interval (CI) 0.77-0.96] and did not differ by menopausal status. Asthma was not associated with breast cancer risk overall; however, among premenopausal women, asthma was associated with a reduced risk of breast cancer (AOR = 0.72, 95 % CI 0.54-0.97).
A history of allergies may be associated with a modest reduction in breast cancer risk. Asthma does not appear to be associated with breast cancer risk overall; however, asthma may be associated with reduced breast cancer risk among premenopausal women.
The MutY human homologue (MYH) gene encodes a member of the base excision repair pathway that is involved in repairing oxidative damage to DNA. Two germline MYH gene mutations that result in Myh proteins containing amino acid substitutions Y165C and G382D (hereafter called the Y165C and G382D mutations) are associated with adenomatous poly-posis and colorectal cancer among patients from several European poly-posis registries. We used a population-based series of 1238 colorectal cancer patients and 1255 healthy control subjects from Ontario, Canada, to examine the risk of colorectal cancer among biallelic and monoallelic germline MYH Y165C and G382D mutation carriers. The entire MYH gene coding region was screened in all MYH Y165C and G382D mutation carriers. Compared with noncarriers, biallelic and monoallelic germline MYH gene mutation carriers had an increased risk of colorectal cancer and were more likely to have first-or second-degree relatives with colorectal cancer (relative risk = 1.54, 95% confidence interval = 1.10 to 2.16). The increased risk of colorectal cancer in biallelic and monoallelic MYH gene mutation carriers was not consistently associated with the development of multiple adenomatous polyps. Loss of heterozygosity in at least one of four loci in MYH was detected in eight (47%) of 17 colorectal tumors from monoallelic MYH gene mutation carriers but in only two (20%) of 10 colorectal tumors from biallelic MYH gene mutation carriers. These two MYH gene mutations may account for a substantial fraction of hereditary colorectal cancer.
Comment In: J Natl Cancer Inst. 2005 Feb 16;97(4):320-1; author reply 321-215713969
Colorectal cancer remains a significant cause of mortality and morbidity in North America. Colorectal cancer survival is highly dependent on stage at diagnosis, therefore it is important to identify factors related to stage. This study evaluated the association between subject factors (e.g., colonic screening, family history) and stage of colorectal cancer at diagnosis.
Population-based colorectal cancer cases recruited by the Ontario Familial Colon Cancer Registry between 1997 and 1999 were staged according to the tumor-nodal-metastasis (TNM) staging system and classified as early (TNM I/II) or late (TNM III/IV) stage. Epidemiologic information and stage was available for 768 cases. Multivariate logistic regression was used to obtain odds ratios (OR) estimates.
Having had screening endoscopy reduced the risk of late stage diagnosis (OR = 0.46, 95% CI 0.22-0.98). Being older (>45 yr) was associated with a reduced risk of late stage cancer (OR = 0.36, 95% CI 0.18-0.74), as was having a first degree relative with colorectal cancer (OR =0.66, 95% CI 0.46-0.95). Rural residence (OR = 1.48, 95% CI 1.01-2.17) and non-white ethnicity (OR = 3.34, 95% CI 1.20-9.36) were associated with an increased risk of late stage cancer.
Several factors are independently associated with late stage colorectal cancer. Colorectal cancer screening awareness and education programs need to consider targeting persons most likely to present with late stage colorectal cancer.
Colorectal cancer screening reduces colorectal cancer incidence and mortality. This population-based study was conducted to evaluate (i) the association between subject factors and colorectal screening participation and (ii) the lifetime prevalence of colorectal screening among the general population of Ontario, Canada. Population-based controls were recruited by the Ontario Familial Colorectal Cancer Registry during 1998-2000. The 1944 persons completed an epidemiologic questionnaire. Descriptive statistics were computed and step-wise multivariate logistic regression was used to estimate odds ratios and 95% confidence intervals. Overall, 23% of persons greater than 50 years of age reported ever having had colorectal cancer screening; 17% reported fecal occult blood test (FOBT), 6% sigmoidoscopy, and 4% colonoscopy. Family history of colorectal cancer, increased age, higher household income, and use of hormone replacement therapy (among women) were all significantly associated with ever having had colorectal cancer screening. The low prevalence of colorectal cancer screening among the target population suggests the need for an increased awareness of the public health importance of colorectal cancer screening.
Diet is regarded as one of the most important environmental factors associated with colorectal cancer (CRC) risk. A recent report comprehensively concluded that total energy intake does not have a simple relationship with CRC risk, and that the data were inconsistent for carbohydrate, cholesterol and protein. The objective of this study was to identify the associations of CRC risk with dietary intakes of total energy, protein, fat, carbohydrate, fiber, and alcohol using data from a large case-control study conducted in Newfoundland and Labrador (NL) and Ontario (ON), Canada.
Incident colorectal cancer cases (n = 1760) were identified from population-based cancer registries in the provinces of ON (1997-2000) and NL (1999-2003). Controls (n = 2481) were a random sample of residents in each province, aged 20-74 years. Family history questionnaire (FHQ), personal history questionnaire (PHQ), and food frequency questionnaire (FFQ) were used to collect study data. Logistic regression was used to evaluate the association of intakes of total energy, macronutrients and alcohol with CRC risk.
Total energy intake was associated with higher risk of CRC (OR: 1.56; 95% CI: 1.21-2.01, p-trend = 0.02, 5th versus 1st quintile), whereas inverse associations emerged for intakes of protein (OR: 0.85, 95%CI: 0.69-1.00, p-trend = 0.06, 5th versus 1st quintile), carbohydrate (OR: 0.81, 95%CI: 0.63-1.00, p-trend = 0.05, 5th versus 1st quintile) and total dietary fiber (OR: 0.84, 95% CI:0.67-0.99, p-trend = 0.04, 5th versus 1st quintile). Total fat, alcohol, saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids, and cholesterol were not associated with CRC risk.
This study provides further evidence that high energy intake may increase risk of incident CRC, whereas diets high in protein, fiber, and carbohydrate may reduce the risk of the disease.