A case-control study of reproductive risk factors associated with cervical cancer

Using the logistic-regression technique, a hospital-based case-control study of 177 married women with invasive squamous-cell cervical cancer and 149 hospital-visiting controls enabled evaluation of selected reproductive factors as risks. Early age at marriage was found to be the single best predictor of the disease status. However, those who married late but gave birth to a large number of children were generally found to be suffering from cervical cancer. The results support the hypothesis that it is not so much parity per se that enhances the risk, but the rapidity of multiple pregnancies that matters. Logistic analysis also revealed the independent influence of birth interval on the risk of cervical cancer. These findings warrant serious consideration in future studies, given the obvious implications for prevention. Other implications for the prevention of cervical cancer are briefly discussed. © 1994 Wiley-Liss, Inc.     

Environmental and occupational factors associated with chronic myeloid leukemia: a case-control study

Background

The relationship between chronic myeloid leukemia (CML) and a broad range of exposures to occupational and environmental factors known to cause leukemia in general is limited. CML is by and large incurable and treatment is just palliative and life prolonging, with high case fatality rate, even in the best centers. Furthermore treatment is very expensive. Identification of leukemogenic factors is therefore important if this can lead to simple public health interventions.

Objective

The objective was to determine key environmental and occupational exposure factors that may be associated with CML.

Methods

This was a case-control study involving CML cases enrolled in Glivec International Patient Assistance Program (GIPAP) clinics at the Nairobi Hospital and Aga Khan University Hospital and two control groups for each case, matched for age and sex: a family- and hospital-based control, was carried out. One hundred and eight cases with ageand-gender-matched family- and hospital-based controls were recruited and a standard questionnaire was administered. Individual data on demographics, occupation, environment, and exposures to benzene and farm organochemical products were obtained. Clinical examination was carried out in control subjects. Statistical analysis was done using bivariate and multivariate analysis to look for associations between exposure factors and CML.

Results

The median age at diagnosis of CML cases was 41.32 years with an age range of 8–81 years and a male to female ratio of 1.7:1. Most of our cases were concentrated in or around Nairobi. There was no significant correlation found for exposure to benzene or pesticides. Long duration of exposure to pesticides in the family control group was significantly associated (t-test, P = 0.017) with risk of CML.

Conclusions

Associations between exposures to organic solvents like pesticides and CML were indicated but were not entirely consistent, although no associations with benzene products were found. Nevertheless, for almost all cases of Ph chromosome-positive CML, other explanations must be sought for.     

Non-occupational risk factors for bladder cancer: a case-control study

AIMS: The aim of this study was to determine non-occupational risk factors for bladder cancer in Serbia. METHODS AND DESIGN: A hospital-based, case-control study included 130 newly diagnosed bladder cancer patients and the same number of individually matched controls with respect to sex, age (+/- 2 years) and type of residence (rural or urban), from the Clinical Center of Serbia in Belgrade and from the Clinical Center in Kragujevac in central Serbia. The study took place from June 1997 to March 1999. RESULTS: According to multivariate logistic regression analysis, there was an association between: frequency of daily urination (OR = 0.18; 95% CI = 0.08-0.39); consumption of liver (OR = 13.81; 95% CI = 2.49-76.69), canned meat (OR = 8.38; 95% CI = 1.74-40.36), fruit juices (OR = 0.08; 95% CI = 0.01-0.56); the highest tertile of pork (OR = 4.55; 95% CI = 1.30-15.93), cabbage (OR = 0.25; 95% CI = 0.06-1.01) and vinegar (OR = 4.41; 95% CI = 1.18-16.50) intake and risk for bladder cancer. CONCLUSIONS: Consumption of liver, canned meat, pork (h vs l tertile) and vinegar (m vs l tertile) was indicated as a risk factor for bladder cancer, whereas frequent daily urination, consumption of fruit juices and cabbage (h vs l tertile) were indicated as protective factors.     

Prenatal and perinatal risk factors and testicular cancer: a hospital-based case-control study

Some evidence exists to support the hypothesis that elevated levels of circulating maternal estrogens during early pregnancy may increase risk of testicular germ cell cancer. However, the results from studies evaluating maternal factors have been mixed. We evaluated maternal factors, particularly those associated with excess estrogen levels, as risk factors for testicular cancer. We conducted a hospital-based case-control study at The University of Texas M. D. Anderson Cancer Center in Houston, Texas of 144 testicular cancer patients diagnosed between 1990 and 1996 and 86 friend controls matched to cases on age, race, and state of residence. Risk factor data about the mother, the son, and the pregnancy were obtained from the mothers by telephone interviews and from the sons by self-administered questionnaires. Extreme nausea during the first trimester of pregnancy was associated with an elevated risk of testicular cancer [odds ratio (OR) = 2.0; 95% confidence interval (CI) = 1.0-3.9]. Adjustment for potential confounders slightly lowered this risk (OR = 1.8; 95% CI = 0.9-3.8). Risks were modestly increased for other factors that are proxy measures for maternal estrogens, including preterm delivery (OR = 2.2; 95% CI = 0.4-12.9), birth weight <3000 g (OR = 2.4: 95% CI = 0.7-8.1), and birth weight >4000 g (OR = 1.7; 95% CI = 0.9-3.2), albeit nonsignificantly so. Our finding that severe nausea was associated with increased testicular cancer risk adds evidence to support the in utero estrogen exposure hypothesis because nausea early in pregnancy is related to rising levels of circulating estrogens. For other factors, which are less direct measures of maternal estrogens, the modest associations found indicate a suggestive pattern in support of the excess estrogen hypothesis.     

Lung cancer risk in never-smokers: a population-based case-control study of epidemiologic risk factors

Background  

We conducted a case-control study in the greater Toronto area to evaluate potential lung cancer risk factors including environmental tobacco smoke (ETS) exposure, family history of cancer, indoor air pollution, workplace exposures and history of previous respiratory diseases with special consideration given to never smokers.     

Rectal cancer and occupational risk factors: a hypothesis-generating, exposure-based case-control study

In 1979, a hypothesis-generating, population-based case-control study was undertaken in Montreal, Canada, to explore the association between occupational exposure to 294 substances, 130 occupations and industries, and various cancers. Interviews were carried out with 3, 630 histologically confirmed cancer cases, of whom 257 had rectal cancer, and with 533 population controls, to obtain detailed job history and data on potential confounders. The job history of each subject was evaluated by a team of chemists and hygienists and translated into occupational exposures. Logistic regression analyses adjusted for age, education, cigarette smoking, beer consumption, body mass index, and respondent status were performed using population controls and cancer controls, e.g., 1,295 subjects with cancers at sites other than the rectum, lung, colon, rectosigmoid junction, small intestine, and peritoneum. We present here the results based on cancer controls. The following substances showed some association with rectal cancer: rubber dust, rubber pyrolysis products, cotton dust, wool fibers, rayon fibers, a group of solvents (carbon tetrachloride, methylene chloride, trichloroethylene, acetone, aliphatic ketones, aliphatic esters, toluene, styrene), polychloroprene, glass fibers, formaldehyde, extenders, and ionizing radiation. The independent effect of many of these substances could not be disentangled as many were highly correlated with each other.     

Never smokers and lung cancer risk: a case-control study of epidemiological factors

We performed an analysis of potential epidemiological risk factors for lung cancer using data from 280 cases and 242 hospital-based controls, all lifetime never smokers (those who had smoked <100 cigarettes in their lifetimes) and frequency matched on age, gender and ethnicity. The data on demographic characteristics, medical history of respiratory diseases (asthma, emphysema, pneumonia and hay fever), weight and height, family history, female characteristics and environmental tobacco smoke (ETS) and dust exposure were derived from personal interviews. We performed a logistic regression analysis of these variables adjusting for age, gender, ethnicity, income and years of education. Exposure to ETS (OR = 2.08, 95% CI [1.25-3.43]) and dusts (OR = 2.43, 95% CI [1.53-3.88]) were associated with significantly increased risk. In the analysis for joint effects, exposure to both ETS and dusts conferred a higher risk (OR = 3.25, 95% CI [1.58-6.70]) than exposure to either alone. Family history of any cancer with onset before age 50 in at least 1 first degree relative was a significant risk predictor (OR = 1.70, 95% CI [1.10-2.64]). Individuals with a self-reported physician-diagnosed history of hay fever, but not asthma, had a decreased lung cancer risk (OR = 0.57, 95% CI [0.35-0.92]). In the multivariate analysis, exposure to ETS and dusts, and family history of cancer with onset before age 50 were significant risk factors, while a history of hay fever (occurring without asthma) was significantly protective.     

Gestational risk factors for Wilms' tumor: results of a case-control study

Gestational risk factors for Wilms' tumor were investigated in a pair-matched case-control study. Cases who were under 15 years of age at diagnosis during 1970-1983 were identified through the registries of the three main hospitals treating childhood cancer in the greater Philadelphia area. Controls were selected by random digit dialing and were matched to cases on race, birth date, and telephone area code and exchange. Because of a low participation rate among nonwhites, results are reported only for the 88 white matched pairs whose parents were interviewed by telephone. Of the hypothesized risk factors, maternal use of hair-coloring products in the year prior to the index child's birth (odds ratio, 3.6; P = 0.003) and hypertension or fluid retention during pregnancy (odds ratio, 5.0, P = 0.01) were significantly associated with increased risk of Wilms' tumor. Use of hair-coloring products was strongly associated with cases in which Wilms' tumor was diagnosed before 2 years of age (odds ratio, 15; P = 0.001). For two other gestational factors, tea drinking and vaginal infection, the odds ratios were significantly elevated for all cases and the effects were concentrated among the nongenetic cases. Bilateral cases had a significantly higher mean birth weight than did their controls. Older maternal age was significantly associated with the genetic form of Wilms' tumor. Adjustment for possible confounders and consideration of the time interval between the index pregnancy and the interview did not substantially alter the findings.     

Breast cancer risk factors in Italian women: a multicentric case-control study

To evaluate the importance of several risk factors for breast cancer in the Italian female population, a large multicentric case-control study was conducted in 10 breast clinics in Italy. The study included 1,556 women affected by breast cancer, histologically and/or cytologically confirmed. Controls were 1,505 women admitted to a hospital in the same town, matched with cases for residence and with the same age distribution of the Italian female population. The risk factors considered in this study were family history of breast cancer, reproductive history, height and weight, use of oral contraceptives, other hormonal therapies and smoking history. The results of this study confirm the significant role of a positive family history of breast cancer (RR = 2.37); the relative risk was even higher when a first-degree relative was affected or the breast cancer was bilateral. The analysis of the reproductive history showed a significant trend of increasing risk with increasing age at first birth and, although less evident, with increasing number of children. Quetelet's index (kg/m-2) was positively correlated with breast cancer risk, mostly in postmenopausal women. Among other studied factors, only late age at menopause confirmed an increased risk for breast cancer, whereas age at menarche, use of oral contraceptives and smoking histories did not show any significant correlation with breast cancer risk. These results are in substantial agreement with other international studies, but represent an interesting contribution to studies about the Italian female population.     

ERCC4 associated with breast cancer risk: a two-stage case-control study using high-throughput genotyping

The failure of linkage studies to identify further high-penetrance susceptibility genes for breast cancer points to a polygenic model, with more common variants having modest effects on risk, as the most likely candidate. We have carried out a two-stage case-control study in two European populations to identify low-penetrance genes for breast cancer using high-throughput genotyping. Single-nucleotide polymorphisms (SNPs) were selected across preselected cancer-related genes, choosing tagSNPs and functional variants where possible. In stage 1, genotype frequencies for 640 SNPs in 111 genes were compared between 864 breast cancer cases and 845 controls from the Spanish population. In stage 2, candidate SNPs identified in stage 1 (nominal P < 0.01) were tested in a Finnish series of 884 cases and 1,104 controls. Of the 10 candidate SNPs in seven genes identified in stage 1, one (rs744154) on intron 1 of ERCC4, a gene belonging to the nucleotide excision repair pathway, was associated with recessive protection from breast cancer after adjustment for multiple testing in stage 2 (odds ratio, 0.57; Bonferroni-adjusted P = 0.04). After considering potential functional SNPs in the region of high linkage disequilibrium that extends across the entire gene and upstream into the promoter region, we concluded that rs744154 itself could be causal. Although intronic, it is located on the first intron, in a region that is highly conserved across species, and could therefore be functionally important. This study suggests that common intronic variation in ERCC4 is associated with protection from breast cancer.     

Gastric cancer risk factors: a case-control study based on medical records

Four hundred and sixty gastric cancer patients who had undergone operation at the National Cancer Center Hospital and an equal number of age-matched controls were analyzed in order to estimate the influence of gastric cancer family inheritance and cigarette smoking habit. Relative risks for cigarette smoking habit, for gastric cancer family inheritance and for both were 2.88, 1.67 and 4.12, respectively. Earlier age of onset of gastric cancer was observed in the gastric cancer cases with both risk factors as compared with the other patients.     

Human papillomavirus infection and other risk factors for cervical neoplasia: a case-control study

A case control design has been used to investigate risk factors associated with the development of cervical squamous intraepithelial lesions (SIL) in a population of urban women in which non-affluent minority groups were heavily represented. Eighty-five women with histologically confirmed SIL were compared to a control group of 70 cytologically normal women. HPV infection was determined using both Southern blot hybridization and polymerase chain reaction (PCR) amplification specific for HPV types 16, 18, and 33. When Southern blot was used to detect HPV, logistic regression analysis identified HPV infection (odds ratio (OR) = 17.9, 95% confidence interval (CI) = 6.2-51.6) and low educational achievement (OR = 3.4, 95% CI = 1.2-10.1) as major independent risk factors. When PCR was employed to detect HPV, the logistic regression model suggested that HPV infection (OR = 10.4, 95% CI = 3.6-30.4) and Hispanic ethnicity (OR = 5.0, 95% CI = 1.2-20.5) represented independent risk factors; low educational achievement and Black ethnicity were risk factors of borderline significance. PCR detection of simultaneous co-infection with more than one HPV type was associated with a very high risk of SIL (OR for one type = 7.2, 95% CI = 2.4-21.9; OR for greater than I type = 43.0, 95% CI = 6.9-266.6). Furthermore, increased viral load determined by either method carried an increased risk of disease. HPV infection with viral types previously reported to be related to neoplastic or dysplastic lesions carried the highest risk of SIL. The association of HPV detected by Southern blot and SIL in women less than 35 years old had an OR of 10.1, whereas in women greater than or equal to 35 the OR was 74.5 (p = 0.09 for homogeneity of ORs). We conclude that infection with HPV is the major risk factor for cervical SIL and suggest that targeted HPV screening of women over age 35 may represent an innovative strategy to detect women at high risk of cervical neoplasia.     

Urinary bladder cancer risk factors in men: a Spanish case-control study.

The rising incidence of urinary bladder cancer is alarming and potential relationships with different risk factors have been postulated. The purpose of this study was to examine the possible relationship between different environmental risk factors and urinary bladder cancer. All men with urinary bladder cancer who were admitted to the Department of Urology of Reina Sofia University Hospital of Cordoba, Spain over 1 year were included in our study. Men were administered an interview questionnaire, which included data on history of known urinary bladder cancer risk factors. Comparisons between men with urinary bladder cancer (cases) and those with nonmalignant urological disease (controls) were made. The study included 74 cases and 89 controls. The variables associated with malignant lesions on univariate analysis were age, smoking and drinking alcohol. Meanwhile, fish, poultry and beef consumption were proved to be protective factors. The risk factors identified by the logistic regression analysis were age, smoking and fluid intake. The independent protective factors on the multivariate analysis were fish and poultry consumptions. Smoking was found to be the principal independent risk factors for urinary bladder cancer. Our results call for further investigation of urinary bladder cancer risk factors; future studies should preferably be performed on large prospective cohorts, to increase their validity.     

Subsite-specific risk factors for colorectal cancer: a hospital-based case-control study in Japan

To investigate the subsite-specific risk factors for colorectal cancer, we conducted a case-control study, using a common questionnaire which inquired about general lifestyles over the past five years (1988–92), at the Aichi Cancer Center Hospital, Nagoya, Japan. This study compared 432 patients with histopathologically diagnosed colorectal cancer (94 proximal colon [cecum, ascending colon, transverse colon]; 137 distal colon [descending colon, sigmoid colon]; 201 rectum [rectosigmoid, rectum]); and 31,782 first-visit outpatient controls who were free from cancer. In both genders, habitual smoking selectively increased the risk for rectum cancer. Soft or loose feces increased the risk for all subsites of colorectal cancer, particularly in female cancer (odds ratio [OR]=4.5). Among female dietary habits, Japanese-style foods decreased the risk factors for distal colon cancer, but increased the risk for proximal colon cancer. These results suggested that the risk factors for colorectal cancer differ by subsite among such a low-risk population as the Japanese. It is suggested also that irritable bowel (soft or loose feces) might be associated with distal subsites of colorectal cancer, independently or combined with habitual smoking. Cancer Causes and Control 1995, 6, 14–22.Drs Inoue and Tajima, Ms Hirose, and Drs Hamajima and Takezaki are with the Division of Epidemiology, Aichi Cancer Center Research Institute, Nagoya, Japan. Authors are also affiliated with the Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Nagoya, Japan (Drs Hirai and Kato), and the Department of Preventive Medicine, Nagoya University School of Medicine, Nagoya, Japan (Drs Inoue and Ohno). Address correspondence to Dr Inoue, Division of Epidemiology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya, Japan, 464. This study was funded in part by a Grant-in-Aid for Cancer Research (4-2) and the Comprehensive 10-year Strategy for Cancer Control from the Ministry of Health and Welfare, Japan.     

Gestational and familial risk factors for childhood astrocytoma: results of a case-control study

Gestational and familial risk factors were investigated for their association with astrocytoma, the most frequently occurring brain tumor in children. A case-control study of 163 matched pairs was performed. Cases under 15 years of age at diagnosis in 1980-1986 were identified through the tumor registries of 8 hospitals in Pennsylvania, New Jersey, and Delaware. Controls were selected by random digit dialing and were matched to cases for age, race, and telephone area code and exchange. Maternal antinausea medications increased the risk of childhood astrocytoma [OR (odds ratio) = 2.0, P = 0.04]. Cured meat consumption during pregnancy was more common among cases (OR = 1.9, P = 0.07), and a significant trend with increasing frequency of consumption was observed (P = 0.04). Results for gestational exposure to marijuana (OR = 2.8, P = 0.07) were of borderline significance. Gestational exposure to neurally active medications, alcohol, and tobacco were not risk factors. There was a significant trend for cases to be of higher birth weight (P = 0.03). Mental retardation (OR = 3.0, P = 0.04) and cancer (OR = 1.7, P = 0.02) in a relative of the child significantly increased the risk of astrocytoma. Significantly increased risks were observed for brain tumors in relatives of children 0-4 years of age at diagnosis (OR = 6/0, P = 0.04). A significant protective effect was observed for maternal history of miscarriage or stillbirth (OR = 0.5, P = 0.01). The results of this study suggest that some gestational and familial factors may increase the risk of childhood astrocytoma.     

Socioeconomic factors and risk of esophageal adenocarcinoma: a nationwide Swedish case-control study.

BACKGROUND: The increase in esophageal adenocarcinoma incidence in developed countries remains unexplained. Although low socioeconomic status (SES) is linked to an increased risk of esophageal squamous cell carcinoma (SCC), the relation with adenocarcinoma is uncertain. METHODS: We addressed the importance of various socioeconomic factors in a Swedish population-based case-control study, where 189 and 262 cases of esophageal adenocarcinoma and the gastric cardia, respectively, 167 cases of esophageal SCC, and 820 control participants underwent personal interviews. Our classification of SES was derived from occupational histories. Relative risks were estimated by odds ratios with 95% confidence intervals (95% CI), derived from conditional logistic regression, in crude and adjusted models. RESULTS: The risk of both esophageal adenocarcinoma and SCC increased with decreasing SES; unskilled workers had 3.7-fold (95% CI, 1.7-7.7) and 2.1-fold (95% CI, 1.0-4.7) increased risks, respectively, compared with age- and sex-comparable professionals. Adjustment for reflux symptoms, body mass, and tobacco smoking attenuated the excess risk for esophageal adenocarcinoma, whereas adjustment for Helicobacter pylori infection in a subset of the interviewed participants did not influence the results. Life without a partner was associated with a >2-fold increased risk of both histologic types of esophageal cancer, associations that remained even after multiple adjustments. CONCLUSIONS: Esophageal adenocarcinoma and SCC are both linked to low SES and a life without a partner. These associations are only partly explained by established risk factors.     

Nutritional factors in colorectal cancer risk: a case-control study in Majorca.

The relationship between energy intake, selected nutrients and colorectal cancer was investigated in the population of Majorca, a Spanish island in the Mediterranean basin. A population-based case-control study using food frequency questionnaires was conducted during the period 1984-1988 and included 286 cases of colorectal cancer, 295 population controls and 203 hospital controls. Food composition tables and ad-hoc estimates of portion sizes were used to derive intake estimates of 29 nutrients and of total calories. Relative risks were calculated for quartiles of consumption of each specific nutrient after adjustment for total calorie intake. Colorectal cancer was found associated with dietary intake of total calories (RRs = 1.0, 1.6, 1.6, 2.6) and cholesterol (RRs = 1.0, 0.9, 1.7, 1.7) and a protective effect was associated with the intake of fibre from legumes (pulses) and folic acid. The associations and the trends were statistically significant. Among the main energy-supplying nutrients, after adjustment for calories from other sources, increased risks were found for protein (RRs = 1.0, 1.1, 1.7, 2.5), notably animal protein, and carbohydrates (RRs = 1.0, 1.5, 1.4, 2.2), whereas no effects were found for increased consumption of lipids or saturated fats.     

Medical history and risk for lymphoma: results of a population-based case-control study in Germany

Since lymphomas are malignancies of cells of the immune system, associations with disorders characterised by impaired immune functions can be assumed. We investigated the relationship between a history of selected medical conditions and the risk for lymphoma including specified subentities within our population-based case-control study of lymphoma among adults conducted in Germany between 1999 and 2002. Overall, we found decreased risks for a history of repeated diarrhoea, warts, arthrosis, allergies, and appendectomy (at a younger age). Elevated risks for lymphoma correlated with tonsillectomy (at a younger age), whereas null results were found for selected auto-immune disorders in adulthood. Although the numbers are small, most of the results for the subentities corresponded with these findings. These results are compatible with the notion that persistent immunological alterations contribute to the aetiology of lymphoma, but partially inconsistent with the Th1/Th2-shift paradigm.