Cancer mortality after nasopharyngeal radium irradiation in the Netherlands: a cohort study.

BACKGROUND: Nasopharyngeal radium irradiation (NRI) was used widely from 1940 through 1970 to treat otitis serosa in children and barotrauma in airmen and submariners. We assessed whether NRI-exposed individuals were at higher risk for cancer-related deaths than were nonexposed individuals. METHODS: We conducted a retrospective cohort study of all-cause and cancer-related mortality in 5358 NRI-exposed subjects and in 5265 frequency-matched nonexposed subjects, who as children were treated at nine ear, nose, and throat clinics in The Netherlands from 1945 through 1981. We recorded personal and medical data from original patient medical records and assessed vital status through follow-up at municipal population registries. Risk of mortality was evaluated by standardized mortality ratios (SMRs). All statistical tests were two-sided. RESULTS: The average radiation doses were 275, 10.9, 1.8, and 1.5 cGy for the nasopharynx, pituitary, brain, and thyroid, respectively. The median follow-up was 31.6 years. Three hundred two NRI-exposed subjects had died, with 269.2 deaths expected (SMR = 1.1; 95% confidence interval [CI] = 1.0 to 1.3); among nonexposed subjects, 315 died, with 283.5 deaths expected (SMR = 1.1; 95% CI = 0.99 to 1.2). Cancer-related deaths of 96 exposed subjects (SMR = 1.2; 95% CI = 0.95 to 1.4) and 87 nonexposed subjects (SMR = 1.0; 95% CI = 0.8 to 1.3) were documented. There were no excess deaths from cancers of the head and neck area among exposed subjects. However, there were excess deaths from cancers of lymphoproliferative and hematopoietic origin (SMR = 1.9; 95% CI = 1.1 to 3.0), mainly from non-Hodgkin's lymphoma (SMR = 2.6; 95% CI = 1.0 to 5.3). We found no evidence that breast cancer deaths were less than expected (SMR = 1.7; 95% CI = 0.9 to 2.8) in contrast to an earlier study. CONCLUSIONS: Our findings do not indicate an increased cancer mortality risk in a population exposed to NRI in childhood. More prolonged follow-up of this and other NRI cohorts is recommended.     

Cancer morbidity in alcohol abusers.

Data on the association between alcohol abuse and cancer morbidity are scarce in large cohorts of non-hospitalised alcoholic men and women. Of 18,368 alcohol abusers who entered an outpatient clinic in Copenhagen during 1954-87, 18,307 were followed and their cancer incidence was compared with that of the total Danish population. On average the 15,214 men were observed for 12.9 years and the 3,093 women for 9.4 years. The overall morbidity of cancer was increased significantly. Of the men, 1,441 developed cancer [relative risk (RR) = 1.6; 95% confidence interval (CI) = 1.5-1.7], while 182 women did (RR = 1.5; 95% CI 1.3-1.8). Significantly increased incidences were found of cancer in the tongue, mouth, pharynx, oesophagus, liver, larynx, lung and pleura and secondary cancer. The women had significantly increased risk of cervical cancer (RR = 2.0; 95% CI 1.2-3.0). The men developed prostatic cancer significantly more frequently than expected (RR = 1.4; 95% CI 1.2-1.8). The risk of melanomas (RR = 0.5; 95% CI 0.2-0.8) was significantly lower than expected. The relative risks of cancer of the stomach, pancreas, kidney and endocrine system were only slightly increased. The study group did not develop more colonic (RR = 1.0; 95% CI 0.8-1.3) or rectal cancer (RR = 1.0; CI 0.7-1.3) than expected. The risk of breast cancer in women was slightly increased (RR = 1.3; 95% CI 0.9-1.7), but not statistically significant. Thus, the associations between alcohol and cancer of the upper digestive and respiratory tract and the liver are confirmed. In addition, this study indicates an increased occurrence of cancer of the prostate gland, pleura and uterine cervix in alcohol abusers.     

Mortality among United States radiologic technologists, 1926-90

The possible mortality risk from low level chronic exposures to ionizing radiation was evaluated among 143,517 United States radiologic technologists certified by the American Registry of Radiologic Technologists between 1926-80. This is one of the few occupational studies of primarily women (73 percent) exposed to radiation during their employment. More than 2.8 million person-years of follow-up were accrued through 1990, and 7,345 deaths were identified. A strong healthy-worker effect was observed (standardized mortality ratios [SMR] for all causes and all cancers were 0.69 and 0.79, respectively). Lung cancer (429 deaths) was not increased with available measures of radiation exposure and no significant associations were observed for acute, myelogenous, and monocytic leukemia (74 deaths). Relative to the general population, the standardized mortality ratio (SMR) for female breast cancer was 0.99 (based on 425 deaths); however, breast cancer was significantly elevated relative to all other cancers in a test of homogeneity of SMRs (ratio of SMRs = 1.3, P < 0.0001). Significant risks were correlated with employment before 1940 (SMR = 1.5; 95 percent confidence interval [CI] = 1.2-1.9), when radiation doses were likely highest, and among women certified for more than 30 years (SMR = 1.4, CI = 1.2-1.7) for whom the cumulative exposure was likely greatest. Using an internal referent group, risk increased with duration of certification among the 1,890 women certified before 1940 (P-trend < 0.001). While the findings for breast cancer are consistent with a radiation effect, possible misclassification in exposure (based on number of years certified) and potential confounding associated with reproductive histories preclude a causal conclusion.     

Cause-specific mortality in long-term survivors of breast cancer: A 25-year follow-up study

PURPOSE: To assess long-term cause-specific mortality in breast cancer patients. PATIENTS AND METHODS: We studied mortality in 7425 patients treated for early breast cancer between 1970 and 1986. Follow-up was 94% complete until January 2000. Treatment-specific mortality was evaluated by calculating standardized mortality ratios (SMRs) based on comparison with general population rates and by using Cox proportional hazards regression. RESULTS: After a median follow-up of 13.8 years, 4160 deaths were observed, of which 76% were due to breast cancer. Second malignancies showed a slightly increased SMR of 1.2 (95% confidence interval [CI], 1.0-1.3). Radiotherapy (RT) as compared with surgery was associated with a 1.7-fold (95% CI, 1.2-2.5) increased mortality from cardiovascular disease (CVD). After postlumpectomy RT, no increased mortality from CVD was observed (hazard ratio, 1.0; 95% CI, 0.5-1.9). Postmastectomy RT administered before 1979 and between 1979 and 1986 was associated with a 2-fold (95% CI, 1.2-3.4) and 1.5-fold (95% CI, 0.9-2.7) increase, respectively. Patients treated before age 45 experienced a higher SMR (2.0) for both solid tumors (95% CI, 1.6-2.7) and CVD (95% CI, 1.3-3.1). CONCLUSION: Currently, a large population of breast cancer survivors is at increased risk of death from CVDs and second cancers, especially when treated with RT at a young age. Patients irradiated after 1979 experience low (postmastectomy RT) or no (postlumpectomy RT) excess mortality from CVD.     

Oral contraceptives and breast cancer in northern Italy. Final report from a case-control study.

To assess the relation between oral contraceptive (OC) use and breast cancer, we analysed data from a case-control study conducted in Northern Italy between 1983 and 1991 on 2,309 cases below age 60 and 1,928 controls admitted to hospital for acute diseases unrelated to OC use and to any of the known or potential risk factors for breast cancer. OC use was reported by 16% of cases and 14% of controls. The multivariate relative risk (RR) for ever vs never use of combination OC was 1.2 (95% confidence interval (CI) 1.0-1.4). However, there was no trend in risk with duration. The RR was elevated for very short use, but declined to 0.8 (95% CI = 0.5-1.0) for five or more years'' use. No noteworthy relationship was found for other major measures of OC use, although RR estimates were above unity for women who had stopped use less than 5 years before (RR = 1.5, 95% CI = 1.1-2.0), started use less than 10 years before (RR = 1.3, 95% CI = 1.0-1.9), started when 25 or more years old (RR = 1.4, 95% CI = 1.1-1.7), or after first birth (RR = 1.2, 95% CI = 1.0-1.5). No interaction was observed between OC use and family history of breast cancer, parity and age at first birth. A separate analysis of 373 cases and 456 control below age 40 showed no association with ever use (RR = 0.9, 95% CI = 0.6-1.2).     

Family history of cancer and risk of ovarian cancer

The aim of this study was to examine the relationship between history of cancer in first-degree relatives and ovarian cancer risk. Between 1992 and 1999, we conducted a case-control study in Italy on 1031 women with epithelial ovarian cancer and 2411 women admitted to hospital for acute non-neoplastic conditions. Odds ratios (OR) were estimated using unconditional logistic regression, adjusted for age and several potential confounders. Overall, 27 cases and nine controls reported a family history of ovarian cancer (OR = 7.0; 95% confidence interval (CI) 3.1-16). The OR was 23 (95% CI 2.6-212) below age 50 years, based on 10 cases and one control only. The risk of ovarian cancer was also increased in women with a family history of cancer of the stomach (OR = 1.5; 95% CI 1.0-2.1), intestine (OR = 1.7; 95% CI 1.2-2.4), lung (OR = 1.3; 95% CI 1.0-1.8), breast (OR = 2.3; 95% CI 1.7-3.1), lymphomas (OR = 2.3; 95% CI 1.0-5.1) and all sites (OR = 1.6; 95% CI 1.4-1.9). Our results confirm the higher ovarian cancer risk in women with a family history of ovarian and breast cancer, and suggest a few associations with other sites.     

Risk of new primary cancer in patients with oropharyngeal cancer.

The relative risk of subsequent cancers was evaluated for a total of 9,092 patients with lip and oropharyngeal cancer recorded between 1953 and 1989 in the nationwide Finnish Cancer Registry. The observed numbers of patients were compared with those expected on the basis of the incidence rates in the Finnish population. There were 1,130 patients (12%) with a new cancer. The standardised incidence ratio (SIR) of contracting a new primary cancer was 1.2 for lip cancer patients (95% CI 1.1-1.3) and 1.4 for patients with oropharyngeal cancer (95% CI 1.2-1.4). Among lip cancer patients, a statistically significant excess risk was found for subsequent cancers in the oropharyngeal area (SIR 1.9, 95% CI 1.1-3.1), larynx (SIR 2.0, 95% CI 1.2-2.9) and lung (SIR 1.4, 95% CI 1.3-1.6), i.e. for cancers with tobacco aetiology. Among patients with oropharyngeal cancer there was an excess of lip cancer (SIR, 3.5, 95% CI 1.5-6.9), lung cancer (SIR 1.8, 95% CI 1.3-2.3) and leukaemia (SIR 2.3, 95% CI 1.0-4.3). Radiotherapy for the first primary did not increase the risk of new cancer.     

Benign thyroid diseases and the risk of death from breast cancer.

A survey of the causes of death among women with benign thyroid disease was conducted to assess the risk of breast cancer mortality in thyroid patients. The study population was all women diagnosed with one of several types of thyroid disease at the Massachusetts General Hospital Thyroid Clinic from 1925 to 1974. A population-based comparison group was matched to the Clinic patients for age and socioeconomic status, resulting in a total of 9,520 matched pairs. A search of the Massachusetts mortality records located death certificates for 10.9% (1,039) of the Thyroid Clinic patients and 10.5% (995) of the comparison women. Cancer was the cause of death in 21% (218) of the Thyroid Clinic patients and 24% (239) of the comparison women. Fewer patients than comparison women died from cancers of the digestive organs (30.2 vs. 45.5%), but more patients died from thyroid cancer (3.7 vs. 0%), lymphatic and hematopoietic cancers (11.5 vs. 4.2%), and cancers of other sites (8.3 vs. 3.8%). Breast cancer deaths accounted for 21.6% of cancer deaths in the patients and 22.2% of cancer deaths in the comparison women. When specific thyroid diagnoses were considered, the percent of all deaths due to breast cancer ranged from 1.9 to 5.6%, compared to 5.3% in the comparison women. Of the diagnostic groups studied, patients with Hashimoto's thyroiditis had the lowest percent of deaths due to breast cancer, while those with nontoxic nodular goiter had the highest.     

Brain cancer mortality and potential occupational exposure to lead: findings from the National Longitudinal Mortality Study, 1979-1989

We evaluated the association between potential occupational lead exposure and the risk of brain cancer mortality in the National Longitudinal Mortality Study (NLMS), which is a prospective census-based cohort study of mortality among the noninstitutionalized United States population (1979-1989). The present study was limited to individuals for whom occupation and industry were available (n = 317,968). Estimates of probability and intensity of lead exposure were assigned using a job-exposure matrix (JEM). Risk estimates for the impact of lead on brain cancer mortality were computed using standardized mortality ratio (SMR) and proportional hazards and Poisson regression techniques, adjusting for the effects of age, gender and several other covariates. Brain cancer mortality rates were greater among individuals in jobs potentially involving lead exposure as compared to those unexposed (age- and gender-adjusted hazard ratio (HR) = 1.5; 95% confidence interval (CI) = 0.9-2.3) with indications of an exposure-response trend (probability: low HR = 0.7 (95% CI = 0.2-2.2), medium HR = 1.4 (95% CI = 0.8-2.5), high HR = 2.2 (95% CI = 1.2-4.0); intensity: low HR = 1.2 (95% CI = 0.7-2.1), medium/high HR = 1.9 (95% CI = 1.0-3.4)). Brain cancer risk was greatest among individuals with the highest levels of probability and intensity (HR = 2.3; 95% CI = 1.3-4.2). These findings provide further support for an association between occupational lead exposure and brain cancer mortality, but need to be interpreted cautiously due to the consideration of brain cancer as one disease entity and the absence of biological measures of lead exposure.     

Second Primary Neoplasms in Thyroid Cancer Patients

To determine risk patterns for second primary neoplasms after the occurrence of thyroid cancer, we conducted a retrospective cohort study of 3321 thyroid cancer patients who were operated and histologically confirmed at the Noguchi Thyroid Clinic and Hospital Foundation between 1946 and 1985. They were followed from the date of operation through the end of 1990 with an observation period from 45 to 5 years. The average observation period of the patients was 13.4 years and the follow-up rate reached 98%. The standardized mortality ratio (SMR) was computed to assess possible risk increase by cancer site. In this computation, the time period less than 5 years after operation was omitted to reduce the influence of deaths related to the original thyroid cancer. A total of 103 deaths from malignant neoplasms other than thyroid cancer were observed during this time period (SMR=1.6, 95% confidence interval [CI]=1.3–2.0). Analyses of site-specific cancer mortality revealed significantly elevated risks for the central nervous system (SMR=16.1, CI=5,2–37.6) and respiratory organs (SMR=2.6, CI=1.5–4.1). Based on a review of available medical records with histological findings, we concluded that the risk increases for these sites were most likely to be attributable to second primary neoplasms. Whether or not the patients had received radiotherapy was not significantly associated with elevated risk. Further investigations are needed to clarify the risk factors responsible for the above findings.     

Long-term mortality of women with a diagnosis of breast cancer

Survival from breast cancer has improved over the last few years, but scanty information is available on the long-term follow-up. We therefore considered data on 1,095 women with breast cancer diagnosed between 1974 and 1984 in the Swiss Cancer Registry of Vaud (population 616,000 inhabitants) who had survived for at least 10 years. Overall, 129 deaths from breast cancer were observed 10-19 years after the original diagnosis, corresponding to a standardized mortality ratio (SMR) of 20.3 (95% confidence interval (CI) 17.0-24.2). An excess mortality from breast cancer was observed 10-14 (SMR = 22.6) and 15-19 (SMR = 13.4) years after the original diagnosis. The SMR was 25.2 for women diagnosed with breast cancer at age <60 years. Consequently, total mortality was also elevated (SMR = 2.0, based on 294 deaths). None of the other causes of death was significantly elevated, but mortality from cardiovascular disease was 1.4 (95% CI 0.9-2.0) 15-19 years after breast cancer diagnosis. A second primary breast cancer was observed in 89 women. Of these, 19 (21%) died of breast cancer. Therefore in women diagnosed with breast cancer, there remains a substantial excess of breast cancer mortality up to 20 years after the original diagnosis.     

Diet and the risk of papillary and follicular thyroid carcinoma: a population-based case-control study in Sweden and Norway

A population-based case-control study was conducted in two regions ofSweden and Norway to investigate the association between dietary habits andthe risk of thyroid cancer. The consumption of selected foods was reported ina self-completed food-frequency questionnaire by 246 cases withhistologically confirmed papillary (n = 209) and follicular (n = 37) thyroidcarcinoma, and 440 age- and gender-matched controls. Odds ratios (OR) andtheir 95 percent confidence interval (CI) were calculated as estimates of therelative risk using conditional logistic regression. High consumption ofbutter (OR = 1.6, CI = 1.1-2.5) and cheese (OR = 1.5, CI = 1.0-2.4) wasassociated with increased risks. Residence in areas of endemic goiter inSweden was associated with an elevated risk, especially among women (OR =2.5, CI = 1.3-4.9). High consumption of cruciferous vegetables was associatedwith increased risk only in persons who ever lived in such areas. A decreasedrisk was associated with consumption of iodized salt in northern Norway, andwith use of iodized salt during adolescence among women (OR = 0.6, CI =0.6-1.0). The results of this study suggest a role of diet and environment inthe risk of thyroid cancer.     

Further follow-up of New Zealand participants in United Kingdom atmospheric nuclear weapons tests in the Pacific

We previously reported a study of deaths and cancer incidence in Royal NewZealand (RNZ) Navy personnel who participated in atmospheric nuclear weaponstests conducted by the United Kingdom in the Pacific in 1957-58. The studyinvolved 528 men known to have participated in the tests, and a control groupof 1,504 men who were in the RNZ Navy during the same period but were notinvolved in the tests. The original follow-up was carried out for the period1957-87 with an observed increase in risk of leukemia and other hematologiccancers, but little or no increase of non-hematologic cancers or non-cancerdeaths in test participants. Follow-up now has been extended for the period1988-92. For the total follow-up period, there were 97 deaths in testparticipants and 256 deaths in controls, a relative risk (RR) of 1.1 (90percent confidence interval [CI] = 0.9-1.3). The RR of death from causesother than cancer was 1.0 (CI = 0.8-1.3), whereas the RR of cancer death was1.2 (CI = 0.8-1 .7) and that of cancer incidence was 1.0 (CI = 0.8-1.4). Forcancers other than hematologic malignancies, the RR was 1.0 (CI = 0.7-1.5)for mortality, and 1.0 (CI = 0.7-1.3) for incidence. However, there wereeight deaths from hematologic cancers in test participants (RR = 3.8, CI =1.4-10.8), including four leukemias (RR = 5.6, CI = 1.0-41.7). The RR forincidence of hematologic cancers was 1.9 (CI = 0.8-4.3), and that forleukemia was 5.6 (CI = 1.0-41.6). We concluded that the evidence is stillconsistent with the hypothesis that some leukemias and other hematologiccancers may have resulted from participation in the nuclear weapons testprogram, but the further follow-up strengthens the evidence that there is noincreased risk for non-hematologic cancers or for causes of death other thancancer in the test participants.     

Thyroid cancer in the Middle Eastern population of California

Objective  To describe and compare the epidemiology of thyroid cancer in the rapidly growing Middle Eastern (ME) population and the non-Hispanic, non-Middle Eastern White (NHNMW) residents of California. Population with ME heritage that is officially not recognized as a distinct ethnicity has rarely been studied in the past. Methods  ME cases in the California cancer registry files for 1988–2004 were identified by surname recognition. ME population was estimated by ancestry from census data. Results  Thyroid cancer in ME group, 869 cases and 56 deaths were compared with 19,182 cases and 1,327 deaths in the NHNMW population. Age-adjusted rate ratio (RR) for incidence was 1.5 (95% CI 1.3–1.7) in men and 1.5 (95% CI 1.4–1.7) in women. RR for mortality was 1.4 (95% CI 0.9–2.4) in men and 2.3 (95% CI 1.4–3.9) in women. Papillary tumors comprised over 80% of all cases and their pattern correlated with the rapid increase in thyroid cancer in recent years. Five-year observed survival in ME men was significantly higher than in NHNMW men, but similar in women. Conclusions  Eighty-five percent of ME cases identified in this study were born in the Middle East. The higher incidence of thyroid cancer in this immigrant population may largely reflect a combination of sequels of radiation treatment for fungal diseases of the scalp that was common in the area in early 1950s, benign proliferative thyroid disease that is common in the area due to dietary iodine imbalance, and possibly genetic predisposition.     

Dietary factors and risk of colon cancer in Shanghai, China.

Colon cancer incidence rates have risen sharply in Shanghai, China, since the early 1970s, and diet may have contributed to the rising incidence. To clarify the role of dietary factors for colon cancer in Shanghai, we analyzed data from a population-based case-control study of 931 cases (462 males and 469 females) and 1552 controls (851 males and 701 females) ages 30-74 years in Shanghai, China, from 1990-1993. Subjects were interviewed in person for a detailed history of dietary practices and food preferences by using a food-frequency questionnaire. Colon cancer risk was estimated by odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, total energy, and other confounding factors. Risk for the highest versus the lowest quartile of intake was elevated for red meat (OR, 1.5; 95% CI, 1.0-2.1 for men and OR, 1.5; 95% CI, 1.0-2.2 for women), fish (OR, 1.7; 95% CI, 1.2-2.4 for men and OR, 1.2; 95% CI, 0.8-1.7 for women), and eggs (OR, 1.4; 95% CI, 1.0-1.9 for men and OR, 1.3; 95% CI, 0.9-1.9 for women), but was reduced for fresh fruit (OR, 0.7; 95% CI, 0.5-1.0 for men and OR, 0.6, 0.4-0.9 for women). High intake of preserved foods, whether animal or plant source, was associated with an excess risk of colon cancer (OR, 2.0; 95% CI, 1.5-2.9 for men and OR, 2.7; 95% CI, 1.9-3.8 for women). For dietary nutrients, risk generally declined with greater consumption of fiber and micronutrients common in fruit and vegetables, including vitamin C, carotene, and vitamin E. Intake of macronutrients in general was not significantly related to risk. Our findings suggest that diets high in fruit and antioxidant vitamins that are common in plant foods reduce the risk of colon cancer, whereas diets high in red meat, eggs, and preserved foods increase the risk.     

Cancer risk among Danish women with cosmetic breast implants

The available epidemiologic evidence does not support a carcinogenic effect of silicone breast implants on breast or other cancers. Data on cancer risk other than breast cancer are limited and few studies have assessed cancer risk beyond 10-15 years after breast implantation. We extended follow-up of our earlier cohort study of Danish women with cosmetic breast implants by 7 years, yielding 30 years of follow-up for women with longest implant duration. The study population consisted of women who underwent cosmetic breast implant surgery at private clinics of plastic surgery (n = 1,653) or public hospitals (n = 1,110), and a control group of women who attended private clinics for other plastic surgery (n = 1,736), between 1973-95. Cancer incidence through 2002 was ascertained using the Danish Cancer Registry. Risk evaluation was based on computation of standardized incidence ratios (SIR) and Cox proportional hazards models, adjusting for age, calendar period and reproductive history. We observed 163 cancers among women with breast implants compared to 136.7 expected based on general population rates (SIR = 1.2; 95% confidence interval [CI] = 1.0-1.4), during a mean follow-up period of 14.4 years (range = 0-30 years). Women with breast implants experienced a reduced risk of breast cancer (SIR = 0.7; 95% CI = 0.5-1.0), and an increased risk of non-melanoma skin cancer (SIR = 2.1; 95% CI = 1.5-2.7). Stratification by age at implantation, calendar year at implantation and time since implantation showed no clear trends, however, the statistical precision was limited in these analyses. When excluding non-melanoma skin cancer, the SIR for cancer overall was 1.0 (95% CI = 0.8-1.2). With respect to other site-specific cancers, no significantly increased or decreased SIR were observed. Similar results were found when directly comparing women who had implants at private clinics with women who attended private clinics for other plastic surgery, with rate ratios for cancer overall, breast cancer and non-melanoma skin cancer of 1.1 (95% CI = 0.8-1.6), 0.7 (95% CI = 0.4-1.3) and 1.5 (95% CI = 0.8-2.7), respectively. In conclusion, our study lends further support to the accumulating evidence that silicone breast implants are not carcinogenic. Reasons for the consistently reported deficit of breast cancer among women with breast implants remain unclear, whereas increased exposure to sunlight may explain the excess occurrence of non-melanoma skin cancer. We found no indication of delayed diagnosis of breast cancer due to the presence of breast implants.     

Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2.

Women with germ-line mutations in the mismatch repair genes (responsible for hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and endometrial cancer. However, these germ-line mutations are rare and are responsible for fewer than 1% of endometrial cancers. Therefore, we examined whether or not common variants of the hereditary nonpolyposis colorectal cancer-associated genes might also be associated with an increased risk of endometrial cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped. Each of these three single-nucleotide polymorphisms was associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt-93 A allele were at a 1.5-fold increased risk of developing endometrial cancer compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001]. The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2-3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95% CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases carried a variant allele in both MLH1 and MSH2. For these women, the risk of endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005). For patients younger than 50 years at diagnosis who carried both variants, the risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two common variant alleles of the MLH1 and MSH2 genes make a substantial contribution to endometrial cancer incidence in Ontario.     

Kidney cancer and occupational exposure to asbestos: a meta-analysis of occupational cohort studies

Objective: To study the risk of kidney cancer following asbestos exposure.Methods: We carried out a meta-analysis of the results of cohort studies of workers predominantly exposed to asbestos. We contacted the authors of 70 cohort studies; published results were available from the reports of 10 cohorts; we obtained the relevant information for an additional 27 cohorts.Results: The studies included in the analysis comprised a total of 169 kidney cancer deaths and 69 incident cases. The overall pooled standardized mortality ratio (SMR) of kidney cancer was 1.1, with a 95% confidence interval (95% CI) of 0.9–1.3. The pooled SMR was higher for workers with undefined asbestos exposure (SMR 1.2, 95% CI 0.9–1.6) than for workers with either predominant chrysotile (SMR 0.9, 95% CI 0.7–1.3) or some amphibole (SMR 0.96, 95% CI 0.6–1.5) exposure. Studies with published results had higher SMRs than studies for which information was obtained from the authors. Studies with high asbestos exposure and an elevated SMR of lung cancer tended to show an increased risk of kidney cancer.Conclusions: It is unlikely that asbestos exposure is responsible for an important increase in kidney cancer risk; however, high asbestos exposure might entail a small increase in risk.     

Polymorphism of the cyclin D1 gene, CCND1, and risk for incident sporadic colorectal adenomas

Cyclin D1, encoded by the CCND1 gene and activated by the adenomatous polyposis coli-beta-catenin-T-cell factor/lymphoid enhancing factor pathway, induces G(1) to S-phase cell cycle transition, promoting cell proliferation. A recently described codon 242, exon 4, G to A single nucleotide polymorphism (A870G) produces a longer half-life cyclin D1. To investigate whether CCND1 genotype influences risk for colorectal adenoma, we genotyped CCND1 by PCR/RFLP on 161 incident sporadic adenoma cases and 213 controls ages 30-74 years in a North Carolina colonoscopy-based case-control study. At least one polymorphic A allele was found in 68% of cases and 60% of controls. Having an A allele was associated with increased risk for adenoma: the age- and sex-adjusted odds ratio (OR) was 1.5 [95% confidence interval (CI) 1.0-2.4], a finding that was stronger for those whose adenomas were multiple (OR 2.9, 95% CI 1.4-6.0), larger (>or=1 cm; OR 2.4, 95% CI 1.2-4.8), had moderate to severe dysplasia (OR 2.1, 95% CI 1.1-3.8), or were in the right side of the colon (OR 3.6, 95% CI 1.3-10.0). Joint risk factor multivariate analyses revealed stronger positive associations among those who were older (>57 years; OR 2.8, 95% CI 1.4-5.5), male (OR 2.8, 95% CI 1.3-5.7), currently smoked (OR 2.7, 95% CI 1.3-5.7), or currently drank alcohol (OR 2.2, 95% CI 1.2-4.2) if they had an A allele and stronger inverse associations among those who used nonsteroidal anti-inflammatory drugs (OR 0.4, 95% CI 0.2-0.9) or had higher calcium intakes (OR 0.4, 95% CI 0.2-0.9) if they had no A allele. These data support the hypothesis that the CCND1 A870G polymorphism may increase risk for colorectal neoplasms.     

Active and passive smoking and breast cancer risk in middle-aged Japanese women

To examine the hypothesis that tobacco smoke is associated with the risk of female breast cancer, we estimated the relative risks of active and passive smoke in middle-aged Japanese women in a population-based prospective study. The cohort consisted of residents in 4 public health center areas, aged 40 to 59 years. A self-administered questionnaire survey was conducted in 1990. This analysis included 21,805 subjects, 180 of whom had developed breast cancer by December 31, 1999. When the reference was defined as never-active smokers without passive smoking, adjusted relative risks (RRs) were 1.9 (95% confidence interval [CI] = 1.0-3.6) in current active smokers, 1.2 (95% CI = 0.4-4.0) in ex-active smokers and 1.2 (95% CI = 0.8-1.6) in never-active smokers with passive smoking. The elevated risk for ever-smokers was clearly observed in premenopausal women at baseline (RR = 3.9, 95% CI = 1.5-9.9) but not in postmenopausal women (RR = 1.1, 95% CI = 0.5-2.5). In never-active smokers, the adjusted RR for passive smoking, residential or occupational/public tobacco smoke exposure was 1.1 (95% CI = 0.8-1.6). In premenopausal women, passive smoking increased the risk (RR = 2.6; 95% CI = 1.3-5.2) but not in postmenopausal women (RR = 0.7; 95% CI = 0.4-1.0). We conclude that tobacco smoking increases the risk of female breast cancer in premenopausal women.