A prospective seroepidemiological study of human herpesvirus-8 infection and the risk of multiple myeloma

Presence of the Human Herpesvirus 8 (HHV8) genome has been reported in the bone marrow of multiple myeloma (MM) patients. So far, serological studies of HHV8 and MM have been inconsistent but have not included prospective epidemiological studies. We evaluated whether HHV8 infection is associated with increased risk for MM in a prospective population-based study of 39 000 Finnish subjects who donated serum samples in the period 1968-72. Serum samples from 47 subjects who developed MM during a 23-year follow-up and 224 age, area of residence and sex-matched subjects who remained healthy over a similar follow-up period were evaluated for HHV8 antibodies at enrollment, as assayed both with an immunofluorescence assay (IFA) for lytic and latent HHV8 antigens and by Western blot (WB) with three recombinant HHV8 proteins (ORFs 65, 73 and K8.1A). HHV8 seropositivity for at least one HHV8 protein on WB was found in 7% of the Finnish population and was not associated with the risk of developing MM (Relative Risk (RR) = 0.89, Confidence Interval (CI): 0.25-3.25). HHV8 seropositivity for lytic and latent antigens in the IFA was found in 16% and 0.4% of the Finnish population and tended to associate with risk of MM (RR = 2.02, CI: 0.94-4.33 and RR = 10.00, CI: 0.91-110.29, respectively). In conclusion, no statistically significant evidence for an association between HHV8 infection and the risk of future MM was found.     

Risk factors for Kaposi's sarcoma among HHV-8 seropositive homosexual men with AIDS

Kaposi's sarcoma (KS) is a frequent complication of the acquired immunodeficiency syndrome (AIDS) in homosexual men. Risk factors for developing this malignancy are uncertain, other than immunosuppression and coinfection with human herpesvirus 8 (HHV-8). We therefore examined factors associated with KS in a cross-sectional analysis of 99 cases among 503 HHV-8 seropositive homosexual men with AIDS. Data were collected by computer-assisted personal interviews and medical chart reviews. HHV-8 seroreactivity was determined by enzyme-linked immunosorbent assay for antibodies against HHV-8 K8.1 glycoprotein. KS was significantly less common in blacks compared to whites [risk ratio (RR) = 0.4; 95% CI = 0.2 =0.8] and more common in subjects who had completed college (RR = 1.7; 95% CI = 1.1-2.7) or had annual income greater than dollar 30,000 (RR = 1.5; 95% CI = 1.1-2.2). KS was less common in cigarette smokers (RR = 0.6; 95% CI = 0.5-0.9) and users of crack cocaine (RR = 0.4; 95% CI = 0.1-0.8). KS was less common in bisexual men compared to men who were exclusively homosexual (estimated RR = 0.6; 95% CI = 0.4-0.9) and inversely associated with number of female partners. KS was also less common in men who had received pay for sex (RR = 0.6; 95% CI = 0.4-1.0). These cross-sectional associations could be biased by potential differences in relative timing of HHV-8 and HIV infection, a postulated determinant of KS risk. Alternatively, our findings may reflect factors protective against KS in individuals infected with HHV-8. Future research should focus on identifying practical measures for countering KS that do not increase the risk of other diseases.     

Multiple myeloma and family history of cancer. A case-control study

A hospital-based case-control study was done to examine the hypothesis that persons with a family history of multiple myeloma (MM) or other cancers are at increased risk of multiple myeloma. Study members were 439 cases of multiple myeloma and 1317 matched controls seen at the Duke University Medical Center. Only 3 cases and 4 controls reported multiple myeloma in their families. The relative risk (RR) was 2.3, but the 95% confidence interval (CI) was 0.5-10.1, allowing no firm conclusion about the risk associated with familial MM. A family history of cancer of any type resulted in a relative risk of MM of 1.4 (CI: 1.1-1.8). This association was strongest (RR = 2.5, CI: 1.1-5.3) among young study members (age less than or equal to 49). A family history of hematologic malignancy (ICD 200-208) resulted in a RR of 2.4 (95% CI: 1.4-4.0). The data also suggested that a family history of lung cancer, breast cancer, and genitourinary cancer may be associated with increased risk of myeloma in older persons.     

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).     

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.     

Alcohol consumption and risk of Hodgkin's lymphoma and multiple myeloma: a multicentre case-control study.

BACKGROUND: Few studies have analysed the association between alcohol intake and Hodgkin's lymphoma (HL) or multiple myeloma (MM) risks. MATERIALS AND METHODS: A multicentre population-based case-control study of 363 HL, 270 MM cases, and 1771 controls offered the opportunity to evaluate the relationship between alcohol and HL/MM risks. Unconditional logistic regression was carried out to estimate odds ratios (ORs) and 95% confidence intervals (CIs), associated with alcohol intake (servings per week, grams per day of ethanol intake) or duration of exposure (year). RESULTS: For HL, considering nonsmokers only, ever drinkers had a significantly decreased risk than never drinkers (OR=0.46). Significantly lower risks in all levels of total alcohol intake were also detected, considering servings per week (OR for one to four servings per week=0.51, 95% CI 0.32-0.82; OR for five to nine servings per week=0.39, 95% CI 0.21-0.73; OR for 10-19 servings per week=0.26, 95% CI 0.12-0.54; OR for >or=20 servings per week=0.34, 95% CI 0.15-0.79) and grams per day of ethanol intake (OR for 0.1-9.0 g/day=0.45, 95% CI 0.27-0.74; OR for 9.1-17.9 g/day=0.52, 95% CI 0.30-0.90; OR for 18.0-31.7 g/day=0.27, 95% CI 0.13-0.57; OR for >31.7 g/day=0.35, 95% CI 0.15-0.79). In the analysis for ever-smoking HL cases and controls, ever drinkers had the same risk as never drinkers. For MM, ever drinkers had a non-significantly decreased risk than non-drinkers (OR=0.74), and ORs in almost all consumption levels were not significant (OR for 0.1-9.0 g/day=0.93; OR for 9.1-17.9 g/day=0.82; OR for 18.0-31.7 g/day=0.47; 95% CI 0.28-0.81; OR for >31.7 g/day=0.68). For HL and MM, the beverage type did not affect the risk significantly, and no consistent dose-response relationships were found, considering intensity or duration of alcohol consumption. CONCLUSIONS: Our study indicates a protective effect of alcohol consumption for nonsmoking HL cases.     

Risk of cervical cancer among immigrants by age at immigration and follow-up time in Sweden, from 1968 to 2004

Because of great variation in the prevalence of human papilloma virus infection and other risk factors of cervical cancer worldwide, migrant studies may help further the understanding of the aetiology and improve prevention of cervical cancer. Our aim was to study the risk of invasive cervical cancer among immigrant women. We followed 758,002 immigrants from different countries who resided in Sweden between 1968 and 2004. Age-standardised incidence rates (ASRs) of immigrants were compared with that in their countries of origin. Poisson regression models estimated the relative risks of cervical cancer among immigrants, overall and stratified by age at migration and follow-up time, compared to Swedish-born women. Overall 1,991 of 19,542 observed cases of cervical cancer occurred among immigrants. Generally they had lower ASRs than in their countries of origin, with the exception of Nordic immigrants. Compared to Swedish-born women, we observed a higher relative risk of cervical cancer among immigrants overall (RR = 1.13, 95% CI 1.08-1.18), and particularly among women from Denmark (RR = 1.8, 95% CI 1.6-2.1), Norway (RR = 1.7, 95% CI 1.5-1.9) and Central America (RR = 2.5, 95% CI 1.3-4.9), while the relative risks were lower in immigrants from Eastern Africa (RR = 0.2, 95% CI 0.1-0.6), South Central Asia (RR = 0.4, 95% CI 0.2-0.6) and South Western Asia (RR = 0.5, 95% CI 0.4-0.7). Follow-up time and age at migration were important effect modifiers for cervical cancer risks. We suggest targeted prevention toward high-risk immigrants, specifically older women, in the first 10 years after arrival into their new homeland.     

Erythrocyte levels of cadmium and lead and risk of B-cell non-Hodgkin lymphoma and multiple myeloma

Cadmium and lead are persistent environmental toxins that are known or probable carcinogens, based on evidence for causality for nonhematologic cancers. Associations of these metals with risk of non-Hodgkin lymphoma (NHL) and multiple myeloma (MM) are unknown but biologically plausible. To examine the associations of circulating levels of lead and cadmium exposure with risk of B-cell NHL (B-NHL) and multiple myeloma, we conducted a nested case-control study among 299 incident B-cell NHLs and 76 MM cases within the Cancer Prevention Study-II Nutrition Cohort (CPS-II NC). Each case was incidence-density matched to two eligible controls on age, race, sex and blood draw date. Conditional logistic regression was used to estimate relative risks (RR) and 95% confidence intervals (CI) for lymphoid malignancies overall and stratified by subtype. We observed a significant positive association between high erythrocyte lead concentration and risk of lymphoid malignancies overall (RR = 1.16, 95% CI: 1.02-1.33 per 17.6 μg/L (1 standard deviation [SD])) and follicular lymphoma in particular (RR = 1.80, 95% CI: 1.15-2.80 per SD). In contrast, there was no association between erythrocyte cadmium and risk of B-NHL (RR = 0.89, 95% CI: 0.75-1.06 per 0.37 μg/L [1 SD]), or any B-NHL subtypes; but a strong inverse association with MM risk (RR = 0.59, 95% CI: 0.38-0.89, per SD). Results from our study suggest a positive association between erythrocyte lead level and risk of lymphoid malignancies and a possible inverse association between cadmium and myeloma. Additional research is needed to confirm and further explore these findings.     

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.     

The Copenhagen case-control study of renal pelvis and ureter cancer: role of smoking and occupational exposures

Smoking habits and occupational exposures were investigated for 96 patients with cancer of the renal pelvis and ureter (including papilloma) and 294 hospital controls. In comparison with persons who never smoked, significantly increased relative risks were seen for smokers of cigarettes alone (RR = 2.6; 95% CI: 1.0-6.7) and in combination with other types of tobacco (RR = 3.8; 95% CI: 1.3-11.5). Non-significantly increased relative risks were observed for pipe smokers (RR = 2.2; 95% CI: 0.1-97) and for mixed pipe, cigar, and cigarillo smokers (RR = 6.5; 95% CI: 0.4-21.2). A strong dose-effect (p less than 0.001) relationship was seen between the lifetime total amount of tobacco smoked and the risk of pelvis-ureter tumors, with the heaviest smokers having an 8-fold risk. Comparison with the dose-effect relationship for a parallel study of bladder cancer indicated that the relationship with tobacco was stronger for pelvis-ureter tumors. Deep inhalation of cigarette smoke increased the risk (RR = 3.4; 95% CI: 1.9-6.1), while stopping smoking (RR = 0.6; 95% CI: 0.3-1.1) and use of filter cigarettes (RR = 0.5; 95% CI: 0.3-0.9) decreased the risk. Significantly increased risks emerged for employment in the chemical, petrochemical and plastics industries (RR = 4.0; 95% CI: 1.6-9.8), and for exposure to coal and coke (RR = 4.0; 95% CI: 1.2-13.6), asphalt and tar (RR = 5.5; 95% CI: 1.6-19.6). Cigarette smoking accounted for 56% of male and 40% of female pelvis and ureter tumors in eastern Denmark.     

Smoking and risk of non-Hodgkin lymphoma subtypes in a cohort of older women

Although non-Hodgkin lymphoma (NHL) has not been considered to be a smoking-related malignancy, recent investigations suggest otherwise. We evaluated this association in a cohort of 37,336 women, aged 55-69 years, who reported in a mailed questionnaire in 1986 information regarding smoking history as well as demographic, medical history and dietary factors. Cancer and mortality experience through 1996 was determined by linkage to the Iowa Cancer Registry and other databases; there were 200 incident cases of NHL during the 380,231 total person-years of follow-up. Compared to never smokers, former (age-adjusted RR = 1.0; 95% CI 0.8-1.5) and current smokers (age-adjusted RR = 1.0; 95% CI 0.7-1.5) were not at elevated risk of NHL, and there was no trend with pack-years smoked (Ptrend = 0.3). Multivariate adjustment for other NHL risk factors did not alter these findings. Age-adjusted analysis by NHL subtype revealed a suggestive positive association of smoking with follicular NHL [(RRformer = 1.3; 95% CI 0.6-2.8), (RRcurrent = 1.8; 95% CI 0.8-3.8)], which strengthened after multivariate adjustment [(RRformer = 1.6; 95% CI 0.7-3.4), (RRcurrent = 2.3; 95% CI 1.0-5.0)]; there was no association for diffuse or small cleaved-cell NHL. Our study findings, which are consistent with other recent investigations, suggest that smoking may be associated with an increased risk of follicular NHL.     

The influence of mammographic screening on national trends in breast cancer incidence.

Introducing an organized mammographic screening programme affects the breast cancer incidence rate in a population. The diagnosis is advanced in time, and initially, an increase will occur in the number of cases, followed by a drop in the rate when women leave the programme. The aim of this study was to quantify the potential effects that mammographic screening programmes have on breast cancer incidence. In addition, we wanted to investigate how the incidence of breast cancer varies between different birth cohorts, age groups and time periods in the five Nordic countries Finland, Denmark, Iceland, Norway and Sweden, adjusting for the effects of the screening programmes. Time trends were analysed over the period 1978-1997, using age-period-cohort models. In Sweden, the rates more than doubled (relative risk (RR)=2.20, 95% confidence interval (CI) 1.8-2.6) in women offered screening for the first time compared with women not offered screening. The risk remained elevated (RR=1.34, 95% CI 1.2-1.6) for women who were continued to be offered screening, compared with women who were not offered screening. Finally, the rates dropped (RR=0.68, 95% CI 0.6-0.8) when the women left the programme. This indicates that screening advances the time of diagnosis, which is a prerequisite to subsequent reduction in mortality. Analysis of secular trends, corrected for the influence of screening, showed that the rates in Finland increased by 13% per 5-year period, with a more modest increase in the other countries. There were strong cohort effects in all Nordic countries, and the risk seemed to be flattening for the youngest cohorts in most of the countries.     

Large bowel cancer in women in relation to reproductive and hormonal factors: a case-control study

A community-based case-control study of the effect of reproductive factors on risk of large bowel cancer in Australia is described. The study involved 155 cases (99 colon cancer, 56 rectal cancer) and 311 controls who were interviewed with regard to pregnancies and their outcomes, lactation, menstrual history, and oral contraceptive (OC) use. Increasing parity was associated with a decreasing risk of colon cancer; para 0, relative risk (RR)=1; para 1-2, RR=0.9, 95% confidence interval (CI)=0.4-1.8; para greater than or equal to 3, RR=0.4, 95% CI=0.2-0.8; later age at first live birth (AFLB) was associated with increasing risk (AFLB less than or equal to 21 yr, RR=1; 22-25 yr, RR=2.3, 95% CI=1.0-5.5; greater than or equal to 26 yr, RR=2.7, 95% CI=1.2-6.2). These effects were independent of each other. Parity appeared to exert its predominant effect on risk of cancer of the right colon. OC use was more common among controls than cases (RR=0.5; 95% CI=0.3-1.2 for ever vs. never users) and showed a dose-response effect in multiple logistic analysis. The pattern of point-estimate RR for rectal cancer was largely congruent with those for colon cancer but was not significantly different from 1.0.     

Surgical margins, local recurrence and metastasis in soft tissue sarcomas: 559 surgically-treated patients from the Scandinavian Sarcoma Group Register

The prognostic importance of surgical margins on local recurrence rates and metastasis-free survival (MFS) was studied in 559 patients with soft tissue sarcoma of the extremities and trunk wall. The patients were all surgically treated, but received no adjuvant treatment. The median follow-up for the survivors was 7.4 (range: 0.1 - 12.5) years. Independent prognostic factors for MFS were analysed by Cox models. The overall 5-year MFS was 0.72 (95% confidence intervals (CI) 0.68 - 0.76). High histopathological malignancy grade (relative risk (RR) 3.0; 95% CI 1.5 - 6.3) and an inadequate surgical margin (RR 2.9; 95% CI 1.8 - 4.6) were independent risk factors for local recurrence. High histopathological malignancy grade and large tumour size (> 7 cm) were the most important risk factors for metastasis. Local recurrence was associated with an increased risk of metastasis (RR 4. 4; 95% CI 2.9-6.8), but an inadequate surgical margin was not a risk factor for metastasis (RR 1.1; 95% CI 0.8-1.7). This study confirms that, as regards metastasis, tumour-related risk factors (malignancy grade and tumour size) are more important risk factors than treatment-related factors. Local recurrence was associated with an increased metastasis rate, whereas inadequate surgical margin was a risk factor for local recurrence but not for metastasis. Hence, the proposed causal association between local recurrence and metastasis is doubtful, and if it exists is a weak association.     

Medical risk factors and the development of brain tumors.

Several diseases and medical treatments are discussed as risk factors for the development of brain tumors. A population-based case-control study in the Rhein-Neckar-Odenwald area (containing 1.3 million inhabitants) of Germany was established to investigate this question. A total of 226 patients (cases) with primary brain tumors (International Classification of Diseases, ninth edition, classes 191, 191.1, and 192.0) and 418 control subjects (controls) were interviewed using a standardized questionnaire over a period of 2 years. No association was seen for head injuries, hereditary diseases, family history, and radiographic examination of the head and teeth. However, more cases than controls had had meningitis (relative risk [RR], 2.7; 95% confidence interval [CI], 0.9 to 8.6) or epilepsy (RR, 2.6; 95% CI, 0.6 to 11.7). The RR was decreased for those who had allergic diseases (RR, 0.7; 95% CI, 0.5 to 1.0), diabetes (RR, 0.7; 95% CI, 0.3 to 1.8), and infections and colds (RR, 0.3; 95% CI, 0.1 to 0.8).     

Human herpesvirus 8 seropositivity and risk of Kaposi's sarcoma and other acquired immunodeficiency syndrome-related diseases.

BACKGROUND: The incidence of Kaposi's sarcoma (KS) is increased severalfold in individuals infected with human immunodeficiency virus-1 (HIV). Human herpesvirus 8 (HHV8) has also been implicated in KS. We investigated several factors that may determine the onset of KS, particularly HHV8 infection in individuals after becoming seropositive for HIV. METHODS: We studied 366 individuals belonging to different HIV-exposure categories (i.e., homosexual activity, intravenous drug use, and heterosexual contact) for whom a negative HIV serologic test and then a positive HIV serologic test were available within a 2-year period. HHV8 antibody testing was performed by use of an immunofluorescence assay on the first serum sample available after the first positive HIV test. Actuarial rates of progression of KS and of other acquired immunodeficiency syndrome (AIDS)-defining diseases were estimated by use of time-to-event statistical methods. All statistical tests were two-sided. RESULTS: Twenty-one of the 366 study participants developed AIDS-related KS, and 83 developed AIDS without KS. One hundred forty (38.3%) participants had detectable anti-HHV8 antibodies. The actuarial progression rate to KS among persons co-infected with HIV/HHV8 was nearly 30% by 10 years after HIV seroconversion. Increasing HHV8 antibody titers increased the risk of developing KS (for seronegative versus highest titer [1:125 serum dilution], adjusted relative hazard [RH] = 51.82; 95% confidence interval [CI] = 6.08-441.33) but not of other AIDS-defining diseases (adjusted RH = 1.14; 95% CI = 0.72-1.80). HHV8-seropositive homosexual men compared with HHV8-seropositive participants from other HIV-exposure categories showed an increased risk of KS that approached statistical significance (adjusted RH = 6.93; 95% CI = 0.88-54.84). CONCLUSIONS: Approximately one third of individuals co-infected with HIV/HHV8 developed KS within 10 years after HIV seroconversion. Progression to KS increased with time after HIV seroconversion. Higher antibody titers to HHV8 appear to be related to faster progression to KS but not to other AIDS-defining diseases.     

Tubal sterilization in relation to breast cancer risk

Tubal sterilization methods may damage surrounding tissue, potentially disrupting the ovarian blood supply and hormonal functioning, and may decrease breast cancer risk. We examined this hypothesis, within the Nurses' Health Study, among 77,511 women, aged 30-55 years and free of cancer at the start of follow-up in 1976. We documented 4,176 cases of invasive breast cancer from 1976 to 2000. Cox proportional hazards models, adjusting for multiple breast cancer risk factors, provided rate ratios (RR) and 95% confidence intervals (CI). Overall, tubal sterilization was not associated with breast cancer risk (RR=0.95, 95% CI=0.88-1.03). However, tubal sterilizations performed from 1970 to 1974 were inversely associated with risk (RR=0.84, 95% CI=0.73-0.97), while procedures performed in other years were not associated with risk. Among women with procedures performed in 1970-1974, those who were >or=35 years old at the time of sterilization were at the lowest risk (RR=0.81, 95% CI=0.66-0.98), while younger women had a suggested decreased risk (RR=0.87, 95% CI=0.72-1.06). Overall, tubal sterilization was not associated with breast cancer risk. However, a modest inverse association was observed at a time when the potentially destructive unipolar electrocautery method was commonly used, providing some support for an association between lower lifetime exposure to hormones and a decreased risk of breast cancer.     

Hormone replacement therapy and risk of non-hodgkin lymphoma and chronic lymphocytic leukemia.

Our objective in this study was to evaluate whether the use of hormone replacement therapy (HRT) is associated with non-Hodgkin lymphoma (NHL) or chronic lymphocytic leukemia (CLL). A cohort of 37,220 Iowa women ages 55 to 69 years in 1986 with no history of prior cancer was linked annually to a population-based cancer registry. Through 1998 (13 years of follow-up), 258 incident cases of NHL were identified, including 135 cases of diffuse NHL, 58 cases of follicular NHL, and 31 cases of small lymphocytic NHL. In addition, 63 cases of CLL were identified. Current and former use of HRT (primarily estrogen) and other cancer risk factors were self-reported on the baseline (1986) questionnaire. Compared with never users of HRT at study baseline, current [multivariate relative risk (RR), 1.4; 95% confidence intervals (CIs), 0.9-2.0) but not former (RR, 1.1; 95% CI, 0.8-1.4) users were at increased risk of NHL after adjustment for age and other confounding factors. This association was seen only in nodal NHL [RR(current), 1.5 (95% CI, 1.0-2.4); RR(former), 1.1 (95% CI, 0.8-1.6)] and was not apparent for extra-nodal sites. Of the common subtypes, there was a strong positive association with follicular NHL [RR(current), 3.3 (95% CI, 1.6-6.9); RR(former), 2.6 (95% CI, 1.4-4.7)], and women who were current users for more than 5 years had the highest risk (RR, 3.9; 95% CI, 1.8-8.6). There was no association with diffuse or small lymphocytic NHL, or with CLL. Most of the follicular NHLs were nodal (88%), and exclusion of extra-nodal sites slightly strengthened the association with HRT. For diffuse NHL, 64% of the cases were nodal, and there was no association of HRT with either nodal or extra-nodal sites. These data suggest that HRT is a risk factor for follicular NHL but not for diffuse or small lymphocyte NHL or CLL.     

Variants in the ATM gene associated with a reduced risk of contralateral breast cancer

Between 5% and 10% of women who survive a first primary breast cancer will subsequently develop a second primary cancer in the contralateral breast. The Women's Environment, Cancer, and Radiation Epidemiology Study was designed to identify genetic and environmental determinants of contralateral breast cancer (CBC). In this study, 708 women with asynchronous CBC served as cases and 1,397 women with unilateral breast cancer served as controls. ATM, a serine-threonine kinase, controls the cellular response to DNA double-strand breaks, and has been implicated in breast cancer risk. Complete mutation screening of the ATM gene in all 2,105 study participants identified 240 distinct sequence variants; only 15 were observed in >1% of subjects. Among the rare variants, deleterious alleles resulting in loss of ATM function were associated with a nonsignificant increase in risk of CBC. In contrast, carriers of common variants had a statistically significant reduction in risk of CBC. Four of these 15 variants were individually associated with a significantly decreased risk of second primary breast cancer [c.1899-55T>G, rate ratio (RR), 0.5; 95% confidence interval (CI), 0.3-0.8; c.3161C>G, RR, 0.5; 95% CI, 0.3-0.9; c.5558A>T, RR, 0.2; 95% CI, 0.1-0.6; c.6348-54T>C RR, 0.2; 95% CI, 0.1-0.8]. These data suggest that some alleles of ATM may exert an antineoplastic effect, perhaps by altering the activity of ATM as an initiator of DNA damage responses or a regulator of p53.     

Fibre intake and laryngeal cancer risk.

BACKGROUND: Consumption of vegetables, fruit and whole grain cereals has been inversely related to laryngeal cancer risk. Among the potential protective agents found in these foods, information on dietary fibres and laryngeal cancer risk are scanty. PATIENTS AND METHODS: A multi-centric, hospital-based case-control study was conducted on 527 patients with squamous-cell carcinoma of the larynx and 1,297 non-neoplastic controls. Cases and controls, frequency matched by age, sex and study centre, were interviewed using a validated food frequency questionnaire. RESULTS: Compared with the lowest quintile of fibre intake, the odds ratios (ORs) for the highest quintile were 0.3 [95% confidence interval (CI) 0.2-0.4] for total fibre, 0.3 (95% CI 0.2-0.5) for soluble non-cellulose polysaccharides (NCP) and for total insoluble fibre, including cellulose (OR = 0.3, 95% CI 0.2-0.4) and insoluble NCP (OR = 0.4, 95% CI 0.3-0.7). The ORs were 0.2 (95% CI 0.1-0.4) for fibre from vegetables, 0.5 (95% CI 0.3-0.7) from fruit and 1.1 (95% CI 0.6-1.9) from grains. The inverse association observed was similar among different subsites of laryngeal cancer, and consistent across strata of various covariates. CONCLUSIONS: This study found a strong inverse association between fibre intake and laryngeal cancer risk, which points to fibre as one of the beneficial components of vegetables and fruit.