Interleukin-6 sequence variants are not associated with prostate cancer risk.
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Biomedical subjects
Publications and source records attributed to Hans-Olov Adami.
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OBJECTIVE: Striking geographic variation and marked increasing secular trends characterize the incidence of testicular cancer. However, it is not known whether these patterns have attenuated in recent years and whether they are similar for seminomas and nonseminomas, the two main histologic groups of testicular cancer. METHOD: Cancer registry data, including 27,030 testicular cancer cases, were obtained from Denmark, Estonia, Finland, Latvia, Lithuania, Norway, Poland, and Sweden. Between 57 (Denmark) and 9 (Poland) years of registration were covered. Country-specific temporal trends were estimated, with focus on the last decade and seminomas and nonseminomas. Data from the Nordic countries were further analyzed using an age-period-cohort approach. RESULTS: Age-standardized incidence rates increased annually by 2.6% to 4.9% during the study period, with marginal differences between seminomas and nonseminomas. In the last decade, the increasing trend attenuated only in Denmark (annual change, -0.3%; 95% confidence interval, -1.5 to 0.9). In 1995, the highest and the lowest age-standardized incidence rates (per 10(5)) were 15.2 in Denmark and 2.1 in Lithuania. Incidence rates (i.e., for all cancers and for seminomas and nonseminomas, separately) depended chiefly on birth cohort rather than on calendar period of diagnosis (although both birth cohort and period determined the Danish incidence rates). CONCLUSIONS: Testicular cancer incidence is still increasing, with the exception of Denmark, and a large geographic difference exists. The increasing trend is mainly a birth cohort phenomenon also in recent cohorts. Temporal trends for seminomas and nonseminomas are similar, which suggests that they share important causal factors.
Although patients with type 2 diabetes have elevated risks of liver, pancreatic, kidney, and endometrial cancer, little is known about the risk of cancer for patients with type 1 diabetes. We conducted a cohort study to examine cancer incidence among 29 187 patients in Sweden who were hospitalized for type 1 diabetes from 1965 through 1999. Relative risks of cancer were estimated by age-, sex- and calendar year of follow-up--adjusted standardized incidence ratios (SIRs), using data for the entire Swedish population as a reference. After excluding cancers diagnosed during the first year after hospital discharge, we observed 355 incident cases of cancer, which corresponded to a 20% increase in overall cancer incidence among type 1 diabetes patients (SIR = 1.2, 95% confidence interval [CI] = 1.0 to 1.3). Patients with type 1 diabetes had elevated risks of cancers of the stomach (SIR = 2.3, 95% CI = 1.1 to 4.1), cervix (SIR = 1.6, 95% CI = 1.1 to 2.2), and endometrium (SIR = 2.7, 95% CI = 1.4 to 4.7). Type 1 diabetes is associated with a modest excess cancer risk overall and risks of specific cancers that differ from those associated with type 2 diabetes.
BACKGROUND: Pathologically, benign prostatic hyperplasia (BPH) is not considered a precursor for prostate carcinoma. However, because the two conditions share not only a similar hormonal environment within the prostate but also several common risk factors, it is possible that men with BPH may be at increased risk of prostate carcinoma due to these shared factors. METHODS: To elucidate this further, the authors used Swedish nationwide population-based record-linkage data to assess prostate carcinoma risk up to 26 years after the diagnosis of BPH among 86,626 men. RESULTS: Overall, relative to the general population, patients with BPH experienced little, if any, excess risk of prostate carcinoma (2% excess incidence after 10 years of follow-up). However, patients with BPH with and without surgical intervention experienced different prostate carcinoma risk patterns. Those undergoing transvesicular adenomectomy had a significant 22% lower incidence and a 23% lower mortality after the first 5 years of follow-up and those undergoing transurethral resection had a significant 10% higher incidence but a 17% lower mortality. In contrast, after the first 5 years, patients with BPH who did not receive surgical intervention experienced significant excesses of both prostate carcinoma incidence (18%) and mortality (77%). CONCLUSIONS: The differences in prostate carcinoma incidence and mortality by BPH treatment type suggest that factors related to treatment or health reasons underlying the selection of treatment influence subsequent prostate carcinoma risk. Further studies are needed to confirm the minimal excess risk of prostate carcinoma among BPH patients overall and the possible impact of BPH treatment methods on subsequent prostate carcinoma risk.
BACKGROUND: Although sun exposure is an established cause of cutaneous malignant melanoma, possible interactions with host factors remain incompletely understood. Here we report the first results from a large prospective cohort study of pigmentation factors and sun exposure in relation to melanoma risk. METHODS: The Women's Lifestyle and Health Cohort Study included 106 379 women from Norway and Sweden who were aged 30-50 years in 1991 or 1992 when they completed an extensive questionnaire on personal characteristics and exposures. Linkages to national registries ensured complete follow-up through December 31, 1999. Poisson regression models were used to estimate relative risks (RRs). All statistical tests were two-sided. RESULTS: During an average follow-up of 8.1 years, 187 cases of melanoma were diagnosed. Risk of melanoma was statistically significantly associated with increasing body surface area (RR for > or =1.79 m2 versus < or =1.61 m2 = 1.60, 95% confidence interval [CI] = 1.03 to 2.48; P(trend) =.02), number of large asymmetric nevi on the legs (RR for > or =7 nevi versus 0 nevi = 5.29, 95% CI = 2.33 to 12.01; P(trend)<.001), hair color (RR for red versus dark brown or black = 4.05, 95% CI = 2.11 to 7.76; P(trend)<.001), sunburns per year at ages 10-19, 20-29, and 30-39 years (P(trend)<.001, P(trend) =.03, and P(trend) =.05, respectively), and use of a device that emits artificial light (solarium) one or more times per month (P =.04). CONCLUSIONS: Our results confirm previous findings that hair color, number of nevi on the legs, and history of sunburn are risk factors for melanoma and suggest that use of a solarium is also associated with melanoma risk. Adolescence and early adulthood appear to be among the most sensitive age periods for the effects of sunburn and solarium use on melanoma risk. However, it may be too early to see the full effect of adult exposures in this cohort.
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OBJECTIVE: To assess pregnancy hormone levels in relation to nausea with or without vomiting. METHODS: In the context of a prospective cohort study, 262 white pregnant women in Boston were observed through delivery. Maternal blood was collected at 16 and 27 weeks' gestation and serum levels of estradiol, estriol, progesterone, prolactin, and sex hormone-binding globulin were determined. Information on sociodemographic and medical variables was collected through an interviewer-administered questionnaire and review of medical records. At the 27th gestational week, nausea with or without vomiting at any time during the index pregnancy was ascertained. RESULTS: By the 27th gestational week, 209 women (79.8%) had experienced nausea with or without vomiting. There was a substantial and statistically significant (P <.01) inverse association of prolactin with nausea with or without vomiting at both the first and the second samplings, with or without adjustment for the other measured compounds. Estradiol was positively associated with nausea with or without vomiting risk, but the association was evident only after adjustment for the other measured compounds (P values of.06 and.07 at the first and second samplings, respectively). We found no evidence that estriol, progesterone, or sex hormone-binding globulin was related to nausea with or without vomiting at either the 16th or the 27th week of pregnancy. CONCLUSION: Our results point to lower levels of prolactin and, perhaps, higher levels of estradiol as contributing to or correlating with the occurrence of nausea with or without vomiting at any time during the pregnancy until the 27th gestational week. We found no evidence that estriol, progesterone, or sex hormone-binding globulin is associated with this condition.
OBJECTIVE: Because birth weight has been positively associated with adult life breast cancer risk and pregnancy estrogens have been hypothesized to affect breast cancer risk in the offspring, we have evaluated the association of pregnancy estriol (E3), estradiol (E2), progesterone and prolactin in maternal serum samples collected during the 16th and 27th gestational week with birth size parameters. METHODS: Prospective study of 230 Caucasian women who delivered a live singleton after 37-42 weeks of gestation. RESULTS: E3 at the 27th gestational week was significantly positively associated with birth weight, birth length and placental weight. Progesterone at the 27th gestational week was also significantly positively associated with birth weight and placental weight but, after mutual adjustment among the studied pregnancy hormones, these associations weakened considerably. There was also inconsistent evidence that SHBG and prolactin at the 27th gestational week may be respectively positively and inversely related with birth size parameters. Measurements during the 16th gestational week were generally unrelated to birth size parameters. CONCLUSIONS: Because E3 is a dominant estrogen during pregnancy, the positive association of it with birth weight allows the use of the latter as a proxy of in utero exposure to estrogens in breast cancer investigations.
BACKGROUND: There has been renewed interest about determinants of birth size following the propagation of hypotheses that birth size parameters may have long-term consequences on the occurrence of common diseases in adulthood, including breast cancer. METHODS: In the context of a cohort study, 296 Caucasian pregnant women in Boston, USA and 329 Chinese pregnant women in Shanghai, China were followed to term. Birth size characteristics of the baby and maternal anthropometry were measured using standardized protocols. Analyses were conducted through multiple regression procedures. RESULTS: No significant difference was found between US and Chinese newborns with respect to gestational age. Among US women, pregravid oral contraceptive use was strongly associated with higher birthweight. In both US and Chinese women, birthweight was positively associated with height, pre-pregnancy body mass index, and weight gain during pregnancy. More importantly, the difference in these three maternal variables between the two samples fully explains the birthweight difference between the two populations. CONCLUSIONS: We postulate that babies in China may have lower birthweight because their mothers' anthropometry imposes constraints on the growth of the fetus. When Chinese women migrate to the US, they tend to grow taller and heavier so that their babies can reach, on the average, a higher birthweight. The recurrence of this process in successive generations could explain why eventually Chinese Americans tend to have comparable birth and adult anthropometric characteristics, as well as comparable breast cancer rates, to those of Caucasian Americans.
BACKGROUND: Breast cancer incidence rates are up to five times higher in white women in the United States compared with Asian women in China and Japan. A search for factors that modify estrogen's biological effect differentially between ethnic groups may add to the understanding of international variations in breast cancer risk. Recent evidence indicates that alpha-fetoprotein, a glycoprotein produced by the fetal liver, has important antiestrogenic properties. During pregnancy, alpha-fetoprotein reaches peak concentrations in maternal serum during the third trimester. METHODS: We compared pregnancy levels of alpha-fetoprotein in a population with high risk of breast cancer (Boston, MA) and low risk (Shanghai, China). Blood samples were collected around the 16th week and around the 27th week of gestation among women enrolled from March 1994 to October 1995. The number of specimens available for alpha-fetoprotein analysis was 1,033. RESULTS: Alpha-fetoprotein levels, adjusted for gestational length, were substantially higher in Shanghai compared with Boston women at both time points. When adjustments were made for prepregnancy weight, parity, offspring's sex and maternal age, alpha-fetoprotein levels remained 13% higher in Shanghai at 16 weeks of pregnancy but not at 27 weeks. CONCLUSIONS: These findings may explain, at least in part, the difference in breast cancer risk between Chinese and American women. On the population level, alpha-fetoprotein may influence risk by modifying the effect of biologically active estrogens both in the mother and in female offspring.
The aim of this study is to prospectively assess pregnancy hormone levels as correlates of subsequent development of pre-eclampsia, a condition that has been shown to be inversely associated with breast cancer risk in the offspring. A cohort of 260 Caucasian women in Boston, Massachusetts, was followed through pregnancy. Maternal blood was collected at the 16th and 27th weeks of gestation, and 18 women were diagnosed with pre-eclampsia after blood collection. Information on sociodemographic variables and risk factors of pre-eclampsia was collected through an interviewer-administered questionnaire and review of medical records. At the 16th week, there was a nonsignificant positive association between progesterone levels and pre-eclampsia [relative risk (RR) = 1.63, 95% confidence interval (CI), 0.97-2.74, per 1 SD increase]. By the 27th week, the association between progesterone and pre-eclampsia was strengthened (RR = 2.65, 95% CI, 1.46-4.81, per SD), and sex hormone-binding globulin levels were somewhat inversely related to pre-eclampsia (RR = 0.61, 95% CI, 0.31-1.20, per SD). No difference was found with respect to prolactin, estradiol, and estriol levels. Our findings indicate that progesterone may have a role in the late manifestation of pre-eclampsia pathology but are also compatible with the hypothesis that increases in progesterone represent an early compensatory mechanism.
Epidemiological evidence is accumulating that sexual history may be associated with prostate cancer, and some studies have suggested a relation between human papilloma virus (HPV) infections and prostate cancer. We measured the presence of antibodies to the major oncogenic HPV types 16, 18, and 33 among 238 subjects with untreated prostate cancer and 210 population-based control subjects. Odds ratios (ORs) were estimated from multivariate logistic regression models, controlling for age and HPV types 16, 18, and 33, simultaneously. HPV types 16 and 18 were not associated with prostate cancer [OR, 0.7; 95% confidence interval (CI), 0.4-1.3 for HPV 16; OR, 0.9; 95% CI, 0.5-1.9 for HPV 18]. There was a possible association between HPV 33 and prostate cancer (OR, 1.6; 95% CI, 1.0-2.7), and there was a significant excess risk for subjects with high antibody levels against HPV 33 (OR when the difference in absorbance exceeded 0.2, 2.3; 95% CI, 1.2-4.1). When HPV antibody levels were modeled as continuous variables, the results were qualitatively similar. The data do not support previous studies that have suggested an association with HPV 16 or 18 and prostate cancer risk. Inconsistent associations with different HPV types seen in different studies suggest that the association may be because of chance, bias, or confounding by some unknown risk factor that may associate with different HPV infections in different populations. Additional studies of the relationship between prostate cancer and other HPV types, notably HPV 33, could be helpful for clarifying the possible role of sexual risk factors.
Although diabetes mellitus is associated with an increased risk of several malignancies, a negative association with prostate cancer is biologically most plausible. The epidemiologic evidence is, however, inconsistent, limited and based mostly on small studies. We present results from a large, population-based cohort study in Sweden, where we assessed prostate cancer risk among patients hospitalized for diabetes mellitus. The cohort was composed of patients identified in the Swedish In-Patient Register as having a hospital discharge diagnosis of diabetes mellitus in 1965-1994. The follow-up was done by linkages with the national cancer register and other population-based registers. Standardized incidence ratios (SIRs), with 95% confidence interval (CI), were used as a measure of relative risk. After complete exclusion of the first year of follow-up (to avoid selection bias), 135,950 men remained in the cohort, contributing 827,099 years of follow-up to the study. A total of 2,455 incident cases of primary prostate cancer were identified during 1-31 years of follow-up, yielding an overall SIR of 0.91 (95% CI 0.87-0.94); this risk reduction was more pronounced among patients who have been hospitalized for diabetic complications (SIR = 0.82; 95% CI 0.74-0.91). We found no consistent trends in risk related to age at first hospitalization or to duration of follow-up. We did find a small, but significantly decreased risk of prostate cancer among men who had been hospitalized for diabetes mellitus.
BACKGROUND: Patients with breast cancer who have mutations in the high penetrance genes BRCA1 and BRCA2, have an increased risk of ovarian cancer. Because these mutations are rare, easily obtained information such as age and family history of breast or ovarian cancer might be preferable for assessment of ovarian cancer risk in clinical practice. METHODS: We linked data from the Swedish Cancer Register to the Swedish Generation Register and generated a cohort of 30552 breast-cancer patients born after 1931, with information on breast and ovarian cancer diagnosis from 146117 first-degree relatives. Standardised incidence ratios (SIRs) with 95% CIs were calculated with nationwide rates of ovarian cancer, adjusted for age and calendar year. FINDINGS: During a mean follow-up of 6 years, 122 incident ovarian cancers were identified in the cohort, yielding an overall SIR of 2.0 (95% CI 1.6-2.4). The risk was higher in breast-cancer patients diagnosed before the age of 40 years, with a family history of breast cancer (5.6; 1.8-13.1) or ovarian cancer (17.0; 3.5-50.0). A consistently increased risk was noted in patients with a relative who was diagnosed before the age of 50 years, with either breast or ovarian cancer. Women with a family history of ovarian cancer have an almost 10% risk of developing ovarian cancer before the age of 70. INTERPRETATION: In young women with breast cancer, the risk of ovarian cancer is greatly raised when a family history of breast or ovarian cancer is present. Close medical surveillance, and perhaps even prophylactic oophorectomy, might be justified in high-risk groups.
BACKGROUND: Radical prostatectomy is widely used in the treatment of early prostate cancer. The possible survival benefit of this treatment, however, is unclear. We conducted a randomized trial to address this question. METHODS: From October 1989 through February 1999, 695 men with newly diagnosed prostate cancer in International Union against Cancer clinical stage T1b, T1c, or T2 were randomly assigned to watchful waiting or radical prostatectomy. We achieved complete follow-up through the year 2000 with blinded evaluation of causes of death. The primary end point was death due to prostate cancer, and the secondary end points were overall mortality, metastasis-free survival, and local progression. RESULTS: During a median of 6.2 years of follow-up, 62 men in the watchful-waiting group and 53 in the radical-prostatectomy group died (P=0.31). Death due to prostate cancer occurred in 31 of 348 of those assigned to watchful waiting (8.9 percent) and in 16 of 347 of those assigned to radical prostatectomy (4.6 percent) (relative hazard, 0.50; 95 percent confidence interval, 0.27 to 0.91; P=0.02). Death due to other causes occurred in 31 of 348 men in the watchful-waiting group (8.9 percent) and in 37 of 347 men in the radical-prostatectomy group (10.6 percent). The men assigned to surgery had a lower relative risk of distant metastases than the men assigned to watchful waiting (relative hazard, 0.63; 95 percent confidence interval, 0.41 to 0.96). CONCLUSIONS: In this randomized trial, radical prostatectomy significantly reduced disease-specific mortality, but there was no significant difference between surgery and watchful waiting in terms of overall survival.
The epidemiologic association between physical activity and breast cancer has been corroborated in many studies. Some inconsistencies remain, possibly due to variation in life periods for exposure assessment, confounding and undetected effect modification. In our cohort study, we address some of these questions by taking into account physical activity in different periods of life and by investigating effect modification by birth cohort and body mass index (BMI). Altogether 9,539 same-sex twin women aged 42-70 years who answered a questionnaire about their work and leisure-time physical exercise from ages 25 to 50 during 1967 and 1970 were included in our cohort. During follow-up, 506 breast cancer cases occurred through 1997. We used multivariate Cox models to estimate relative risk (RR) with 95% confidence interval (CI). We found no associations between physical activity and breast cancer overall. Women born between 1901 and 1917 (aged 51-70 at baseline) who reported regular leisure-time activity had a borderline significant 40% lower risk compared with those who reported no activity (RR 0.6; 95% CI 0.4-1.0; test for trend, p = 0.07). This association appeared to be confined to women with a low BMI after the age of 50 and to women with a high BMI during the premenopausal period. We found no evidence that work activity reduces risk for breast cancer. The importance of physical activity for breast cancer risk seems to depend on birth cohort. The association may be limited to normal-weight postmenopausal women and overweight premenopausal women.