A prospective nested case-control study of vitamin D status and pancreatic cancer risk in male smokers

Sun exposure is associated with lower death rates for pancreatic cancer in some ecological studies. Skin exposure to UVB light induces cutaneous production of precursors to 25-hydroxyvitamin D [25(OH)D]. Pancreatic islet and duct cells express 25(OH)D(3)-1alpha-hydroxylase that generates the biologically active 1,25(OH)(2) vitamin D form. Thus, 25(OH)D concentrations could affect pancreatic function and possibly pancreatic cancer etiology. We conducted a prospective nested case-control study in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention cohort of male Finnish smokers, ages 50 to 69 years at baseline, to test whether more adequate vitamin D status, as determined by prediagnostic serum 25(OH)D concentrations, was associated with lower pancreatic cancer risk. Two hundred incident exocrine pancreatic cancer cases that occurred between 1985 and 2001 (up to 16.7 years of follow-up) were matched by age and date of blood draw to 400 controls who were alive and free of cancer at the time the case was diagnosed. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated using conditional logistic regression. Higher vitamin D concentrations were associated with a 3-fold increased risk for pancreatic cancer (highest versus lowest quintile, >65.5 versus <32.0 nmol/L: OR, 2.92; 95% CI, 1.56-5.48, P(trend) = 0.001) that remained after excluding cases diagnosed early during follow-up. Contrary to expectations, subjects with higher prediagnostic vitamin D status had an increased pancreatic cancer risk compared with those with lower status. Our findings need to be replicated in other populations and caution is warranted in their interpretation and implication. Our results are intriguing and may provide clues that further the understanding of the etiology of this highly fatal cancer.     

Circulating enterolactone and prostate cancer risk: a Nordic nested case-control study

Enterolactone, a phytoestrogen belonging to the class of lignans, is produced by the intestinal microflora from precursors in plant foods and has been implicated in protection against cancer. We study the effect of enterolactone on the risk of a subsequent diagnosis of prostate cancer. We conducted a longitudinal, nested case-control study by linkage of 3 biobanks to the cancer registries in Finland, Norway and Sweden, respectively. Enterolactone concentrations were measured by time-resolved fluoroimmunoassay in serum from 794 men who had a diagnosis of prostate cancer at a mean follow-up time of 14.2 years after blood collection and among 2,550 control men matched within each cohort for age (+/-2 years), date of blood collection (+/-2 months) and county. The median enterolactone concentrations did not differ between case and control subjects in the full study group (8.4 nmol/L [25th-75th percentile = 4.5-15.0] vs. 8.5 nmol/L [25th-75th percentile = 4.3-15.9]), nor in the national groups. Odds ratios of prostate cancer risk estimated by conditional logistic regression for increasing concentrations of enterolactone in quartiles in the full study group were 1.00 (referent), 1.21 (95% confidence interval [CI] = 0.96-1.52), 1.16 (95% CI = 0.91-1.47) and 1.08 (95% CI = 0.83-1.39). The OR estimate for the highest vs. the lowest quartile of enterolactone in separate analyses of the Norwegian, Finnish and Swedish cohort was 1.21 (95% CI = 0.91-1.60), 1.02 (95% CI = 0.59-1.76) and 0.87 (95% CI = 0.45-1.67), respectively. No support for the hypothesis that high circulating enterolactone is protective against prostate cancer was found.     

Serum phytoestrogens and prostate cancer risk in a nested case-control study among Japanese men

The purpose of this study was to examine whether a high serum concentration of phytoestrogens reduces the risk of prostate cancer in a case-control study nested in a community-based cohort in Japan (Japan Collaborative Cohort (JACC) Study). Information on lifestyles and sera of the subjects were collected in 1988–90, and they were followed up to 1999. Incident and dead cases of prostate cancer and controls were matched for study area and age. Phytoestrogens and sex hormones in sera stored at −80°C were measured in 2002. Of 14,105 male subjects of the cohort who donated their sera, 52 cases and 151 controls were identified. Three datasets were analyzed; 1) all subjects, 2) 40 cases and 101 controls after excluding subjects with low testosterone levels who were suspected of having had medical intervention, and 3) 28 cases and 69 controls with prostate specific antigen level of ∼10.0 ng/ml. The odds ratio (OR) for the highest level to the lowest was 0.38 (95% confidence interval (CI); 0.13, 1.13) for genistein, 0.41 (0.15, 1.11) for daidzein, and 0.34 (0.11, 1.10) for equol for the second dataset. Genistein and daidzein showed similar findings in the third one. Equol and equol/daidzein ratio showed consistent findings in all three datasets (OR=0.39, 95% CI; 0.13, 0.89, trend P=0.02 for the first dataset). Their effects seemed to be independent of serum sex hormones. In conclusion, serum genistein, daidzein, and equol seemed to dose-dependently reduce prostate cancer risk. (Cancer Sci 2004; 95: 65–71)     

Polymorphisms of methylenetetrahydrofolate reductase and the risk of prostate cancer: a nested case-control study.

It has been proposed that folate and polymorphisms of the enzyme methylenetetrahydrofolate reductase (MTHFR), which regulates influx of folate from DNA synthesis and repair to methylation reactions, are involved in the aetiology of cancer. To relate the MTHFR 677C-->T and 1298A-->C polymorphisms to the risk of prostate cancer, taking into consideration prospective plasma levels of folate, vitamin B12 and homocysteine. The design was a case-control study of 223 prostate cancer cases and 435 matched controls nested within the population-based Northern Sweden Health and Disease Cohort. Neither the MTHFR 677C-->T nor the MTHFR 1298A-->C polymorphism was statistically significantly associated with the risk of prostate cancer in univariate analysis by conditional logistic regression. After adjustment for MTHFR 1298A-->C, plasma folate, vitamin B12, homocysteine, body mass index and smoking, the odds ratios were, for the 677 CT genotype, 1.52 [95% confidence interval (CI) 1.02-2.26], and for TT, 0.91 (95% CI 0.41-2.04). Our previously reported observation of a possible increase in the risk of prostate cancer at high plasma folate levels was attributable in this study to subjects having the MTHFR 677C-->T polymorphism. We found that the MTHFR 677C-->T polymorphism is not likely to have a major role in the development of prostate cancer, although it may possibly increase the risk in combination with high plasma folate levels. Further investigation in larger studies is warranted.     

Plasma and dietary carotenoids, and the risk of prostate cancer: a nested case-control study.

The association between plasma carotenoids and prostate cancer risk was investigated in a case-control study nested within the prospective Health Professionals Follow-up Study. We matched 450 incident prostate cancer cases diagnosed from 1993-1998 to 450 controls by age, time, month, and year of blood donation. Modest inverse, but not statistically significant, associations were observed among plasma alpha-carotene, beta-carotene, and lycopene concentrations, and overall risk of prostate cancer diagnosis [odds ratio (highest versus lowest quintile; OR), alpha-carotene: OR, 0.67 [95% confidence interval (CI), -0.40-1.09]; beta-carotene: OR, 0.78 (95% CI, 0.48-1.25); lycopene: OR, 0.66 (95% CI, 0.38-1.13)]. The inverse association between plasma lycopene concentrations and prostate cancer risk was limited to participants who were 65 years or older (OR, 0.47; 95% CI, 0.23-0.98) and without a family history of prostate cancer (OR, 0.48; 95% CI, 0.26-0.89). Combining, older age and a negative family history provided similar results (OR, 0.43; 95% CI, 0.18-1.02). Inverse associations between beta-carotene and prostate cancer risk were also found among younger participants (<65 years of age; OR, 0.36; 95% CI, 0.14-0.91; P(trend) = 0.03). Combining dietary intake and plasma data confirmed our results. We found a statistically significant inverse association between higher plasma lycopene concentrations and lower risk of prostate cancer, which was restricted to older participants and those without a family history of prostate cancer. This observation suggests that tomato products may exhibit more potent protection against sporadic prostate cancer rather than those with a stronger familial or hereditary component. In addition, our findings also suggest that among younger men, diets rich in beta-carotene may also play a protective role in prostate carcinogenesis.     

Height and prostate cancer risk: a large nested case-control study (ProtecT) and meta-analysis

BACKGROUND: Height, a marker of childhood environmental exposures, is positively associated with prostate cancer risk, perhaps through the insulin-like growth factor system. We investigated the relationship of prostate cancer with height and its components (leg and trunk length) in a nested case-control study and with height in a dose-response meta-analysis. METHODS: We nested a case-control study within a population-based randomized controlled trial evaluating treatments for localized prostate cancer in British men ages 50 to 69 years, including 1,357 cases detected through prostate-specific antigen testing and 7,990 controls (matched on age, general practice, assessment date). Nine bibliographic databases were searched systematically for studies on the height-prostate cancer association that were pooled in a meta-analysis. RESULTS: Based on the nested case-control, the odds ratio (OR) of prostate-specific antigen-detected prostate cancer per 10 cm increase in height was 1.06 [95% confidence interval (95% CI): 0.97-1.16; p(trend) = 0.2]. There was stronger evidence of an association of height with high-grade prostate cancer (OR: 1.23; 95% CI: 1.06-1.43), mainly due to the leg component, but not with low-grade disease (OR: 0.99; 95% CI: 0.90-1.10). In general, associations with leg or trunk length were similar. A meta-analysis of 58 studies found evidence that height is positively associated with prostate cancer (random-effects OR per 10 cm: 1.06; 95% CI: 1.03-1.09), with a stronger effect for prospective studies of more advanced/aggressive cancers (random-effects OR: 1.12; 95% CI: 1.05-1.19). CONCLUSION: These data indicate a limited role for childhood environmental exposures-as indexed by adult height-on prostate cancer incidence, while suggesting a greater role for progression, through mechanisms requiring further investigation.     

Endogenous sex hormones and prostate cancer risk: a case-control study nested within the Carotene and Retinol Efficacy Trial.

To examine whether endogenous androgens influence the occurrence of prostate cancer, we conducted a nested case-control study among participants enrolled in the Carotene and Retinol Efficacy Trial. We analyzed serum samples of 300 cases diagnosed between 1987 and 1998, and 300 matched controls. Higher concentrations of testosterone (T) were not associated with increased prostate cancer risk. Relative to men with levels in the lowest fourth of the distribution, men in the upper fourth of total T had a risk of 0.82 [95% confidence interval (CI), 0.52-1.29]. The corresponding relative risks for free T (0.72; 95% CI, 0.45-1.14), percentage of free T (0.74; 95% CI, 0.46-1.19), and total T:sex hormone binding globulin ratio (0.52; 95% CI, 0.32-0.83) similarly were not elevated. Higher concentrations of androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were weakly associated with risk. Relative risks associated with being in the highest fourth for androstenedione, dehydroepiandrosterone sulfate, and 3 alpha-androstanediol glucuronide were 1.20 (95% CI, 0.76-1.89), 1.38 (95% CI, 0.86-2.21), and 1.27 (95% CI, 0.80-2.00), respectively. Men in the upper fourth of total estradiol (E2), free E2 and percentage of free E2 had relative risks of 0.71 (95% CI, 0.42-1.13), 0.52 (95% CI, 0.33-0.82), and 0.65 (95% CI, 0.40-1.05), respectively. The inverse association between E2 and prostate cancer risk was largely restricted to men with blood collection within 3 years of diagnosis. Our results add to the evidence that serum testosterone is unrelated to prostate cancer incidence. The suggestions that intraprostatic androgen activity may increase risk and that serum estrogens may decrease risk, warrant additional study.     

Premenopausal serum androgens and breast cancer risk: a nested case-control study

Introduction

Prospective epidemiologic studies have consistently shown that levels of circulating androgens in postmenopausal women are positively associated with breast cancer risk. However, data in premenopausal women are limited.

Methods

A case-control study nested within the New York University Women's Health Study was conducted. A total of 356 cases (276 invasive and 80 in situ) and 683 individually-matched controls were included. Matching variables included age and date, phase, and day of menstrual cycle at blood donation. Testosterone, androstenedione, dehydroandrosterone sulfate (DHEAS) and sex hormone-binding globulin (SHBG) were measured using direct immunoassays. Free testosterone was calculated.

Results

Premenopausal serum testosterone and free testosterone concentrations were positively associated with breast cancer risk. In models adjusted for known risk factors of breast cancer, the odds ratios for increasing quintiles of testosterone were 1.0 (reference), 1.5 (95% confidence interval (CI), 0.9 to 2.3), 1.2 (95% CI, 0.7 to 1.9), 1.4 (95% CI, 0.9 to 2.3) and 1.8 (95% CI, 1.1 to 2.9; P _trend = 0.04), and for free testosterone were 1.0 (reference), 1.2 (95% CI, 0.7 to 1.8), 1.5 (95% CI, 0.9 to 2.3), 1.5 (95% CI, 0.9 to 2.3), and 1.8 (95% CI, 1.1 to 2.8, P _trend = 0.01). A marginally significant positive association was observed with androstenedione (P = 0.07), but no association with DHEAS or SHBG. Results were consistent in analyses stratified by tumor type (invasive, in situ), estrogen receptor status, age at blood donation, and menopausal status at diagnosis. Intra-class correlation coefficients for samples collected from 0.8 to 5.3 years apart (median 2 years) in 138 cases and 268 controls were greater than 0.7 for all biomarkers except for androstenedione (0.57 in controls).

Conclusions

Premenopausal concentrations of testosterone and free testosterone are associated with breast cancer risk. Testosterone and free testosterone measurements are also highly reliable (that is, a single measurement is reflective of a woman's average level over time). Results from other prospective studies are consistent with our results. The impact of including testosterone or free testosterone in breast cancer risk prediction models for women between the ages of 40 and 50 years should be assessed. Improving risk prediction models for this age group could help decision making regarding both screening and chemoprevention of breast cancer.     

Human papillomavirus 16, 18, and 33 infections and risk of prostate cancer: a Nordic nested case-control study.

Epidemiologic evidence of sexual history has emerged as a consistently found risk factor for prostate cancer. Some studies have reported an association between human papillomavirus (HPV) infections and prostate cancer. We did a nested case-control study within cohorts of more than 200,000 men enrolled in three Nordic biobanking projects. Follow-up using cancer registry linkages identified 804 prospectively occurring prostate cancer cases. Four control subjects per case were randomly selected from eligible sets of matched subjects that were alive and free of cancer at the time of diagnosis of the corresponding case and were matched to cases on biobank cohort, age (+/-2 years), county of residence, and date of blood sampling (+/-2 months in the Finnish and Swedish cohorts, +/-6 months in the Norwegian cohort). The serum samples were analyzed by standard ELISAs for the presence of immunoglobulin G antibodies against HPV types 16, 18, and 33. The joint HPV-16/HPV-18/HPV-33 seroprevalence in the joint cohort was 13.4% (107 of 799) among cases and 14.0% (363 of 2,596) among controls (odds ratio, 0.94; 95% confidence interval, 0.74-1.19). There were no noteworthy differences when the data were analyzed by different HPV type, country, or antibody levels. Our data do not support an association between serologic markers of HPV-16, HPV-18, and HPV-33 infections and risk of prostate cancer.     

Serum concentrations of Fatty acids and colorectal adenoma risk: a case-control study in Japan.

Background: Epidemiologic studies of n-3 fatty acids (FAs) and risk of colorectal cancer have generated inconsistent results, and relations with precursor colorectal adenomas (CRA) have not been evaluated in detail. We here focused on possible associations of serum FAs with CRA in the Japanese population. Methods: We conducted a case-control study of 203 asymptomatic CRA cases (148 men, 55 women) and 179 healthy controls (67 men, 112 women) during 1997-2003 in Nagoya, Japan. Baseline information was obtained using a lifestyle questionnaire and serum FA levels were measured by gas chromatography. Results: A non-significant inverse association with CRA was observed for eicosapentaenoic acid (EPA) among women. Moreover, the concentrations of docosahexaenoeic acid (DHA), a major component of n-3 highly-unsaturated FAs (HUFAs), were significantly lower in cases in both sexes. In addition, serum concentrations of total FAs, saturated FAs (SFAs) and mono-unsaturated FAs (MUFAs) had strong positive links with CRA risk. In contrast, arachidonic acid (AA) and DHA were inversely related, with 66% and 59% risk reduction, respectively. Ratios of SFAs/n-3 PUFAs and SFAs/n-3 HUFAs exhibited significant positive relations with CRA risk but there was no clear link with n-6 PUFAs/n-3 PUFAs. Conclusions: Our findings suggest a promoting influence of SFAs and MUFAs along with a protective effect of DHA on CRA risk. However, further research is needed to investigate the observed discrepancy with the generally accepted roles of the AA cascade in carcinogenesis.     

Serum fatty acids and risk of breast cancer in a nested case-control study of the New York University Women's Health Study.

Migrant and experimental animal studies suggest that differences in breast cancer incidence rates may be related, in part, to intake of dietary fat. The experimental evidence indicates that total fat, saturated, and n-6 polyunsaturated fatty acids (PUFAs) may stimulate both mammary tumor growth and metastasis, whereas n-3 PUFAs may have a tumor-inhibiting effect. Overall, epidemiological studies do not appear to confirm such observations. Within a cohort of women in the New York University Women's Health Study, the fatty acid composition of serum phospholipids was analyzed by gas chromatography among 197 pre- and postmenopausal clinically identified breast cancer subjects and their matched controls. Individual fatty acids in serum phospholipids were expressed as a percentage of total fatty acids. No significant difference was observed in the proportion of saturated fatty acids (SFAs), monounsaturated fatty acids, or n-6 and n-3 PUFAs between cases and controls. After menopause, total SFAs were positively associated with the risk of breast cancer [odds ratio (OR) = 1.96, 95% confidence interval (CI): 0.73-5.25; P = 0.05] after adjustment for potential confounding factors. Myristc acid (C14:0) was suggestive of a small increase in breast cancer risk in premenopausal women (OR = 2.22, 95% CI: 0.78-6.31), whereas palmitic acid (C16:0) showed similar trends in postmenopausal women (OR = 2.57, 95% CI: 0.99-6.61). Overall, total PUFAs (n-6 and n-3) were suggestive of a small protective effect (OR = 0.59, 95% CI: 0.31-1.09). No significant associations were found between other fatty acids and the risk of breast cancer. The study suggested evidence of an association between serum levels of SFAs and the risk of breast cancer in postmenopausal women. Neither individual n-3 fatty acids of marine origin, eicosapentaenoic acid (C20:5 n-3), and docosahexaenoic acid (C22:6 n-3), nor n-6 PUFAs were related to cancer risk in this study.     

Alpha-linolenic acid and risk of prostate cancer: a case-control study in Uruguay.

In the time period of 1994-1998, a case-control study on diet and prostate cancer was carried out in Uruguay to examine the risk associated with fat intake. Two hundred and seventeen (217) incident cases afflicted with advanced prostate cancer were frequency-matched with 431 controls on age, residence, and urban/rural status. The analysis was carried out using unconditional multiple logistic regression. Alpha-linolenic acid was associated with a strong positive association (fourth quartile of intake odds ratio, 3.91; 95% confidence interval, 1.50-10.1) after controlling for total calorie intake and for the other types of fat. The effect was similar when alpha-linolenic acid was analyzed by its sources of origin (odds ratio for vegetable linolenic acid, 2.03; 95% confidence interval, 1.01-4.07). Including this report, five of six studies that have examined the relationship between alpha-linolenic acid and prostate cancer yielded a positive association, which was significant in four studies. Thus, there appears to be evidence of a role of alpha-linolenic acid in prostate carcinogenesis.     

Insulin-like growth factors and ovarian cancer risk: a nested case-control study in three cohorts.

Insulin-like growth factor (IGF)-related hormones and binding proteins (IGFBP) have been implicated in cancer risk. Specifically, two recent, small prospective studies reported a significant positive association between IGF-I and ovarian cancer risk among women diagnosed before age 55 years. Therefore, we examined whether plasma concentrations of IGF-I, IGFBP-3, and IGFBP-2 were associated with risk of epithelial ovarian cancer in a nested case-control study using data from three prospective cohorts: the Nurses' Health Study (NHS), NHSII, and the Women's Health Study (WHS). The present study had 222 cases (159 from NHS/NHSII and 63 from WHS) and 599 controls (matching ratio, 1:3 for NHS/NHSII and 1:2 for WHS). Women ranged in age from 34 to 73 years (mean, 56 years). The relative risk (RR) comparing the top versus bottom quartile of IGF-I was 0.56 (95% confidence interval, 0.32-0.97; P(trend) = 0.14). The risk did not differ by age at diagnosis (comparable RR for age <55 years at diagnosis, 0.70; RR for age >/=55 years at diagnosis, 0.52). We did not observe any association between IGFBP-3, IGFBP-2, and the ratio of IGF-I to either binding protein and ovarian cancer risk. Overall, our results do not support a positive association between IGF-related proteins and ovarian cancer risk. (Cancer Epidemiol Biomarkers Prev 2007;16(8):1691-5).     

Columnar cell lesions and subsequent breast cancer risk: a nested case-control study

Introduction  

Histologic and genetic evidence suggests that at least some columnar cell lesions (CCL) of the breast represent precursor lesions in the low-grade breast neoplasia pathway. However, the risk of subsequent breast cancer associated with the presence of CCL in a benign breast biopsy is poorly understood.     

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.     

吸烟与原发性肝癌关系的巢式病例对照研究

目的 分析吸烟与上海市区中老年男性原发性肝癌的关系.方法 应用巢式病例对照研究方法,对一个18 244名男性队列随访11年,以队列中213例新发肝癌患者作为病例组,按照患者年龄、采样日期、同居住区等配对条件,从队列中随机抽取1094名健康人作为对照组.使用配对Logistic回归分析,调整可能的混杂因素,估计吸烟对肝癌发生的危险度和95%可信区间(CI).结果 调整肝炎、肝硬化、胆石症或其他胆囊病史及乙型肝炎病毒感染等可能的混杂因素后,男性吸烟者患肝痛的危险性是不吸烟者的1.91倍(95%CI为1.28～2.86),日随着每天吸烟量、吸烟年限和吸烟包年数的增加而增加.每天吸烟≥20支者、吸烟≥40年者和吸烟37包年者患肝癌的相对危险度分别为2.16(95%CI为1.37～3.40)、2.14(95%CI为1.18～3.87)和2.12(95%CI为1.21～3.74).吸烟开始年龄越小,危险性越大,吸烟开始年龄<20岁者患肝癌的危险性为2.57(95%CI为1.50～4.40).结论 吸烟是上海市区男性原发性肝癌的危险因素.