Work stress and the risk of cancer: A meta-analysis of observational studies

Epidemiological studies have explored the relationship between work stress and the risk of cancer, but it remains unclear on whether work stress could increase the risk of cancer, or by other factors such as smoking and physical activity. Our study aimed to investigate the association between work stress and the risk of cancer and in relation to major potential confounding and modifying factors. We systematically searched three electronic databases, hand-searched references and citations of retrieved articles, and consulted experts to identify studies on assessing the association between work stress and the risk of cancer. The relative risks (RRs) of cancer associated with work stress were estimated using a random-effects model, and stratified by exposure measurement, study design, gender, study location, cancer site, smoking, drinking, body mass index, and physical activity. A total of 281,290 participants were included in this analysis. The significant association between work stress and the risk of colorectal (RR = 1.36; 95%CI: 1.16–1.59), lung (RR = 1.24; 95%CI: 1.02–1.49), and esophagus (RR = 2.12; 95%CI: 1.30–3.47) cancers were found. A statistically significant effect of work stress on colorectal cancer risk was observed in North America (RR = 1.51, 95% CI: 1.23–1.86, but not significant in Europe (RR = 1.16, 95% CI: 0.90–1.48). By contrast, a significant association between work stress and esophagus cancer was found in Europe, but not in North America. In addition, we did not observe any association between work stress and the risk of prostate, breast, or ovarian cancers. Findings of our study show that work stress is an important risk factor for colorectal, lung, and esophagus cancers. General public should be aware of the increased risk of cancer in employers with work stress. More efforts should be focused on understanding and studying the potential mechanisms which would help to identify employees at higher risk of these cancers.     

Risk of cancer in first‐ and second‐degree relatives of testicular germ cell tumor cases and controls

Risk factors for testicular germ cell tumors (TGCT) have not been well identified; however, data suggest that risks of cancer in family members of men with TGCT is elevated. Using family history data from 738 cases and 904 controls enrolled in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants (STEED) Study from 2002 to 2005, the risk of cancer in first‐ and second‐degree family members of these men was examined. Relative risks (RRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models, adjusting for reference age of case or control, race/ethnicity of case or control, sex of family member and lineage (maternal vs. paternal). An increased risk of all cancer among first‐degree relatives of cases compared to controls was observed (RR = 1.17, 95% CI: 1.01–1.35). There were suggestions of differences in risk when stratifying all relatives by lineage. For maternal relatives, there was a statistically significant increased risk of all cancer (RR = 1.16, 95% CI: 1.04–1.30), digestive tract (RR = 1.52, 95% CI: 1.15–2.00) and male genital organ cancer (RR = 1.70, 95% CI: 1.15–2.51); there was also a suggestion of increased risks of hematopoetic cancers, cancers in the female genital organs and nonmelanoma skin cancer. For paternal relatives, there was a statistically significant association only with decreased risk of lung cancer (RR = 0.69, 95% CI: 0.51–0.94). Thus, this study suggests that there may be aggregation of cancer among families of men diagnosed with TGCT. Published 2008 Wiley‐Liss, Inc.     

Effects of α‐tocopherol and β‐carotene supplementation on cancer incidence and mortality: 18‐Year postintervention follow‐up of the Alpha‐Tocopherol,Beta‐Carotene Cancer Prevention Study

In the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention Study among 29,133 Finnish male smokers aged 50–69 years, daily α‐tocopherol (50 mg) for a median of 6.1 years decreased the risk of prostate cancer, whereas β‐carotene (20 mg) increased risk of lung cancer and overall mortality. To determine the postintervention effects of α‐tocopherol and β‐carotene, 25,563 men were followed 18 years for cancer incidence and all causes of mortality through national registers. Neither supplement had significant effects on post‐trial cancer incidence. Relative risk (RR) for lung cancer (n = 2,881) was 1.04 (95% confidence interval [CI], 0.96–1.11) among β‐carotene recipients compared with nonrecipients. For prostate cancer (n = 2,321), RR was 0.97 (95% CI, 0.89–1.05) among α‐tocopherol recipients compared with nonrecipients with the preventive effect of α‐tocopherol continuing ～8 years postintervention. Body mass index significantly modified the effect of α‐tocopherol on prostate cancer (p for interaction = 0.01) RR 1.00 (95% CI, 0.88–1.14) in normal‐weight men, 0.87 (95% CI, 0.77–0.98) in overweight men, and 1.25 (95% CI, 1.01–1.55) in obese men. The post‐trial relative mortality (based on 16,686 deaths) was 1.02 (95% CI, 0.98–1.05) for α‐tocopherol recipients compared with nonrecipients and 1.02 (95% CI, 0.99–1.05) for β‐carotene recipients compared with nonrecipients. α‐Tocopherol decreased post‐trial prostate cancer mortality (RR, 0.84; 95% CI, 0.70–0.99), whereas β‐carotene increased it (RR, 1.20; 95% CI, 1.01–1.42). In conclusion, supplementation with α‐tocopherol and β‐carotene appeared to have no late effects on cancer incidence. The preventive effect of moderate‐dose α‐tocopherol on prostate cancer continued several years post‐trial and resulted in lower prostate cancer mortality.     

Association between height and thyroid cancer risk: A meta‐analysis of prospective cohort studies

While several epidemiological studies have investigated the relationship between height and risk for thyroid cancer, the results were inconsistent. In the present study, a systematic review and meta‐analysis of prospective cohort studies was conducted to assess the impact of height on thyroid cancer risk. Online databases were searched up to December 30, 2014, for prospective cohort studies on the association between height and thyroid cancer risk. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using a random‐effects model of meta‐analysis. In all, 11 articles were included in this meta‐analysis, including 15 prospective cohort studies, containing 6,695,593 participants and 7,062 cases of thyroid cancer. By comparing the highest versus the lowest categories of height, we reported that risk of thyroid cancer was increased with height in both men (summary RR = 1.40, 95%CI 1.09–1.78, p = 0.008) and women (summary RR = 1.54, 95%CI 1.30–1.83, p < 0.001). The summary RR of thyroid cancer per 5‐cm increase in height was 1.16 (95%CI 1.09–1.23, p < 0.001). The results were similar among men (per 5‐cm increase RR = 1.13, 95%CI 1.03–1.23, p = 0.011) and women (per 5‐cm increase RR = 1.18, 95%CI 1.10–1.27, p < 0.001). No obvious risk of publication bias was observed. Our meta‐analysis provides strong evidence for a dose–response relationship between height and risk of thyroid cancer in both men and women.     

2型糖尿病患者罹患生殖系统恶性肿瘤危险性的Meta分析

[目的]探讨2型糖尿病与生殖系统恶性肿瘤发生风险的关系。[方法]检索1979年1月至2012年10月Medline、Embase和Web of Science数据库公开发表的有关2型糖尿病与生殖系统恶性肿瘤关系的队列研究文献,按纳入和排除标准进行筛选,利用R软件及其Meta程序包对检索结果进行综合分析。[结果]共纳入39篇文献,包括10778543名观察对象。与非糖尿病人群相比,2型糖尿病患者发生生殖系统恶性肿瘤的合并相对危险度（RR）为1．15（95％CI：1．03～1．28）。2型糖尿病与女性生殖系统恶性肿瘤发生的相对危险度RR为l-39f95％CI：1．23－1．57）。2型糖尿病可以增加子宫内膜癌、宫颈癌和女性乳腺癌的发病风险,合并RR分别为1．83（95％CI：1．58-2．12）、2．13（95％CI：1．86－2．43）和1．16f95％CI：1．03-1.32）。卵巢癌风险的增加接近临界（RR=I．21,95％CI：0．99～1．48）;与前列腺癌的发病风险无关（RR=0．92,95％CI：0．78～1．09）。亚组分析提示,在欧美人群中2型糖尿病患者发生前列腺癌的风险降低．RR为0．80（95％CI：0．74－0．87）。[结论]2型糖尿病可能是子宫内膜癌、宫颈癌、乳腺癌的危险因素之一,可能是欧美人群前列腺癌保护因素。     

History of diabetes mellitus and subsequent prostate cancer risk in the NIH-AARP Diet and Health Study

Objective A history of diabetes has been hypothesized to decrease prostate cancer risk, but studies have not always considered confounding or effect modification by dietary or lifestyle factors. Methods We examined the association between diabetes history and subsequent prostate cancer risk in 328,316 men enrolled in the NIH-AARP Diet and Health Study. Participants were ages 50–71 years and without a prostate cancer diagnosis at baseline in 1995. A prior history of physician-diagnosed diabetes was assessed using a self-administered mailed questionnaire. Cases of prostate cancer were ascertained by matching the cohort to state cancer registries. Multivariable relative risks (RR) and 95% confidence intervals (CI) of prostate cancer were estimated using Cox regression. Results During 5 years and 1,432,676 person-years of follow-up, 11,193 prostate cancer cases were ascertained. The age-adjusted and multivariable RRs of prostate cancer comparing men with diabetes to those without diabetes were 0.69 (95% CI = 0.64, 0.74) and 0.71 (95% CI = 0.66, 0.76), respectively, indicating no important confounding. The inverse association between diabetes and prostate cancer was particularly strong among men in the highest category of routine physical activity at work or home (RR = 0.41; 95% CI = 0.23, 0.74; p value for test of interaction = 0.03). Findings were similar for organ-confined and advanced prostate cancer. Conclusion Results from this large prospective study suggest that a history of diabetes is associated with a decreased risk of prostate cancer. The relationship strengthened with high levels of routine physical activity. Because increased physical activity is associated with lower circulating levels of insulin and testosterone, our findings support a role of hypoinsulinemia and low androgenicity linking diabetes to decreased prostate cancer risk.     

A prospective study of cruciferous vegetables and prostate cancer.

High intake of cruciferous vegetables may offer some protection against prostate cancer, but overall data are inconclusive. Thus, we examined the association between cruciferous vegetable intake and risk of prostate cancer in the Health Professionals Follow-Up Study. Between 1986 and 2000, 2,969 cases of nonstage T1a prostate cancer were diagnosed in 47,365 men who completed dietary assessments in 1986, 1990, and 1994. We calculated the multivariate relative risk (RR) and 95% confidence intervals (CIs) using Cox regression. Overall, we found no appreciable association between baseline intake of cruciferous vegetables and risk of prostate cancer (RR, 0.93; 95% CI, 0.82-1.05, for > or = 5 versus < or = 1 serving/week; P for trend = 0.30), and only a slight suggestive association for organ-confined prostate cancer (RR, 0.88; 95% CI, 0.74-1.05; P for trend = 0.06). The inverse association was stronger for men under the age of 65 years (RR, 0.81; 95% CI, 0.64-1.02; P for trend = 0.02), especially for organ-confined cancers (RR, 0.72; 95% CI, 0.54-0.97; P for trend = 0.007). In addition, this inverse association was stronger when we restricted the analysis to men with more consistent intake of vegetables over the 10 years before 1986, when we limited the analysis to men who had had a prostate-specific antigen test, and when we considered an 8-year time lag. This study does not provide compelling evidence of a protective influence of cruciferous vegetables on prostate cancer risk. However, if cruciferous vegetables are protective early in prostate carcinogenesis, as suggested by proposed mechanisms, we may expect stronger associations, as observed, for more remote diet for prostate-specific antigen-detected early stage (organ-confined) cancers in younger men. In contrast, for advanced cancers in older men, which were probably initiated decades in the past, recent dietary intakes of cruciferous vegetables may be irrelevant. These findings suggest that future studies of cruciferous vegetables should focus on early stages of prostate cancer.     

Alcohol consumption and risk of breast cancer by molecular subtype: Prospective analysis of the nurses' health study after 26 years of follow‐up

Alcohol consumption is a consistent risk factor for breast cancer, although it is unclear whether the association varies by breast cancer molecular subtype. We investigated associations between cumulative average alcohol intake and risk of breast cancer by molecular subtype among 105,972 women in the prospective Nurses' Health Study cohort, followed from 1980 to 2006. Breast cancer molecular subtypes were defined according to estrogen receptor (ER), progesterone receptor, human epidermal growth factor 2 (HER2), cytokeratin 5/6, and epidermal growth factor status from immunostained tumor microarrays in combination with histologic grade. Multivariable Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Competing risk analyses were used to assess heterogeneity by subtype. We observed suggestive heterogeneity in associations between alcohol and breast cancer by subtype (p_het = 0.06). Alcohol consumers had an increased risk of luminal A breast cancers [n = 1,628 cases, per 10 g/day increment HR (95%CI) = 1.10(1.05–1.15)], and an increased risk that was suggestively stronger for HER2‐type breast cancer [n = 160 cases, HR (95%CI) = 1.16(1.02–1.33)]. We did not observe statistically significant associations between alcohol and risk of luminal B [n = 631 cases, HR (95%CI) = 1.08(0.99–1.16)], basal‐like [n = 254 cases, HR (95%CI) = 0.90(0.77–1.04)], or unclassified [n = 87 cases, HR (95%CI) = 0.90(0.71–1.14)] breast cancer. Alcohol consumption was associated with increased risk of luminal A and HER2‐type breast cancer, but not significantly associated with other subtypes. Given that ERs are expressed in luminal A but not in HER2‐type tumors, our findings suggest that other mechanisms may play a role in the association between alcohol and breast cancer.     

Risks of cancer among a cohort of 23,935 men and women with osteoporosis

Low hormone levels among persons with osteoporosis may decrease risk of some cancers. Other osteoporosis risk factors, such as smoking and alcohol consumption, however, may increase risk. As these deleterious factors are more often associated with osteoporosis diagnosed prior to age 70 years, cancer risk may be higher in these younger persons than in the general population. To examine this hypothesis, a cohort study of 23,935 persons with osteoporosis was conducted in Denmark. Patients hospitalized with osteoporosis between 1978 and 1993 were identified in the Danish Inpatient Register. Linkage to the Danish Cancer Registry identified all cancer outcomes through 2003. Standardized incidence ratios (SIR) and 95% confidence intervals (95%CI) were calculated to compare cancer incidence in the cohort with that in the general population. Persons diagnosed prior to age 70 years were at increased cancer risk (women: SIR = 1.11, 95%CI = 1.04-1.19; men: SIR = 1.31, 95%CI = 1.13-1.50) due, in part, to increased risks of cancers of the buccal cavity, esophagus, liver, pancreas and lung. Persons diagnosed at ages 70 and older were at decreased risk (women: SIR = 0.91, 95%CI = 0.87-0.96; men: SIR = 0.89, 0.77-1.01) due, in part, to decreased risks of breast, endometrial, colon, rectal and brain cancers in women and prostate cancer in men. These results suggest that risk factors associated with earlier onset osteoporosis may be associated with increased risk of cancer. Conversely, factors associated with later onset osteoporosis may be related to a decreased risk of cancer.     

2型糖尿病与消化系统恶性肿瘤队列研究的Meta分析

[目的]探讨2型糖尿病与消化系统恶性肿瘤的关系。[方法]利用Medline、Embase与Web of Science检索2012年10月之前国外公开发表的关于2型糖尿病与消化系统恶性肿瘤关系的队列研究文献。利用R软件及其Meta程序包对检索结果进行综合分析。[结果]纳入分析的文献共41篇。经Meta分析后结果显示,2型糖尿病与消化系统恶性肿瘤间的相对危险度及95%可信区间为1.52（95%CI：1.40~1.66）。2型糖尿病与肝癌、食管癌、胃癌、胰腺癌、结直肠癌以及结肠癌的关联均有统计学意义,合并相对危险度分别为1.79（95%CI：1.61~1.99）,1.16（95%CI：1.07~1.27）,1.34（95%CI：1.11~1.61）,1.56（95%CI：1.49~1.64）,1.32（95%CI：1.23~1.40）和1.24（95%CI：1.15~1.33）。2型糖尿病与直肠癌合并相对危险度为1.07（95%CI：0.91~1.25）,无统计学意义。[结论]2型糖尿病与消化系统恶性肿瘤密切相关,可能是肝癌、食管癌、胃癌、胰腺癌、结肠癌的危险因素之一。     

A prospective study of lycopene and tomato product intake and risk of prostate cancer.

BACKGROUND: Dietary lycopene and tomato products may reduce risk of prostate cancer; however, uncertainty remains about this possible association.METHODS: We evaluated the association between intake of lycopene and specific tomato products and prostate cancer risk in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to investigate cancer early detection methods and etiologic determinants. Participants completed both a general risk factor and a 137-item food frequency questionnaire at baseline. A total of 1,338 cases of prostate cancer were identified among 29,361 men during an average of 4.2 years of follow-up.RESULTS: Lycopene intake was not associated with prostate cancer risk. Reduced risks were also not found for total tomato servings or for most tomato-based foods. Statistically nonsignificant inverse associations were noted for pizza [all prostate cancer: relative risk (RR), 0.83; 95% confidence interval (95% CI), 0.67-1.03 for >or=1 serving/wk versus < 0.5 serving/mo; P(trend)=0.06 and advanced prostate cancer: RR, 0.79; 95% CI, 0.56-1.10; P(trend)=0.12] and spaghetti/tomato sauce consumption (advanced prostate cancer: RR=0.81, 95% CI, 0.57-1.16 for >or=2 servings/wk versus<1 serving/mo; P(trend)=0.31). Among men with a family history of prostate cancer, risks were decreased in relation to increased consumption of lycopene (P(trend)=0.04) and specific tomato-based foods commonly eaten with fat (spaghetti, P(trend)=0.12; pizza, P(trend)=0.15; lasagna, P(trend)=0.02).CONCLUSIONS: This large study does not support the hypothesis that greater lycopene/tomato product consumption protects from prostate cancer. Evidence for protective associations in subjects with a family history of prostate cancer requires further corroboration.     

Serum testosterone and the risk of prostate cancer: potential implications for testosterone therapy.

OBJECTIVE: A potential risk of testosterone replacement therapy is an increase in the incidence of prostate cancer, but it is unclear whether higher levels of serum testosterone are associated with a higher risk of prostate cancer. We prospectively evaluated serum androgen concentrations and prostate cancer risk. METHOD: Included were 794 members of the Baltimore Longitudinal Study of Aging. We estimated the rate ratio (RR) of prostate cancer by entering serial measures of serum total testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, calculated free testosterone, and free testosterone index (FTI) into a Cox proportional hazards regression model with simple updating. RESULTS: Higher calculated free testosterone was associated with an increased age-adjusted risk of prostate cancer {RRs by quartile: 1.00, 1.52 [95% confidence interval (95% CI), 0.93-2.50], 1.16 (95% CI, 0.61-2.20), 2.59 (95% CI, 1.28-5.25); P(trend) = 0.03}, which persisted after excluding measures in men <45 years of age [RRs by quartile: 1.00, 1.33 (95% CI, 0.78-2.25), 1.26 (95% CI, 0.68-2.33), 1.89 (95% CI, 0.99-3.61); P(trend) = 0.03]. Compared to men with eugonadal FTI (> or = 0.153), men with hypogonadal FTI had a decreased risk of prostate cancer (RR, 0.51; 95% CI, 0.31-0.82). CONCLUSION: Higher levels of calculated serum free testosterone are associated with an increased risk of prostate cancer. These findings suggest that men receiving testosterone therapy should be regularly monitored for prostate cancer and underscore the need for prospective trials of testosterone therapy incorporating incidence of prostate cancer as a primary safety end point.     

Use of acetochlor and cancer incidence in the Agricultural Health Study

Since its registration in 1994 acetochlor has become a commonly used herbicide in the US, yet no epidemiologic study has evaluated its carcinogenicity in humans. We evaluated the use of acetochlor and cancer incidence among licensed pesticide applicators in the Agricultural Health Study. In telephone interviews administered during 1999–2005, participants provided information on acetochlor use, use of other pesticides and additional potential confounders. We used Poisson regression to estimate relative risks (RR) and 95% confidence intervals (95% CI) for cancers that occurred from the time of interview through 2011 in Iowa and 2010 in North Carolina. Among 33,484 men, there were 4,026 applicators who used acetochlor and 3,234 incident cancers, with 304 acetochlor‐exposed cases. Increased risk of lung cancer was observed among acetochlor users (RR = 1.74; 95% CI: 1.07–2.84) compared to nonusers, and among individuals who reported using acetochlor/atrazine product mixtures (RR = 2.33; 95% CI: 1.30–4.17), compared to nonusers of acetochlor. Colorectal cancer risk was significantly elevated among the highest category of acetochlor users (RR = 1.75; 95% CI: 1.08–2.83) compared to never users. Additionally, borderline significantly increased risk of melanoma (RR = 1.61; 95% CI: 0.98–2.66) and pancreatic cancer (RR = 2.36; 95% CI: 0.98–5.65) were observed among acetochlor users. The associations between acetochlor use and lung cancer, colorectal cancer, melanoma and pancreatic cancer are suggestive, however the lack of exposure‐response trends, small number of exposed cases and relatively short time between acetochlor use and cancer development prohibit definitive conclusions.     

Folic acid supplementation and cancer risk: A meta‐analysis of randomized controlled trials

There are growing data and a continuing controversy over the effect of folic acid supplementation on cancer risk. We conducted a meta‐analysis based on up‐to‐date published relevant randomized trials to further examine this issue. Relative risk (RR) was used to measure the effect of folic acid supplementation on risk of cancer using a random‐effects model. Overall, folic acid supplementation had no significant effect on total cancer incidence (13 trials, n = 49,406, RR = 1.05; 95% CI: 0.99–1.11, p = 0.13), colorectal cancer (seven trials, n = 33,824, 1.01; 0.82–1.23, p = 0.95), other gastrointestinal cancer (two trials, n = 20,228, 1.00; 0.75–1.33, p = 0.99), prostate cancer (five trials, n = 27,065, 1.17; 0.84–1.62, p = 0.35), other genitourinary cancer (two trials, n = 20,228, 0.97; 0.75–1.27, p = 0.84), lung cancer (five trials, n = 31,864, 1.00; 0.84–1.21, p = 0.97), breast cancer (four trials, n = 19,800, 0.82; 0.63–1.07, p = 0.15), hematological malignancy (three trials, n = 25,670, 0.87; 0.64–1.17, p = 0.35) and total cancer mortality (six trials, n = 31,930, 1.02; 0.90–1.15, p = 0.81). However, a significantly reduced risk was observed for melanoma (three trials, n = 19,128, 0.47; 0.23–0.94, p = 0.03). Furthermore, higher total cancer incidence risk was observed among those trials with a higher percent use of lipid‐lowering drugs (>60%, 1.10; 1.00–1.20, p = 0.04), or with lower percent baseline hypertension (≤70%, 1.08; 1.00–1.16, p = 0.057).Consistently, meta‐regression analyses suggested that the similar trend between percent use of lipid‐lowering drugs (p = 0.084) or percent baseline hypertension (p = 0.056) and log‐RR for total cancer incidence associated with folic acid supplementation. Our findings indicate that folic acid supplementation has no significant effect on total cancer incidence, colorectal cancer, prostate cancer, lung cancer, breast cancer or hematological malignancy, but reduces the risk of melanoma.     

Radiotherapy for oral cancer as a risk factor for second primary cancers

Radiation exposure, known to cause DNA damage, may be a potential source of field cancerization of the upper aerodigestive tract. Radiotherapy for head and neck cancers has been examined as a possible risk factor for second primary cancers, but the results have been equivocal. We evaluated the impact of therapeutic radiation for oral cancer on the risk of second primary cancers with data from the Surveillance, Epidemiology, and End Results (SEER) program for 1973–1999. Among 30,221 first primary oral squamous cell carcinoma patients, 6163 (20.4%) patients developed a second primary cancer, 5042 of which were metachronous. Patients treated with radiation only (RR=1.64, 95%CI=1.18–2.29) or radiation with surgery (RR=1.49, 95%CI=1.07, 2.06) had elevated risks of developing a second primary tumor, whereas patients treated with surgery only did not appear to be at increased risk (RR=1.28, 95%CI=0.93, 1.76). Consistent with an expected latent period between radiation exposure and tumor occurrence, radiation became a risk factor after 10 years of follow-up for solid cancers of the oral cavity (RR=2.8, 95%CI=1.5, 5.2), pharynx (RR=5.9, 95%CI=1.7, 20.7), esophagus (RR=3.9, 95%CI=1.1, 13.4) and lung (RR=1.5, 95%CI=1.0, 2.4), and after 1–5 years of follow-up for second primary leukemia (RR=2.5, 95%CI=1.0, 6.7). Radiotherapy for oral cancer appears to be a risk factor for second primary tumors. Further studies that account for chemotherapy and examine frequency and duration of radiotherapy would be of interest in confirming the observed association.     

Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States)

Objectives: The Physicians' Health Study (PHS) was a randomized trial of beta-carotene (50 mg, alternate days) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians. This report updates results for beta-carotene and examines effect modification by baseline characteristics. Methods: Beta-carotene's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models. Results: 2667 incident cancers were confirmed, with 1117 prostate, 267 colon, and 178 lung cancers. There were no significant differences with supplementation in total (relative risk (RR) = 1.0, 95% confidence interval (CI) = 0.9–1.0); prostate (RR = 1.0, 95% CI = 0.9–1.1); colon (RR = 0.9, 95% CI = 0.7–1.2); or lung (RR = 0.9, 95% CI = 0.7–1.2) cancer, and no differences over time. In subgroup analyses, total cancer was modestly reduced with supplementation among those aged 70+ years (RR = 0.8, 95% CI = 0.7–1.0), daily drinkers of alcohol (RR = 0.9, 95% CI = 0.8–1.0), and those in the highest BMI quartile (RR = 0.9, 95% CI = 0.7–1.0). Prostate cancer was reduced with supplementation among those in the highest BMI quartile (RR = 0.8, 95% CI = 0.6–1.0), and colon cancer was reduced among daily drinkers of alcohol (RR = 0.5, 95% CI = 0.3–0.8). Conclusions: The PHS found no overall effect of beta-carotene on total cancer, or the three most common site-specific cancers. The possibility of risk reduction within specific subgroups remains.     

Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial.

Studies on the relationship between obesity and prostate cancer incidence are inconsistent. In part, this inconsistency may be due to a differential effect of obesity on low-grade and high-grade cancer or confounding of the association of obesity with prostate cancer risk by diabetes. We investigated the associations of obesity and diabetes with low-grade and high-grade prostate cancer risk. Data were from 10,258 participants (1,936 prostate cancers) in the Prostate Cancer Prevention Trial who all had cancer presence or absence determined by prostate biopsy. Multiple logistic regression was used to model the risk of total prostate cancer, and polytomous logistic regression was used to model the risk of low-grade and high-grade prostate cancer. Compared with men with body mass index < 25, obese men (body mass index > or =30) had an 18% [odds ratio (OR), 0.82; 95% confidence interval (95% CI), 0.69-0.98] decreased risk of low-grade prostate cancer (Gleason <7) and a 29% (OR, 1.29; 95% CI, 1.01-1.67) increased risk of high-grade prostate cancer (Gleason > or =7) or, alternatively, a 78% (OR, 1.78; 95% CI, 1.10-2.87) increased risk defining high-grade cancer as Gleason sum 8 to 10. Diabetes was associated with a 47% (OR, 0.53; 95% CI, 0.34-0.83) reduced risk of low-grade prostate cancer and a 28% (OR, 0.72; 95% CI, 0.55-0.94) reduced risk of high-grade prostate cancer. Associations of obesity or diabetes with cancer risk were not substantially changed by mutually statistical controlling for each other. Obesity increases the risk of high-grade but decreases the risk of low-grade prostate cancer, and this relationship is independent of the lower risk for prostate cancer among men with diabetes.     

Associations between unprocessed red and processed meat,poultry, seafood and egg intake and the risk of prostate cancer: A pooled analysis of 15 prospective cohort studies

Reports relating meat intake to prostate cancer risk are inconsistent. Associations between these dietary factors and prostate cancer were examined in a consortium of 15 cohort studies. During follow‐up, 52,683 incident prostate cancer cases, including 4,924 advanced cases, were identified among 842,149 men. Cox proportional hazard models were used to calculate study‐specific relative risks (RR) and then pooled using random effects models. Results do not support a substantial effect of total red, unprocessed red and processed meat for all prostate cancer outcomes, except for a modest positive association for tumors identified as advanced stage at diagnosis (advanced(r)). For seafood, no substantial effect was observed for prostate cancer regardless of stage or grade. Poultry intake was inversely associated with risk of advanced and fatal cancers (pooled multivariable RR [MVRR], 95% confidence interval, comparing ≥45 vs. <5 g/day: advanced 0.83, 0.70–0.99; trend test p value 0.29), fatal, 0.69, 0.59–0.82, trend test p value 0.16). Participants who ate ≥25 versus <5 g/day of eggs (1 egg ～ 50 g) had a significant 14% increased risk of advanced and fatal cancers (advanced 1.14, 1.01–1.28, trend test p value 0.01; fatal 1.14, 1.00–1.30, trend test p value 0.01). When associations were analyzed separately by geographical region (North America vs. other continents), positive associations between unprocessed red meat and egg intake, and inverse associations between poultry intake and advanced, advanced(r) and fatal cancers were limited to North American studies. However, differences were only statistically significant for eggs. Observed differences in associations by geographical region warrant further investigation.     

A prospective cohort study of cancer incidence following the diagnosis of Parkinson's disease.

BACKGROUND: Prior studies suggest a decreased risk of cancer among patients with Parkinson's disease (PD). METHODS: Matched cohort analysis among the 22,071 participants in the Physician's Health Study. A total of 487 incident cases of PD without preceding cancer were identified by self-report. Each PD case was matched by age to a reference participant who was alive and cancer free at the time of PD diagnosis. Both cohorts were followed for incident cancer. We used proportional hazards models to calculate adjusted relative risks (RR) for cancer. RESULTS: A total of 121 cancers were confirmed during a median follow-up of 5.2 years (PD) and 5.9 years (reference). Those with PD developed less cancer (11.0% versus 14.0%), with an adjusted RR of 0.85 [95% confidence interval (95% CI), 0.59-1.22]. Reduced risk was present for smoking-related cancers such as lung (RR, 0.32), colorectal (RR, 0.54), and bladder (RR, 0.68), as well as for most non-smoking-related cancers such as prostate cancer (RR, 0.74). In contrast, PD patients were at significantly increased risk (RR, 6.15; 95% CI, 1.77-21.37) for melanoma. PD patients who smoked were at reduced risk for smoking-related cancer (RR, 0.33; 95% CI, 0.12-0.92), whereas nonsmokers with PD were at increased risk (RR, 1.80; 95% CI, 0.60-5.39). This interaction was statistically significant (P(interaction) = 0.02). CONCLUSIONS: Our results suggest a decreased incidence of most cancers in patients with PD. PD patients had a significantly increased risk of malignant melanoma, a finding consistent with prior studies. We confirmed an interaction between smoking and the relationship of PD to smoking-related cancer that may fit the pattern of a gene-environment interaction.     

Midlife metabolic factors and prostate cancer risk in later life

Metabolic syndrome is associated with several cancers, but evidence for aggressive prostate cancer is sparse. We prospectively investigated the influence of metabolic syndrome and its components on risk of total prostate cancer and measures of aggressive disease in a cohort of Icelandic men. Men in the Reykjavik Study (n = 9,097, enrolled 1967–1987) were followed for incident (n = 1,084 total; n = 378 advanced; n = 148 high‐grade) and fatal (n = 340) prostate cancer until 2014. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for (1) measured metabolic factors at cohort entry (body mass index (BMI), blood pressure, triglycerides, fasting blood glucose) and (2) a metabolic syndrome score (range 0–4) combining the risk factors: BMI ≥30 kg/m²; systolic blood pressure (SBP) ≥130 or diastolic blood pressure (DBP) ≥85 mm Hg or taking antihypertensives; triglycerides ≥150 mg/dl; fasting blood glucose ≥100 mg/dl or self‐reported type 2 diabetes. Hypertension and type 2 diabetes were associated with a higher risk of total, advanced, high‐grade, and fatal prostate cancer, independent of BMI. Neither BMI nor triglycerides were associated with prostate cancer risk. Higher metabolic syndrome score (3–4 vs 0) was associated with a higher risk of fatal prostate cancer (HR 1.55; 95% CI: 0.89, 2.69; p trend = 0.08), although this finding was not statistically significant. Our findings suggest a positive association between midlife hypertension and diabetes and risk of total and aggressive prostate cancer. Further, metabolic syndrome as a combination of factors was associated with an increased risk of fatal prostate cancer.