Sex hormones and cancer.

There are few instances in which a clear effect of hormones on cancer risk is known and in which the effects of those hormones on the cells concerned are also known. The best examples are the relationships between sex hormones and cancer in women. The effects of sex hormones both on the risk for endometrial cancer and on the cells of the endometrium are well understood, and the evidence strongly suggests that hormones act by altering the rate of cell division. The same mechanism may explain the relationships between sex hormones and the risk for breast cancer, but our understanding of cancers at this site is incomplete. Less still is known about the mechanisms of the effects of sex hormones on other hormone-related cancers, such as those of the ovary and cervix. Most sex hormones are not genotoxic.     

我国农村地区宫颈癌筛查中人乳头瘤病毒检测阳性女性的分流策略

目的探讨适用于我国农村地区宫颈癌筛查人乳头瘤病毒(HPV)阳性女性的分流策略。方法选取2015年7月至2015年10月间,在山西省襄垣县和阳城县招募35~64岁女性进行宫颈癌及其癌前病变筛查,采用宫颈癌快速筛查技术(care HPV检测法)进行初筛,后采用随机数表法将初筛结果阳性女性(248例)分成三组:细胞学分流(82例)、醋酸或碘染色肉眼观察法(VIA/VILI)分流(83例)和不分流直接转诊阴道镜(83例)。细胞学和VIA/VILI检查阳性者转诊阴道镜。阴道镜异常者在病变处取活检进行病理诊断。结果共有1 503名女性参加筛查,HPV阳性检出率为16.5%(248/1503),中度及以上宫颈上皮内瘤样病变(CIN2+)的检出率为0.7%(11/1503),248例中有237例完成分流检查,依从率为95.6%(237/248),细胞学分流组、VIA/VILI分流组和不分流直接阴道镜组检查的人数分别为81例、79例和77例。细胞学分流组中,分流结果阳性率、CIN2+检出率和阳性预测值依次为:19.8%、1.2%和11.1%;VIA/VILI分流组中上述指标依次为:17.5%、3.6%和21.4%;不分流直接阴道镜组中上述指标依次为:19.5%、8.4%和9.5%。上述阳性检出率和CIN2+检出率差异均无统计学意义(均P>0.05)。随着年龄的增加,HPV阳性率趋于上升趋势,而直接阴道镜组阳性检出率趋于下降趋势,差异均有统计学意义(均P<0.05)。细胞学分流组和VIA/VILI分流组随年龄的增加未发现显著的变化趋势,差异无统计学意义(P>0.05)。结论三组方法中,VIA/VILI较适用于我国农村地区宫颈癌筛查HPV阳性女性的分流。     

Cost-effectiveness of breast cancer screening programme for women in rural China

In low and middle-income countries mammographic breast cancer screening is prohibitively expensive and a cheaper alternative option is to use ultrasound as the primary screening test. In 2009, China launched a breast cancer screening programme for rural women aged 35–64 years with clinical breast examination coupled with ultrasound as the primary tool. Our study aimed to analyse the cost-effectiveness of breast screening compared to no screening among Chinese rural women. We developed a Markov model to estimate the lifetime costs and effects for rural women aged 35 years from a societal perspective. Asymptomatic women in the intervention arm were screened every 3 years before age 64 years. Breast cancer in the non-screening arm can only be diagnosed on presentation of symptoms. Parameter uncertainty was explored using one-way and probabilistic sensitivity analyses. Compared to no screening, breast cancer screening cost $186.7 more and led to a loss of 0.20 quality-adjusted life years (QALYs). Breast screening was more expensive and did harm to health among rural women with an incremental cost-effectiveness ratio (ICER) of $-916/QALY. The sensitivity analysis identified utility loss from false positives as the factor that most influenced the results, but this did not affect the conclusions. In a rural setting with such low breast cancer incidence, screening for asymptomatic disease is not cost-effective with current screening tools. Priority should be given to ensure that symptomatic women have proper access to diagnosis and treatment at an early stage as this will lead to mortality reductions without the usual screening harms.     

性激素及其受体与食管癌的关系

研究表明食管癌组织上存在性激素受体,但食管癌内分泌治疗的研究尚存在许多不一致的结果.现就性激素(雌雄激素)、性激素受体(ER、AR)与食管癌的关系作一综述,以分析食管癌内分泌治疗的可行性及存在的问题.     

Sex hormones in patients with liver cirrhosis and hepatocellular carcinoma

Sex hormones have been proposed to play an important role in promoting liver cancer transformation. The aim of our study was to evaluate changes in circulating levels of estradiol (EII), testosterone (T) and the EII/T relationship (ETR) in patients with liver cirrhosis (LC) and hepatocellular carcinoma (HCC) of viral origin compared with a group of healthy controls (C). The study population included 64 patients (41 M) mean age 62.5 years with HCC; 68 patients (41 M) mean age 61.3 years suffering from LC, while the C included 59 subjects (39 M) mean age 60.0 years recruited from voluntary blood donors. EII and T were assayed using the IEMA method; ultrasonography was performed using a Toshiba SSA 240 A scanner with a convex 3.75 MHz probe. Serum EII levels progressively increased from C to LC and HCC with statistically significant values (H=36.9, p<0.0001). Serum values of T progressively decreased from C to LC and HCC but the difference was not significant (H=3.84, p=ns). ETR values differed in the three groups, with a significant difference between C vs LC and HCC (p<0.0001). There was also a significant difference for EII, with values decreasing as the neoplasm dimension increased (p<0.04), and in particular there were differences between HCC <5 cm vs >5 cm (p<0.05). In contrast, ETR progressively increased as the diameter of neoplasm increased, but differences were significant only between <3 cm vs >5 cm (p<0.05). In conclusion, our data confirm that in LC and HCC there is an increase in serum EII levels, which can be important in the genesis of liver carcinoma. Progressive serum reduction in T may be due to increased androgen uptake and progressive accumulation within the neoplastic mass. Further studies are necessary to determine whether subjects with LC and elevated serum levels of estrogens are at higher risk of developing HCC.     

Reproducibility of serum pituitary hormones in women

Endogenous pituitary hormones are commonly used in clinical and epidemiologic studies and some of them are thought to influence the risk of several diseases in women. In most studies, endogenous levels of pituitary hormones are usually assessed at a single point in time, assuming that this single measurement represents the long-term biomarker status of the individual. Such an assumption is rarely tested and may not always be valid. This study examined the reproducibility of the following pituitary hormones: adrenocorticotropic hormone (ACTH), growth hormone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and prolactin, measured using the Luminex xMap method in sera of healthy premenopausal and postmenopausal women. The study included 30 premenopausal women with three yearly samples and 35 postmenopausal women with two repeated yearly samples randomly selected from an existing prospective cohort. Analysis of intraclass correlation coefficients suggested higher reproducibility in postmenopausal women compared with premenopausal women for the following hormones: FSH (0.72 and 0.37, respectively), LH (0.83 and 0.44, respectively), and growth hormone (0.60 and 0.35, respectively). The intraclass correlation coefficients were relatively high and similar between postmenopausal and premenopausal women for ACTH (0.95 and 0.94, respectively), TSH (0.85 and 0.85, respectively), and prolactin (0.72 and 0.69, respectively). This study found that serum concentrations of FSH, LH, and growth hormone are stable in postmenopausal women and that ACTH, TSH, and prolactin are stable in both premenopausal and postmenopausal women, suggesting that a single measurement may reliably categorize average levels over at least a 2-year period.     

Sex hormones, risk factors, and risk of estrogen receptor-positive breast cancer in older women: a long-term prospective study.

OBJECTIVE: Antiestrogens reduce the risk of estrogen receptor-positive (ER+) but not ER-negative (ER-) breast cancer. Women at high risk of ER+ cancer would be the most likely to benefit from these treatments, but the best approach to predicting ER+ cancer is uncertain. METHODS: We prospectively assessed putative risk factors for breast cancer and archived serum at -190 degrees C from a community-based cohort of 7,676 women ages > or =65 years who had no history of breast cancer. Follow-up for breast cancer over 10.5 years was 99% complete. Using a case-cohort design, we measured baseline levels of estradiol and testosterone in 196 cases of invasive ER+ cancer and 378 randomly selected controls. RESULTS: Women whose testosterone level in highest two quintiles had a 4-fold increased risk of ER+ breast cancer (P < 0.0001). High estradiol concentration also indicated an increased risk but was not a significant predictor after adjustment for testosterone. Women with >16 years of education had a 2.1 times increased risk (P = 0.03) of ER+ cancer, but no other risk factors were significantly related to an increased risk of ER+ cancer. Women with a family history of breast cancer had a 2.9-fold increased risk of ER- cancer (P = 0.002) but no increased risk of ER+ cancer (relative hazard = 1.2, 0.8-1.8). CONCLUSIONS: High serum testosterone and advanced education predicted ER+ breast cancer. If confirmed, high testosterone level may be more accurate than family history of breast cancer and other conventional risk factors for identifying older women who are most likely to benefit from antiestrogen chemoprevention.     

Cooking oil fumes and risk of lung cancer in women in rural Gansu, China.

Cooking oil fumes have been suggested to increase the risk of lung cancer in Chinese women by exposing them to mutagenic substances. We investigated the association between lung cancer and locally made rapeseed and linseed oils in a population-based case-control study in Gansu Province, China. Two hundred and thirty-three incident, female lung cancer cases diagnosed from 1994-98 were identified. A control group of 459 women was selected from census lists and were frequency matched on age and prefecture. Interviewers obtained information on cooking practices and cooking oil use. The odds ratio (OR) for lung cancer associated with ever-use of rapeseed oil, alone or in combination with linseed oil, was 1.67 (95% CI 1.0-2.5), compared to use of linseed oil alone. ORs for stir-frying with either linseed or rapeseed oil 15-29, 30 and > or =31 times per month were 1.96,1.73, and 2.24, respectively (trend, P=0.03), relative to a lower frequency of stir-frying. Lung cancer risks also increased with total number of years cooking (trend, P<0.09). Women exposed to cooking fumes from rapeseed oil appeared to be at increased risk of lung cancer, and there was some evidence that fumes from linseed oil may have also contributed to the risk.     

Sex hormone binding globulin and risk factors for breast cancer in a population of normal women who had never used exogenous sex hormones

Sex hormone binding globulin (SHBG) concentrations were measured by immunoradiometric assay in serum samples from 1,221 healthy female volunteers aged 34-79 who had never used oral contraceptives or hormone replacement therapy, had no history of thyroid disease or cancer, and had not used any drugs known to influence SHBG in the 14 days preceding blood sampling. There were 616 premenopausal and 605 naturally postmenopausal women. In both premenopausal and postmenopausal women, SHBG decreased with increasing weight (Quetelt's Index) and was lower in single nulliparous women than in married nulliparous women or parous women. In premenopausal women, SHBG was higher in women with late menarche, was higher in smokers than in non-smokers, and was higher in blood samples taken during the first 12 days of the luteal phase than during the rest of the menstrual cycle. In postmenopausal women, SHBG increased with years since the menopause. The possible biological importance of these findings is discussed with particular reference to risk factors for breast cancer.     

Serum hormones and the alcohol-breast cancer association in postmenopausal women

BACKGROUND: Alcohol ingestion is associated with an increased risk of breast cancer in most epidemiologic studies. Results, however, are heterogeneous at lower levels of alcohol intake, and a biologic mechanism for the association has not been clearly identified. To determine whether alcohol consumption by postmenopausal women elevates serum levels of hormones associated with an increased risk of breast cancer, we performed a controlled feeding study. METHODS: Participants were 51 healthy postmenopausal women not using hormone replacement therapy. Each participant rotated through three 8-week dietary periods in which she consumed 15 or 30 g of alcohol per day or an alcohol-free placebo beverage. The order of assignment to the three alcohol levels was random. During the dietary periods, all food and beverages were supplied by the study, and energy intake was adjusted to keep body weight constant. Levels of estradiol, estrone, estrone sulfate, testosterone, androstenedione, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), and androstenediol were measured by radioimmunoassays in serum collected at the end of each dietary period. All statistical tests are two-sided. RESULTS: When women consumed 15 or 30 g of alcohol per day, respectively, estrone sulfate concentrations increased by 7.5% (95% confidence interval [CI] = -0.3% to 15.9%; P =.06) and 10.7% (95% CI = 2.7% to 19.3%; P =.009) and DHEAS concentrations increased by 5.1% (95% CI = 1.4% to 9.0%; P =.008) and 7.5% (95% CI = 3.7% to 11.5%; P<.001) relative to levels when women consumed placebo. None of the other hormones measured changed statistically significantly when women consumed alcohol. CONCLUSIONS: Results suggest a possible mechanism by which consumption of one or two alcoholic drinks per day by postmenopausal women could increase their risk of breast cancer.     

Plasma hormones in parous, nulliparous and postmenopausal Japanese women

Mechanisms associated with protection against breast cancer in parous women with an early pregnancy are unknown. Elevated or deficient steroid hormone levels or dysfunctional release of prolactin have been postulated. Since these effects have not been reported in low-risk Japanese women, we have compared the hormone levels in age-weight-risk factor matched premenopausal nulliparous and parous Japanese women with established menstrual regularity. Higher luteal phase plasma levels of estradiol and estrone occurred in parous versus nulliparous women, while plasma prolactin and androgen levels were unaltered. It is suggested that the higher estrogen and lower LH levels, as in short versus long menstrual cycles, results from failure of the opioid GnRH. LH axis to return to pre-pregnancy levels.     

Endogenous sex hormones and subsequent breast cancer in premenopausal women

Because of large intra-individual variation in hormone levels, few studies have investigated the relation of serum sex hormones to breast cancer (BC) in premenopausal women. We prospectively studied this relation, adjusting for timing of blood sampling within menstrual cycle. Premenopausal women (5,963), recruited to the Hormones and Diet in the Etiology of Breast Tumors (ORDET) cohort study, provided a blood sample in the 20-24th day of their menstrual cycle. After 5.2 years of follow-up, 65 histologically confirmed BC cases were identified and matched individually to 4 randomly selected controls. Sera, stored at -80 degrees C, were assayed blindly for dehydroepiandrosterone sulfate, total and free testosterone (FT), androstenedione, androstanediol-glucoronide, progesterone, 17-OH-progesterone, sex hormone-binding globulin, follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Fifty-five cases had information for multivariate analyses. Compared to controls, BC cases had shorter cycles and intervals between blood sampling and bleeding, and lower LH and FSH. FT was significantly associated with BC risk: relative risk (RR; adjusted for age, body mass index and ovarian cycle variables) of highest vs. lowest tertile was 2.85 [95% confidence interval (CI) = 1.11-7.33, p for trend = 0.030]. Progesterone was inversely associated with adjusted RR for highest vs. lowest tertile of 0.40 (95% CI = 0.15-1.08, p for trend = 0.077), significantly so in women with regular menses, where adjusted RR was 0.12 (95% CI = 0.03-0.52, p for trend = 0.005). These findings support the hypothesis that ovarian hyperandrogenism associated with luteal insufficiency increases the risk of BC in premenopausal women.     

Tuberculosis and oncogenic HPV: potential co-infections in women at high-risk of cervical cancer in rural China

The study was embedded in Shanxi Province Cervical Cancer Screening Study II with the aim of examining the association between history of diagnosed tuberculosis or cervical inflammation and oncogenic human papillomavirus (HPV) infection, persistent oncogenic HPV infection, cervical intraepithelial neoplasia grade 3 or cervical cancer (CIN3+) in an isolated rural population of China. A total of 8,798 women were recruited for cervical cancer screening and an interviewer-administered questionnaire. Of the women in the study, 2.7% and 34% reported a diagnosis of tuberculosis and cervical inflammation, respectively. In the model for HPV infection, HPV persistence and CIN3+, we show an increasing magnitude of effect of tuberculosis with increasing severity of disease, as demonstrated by the increasing odds ratios from 1.68 for HPV positivity, to 1.75 for persistent HPV and then 2.08 for CIN3+. Women reporting a diagnosis of tuberculosis, cervical inflammation or both tuberculosis and cervical inflammation were at 75%, 22% and 113% higher odds of persistent HPV infection, respectively. One percent of the study population was diagnosed with tuberculosis and cervical inflammation, placing them at 90% and 113% higher odds of infection with HPV and persistent HPV, respectively. Tuberculosis and oncogenic HPV are identified for the first time as co-infections in rural unscreened women in Shanxi Province, China, highlighting the importance of infection history in assessing an individual' s risk for HPV infection, persistence and CIN3+.     

Papillomavirus infection in rural women in southern India

To investigate the prevalence of, and the risk factors for, cervical infection with 44 types of human papillomavirus (HPV) in a rural area in the Dindigul District, Tamil Nadu, India, we interviewed and obtained cervical cell samples from 1891 married women aged 16-59 years. HPV prevalence was 16.9% overall and 14.0% among women without cervical abnormalities, or 17.7 and 15.2%, respectively, age-standardised to the world standard population. In all, 21.9% of infections involved more than one HPV type. High-risk HPV types predominated, particularly HPV 16 (22.5% of women infected), followed by HPV 56, HPV 31, HPV 33 and HPV 18. Unlike most populations studied in developed countries, HPV prevalence was constant across the age groups. HPV positivity was inversely associated with education level (odds ratio (OR) among women with high school vs no education=0.6) and positively associated with widowhood and divorce (OR=1.7), nulligravidity (OR=2.3), and condom use (OR=2.6). It is unclear how much low clearance of, or frequent reinfection with HPV accounted for the study prevalence of infection in different age groups.     

Sex hormones and the risk of keratinocyte cancers among women in the United States: A population‐based case–control study

Men are at a higher risk of developing both squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) than women, but there is emerging evidence that women may be experiencing greater increases in the incidence rates of these malignancies than men. One possible explanation is the expanding use of sex steroids among women, although only a few studies have examined this hypothesis. As part of a population‐based, case–control study of women in New Hampshire, USA, we sought to evaluate the risk of SCC, BCC, and early‐onset BCC in relation to exogenous and endogenous sex hormones. We found that oral contraceptive (OC) use was associated with an increased risk of SCC (OR = 1.4, 95% CI = 1.1–1.8) and BCC (OR = 1.4, 95% CI = 1.0‐1.8), particularly high estrogen dose (>50 mg) OC use. Hormone replacement therapy (HRT) use also related to SCC, with an elevated OR largely for progestin use (OR = 1.4, 95% CI = 1.1–1.8). Additionally, both OC use and combination HRT use were associated with more aggressive BCC subtypes. In contrast, menstrual and reproductive history did not appear to influence keratinocyte cancer risk in our data. Our findings provide evidence that use of sex steroids may enhance risk of keratinocyte cancer.     

Seasonal variation in the secretion of mammotrophic hormones in normal women and women with previous breast cancer

Hormones such as melatonin whose serum concentrations vary seasonally have been previously implicated in the growth of breast cancer. The present study was undertaken to identify possible seasonal variation in a range of mammotrophic hormones which could exert a chronobiologic influence in women with breast tumours. Fifteen premenopausal women with a history of previous breast cancer (BC subjects) and 10 control women underwent 2-hourly serum sampling for 24 h at both summer and winter solstice for measurement of melatonin, growth hormone (GH), insulin-like growth factor-I (IGF-I), cortisol, prolactin and thyrotrophin (TSH). Hormone secretion at the different seasons was compared by measuring the area under the 24 h serum hormone concentration × time curves and by time series analysis of summer-to-winter differences in hormone concentration. Control women had significantly higher GH and IGF-I levels in summer compared to winter and significantly higher cortisol secretion in winter than summer. In contrast, BC women had no significant seasonal difference in IGF-I concentrations and had a reversal of the normal seasonal pattern of melatonin secretion, although seasonal changes in GH production were similar to controls. Prolactin and TSH showed no significant summer/winter variation in either group. Thus, seasonal variations in hormone secretion seen in normal women were, with exception of GH, absent or reversed in women with a previous history of breast cancer. As a result these individuals may be exposed to an asynchronous hormonal stimulus which could influence tumour growth. These changes could reflect a constitutional abnormality in BC women or may have been induced by the previous breast tumour.     

Risk factors for HPV infection and cervical cancer among unscreened women in a high-risk rural area of China

We report a prevalence rate of 23.6% human papillomavirus (HPV) infection with oncogenic subtypes and 2.4% cervical intraepithelial neoplasia (CIN) III and cervical cancer (CC) in rural middle-aged women in 2 counties with the highest CC mortality in Shanxi Province, China. We examined the association of risk factors to HPV infection and to CIN III and CC in 8,798 unscreened women aged 35-50 years. Multivariate odds ratios (OR) and 95% confidence intervals (CI) for each endpoint were obtained for risk factors after adjustment for covariates. The OR of oncogenic HPV were: 1.41 (95% CI = 1.25-1.60) and 1.42 (95% CI = 1.24-1.61) for the participant and her husband having multiple sexual partners, respectively; 1.67 (95% CI = 1.37-2.04), 1.15 (95% CI = 1.04-1.26), and 0.82 (95% CI = 0.72-0.94) for ever (vs. never) diagnosed with tuberculosis, cervical inflammation and vaginal trichomoniasis, respectively; while bathing in a public (v. private) facility had an OR of 1.23 (95% CI =1.11-1.35). Seasonal fluctuations in HPV infection, but not CC, appeared in Xiangyuan County, with OR of 1.23 (95% CI = 1.14-1.33) and 1.51 (95% CI = 1.35-1.67) in Spring and Winter compared to Summer, respectively. The OR of CIN III and CC in the HPV positives were: 2.03 (95% CI = 1.63-2.53) for ages > or =45 years (vs. <40); and 4.01 (95% CI = 1.46-11.0) for > or =3 (vs. no) home births. Public health interventions and control strategies for improving the reproductive health of women in these rural populations need to be developed to reduce risk of HPV and subsequent CC.     

Sex hormones, hormonal interventions, and gastric cancer risk: a meta-analysis

Estrogens may influence gastric cancer risk, but published studies are inconclusive. We therefore carried out a meta-analysis addressing the associations of gastric cancer in women with menstrual and reproductive factors and with use of estrogen- and antiestrogen-related therapies. Searches of PubMed up to June, 2011 and review of citations yielded a total of 28 independent studies, including at least one exposure of interest. Random effects pooled estimates of relative risk (RR) and corresponding 95% CIs were calculated for eight exposures reported in at least five studies, including: age at menarche, age at menopause, years of fertility, parity, age at first birth, oral contraceptive use, hormone replacement therapy (HRT), and tamoxifen treatment. Longer years of fertility (RR = 0.74, 95% CI: 0.63-0.86) and HRT (RR = 0.77; 95% CI: 0.64-0.92) were each associated with decreased gastric cancer risk. Conversely, tamoxifen treatment was associated with increased risk (RR = 1.82; 95% CI: 1.39-2.38). The other five exposures were not significantly associated. Our analysis supports the hypothesis that longer exposure to estrogen effects of either ovarian or exogenous origin may decrease risk of gastric cancer. Additional studies are warranted to extend this finding and to identify the underlying mechanisms.     

Serum sex hormones and breast cancer risk factors in postmenopausal women.

Postmenopausal women with elevated serum estrogens and androgens are at an increased risk of breast cancer. We evaluated associations of serum estrogen and androgen levels with age, anthropometry, and reproductive history to assess whether these characteristics could potentially modify breast cancer risk through hormonal mechanisms. A cross-sectional study was conducted among 133 postmenopausal women who donated blood to the serum bank (Columbia, MO) and served as controls in a previous prospective nested case control study of serum hormones and breast cancer risk. Standard regression methods were used to calculate adjusted means and test for trends in relationships of serum hormone concentrations with breast cancer risk factors. All analyses were performed on the log(e) scale, and all models included assay batch, date, and time of blood collection. Serum levels of estradiol, non-sex hormone binding globulin bound estradiol, estrone, estrone sulfate, and testosterone increased significantly with increasing body mass index (BMI), whereas sex hormone binding globulin levels decreased. After adjusting for BMI, nulliparous women tended to have higher testosterone levels compared with parous women (P = 0.05), but there was no evidence of a trend of decreasing testosterone with increasing parity. Dehydroepiandrosterone, its sulfate, and androstenediol decreased significantly with increasing age. Although BMI and parity could potentially modify breast cancer risk through hormonal mechanisms, age-related increases in breast cancer incidence do not appear to be mediated through changes in serum levels of the hormones evaluated.