Reproductive factors,hormone use and gastric cancer risk: The Singapore Chinese Health Study

Gastric cancer incidence varies greatly worldwide, but is consistently twice as high in men than in women. The hormone‐related factors hypothesized to be associated with lower risk of gastric cancer in women have not been fully explored in populations with a high background risk of gastric cancer. The Singapore Chinese Health Study (SCHS) is a prospective cohort study in which 34,022 of the participants enrolled between 1993 and 1998 were women between 45 and 74 years of age. Information on reproductive histories, hormone replacement therapy (HRT) and oral contraceptive (OC) use was collected through in‐person interviews at baseline. As of December 31, 2013, 269 incident gastric cancer cases were identified. Multivariable‐adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to evaluate gastric cancer risk associations. Older age at natural menopause (≥55 versus <45 years: HR = 0.50, 95% CI: 0.25–0.99), type of menopause (other versus natural: HR = 0.48, 95% CI: 0.27–0.87) and greater years of menstrual cycling (fourth versus first quartile: HR = 0.67, 95% CI: 0.46–0.96) were associated with a decreased risk of gastric cancer. Ever use of OCs and HRT was also associated with reduced risk of gastric cancer; the multivariable‐adjusted HRs (95% CIs) were 0.40 (0.17–0.90) for use of HRT >3 years and 0.67 (0.47–0.94) for ever use of OCs, compared with never use. Reproductive factors associated with a longer window of fertility and the use of exogenous hormones were shown to reduce gastric cancer development in a cohort of Chinese women with a high background risk of gastric cancer.     

Flavonoid and lignan intake and pancreatic cancer risk in the European prospective investigation into cancer and nutrition cohort

Despite the potential cancer preventive effects of flavonoids and lignans, their ability to reduce pancreatic cancer risk has not been demonstrated in epidemiological studies. Our aim was to examine the association between dietary intakes of flavonoids and lignans and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 865 exocrine pancreatic cancer cases occurred after 11.3 years of follow‐up of 477,309 cohort members. Dietary flavonoid and lignan intake was estimated through validated dietary questionnaires and the US Department of Agriculture (USDA) and Phenol Explorer databases. Hazard ratios (HR) and 95% confidence intervals (CIs) were calculated using age, sex and center‐stratified Cox proportional hazards models, adjusted for energy intake, body mass index (BMI), smoking, alcohol and diabetes status. Our results showed that neither overall dietary intake of flavonoids nor of lignans were associated with pancreatic cancer risk (multivariable‐adjusted HR for a doubling of intake = 1.03, 95% CI: 0.95–1.11 and 1.02; 95% CI: 0.89–1.17, respectively). Statistically significant associations were also not observed by flavonoid subclasses. An inverse association between intake of flavanones and pancreatic cancer risk was apparent, without reaching statistical significance, in microscopically confirmed cases (HR for a doubling of intake = 0.96, 95% CI: 0.91–1.00). In conclusion, we did not observe an association between intake of flavonoids, flavonoid subclasses or lignans and pancreatic cancer risk in the EPIC cohort.     

Incident cancer risk after the start of aspirin use: Results from a Dutch population‐based cohort study of low dose aspirin users

Observational and intervention studies suggest that low dose aspirin use may prevent cancer. The objective of this study was to investigate the protective effect of long term low dose aspirin use (≤100 mg daily) on cancer in general and site‐specific cancer among low dose aspirin users in the Dutch general population. We conducted a population‐based cohort study with detailed information on aspirin exposure and cancer incidence. Only incident (new) low dose aspirin users, who were included in the linkage between PHARMO and the Eindhoven Cancer Registry (1998–2010) and free of cancer before the start of follow up were included. A Cox proportional hazard model with cumulative aspirin use as a time‐varying determinant was used to obtain hazard ratios (HR). Duration of aspirin use amongst 109,276 incident low dose aspirin users was not associated with a decreased risk of any of the site‐specific cancers or cancer in general (adjusted HR per year of aspirin use for all cancers: 1.02, 95% confidence interval [CI] 1.00–1.04, HR of >6 years aspirin use compared to <2 years: 1.17, 95% CI 1.02–1.34). After adjusting for current and past aspirin use, 2–6 years of low dose aspirin use was associated with a reduced colorectal cancer risk compared to <2 years of aspirin use (adjusted HR 0.75, 95% CI 0.59–0.96). However, a clear dose‐response relationship was not observed (adjusted HR >6 years aspirin use 0.95, 95% CI 0.60–1.49). Our results do not support the primary prevention of cancer among long term aspirin users.     

The influence of smoking,age and stage at diagnosis on the survival after larynx,hypopharynx and oral cavity cancers in Europe: The ARCAGE study

Head and neck cancer (HNC) is a preventable malignancy that continues to cause substantial morbidity and mortality worldwide. Using data from the ARCAGE and Rome studies, we investigated the main predictors of survival after larynx, hypopharynx and oral cavity (OC) cancers. We used the Kaplan–Meier method to estimate overall survival, and Cox proportional models to examine the relationship between survival and sociodemographic and clinical characteristics. 604 larynx, 146 hypopharynx and 460 OC cancer cases were included in this study. Over a median follow‐up time of 4.6 years, nearly 50% (n = 586) of patients died. Five‐year survival was 65% for larynx, 55% for OC and 35% for hypopharynx cancers. In a multivariable analysis, we observed an increased mortality risk among older (≥71 years) versus younger (≤50 years) patients with larynx/hypopharynx combined (LH) and OC cancers [HR = 1.61, 95% CI 1.09–2.38 (LH) and HR = 2.12, 95% CI 1.35–3.33 (OC)], current versus never smokers [HR = 2.67, 95% CI 1.40–5.08 (LH) and HR = 2.16, 95% CI 1.32–3.54 (OC)] and advanced versus early stage disease at diagnosis [IV versus I, HR = 2.60, 95% CI 1.78–3.79 (LH) and HR = 3.17, 95% CI 2.05–4.89 (OC)]. Survival was not associated with sex, alcohol consumption, education, oral health, p16 expression, presence of HPV infection or body mass index 2 years before cancer diagnosis. Despite advances in diagnosis and therapeutic modalities, survival after HNC remains low in Europe. In addition to the recognized prognostic effect of stage at diagnosis, smoking history and older age at diagnosis are important prognostic indicators for HNC.     

Central adiposity,obesity during early adulthood,and pancreatic cancer mortality in a pooled analysis of cohort studies

BackgroundBody mass index (BMI), a measure of obesity typically assessed in middle age or later, is known to be positively associated with pancreatic cancer. However, little evidence exists regarding the influence of central adiposity, a high BMI during early adulthood, and weight gain after early adulthood on pancreatic cancer risk.DesignWe conducted a pooled analysis of individual-level data from 20 prospective cohort studies in the National Cancer Institute BMI and Mortality Cohort Consortium to examine the association of pancreatic cancer mortality with measures of central adiposity (e.g. waist circumference; n = 647 478; 1947 pancreatic cancer deaths), BMI during early adulthood (ages 18–21 years) and BMI change between early adulthood and cohort enrollment, mostly in middle age or later (n = 1 096 492; 3223 pancreatic cancer deaths). Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models.ResultsHigher waist-to-hip ratio (HR = 1.09, 95% CI 1.02–1.17 per 0.1 increment) and waist circumference (HR = 1.07, 95% CI 1.00–1.14 per 10 cm) were associated with increased risk of pancreatic cancer mortality, even when adjusted for BMI at baseline. BMI during early adulthood was associated with increased pancreatic cancer mortality (HR = 1.18, 95% CI 1.11–1.25 per 5 kg/m²), with increased risk observed in both overweight and obese individuals (compared with BMI of 21.0 to <23 kg/m², HR = 1.36, 95% CI 1.20–1.55 for BMI 25.0 < 27.5 kg/m², HR = 1.48, 95% CI 1.20–1.84 for BMI 27.5 to <30 kg/m², HR = 1.43, 95% CI 1.11–1.85 for BMI ≥30 kg/m²). BMI gain after early adulthood, adjusted for early adult BMI, was less strongly associated with pancreatic cancer mortality (HR = 1.05, 95% CI 1.01–1.10 per 5 kg/m²).ConclusionsOur results support an association between pancreatic cancer mortality and central obesity, independent of BMI, and also suggest that being overweight or obese during early adulthood may be important in influencing pancreatic cancer mortality risk later in life.     

Are meat and heme iron intake associated with pancreatic cancer? Results from the NIH‐AARP diet and health cohort

Several studies on pancreatic cancer have reported significant positive associations for intake of red meat but null associations for heme iron. We assessed total, red, white and processed meat intake, meat cooking methods and doneness and heme iron and mutagen intake in relation to pancreatic cancer in the NIH‐AARP Diet and Health Study cohort. A total of 322,846 participants (187,265 men and 135,581 women) successfully completed and returned the food frequency questionnaire between 1995 and 1996. After a mean follow‐up of 9.2 years (up to 10.17 years), 1,417 individuals (895 men and 522 women) developed exocrine pancreatic cancer. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), and trends were calculated using the median value of each quantile. Models incorporated age as the time metric and were adjusted for smoking history, body mass index, self‐reported diabetes and energy‐adjusted saturated fat. Pancreatic cancer risk significantly increased with intake of total meat (Q5 vs. Q1: HR = 1.20, 95% CI 1.02–1.42, p‐trend = 0.03), red meat (HR = 1.22, 95% CI 1.01–1.48, p‐trend = 0.02), high‐temperature cooked meat (HR = 1.21, 95% CI 1.00–1.45, p‐trend = 0.02), grilled/barbequed meat (HR = 1.24, 95% CI 1.03–1.50, p‐trend = 0.007), well/very well done meat (HR = 1.32, 95% CI 1.10–1.58, p‐trend = 0.005) and heme iron from red meat (Q4 vs. Q1: HR = 1.21, 95% CI 1.01–1.45, p‐trend = 0.04). When stratified by sex, these associations remained significant in men but not women except for white meat intake in women (HR = 1.33, 95% CI 1.02–1.74, p‐trend = 0.04). Additional studies should confirm our findings that consuming heme iron from red meat increases pancreatic cancer risk.     

Use of oral contraceptives,intrauterine devices and tubal sterilization and cancer risk in a large prospective study,from 1996 to 2006

The association of contraceptive methods, including oral contraceptives (OC), intrauterine devices (IUD) and tubal sterilization (TS), with overall and site‐specific cancer were prospectively investigated in a cohort of 66,661 Chinese women in Shanghai, 76.7% of whom used contraception. During a median follow‐up time of 7.5 years, 2,250 women were diagnosed with cancer. Ever‐use of any contraceptive method was not associated with overall cancer risk [adjusted hazard ratio (HR_adj) = 1.02, 95% CI, 0.92–1.12]. Use of any contraceptive method was associated with increased risk of rectal cancer (HR_adj = 1.68, 95% CI, 1.08–2.62) and reduced risk of thyroid cancer (HR_adj = 0.63, 95% CI, 0.38–1.04). Risk of gallbladder cancer increased with ever use of OC (HR_adj = 2.38, 95% CI, 1.26–4.49). IUD use was associated with a possible reduced risk of thyroid cancer (HR_adj = 0.64, 95% CI, 0.38–1.07). Longer duration of IUD use decreased risk for breast, thyroid and lung cancers. Ever having a TS was associated with increased uterine body cancer (HR_adj = 2.50, 95% CI, 1.47–4.25) and decreased risk of stomach cancer (HR_adj = 0.59, 95% CI, 0.39–0.91). We did not find any contraceptive method to be related to the risk of ovarian cancer but the analyses were based on few events. Although chance findings are a likely explanation for some of the associations found in our study, these findings suggest that various contraceptive methods or reproductive patterns may play a role in the etiology of cancer. © 2008 Wiley‐Liss, Inc.     

Associations of metabolic syndrome and C‐reactive protein with mortality from total cancer,obesity‐linked cancers and breast cancer among women in NHANES III

Although metabolic syndrome (MetS) is a prognostic factor for cancer occurrence, the association of MetS and cancer mortality remains unclear. The purpose of this study was to evaluate whether MetS, components of MetS and C‐reactive protein (CRP) are associated with cancer mortality in women. A total of 400 cancer deaths, with 140 deaths from obesity‐linked‐cancers (OLCas), [breast (BCa), colorectal, pancreatic and endometrial], linked through the National Death Index, were identified from 10,104 eligible subjects aged ≥18 years. Cox proportional hazards regression was used to estimate multivariable‐adjusted hazard ratios (HR) for cancer mortality. MetS was associated with increased deaths for total cancer [HR = 1.33, 95% confidence interval (CI) 1.04–1.70] and BCa [HR = 2.1, 95% CI, 1.09–4.11]. The risk of total cancer [HR = 1.7, 95% CI, 1.12–2.68], OLCas [HR = 2.1, 95% CI, 1.00–4.37] and BCa [HR = 3.8, 95% CI, 1.34–10.91] mortality was highest for women with all MetS components abnormal, compared to those without MetS. Linear associations of blood‐pressure [HR = 2.5, 1.02–6.12, Quartile (Q) 4 vs Q1, p trend = 0.004] and blood‐glucose [HR = 2.2, 1.04–4.60, Q4 vs. Q1, p trend = 0.04] with total‐OLCas mortality were observed. A threefold increased risk of BCa mortality was observed for women with enlarged waist circumference, ≥100.9 cm, [HR = 3.5, 1.14–10.51, p trend = 0.008] and in those with increased blood glucose, ≥101 mg/dL, [HR = 3.2, 1.11–9.20, p trend = 0.03] compared to those in Q1. None of the components of MetS were associated with total‐cancer mortality. CRP was not associated with cancer mortality. In conclusion, MetS is associated with total‐cancer and breast‐cancer mortality, with waist circumference, blood pressure and blood glucose as independent predictors of OLCas and BCa mortality.     

Impact of teenage oral contraceptive use in a population-based series of early-onset breast cancer cases who have undergone BRCA mutation testing

Oral contraceptive (OC) use in young women has been associated with an increased risk of breast cancer. This matched case-control study aims to elucidate the combined effects of OC use and genetic factors in a population-based series of BRCA1/2 mutation-tested early-onset breast cancers. A first invasive breast cancer was diagnosed in 259 women aged 40 years between 1990 and 1995 in the South Swedish Health Care Region. A total of 245 women were included in this study. Information on family history of cancer, reproductive factors, smoking and OC use was obtained from questionnaires or patient charts. Three age-matched controls per case were chosen from a prospective South Swedish cohort. Ever OC use and current OC use were not associated with breast cancer. Cases were more likely to have used OCs before age 20 years (adjusted odds ratio (OR) 2.10 (95% CI 1.32-3.33)) and before their first child (adjusted OR 1.63 (95% CI 1.02-2.62)). When stratified by age, the effect of early OC use was limited to women diagnosed prior to age 36 years (OR 1.53 (1.17-1.99) per year of OC use prior to age 20 years). The risks were similar for low-dose and high-dose OCs. The probability of being a BRCA1/2 mutation carrier was three times higher among cases who started OC use prior to age 20 years compared with cases who started at age 20 years or older or who had never used OCs. However, the duration of OC use was similar among cases with and without BRCA1/2 mutations. No association was seen with a first-degree family history of breast cancer. Each year of OC use prior to age 20 years conferred a significantly increased risk for early-onset breast cancer, while there was no risk associated with use after age 20 years.     

Modest increase in risk of specific types of cancer types in type 2 diabetes mellitus patients

Most studies associated diabetes mellitus (DM) with risk of cancer have focused on the Caucasian population and only a few types of cancer. Therefore, a large and comprehensive nationwide retrospective cohort study involving an Asian population was conducted to evaluate the risk of several major types of cancer among Type 2 DM patients. The study analyzed the nationwide population‐based database from 1996 to 2009 released by the National Health Research Institute in Taiwan. Incidence and hazard ratios (HRs) were calculated for specific types of cancer. The overall risk of cancers was significantly greater in the DM cohort [N = 895,434; HR = 1.19, 95% confidence interval (CI) = 1.17–1.20], compared with non‐DM controls (N = 895,434). Several organs in the digestive and urogenital systems showed increased risk of cancer. The three highest HRs were obtained from cancers of the liver (HR = 1.78, 95% CI = 1.73–1.84), pancreatic (HR = 1.52, 95% CI = 1.40–1.65), and uterus and corpus (HR = 1.38, 95% CI = 1.22–1.55). The risk increased with age, and men with DM aged ≥75 years exhibited the highest risk (HR = 7.76, 95% CI = 7.39–8.15). Subjects with DM in this population have a modest increased risk of cancer, similar to the Caucasian population for several specific types of cancer. Old men with DM have the highest risk of cancer. Careful screening for cancer in DM patients is important for early diagnosis and effective treatment.     

Allergies,obesity, other risk factors and survival from pancreatic cancer

Survival from pancreatic adenocarcinoma remains extremely poor, approximately 5% at 5 years. Risk factors include smoking, high body mass index (BMI), family history of pancreatic cancer, and long‐standing diabetes; in contrast, allergies are associated with reduced risk. Little is known about associations between these factors and survival. We analyzed overall survival in relation to risk factors for 475 incident cases who took part in a hospital based case–control study. Analyses were conducted separately for those who did (160) and did not (315) undergo tumor resection. Kaplan‐Meier methods were used to describe survival according to smoking, BMI, family history, diabetes, and presence of allergies. Cox proportional hazards models were used to adjust for covariates. There was no association with survival based on smoking, family history, or history of diabetes in either group. Among patients with resection, those with allergies showed nonstatistically significant longer survival, a median of 33.1 months (95% CI: 19.0–52.5) vs. 21.8 months (95% CI: 18.0–33.1), p = 0.25. The adjusted hazard ratio (HR) was 0.72 (95% CI: 0.43–1.23), p = 0.23. Among patients without resection, those with self‐reported allergies survived significantly longer than those without allergies: 13.3 months (95% CI: 10.6–16.9) compared to 10.4 months (95% CI: 8.8–11.0), p = 0.04, with an adjusted HR of 0.68 (95% CI: 0.49–0.95), p = 0.02. Obesity was nonsignificantly associated with poorer survival, particularly in the resected group (HR = 1.62, 95% CI: 0.76–3.44). The mechanisms underlying the association between history of allergies and improved survival are unknown. These novel results need to be confirmed in other studies.     

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.     

A population-based cohort study of HRT use and breast cancer in southern Sweden

The overall tumour incidence and breast cancer incidence related to hormone replacement therapy (HRT) were followed in a population-based cohort of 29 508 women, aged 25-65 when interviewed in 1990-92. By the end of the follow up in December 1999, there were 226 611 person-years of observation. A total of 1145 malignant tumours were recorded (expected 1166.6; SIR = 0.98, 95% CI 0.93-1.04). There was a small excess of breast cancer with 434 observed and 387.69 expected (SIR = 1.12, 95% CI 1.02-1.23). Among about 3 663 ever users of HRT, there was no increase in overall tumour incidence (SIR = 0.98, 95% CI 0.86-1.12) but a significant excess of breast cancer (SIR = 1.35, 95% CI 1.09-1.64) compared with never users (SIR = 1.07, 95% CI 0.96-1.19). Breast cancer increased with increasing duration of use and for 48-120 months use the SIR was 1.92 (95% CI 1.32-2.70). There was no significant interaction with family history of breast cancer although an independent additive effect was suggested between HRT use and family history. In a Cox regression model time to breast cancer in relation to duration of HRT use was analysed adjusting for age at menarche, age at menopause, age at first full term pregnancy, parity and age at diagnosis. A significantly higher risk was seen for longer duration of HRT use compared with never users. No increased risk is seen in women beyond 5 years after stopping HRT. There was no interaction between previous use of oral contraceptives and later HRT use.     

Snus use,smoking and survival among prostate cancer patients

Smoking is associated with prostate cancer mortality. The Scandinavian smokeless tobacco product snus is a source of nicotine but not the combustion products of smoke and has not been studied with respect to prostate cancer survival. The study is nested among 9,582 men with incident prostate cancer within a prospective cohort of 336,381 Swedish construction workers. Information on tobacco use was collected at study entry between 1971 and 1992, and categorized into (i) never users of any tobacco, (ii) exclusive snus: ever users of snus only, (iii) exclusive smokers: ever smokers (cigarette, cigar and/or pipe) only and (iv) ever users of both snus and smoking. Hazard ratios for prostate cancer‐specific and total mortality for smoking and snus use based on Cox proportional hazards models adjusted for age, calendar period at diagnosis and body mass index at baseline. During 36 years of follow‐up, 4,758 patients died—2,489 due to prostate cancer. Compared to never users of tobacco, exclusive smokers were at increased risk of prostate cancer mortality (HR 1.15, 95% CI: 1.05–1.27) and total mortality (HR 1.17, 95% CI: 1.09–1.26). Exclusive snus users also had increased risks for prostate cancer mortality (HR 1.24, 95% CI: 1.03–1.49) and total mortality (HR 1.19, 95% CI: 1.04–1.37). Among men diagnosed with nonmetastatic disease, the HR for prostate cancer death among exclusive snus users was 3.17 (95% CI: 1.66–6.06). The study is limited by a single assessment of tobacco use prior to diagnosis. Snus use was associated with increased risks of prostate cancer and total mortality among prostate cancer patients. This suggests that tobacco‐related components such as nicotine or tobacco‐specific carcinogens may promote cancer progression independent of tobacco's combustion products.     

Smoking,snus use and risk of right‐ and left‐sided colon,rectal and anal cancer: A 37‐year follow‐up study

Although some authorities consider smoking to be an established risk factor for colorectal cancer, the international literature is not entirely consistent. Further, only 1 study has addressed the association with smokeless tobacco and none with Scandinavian moist snuff (snus). This retrospective cohort study included 336,381 male Swedish construction workers with detailed information on tobacco use at cohort entry in 1971–1992. Complete follow‐up through 2007 was accomplished by means of linkage to population and health registers. Hazard ratios (HRs) and 95% confidence intervals (CIs) derived from Cox proportional hazards regression models estimated relative risks, adjusted for age and body mass index. Subjects who were never‐users of any tobacco served as reference. After up to 37 years of follow‐up, pure smoking was associated with a marginally increased risk of colon cancer (HR 1.08, 95% CI 0.99–1.19), a modestly elevated risk of rectal cancer (HR 1.16, 95% CI 1.04–1.30) and a substantial excess risk of anal cancer (HR 2.41, 95% CI 1.06–5.48). Snus use was not significantly associated with an increased risk of colorectal or anal cancer, although the point estimate for colon cancer was similar to that observed among smokers. Swedish data provide meager support for the association between tobacco use and colorectal cancer. A general tendency among Swedish men to quit smoking in recent decades might have attenuated true associations. A link between smoking and anal cancer was confirmed.     

Hormone replacement therapy and oral contraceptives and risk of oesophageal adenocarcinoma: A systematic review and meta‐analysis

There is an unexplained strong male predominance in the aetiology of oesophageal adenocarcinoma (OAC). The hypothesis that oestrogens are protective, deserves attention. A potential protective influence of exogenous oestrogen exposure, that is, hormone replacement therapy (HRT) and oral contraceptives (OC) has been addressed only in studies of limited statistical power, and the individual studies have not provided conclusive results. We conducted a systematic literature search and meta‐analysis on HRT and OC and the risk of OAC. We used the databases PubMed and the Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by the Mantel–Haenszel random‐effect method. A total of five studies were included. Compared to never users, ever users of HRT had a statistically significantly decreased risk of OAC (pooled OR = 0.75; 95% CI: 0.58–0.98), and ever users of OC had a borderline significantly decreased risk of this cancer (pooled OR = 0.76; 95% CI: 0.57–1.00). In conclusion, HRT and OC use seems to be associated with a decreased risk of OAC. However, further research is warranted.     

A prospective analysis of telomere length and pancreatic cancer in the alpha‐tocopherol beta‐carotene cancer (ATBC) prevention study

Smoking and diabetes, consistent risk factors for pancreatic cancer, are also factors that influence telomere length maintenance. To test whether telomere length is associated with pancreatic cancer risk, we conducted a nested case–control study in the Alpha‐Tocopherol, Beta‐Carotene Cancer Prevention (ATBC) Study cohort of male smokers, aged 50–69 years at baseline. Between 1992 and 2004, 193 incident cases of pancreatic adenocarcinoma occurred (mean follow‐up from blood draw: 6.3 years) among participants with whole blood samples available for telomere length assays. For these cases and 660 controls, we calculated odds ratios (OR) and 95% confidence intervals using unconditional logistic regression, adjusting for age, number of years smoked regularly, and history of diabetes mellitus. Telomere length was categorized into quartiles (shortest to longest) and analyzed as both a categorical and a continuous normal variable (reported per 0.2 unit increase in telomere length). All statistical tests were two‐sided. Longer telomere length was significantly associated with increased pancreatic cancer risk (continuous OR = 1.26 95% CI = 1.09–1.46; highest quartile compared to lowest, OR = 1.57, 95% CI = 1.01–2.43, p‐trend = 0.007). This association remained for subjects diagnosed within the first five years of blood draw (continuous OR = 1.46, 95% CI = 1.19–1.79 highest quartile OR = 2.92, 95% CI = 1.47–5.77, p‐trend = 0.002), but not those diagnosed greater than five years after blood draw (continuous OR = 1.03, 95% CI = 0.85–1.22; highest quartile OR = 1.04, 95% CI = 0.60–1.79). This is the first prospective study to suggest an association between longer blood leukocyte telomere length and increased pancreatic cancer risk.     

Tobacco smoking and alcohol drinking at diagnosis of head and neck cancer and all‐cause mortality: Results from head and neck 5000, a prospective observational cohort of people with head and neck cancer

Tobacco smoking and alcohol consumption are well‐established risk factors for head and neck cancer. The prognostic role of smoking and alcohol intake at diagnosis have been less well studied. We analysed 1,393 people prospectively enrolled into the Head and Neck 5000 study (oral cavity cancer, n=403; oropharyngeal cancer, n=660; laryngeal cancer, n=330) and followed up for a median of 3.5 years. The primary outcome was all‐cause mortality. We used Cox proportional hazard models to derive minimally adjusted (age and gender) and fully adjusted (age, gender, ethnicity, stage, comorbidity, body mass index, HPV status, treatment, education, deprivation index, income, marital status, and either smoking or alcohol use) mortality hazard ratios (HR) for the effects of smoking status and alcohol intake at diagnosis. Models were stratified by cancer site, stage and HPV status. The fully‐adjusted HR for current versus never‐smokers was 1.7 overall (95% confidence interval [CI] 1.1, 2.6). In stratified analyses, associations of smoking with mortality were observed for oropharyngeal and laryngeal cancers (fully adjusted HRs for current smokers: 1.8 (95% CI=0.9, 3.40 and 2.3 (95% CI=0.8, 6.4)). We found no evidence that people who drank hazardous to harmful amounts of alcohol at diagnosis had a higher mortality risk compared to non‐drinkers (HR=1.2 (95% CI=0.9, 1.6)). There was no strong evidence that HPV status or tumour stage modified the association of smoking with survival. Smoking status at the time of a head and neck cancer diagnosis influenced all‐cause mortality in models adjusted for important prognostic factors.     

Reproductive factors and menopausal hormone therapy and bladder cancer risk in the NIH‐AARP Diet and Health Study

The incidence of bladder cancer among women is at least one‐third to one‐fourth that observed among men in many countries. Even after accounting for known risk factors, the reason for this gender disparity remains unexplained. We conducted a comprehensive evaluation of reproductive factors and exogenous hormone use with a primary focus on menopausal hormone therapy use and risk of bladder cancer in women in the NIH‐AARP Diet and Health Study. Reproductive and hormonal factors were ascertained on the baseline questionnaire in 1995–1996 among 201,492 females who were followed until December 31, 2006. During follow‐up, 651 cases of bladder cancer were diagnosed. A subset of women provided detailed information on use of MHT in a second questionnaire in 1996–1997. In this analysis, 127,361 females were followed through June 30, 2002 and 198 incident bladder cancer cases were identified. Cox proportional hazard models, adjusted for smoking status, cigarettes per day and body mass index using age as the time metric, were used to obtain hazard ratios (HRs). A reduced risk was observed among parous women (HR=0.76; 95% CI 0.62–0.93) and women who reported late age at menarche (≥15 years) (HR=0.57; 95% CI 0.39–0.84). Women who reported ever using estrogen and progestin therapy had a decreased risk (HR=0.53; 95% CI: 0.34–0.83) compared with women who did not report MHT use. No association was observed for estrogen only users (HR=0.82; 95% CI: 0.58–1.15). Our results suggest a putative role for sex hormones in the etiology of bladder cancer among women.     

Risk of endometrial cancer in relationship to cigarette smoking: results from the EPIC study

Current epidemiologic evidence indicates that cigarette smoking reduces the risk of endometrial cancer. We examined data from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to analyze further aspects of the smoking-endometrial cancer relationship, such as possible modifying effects of menopausal status, HRT use, BMI and parity. In a total of 249,986 women with smoking exposure and menopausal status information, 619 incident endometrial cancer cases were identified during 1.56 million person-years of follow-up. Among postmenopausal women, the hazard ratio (HR) for current smokers versus never smokers was 0.70 (95% CI = 0.53-0.93), while it was 1.75 (95% CI = 1.13-2.70) among premenopausal women at recruitment. After adjustment for risk factors, the HR for postmenopausal women was slightly attenuated to 0.78 (95% CI = 0.59-1.03). No heterogeneity of effect was observed with HRT use or BMI. Among premenopausal women, current smokers of more than 15 cigarettes per day or who smoked for 30 years or more at the time of recruitment had a more than 2-fold increased risk of endometrial cancer compared to never smokers (HR = 2.54; 95% CI = 1.47-4.38 and HR = 2.23; 95% CI = 1.04-4.77, respectively). Past smoking was not associated with endometrial cancer risk, either among pre- or postmenopausal women. In this prospective study, we observed an increased risk of endometrial cancer with cigarette smoking in premenopausal women. The reduction of endometrial cancer risk observed among postmenopausal women does not have direct public health relevance since cigarette smoking is the main known risk factor for cancer.