Breast cancer risk factors and age at diagnosis: an Icelandic cohort study

An increasing number of studies indicates that the strength and even direction of association between breast cancer and established risk factors differ according to the woman's age when she develops the disease. This was studied in the setting of a population based cancer registry using a databank with information on age at menarche, parity, age at first birth, oral contraceptive (OC) use, lactation, height and weight. From a cohort of 80.219 women attending population-based cervical and breast cancer screening in Iceland, 1120 cases were identified, aged 26-90 years at diagnosis and 10,537 controls, individually matched to the cases on birth year and age when attending. Information given at last visit before diagnosis was used in the analysis, applying conditional logistic regression. Odds ratios and statistical strength of relationships varied according to age at diagnosis for age at first birth, number of births, duration of lactation, height and weight. The decreased risk associated with young age at first birth and increasing duration of breast feeding became less pronounced with advancing age at diagnosis. A reduced risk associated with an increasing number of births was not detected in women diagnosed under the age of 40. An increased risk associated with giving first birth after 30 years of age was mainly detected in women who had only given 1 birth and were diagnosed under the age of 40 (OR = 7.06 95% CI = 2.16-23.01). A positive association with height and especially with weight was confined to women diagnosed after the age of 55. The results confirm that age at diagnosis should be taken into account when studying the effects of breast cancer risk factors.     

Risk of cholecystitis in patients with cancer: a population-based cohort study in Denmark

BACKGROUND.

To the authors' knowledge, little information is available regarding the incidence of cholecystitis among patients with cancer.

METHODS.

The authors conducted a population‐based historical cohort study of 51,228 patients with incident cancer, identified in medical databases of western Denmark between 1995 and 2003. A general population comparison cohort of 512,280 persons was assembled using the Danish Civil Registration System. The occurrence of cholecystitis in the 2 groups was determined by linkage to the regional Hospital Discharge Registry.

RESULTS.

In all, 230 incident diagnoses of cholecystitis were identified in the cancer cohort during 130,185 person‐years (median follow‐up time: 1.6 years), corresponding to an incidence rate of 1.8 of 1000 person‐years. After adjustment for confounders, the relative risk (RR) for cholecystitis among cancer patients compared with the general population cohort was 1.38 (95% confidence interval [95% CI], 1.20‐1.58). Overall, the RR for cholecystitis was doubled during the first 6 months after cancer diagnosis (RR = 1.95; 95% CI, 1.50‐2.54), after which the RR declined but remained greater than 1 throughout the rest of the follow‐up period (RR = 1.23; 95% CI, 1.05‐1.45). Cancer patients between the ages of 51 and 70 years had the highest risk increase for cholecystitis compared with other age groups. During the first 6 months after a cancer diagnosis, pancreatic cancers (12 cholecystitis events; RR = 9.44 [95% CI, 5.18‐17.18]) and colorectal cancers (10 cholecystitis events; RR = 4.98 [95% CI, 2.65‐9.34]) were found to be associated with the greatest cholecystitis risk increase compared with other tumor types. After 6 months, most cancers were associated with a relatively small increased risk, although there was an RR of 4.72 (95% CI, 1.99‐11.21) based on 5 cholecystitis events among thyroid cancer patients.

CONCLUSIONS.

The results of the current study indicate that cholecystitis occurs more frequently among cancer patients than in the general population, particularly within the first 6 months after a cancer diagnosis. Clinicians who treat cancer patients should remain vigilant about this type of infection. Cancer 2008. © 2008 American Cancer Society.     

Retrospective cohort study of risk-factors for esophageal cancer in Linxian,People's Republic of China

A retrospective cohort study of esophageal (including gastric cardia) cancer was conducted to examine dietary and other potential risk factors in Linxian, a high-risk area in P.R. China. Study subjects were identified based on participation in a cytology examination conducted in 1974. They were interviewed in 1989 to obtain information on esophageal cancer risk-factors and identify new cases and deaths. A total of 1,162 subjects from the analytic cohort of 12,693 were determined to have developed esophageal cancer over the 15-year follow-up period. Results indicate that increased age, male gender, a positive family history, low education level, surface-water use, and pork consumption were the strongest risk factors for esophageal cancer identified in this cohort, while use of corn as a primary staple and infrequent consumption of fresh vegetables also were possible risk factors. Traditional or suspected risk factors for esophageal cancer in this and other populations—smoking and alcohol use, and pickled vegetable and moldy food consumption—were not risk factors in this study. Some variation in risk was seen based on the subject's cytology result from 1974. We conclude that dietary factors appear to play a role in the etiology of esophageal cancer in this high-risk population, but are less important than other constitutional factors such as age, gender, and family history.Drs Yu, Li, Wang, Guo, Wang, Liu, and Li are with the Cancer Institute of the Chinese Academy of Medicinal Sciences in Beijing, PRC. Drs Taylor, Dawsey, and Blot are with the National Cancer Institute in Bethesda, MD, USA. Dr Shen is with Henan Medical University in Zhengzhou, PRC. This project was funded partially by contract # NO1-CP-41019 from the US National Cancer Institute.     

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow‐up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non‐significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non‐aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers.     

Modifiable risk factors for advanced vs. early breast cancer in the French E3N cohort

Advanced breast cancer (BC) is associated with heavier treatments and poorer prognosis than early BC. Despite mammographic screening, advanced BC incidence remains stable. Little is known about risk factors differentially associated with advanced BC. We analyzed factors predicting for postmenopausal advanced vs. early BC in the E3N cohort. E3N has been prospectively following 98,995 French women aged 50–65 years at baseline since 1990. Hazard ratios (HRs) and 95% confidence intervals (CIs) for advanced and early invasive BC were estimated with multivariate Cox competing risk hazard models. With a median follow-up of 15.7 years, 4,941 postmenopausal BC were diagnosed, including 1,878 (38%) advanced BC. Compared to early BC, advanced BC was differentially associated with excess weight (HR 1.39 [95% CI = 1.26–1.53] vs. 1.08 [95% CI = 1.00–1.17], p_homogeneity < 0.0001) and living in a rural area (HR 1.14 [95% CI = 1.00–1.31] vs. 0.93 [95% CI = 0.82–1.04], p_homogeneity 0.02). Excess weight was the only differential risk factor for advanced BC for hormone-dependent BC and for women compliant with screening recommendations. Previous mammography was associated with reduced advanced BC risk (HR 0.86 [95% CI = 0.73–1.00]) and increased early BC risk (HR 1.36 [95% CI = 1.18–1.56], p_homogeneity < 0.0001), but only for hormone-dependent BC. Excess weight appears to be mostly associated with advanced BC, especially hormone-dependent BC. These results add to the evidence for maintaining weight within the recommended limits.     

Differential effects of reproductive factors on the risk of pre- and postmenopausal breast cancer. Results from a large cohort of French women

The aim of this study was to obtain a better understanding of the role of hormonal factors in breast cancer risk and to determine whether the effect of reproductive events differs according to age at diagnosis. It analysed the effect of age at menarche, age at first full-term pregnancy, number of full-term pregnancies and number of spontaneous abortions both on the overall risk of breast cancer and on its pre- or postmenopausal onset, using the data on 1718 breast cancer cases, obtained from a large sample of around 100000 French women participating in the E3N cohort study. The results provide further evidence that the overall risk of breast cancer increases with decreasing age at menarche, increasing age at first pregnancy and low parity. No overall effect of spontaneous abortions was observed. The effect of these reproductive factors differed according to menopausal status. Age at menarche had an effect on premenopausal breast cancer risk, with a decrease in risk with increasing age of 7% per year (P<0.05). Compared to those who had their first menstrual periods at 11 or before, women experiencing menarche at 15 or after had an RR of 0.66 (95% CI 0.45-0.97) in the premenopausal group. Age at first full-term pregnancy had an effect on both pre- and postmenopausal breast cancer risk, with significant tests showing increasing risk per year of increasing age (P=0.001 and P<0.05 respectively). A first full-term pregnancy above age 30 conveyed a risk of 1.63 (95% CI 1.12-2.38) and 1.35 (95% CI 1.02-1.78) in the pre- and postmenopausal groups respectively. A protective effect of high parity was observed only for postmenopausal breast cancer risk (P for trend test =0.001), with point estimates of 0.79 (95% CI 0.60-1.04), 0.69 (95% CI 0.54-0.88), 0.66 (95% CI 0.51-0.85) and 0.64 (95% CI 0.48-0.86) associated to a one, two, three and four or more full-term pregnancies. A history of spontaneous abortion had no significant effect on the risk of breast cancer diagnosed before or after menopause. Our results suggest that reproductive events have complex effects on the risk of breast cancer.     

Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the nutrition intervention trial cohort

Helicobacter pylori (H. pylori) infection is the strongest known risk factor for gastric noncardia adenocarcinoma (GNCA). We used multiplex serology to determine whether seropositivity to 15 H. pylori proteins is associated with the subsequent development of noncardia gastric cancer in Linxian, China. We included 448 GNCA cases and 1242 controls from two time points within the Linxian General Population Nutrition Intervention Trial, Linxian. H. pylori multiplex seropositivity was defined as positivity to ≥4 of the 15 included antigens. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for major GNCA risk factors. In addition, we undertook a meta‐analysis combining H. pylori multiplex serology data from both time points. H. pylori multiplex seropositivity was associated with a significant increase in risk of GNCA at one time point (1985; OR: 3.44, 95% CI: 1.91, 6.19) and this association remained significant following adjustment for H. pylori or CagA ELISA seropositivity (OR: 2.92, 95% CI: 1.56, 5.47). Combining data from both time points in a meta‐analysis H. pylori multiplex seropositivity was associated with an increased risk of GNCA, as were six individual antigens: GroEL, HP0305, CagA, VacA, HcpC and Omp. CagM was inversely associated with risk of GNCA. We identified six individual antigens that confer an increase in risk of GNCA within this population of high H. pylori seroprevalence, as well as a single antigen that may be inversely associated with GNCA risk. We further determined that the H. pylori multiplex assay provides additional information to the conventional ELISA methods on risk of GNCA.     

The preventable burden of breast cancers for premenopausal and postmenopausal women in Australia: A pooled cohort study

Estimates of the future breast cancer burden preventable through modifications to current behaviours are lacking. We assessed the effect of individual and joint behaviour modifications on breast cancer burden for premenopausal and postmenopausal Australian women, and whether effects differed between population subgroups. We linked pooled data from six Australian cohort studies (n = 214,536) to national cancer and death registries, and estimated the strength of the associations between behaviours causally related to cancer incidence and death using adjusted proportional hazards models. We estimated exposure prevalence from representative health surveys. We combined these estimates to calculate Population Attributable Fractions (PAFs) with 95% confidence intervals (CIs), and compared PAFs for population subgroups. During the first 10 years follow-up, there were 640 incident breast cancers for premenopausal women, 2,632 for postmenopausal women, and 8,761 deaths from any cause. Of future breast cancers for premenopausal women, any regular alcohol consumption explains 12.6% (CI = 4.3–20.2%), current use of oral contraceptives for ≥5 years 7.1% (CI = 0.3–13.5%), and these factors combined 18.8% (CI = 9.1–27.4%). Of future breast cancers for postmenopausal women, overweight or obesity (BMI ≥25 kg/m²) explains 12.8% (CI = 7.8–17.5%), current use of menopausal hormone therapy (MHT) 6.9% (CI = 4.8–8.9%), any regular alcohol consumption 6.6% (CI = 1.5–11.4%), and these factors combined 24.2% (CI = 17.6–30.3%). The MHT-related postmenopausal breast cancer burden varied by body fatness, alcohol consumption and socio-economic status, the body fatness-related postmenopausal breast cancer burden by alcohol consumption and educational attainment, and the alcohol-related postmenopausal breast cancer burden by breast feeding history. Our results provide evidence to support targeted and population-level cancer control activities.     

Prospective study of risk factors for esophageal and gastric cancers in the Linxian general population trial cohort in China

Esophageal cancer incidence and mortality rates in Linxian, China are among the highest in the world. We examined risk factors for esophageal squamous cell carcinoma (ESCC), gastric cardia cancer (GCC), and gastric noncardia cancer (GNCC) in a population-based, prospective study of 29,584 adults who participated in the Linxian General Population Trial. All study participants completed a baseline questionnaire that included questions on demographic characteristics, personal and family history of disease, and lifestyle factors. After 15 years of follow-up, a total of 3,410 incident upper gastrointestinal cancers were identified, including 1,958 ESCC, 1,089 GCC and 363 GNCC. Cox proportional hazard models were used to estimate risks. Increased age and a positive family history of esophageal cancer (including ESCC or GCC) were significantly associated with risk at all 3 cancer sites. Additional risk factors for ESCC included being born in Linxian, increased height, cigarette smoking and pipe smoking; for GCC, male gender, consumption of moldy breads and pipe smoking; and for GNCC, male gender and cigarette smoking. Protective factors for ESCC included formal education, water piped into the home, increased consumption of meat, eggs and fresh fruits and increased BMI; for GCC, formal education, water piped into the home, increased consumption of eggs and fresh fruits and alcohol consumption; and for GNCC, increased weight and BMI. General socioeconomic status (SES) is a common denominator in many of these factors and improving SES is a promising approach for reducing the tremendous burden of upper gastrointestinal cancers in Linxian.     

Body mass index and risk of gastric cancer: A 30‐year follow‐up study in the Linxian general population trial cohort

Although a number of previous studies have noted either positive or no association for body mass index (BMI) and gastric cancer risk, little evidence exists in the Chinese population. We prospectively examined the associations of BMI with risk of gastric cancer in the Linxian General Population Trial cohort, with 29 584 healthy adults enrolled in 1985 and followed through to the end of 2014. Body weight and height were measured during physical examination at baseline and BMI was calculated as weight in kilograms divided by height in meters squared. Body mass index from 138 subjects was missing, and a total of 29 446 participants were included in the final analysis. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals. During 30 years of follow‐up, we confirmed 1716 newly diagnosed gastric cardia adenocarcinoma (GCA) cases and 626 new gastric non‐cardia adenocarcinoma (GNCA) cases. Overall, compared to the lowest quartile (BMI <20.32 kg/m²), subjects in the fourth quartile (BMI ≥23.31 kg/m²) subjects had lower risk of developing GNCA (hazard ratio, 0.65; 95% confidence interval, 0.51–0.83). Age‐ and sex‐specific analyses showed that this protective effect was only observed in men and older (52 + years) persons. No associations were observed for BMI with GCA incidence. Higher BMI was associated with decreased risk of GNCA in this population, particularly in men and older persons. Future studies are needed to confirm these findings. The trial is registered with ClinicalTrials.gov: NCT00342654.     

Impact of alcohol drinking on total cancer risk: data from a large-scale population-based cohort study in Japan

We conducted a cohort study of alcohol consumption and total cancer incidence and mortality in 73,281 subjects (35,007 men and 38,274 women) aged 40-59 years old at baseline over a 10-year follow-up period. During 1990-2001, a total of 3403 cases of newly diagnosed cancer and 1208 cancer deaths were identified. In men, the lowest risk of developing cancer was observed among occasional drinkers, and a linear positive association with increased ethanol intake was noted (hazard ratio 1.18 for 1-149 g per week, 1.17 for 150-299 g per week, 1.43 for 300-449 g per week, 1.61 for > or = 450 g per week, P for trend < 0.001). The positive relation was similar for cancer incidence and mortality, but was more striking among current smokers and alcohol-related cancers. Relatively few women were regular drinkers. Our results suggest that increased ethanol intake linearly elevates the risk of cancer, and that nearly 13% of cancers among males in this study were due to heavy drinking (> or = 300 g per week of ethanol), to which smoking substantially contributed. The simultaneous reduction of smoking is therefore important for reducing the effect of alcohol on cancer risk.     

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

Background:

Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk.

Methods:

Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method.

Results:

No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HR_Q5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203).

Conclusions:

Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers.     

Reproductive Risk Factors for Thyroid Cancer: A Prospective Cohort Study in Khon Kaen,Thailand

Background: Because of the gender disparity in the incidence of thyroid cancer, this study aimed to determinethe association between reproductive factors and thyroid cancer. Methods: A total of 10,767 eligible women fromthe Khon Kaen Cohort, recruited and interviewed between 1990 and 2001, were followed up until 2011. Thedata were linked to the Khon Kaen Population-Based Cancer Registry to detect thyroid cancer cases. Results:There was 17 thyroid cancer cases detected, an incidence of 11.2 per 100,000 person-years, of which 70.6 % werepapillary tumors. The incidence was apparently greater among those with an early age of menarche, nulligravidawomen, and oral contraceptive users. Conlusions: There was a trend for thyroid cancer to develop in relationto longer estrogen exposure. This evidence is inconclusive but warrants further investigation.