Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m²: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.     

Hormonal factors and pancreatic cancer risk in women: The Malmö Diet and Cancer Study

The incidence of pancreatic cancer is leveling between sexes. Smoking, high age and heredity are established risk factors, but evidence regarding the influence of hormonal factors is unclear. In this study, we investigated the associations of reproductive factors, use of oral contraceptives (OC) and hormone replacement therapy (HRT) with pancreatic cancer risk in the Malmö Diet and Cancer Study, a prospective, population‐based cohort encompassing 17,035 women. Up until 31 December 2015, 110 women were identified with incident pancreatic cancer through the Swedish Cancer Registry. Higher age at menarche was significantly associated with pancreatic cancer risk (age‐adjusted [hazard ratio] HR = 1.17; 95% confidence interval [CI] 1.04–1.32, and fully adjusted HR = 1.17; 95% CI 1.04–1.32). Ever use of OC was not significantly associated with pancreatic cancer risk but ever use of HRT was significantly associated with a decreased risk of pancreatic cancer (age‐adjusted HR = 0.47, 95% CI 0.23–0.97, and fully adjusted HR = 0.48, 95% CI 0.23–1.00), in particular use of estrogen‐only regimen (age‐adjusted HR = 0.21; 95% CI 0.05–0.87 and fully adjusted HR = 0.22; 95% CI 0.05–0.90). Age at menopause or first childbirth, parity and breastfeeding history were not significantly associated with pancreatic cancer risk. Collectively, these findings suggest a protective role of female hormones against pancreatic cancer. Further studies are needed, and potential modifying genetic factors and indirect hazardous effects of smoking should also be considered.     

Use of anti-androgenic 5α-reductase inhibitors and risk of oesophageal and gastric cancer by histological type and anatomical sub-site

Background To investigate if anti-androgenic medications 5α-reductase inhibitors (5-ARIs) decrease the risk of developing oesophageal and gastric tumours, analysed by histological type and anatomical sub-site.Methods A Swedish population-based cohort study between 2005 and 2018 where men using 5-ARIs were considered exposed. For each exposed participant, ten male age-matched non-users of 5-ARIs (non-exposed) were included. Multivariable Cox regression provided hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, calendar year, smoking, non-steroidal anti-inflammatory drugs/aspirin use, and statins use. Further adjustments were made depending on the tumour analysed.Results The cohort included 191,156 users of 5-ARIs and 1,911,560 non-users. Overall, the use of 5-ARIs was not associated with any statistically significantly reduced risk of oesophageal or cardia adenocarcinoma (adjusted HR 0.92, 95% CI 0.82–1.02) or gastric non-cardia adenocarcinoma (adjusted HR 0.90, 95% CI 0.80–1.02). However, the use of 5-ARIs indicated a decreased risk of oesophageal or cardia adenocarcinoma among obese or diabetic participants (adjusted HR 0.55, 95% CI 0.39–0.80) and a reduced risk of oesophageal squamous cell carcinoma (adjusted HR 0.49, 95% CI 0.37–0.65).Conclusion Users of 5-ARIs may have a decreased risk of developing oesophageal or cardia adenocarcinoma among those obese or diabetic, and a decreased risk of oesophageal squamous cell carcinoma.Subject terms: Risk factors, Epidemiology     

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.     

Hormone replacement therapy and risks of oesophageal and gastric adenocarcinomas

Oesophageal and gastric adenocarcinoma share an unexplained male predominance, which would be explained by the hypothesis that oestrogens are protective in this respect. We carried out a nested case-control study of hormone replacement therapy (HRT) among 299 women with oesophageal cancer, 313 with gastric cancer, and 3191 randomly selected control women, frequency matched by age and calendar year in the General Practitioners Research Database in the United Kingdom. Data were adjusted for age, calendar year, tobacco smoking, alcohol consumption, body mass index, hysterectomy, and upper gastrointestinal disorders. Among 1 619 563 person-years of follow-up, more than 50% reduced risk of gastric adenocarcinoma was found among users of HRT compared to nonusers (odds ratio (OR), 0.48, 95% confidence interval (CI) 0.29-0.79). This inverse association appeared to be stronger for gastric noncardia (OR 0.34, 95% CI 0.14-0.78) and weaker for gastric cardia tumours (OR 0.68, 95% CI 0.23-2.01). There was no association between HRT and oesophageal adenocarcinoma (OR 1.17, 95% CI 0.41-3.32).     

Male pattern baldness and risk of incident skin cancer in a cohort of men

We examined the association between male‐pattern baldness and risk of incident skin cancer, including invasive melanoma, invasive squamous cell carcinoma (SCC), and basal cell carcinoma (BCC) in a prospective analysis, based on 36,032 participants from the Health Professionals' Follow‐up Study. In 1992, participants reported their status of male‐pattern baldness at age 45 years by choosing from five crown‐view pictograms based on Norwood's classification. Diagnosis of skin cancers was reported biennially and information on melanoma and SCC was pathologically confirmed. We identified 327 melanoma cases, 1324 SCC cases, and 8438 BCC cases during the follow‐up. Male‐pattern baldness was not significantly associated with risk of incident melanoma, but was significantly associated with increased risk of SCC and BCC. The multivariate‐adjusted hazard ratio (HR) (95% confidence interval, CI) for the highest category of baldness (frontal plus severe vertex baldness) was 1.33 (1.06–1.68) for SCC (p_trend = 0.001) and 1.23 (1.12–1.35) for BCC (p_trend < 0.0001), compared with no baldness. Analyses by body sites found significant associations between frontal plus moderate to severe vertex baldness and risk of melanoma (HR = 1.83, 95% CI: 1.01–3.34) and SCC (HR = 1.30, 95% CI: 1.02–1.66) at head and neck. The associations were particularly stronger for scalp melanoma (HR = 7.15, 95% CI: 1.29–39.42) and scalp SCC (HR = 7.09, 95% CI: 3.84–13.08), but not for non‐scalp head and neck sites. Information on body sites was not available for BCC. In conclusion, male pattern baldness may be associated with increased risk of skin cancer, but the associations may only exist for those occurring at head and neck, particularly at scalp.     

Self-reported goiter is associated with a significantly increased risk of gastric noncardia adenocarcinoma in a large population-based Chinese cohort

Iodine is concentrated by the gastric mucosa, where it may act as an antioxidant. Therefore, iodine deficiency, and its sequelae goiter, may be associated with an increased risk of gastric cancer. We examined the association between self-reported goiter and upper gastrointestinal cancer in a Chinese cohort of 29,584 adults. Using multivariate adjusted Cox models, we found goiter associated with a significantly increased risk of gastric noncardia adenocarcinoma, HR (95% CI) 2.04 (1.01, 4.11) and nonsignificantly with gastric cardia adenocarcinoma, HR (95% CI) 1.45 (0.91, 2.30). We also found a borderline, insignificant increased risk of esophageal squamous cell carcinoma, HR (95% CI) 1.37 (0.97, 1.94). Our findings are consistent with the hypothesis that iodine deficiency is associated with an increased risk of gastric cancer.     

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.     

Reproductive and sex hormonal factors and oesophageal and gastric junction adenocarcinoma: A pooled analysis

BackgroundThe rapidly rising incidence and the striking male predominance are as yet unexplained features of oesophageal and gastric junction adenocarcinoma. Few and underpowered studies have examined the impact of female reproductive factors on risk of these adenocarcinomas in women. We therefore pooled data on women from four population-based case-control studies to examine the association of female reproductive and sex hormonal factors with oesophageal and gastric junction adenocarcinoma.MethodsData on women from case-control studies conducted in Ireland, the United Kingdom (UK), Australia and United States of America (USA) were pooled. Multivariable logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for a range of reproductive factors, adjusted for age, study and major risk factors for oesophageal and gastric junction adenocarcinoma.ResultsWe included 218 cases and 862 controls. Among parous women, a reduced risk of oesophageal and gastric junction adenocarcinoma was found after breastfeeding (OR = 0.58, 95% CI = 0.37–0.92) and the risk decreased with increased duration of breastfeeding (>12 months OR = 0.42, 95% CI = 0.23–0.77). The endogenous reproductive factors such as parity, menstruation, history of pregnancy and the exogenous factors such as use of oral contraceptives and of hormone replacement therapy were not statistically significantly associated with oesophageal and gastric junction adenocarcinoma.ConclusionOur findings suggest that breastfeeding is associated with a decreased risk of oesophageal and gastric junction adenocarcinoma. The potential mechanism of this association warrants further investigation.     

Oral disease and risk of oesophageal and gastric cancer in a nationwide nested case-control study in Sweden

The association between the exposure to oral disease and the outcomes of oesophageal and gastric cancer was examined in a Swedish nationwide inpatient register-based nested case-control study in 1964-2008. The study included 6,156 oesophageal squamous-cell carcinoma cases that were compared with 29,993 controls, 2684 oesophageal adenocarcinoma cases that were compared with 15,036 controls and 38,308 gastric cancer cases that were compared with 99,991 controls. For oesophageal squamous cell carcinoma, the age and sex adjusted odds ratio (OR) among patients with a history of oral disease was 1.3 (95% confidence interval (95% CI): 0.9,−1.9), and 1.1 (95% CI 0.8,−1.7) after adjustment for diseases related to alcohol consumption or tobacco smoking. For oesophageal adenocarcinoma, the age and sex adjusted OR was increased (OR 1.7, 95% CI 1.1-2.6), and remained increased (OR 1.6, 95% CI 1.0-2.4) after adjustment for diseases related to smoking or alcohol consumption, gastroesophageal reflux, obesity and ulcer disease. For gastric cancer, no statistically significantly increased risk was observed (age and sex adjusted OR 0.9, 95% CI 0.7-1.1, and fully adjusted OR 0.9, 95% CI 0.7-1.1). In conclusion, this study supports the hypothesis that oral disease increases the risk of oesophageal adenocarcinoma, but not for oesophageal squamous cell carcinoma or gastric cancer. Further investigations are warranted.     

Risk of adenocarcinomas of the oesophagus and gastric cardia in patients hospitalized for asthma.

In the first cohort study of the question we followed 92 986 (42 663 men and 50 323 women) adult patients hospitalized for asthma in Sweden from 1965 to 1994 for an average of 8.5 years to evaluate their risk of oesophageal and gastric cardia adenocarcinoma. Standardized incidence ratio (SIR) adjusted for gender, age and calendar year was used to estimate relative risk, using the Swedish nationwide cancer incidence rates as reference. Asthmatic patients overall had a moderately elevated risk for oesophageal adenocarcinoma (SIR = 1.5, 95% confidence interval CI, 0.9-2.5) and gastric cardia cancer (SIR = 1.4, 95% CI, 1.0-1.9). However, the excess risks were largely confined to asthmatic patients who also had a discharge record of gastro-oesophageal reflux (SIR = 7.5, 95% CI, 1.6-22.0 and SIR = 7.1, 95% CI, 3.1-14.0, respectively). No significant excess risk for oesophageal squamous-cell carcinoma or distal stomach cancer was observed. In conclusion, asthma is associated with a moderately elevated risk of developing oesophageal or gastric cardia adenocarcinoma. Special clinical vigilance vis-à-vis gastro-esophageal cancers seems unwarranted in asthmatic patients, but may be appropriate in those with clinically manifest gastro-oesophageal reflux.     

Age, sexual behavior and human papillomavirus infection in oral cavity and oropharyngeal cancers

There are few well-established patient risk factors associated with human papillomavirus (HPV) infection in cancers of the oral cavity and oropharynx. The purpose of this study was to determine if there were significant different risk factors and tumor characteristics between HPV-positive and HPV-negative cancer cases. HPV was evaluated in cancer tissue and exfoliated oral cells of 193 oral cavity/oropharynx cancer patients using PCR and direct DNA sequencing. A patient questionnaire collected information about risk factors, sexual practices and medical history. The prevalence of HPV high-risk (HR) types was 20% in cancer cases. Three types were identified: HPV-16 (87%), HPV-18 (3%) and HPV-33 (11%). Risk factors for HPV-HR included younger age (< or = 55 years vs. > 55 years; adjusted OR = 3.4; 95% CI = 1.6-7.3) and younger-age cases who had more lifetime sex partners (adjusted OR = 3.8; 95% CI = 1.4-10.1), practiced oral-genital sex (adjusted OR = 4.3; 95% CI = 1.8-10.4) or oral-anal sex (adjusted OR = 19.5; 95% CI = 3.4-113). Compared to HPV-negative cancers, HPV-HR cancers were more likely to have a positive HPV-HR exfoliated oral cytology test (adjusted OR = 7.8; 95% CI = 3.4-18.4), later stage (adjusted OR = 3.0), nodal involvement (adjusted OR = 4.1) and advanced grade (adjusted OR = 3.0). This study shows new evidence that the prevalence of oncogenic mucosal HPV is higher in younger-age oral cavity/oropharynx cancer cases whose sexual practices are typically associated with sexual transmission of the virus. HPV detection also appears to be an indicator of advanced disease characteristics that may require different clinical treatment for this subset of patients. An exfoliated oral cytology test for HPV was a significant predictor of HR types in the cancers, suggesting that an oral rinse may provide an early biomarker of infected tumors.     

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers

We prospectively examined the relation between pretrial serum vitamin D status and risk of oesophageal and gastric cancers among subjects who developed cancer over 5.25 years of follow-up, including 545 oesophageal squamous cell carcinomas (ESCC), 353 gastric cardia adenocarcinomas, 81 gastric noncardia adenocarcinomas, and an age- and sex-stratified random sample of 1105 subjects. The distribution of serum 25(OH)D was calculated using the known sampling weights. For the cohort as a whole, the 25th, 50th, and 75th percentile concentrations of 25(OH)-vitamin D were 19.6, 31.9, and 48.7 nmol l(-1), respectively, and we found that higher serum 25(OH)D concentrations were associated with monotonically increasing risk of ESCC in men, but not in women. Comparing men in the fourth quartile of serum 25(OH)D concentrations to those in the first, we found a hazard ratio (HR) (95% confidence interval (CI)) of 1.77 (1.16-2.70), P trend=0.0033. The same comparison in women had a HR (95% CI) of 1.06 (0.71-1.59), P trend=0.70. We found no associations for gastric cardia or noncardia adenocarcinoma. Among subjects with low vitamin D status, higher serum 25(OH)D concentrations were associated with significantly increased risk of ESCC in men, but not in women. Further refinements of the analysis did not suggest any factors, which could explain this unexpected result.     

Risk factors for oesophageal,lung, oral and laryngeal cancers in black South Africans

The authors used data collected from 1995 to 1999, from an on-going cancer case-control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5-4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6-204.6) for lung cancer in women, and 23.9 (95% CI 9.5-60.3) for lung cancer and 23.6 (95% CI 4.6-121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7-46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1-7.5) in men working in 'potentially noxious' industries. 'Frequent' alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0-2.9, for women and odds ratio=1.8, 95% CI 1.2-2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8-7.9 in males and odds ratio=4.8, 95% CI 3.2-6.1 in females). The above results are broadly in line with international findings.     

Reproductive and hormonal factors and risk of lung cancer in women: a prospective cohort study

Several lines of evidence suggest that endocrine factors may play a role in the development of lung cancer, but the evidence is limited and inconsistent. We investigated the association of reproductive and hormonal factors with risk of lung cancer in the National Breast Screening Study, which included 89,835 Canadian women aged 40-59 years at recruitment between 1980 and 1985. Linkages to national cancer and mortality databases provided data on cancer incidence and deaths from all causes, respectively, with follow-up ending between 1998 and 2000. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between hormonal factors and lung cancer. During a mean of 16.4 years of follow-up, we observed 750 incident lung cancer cases. After adjustment for covariates, parous women were not at increased risk of lung cancer (HR = 1.18, 95% CI 0.94-1.47) relative to nulliparous women; however, there was a modest increase in risk with increasing parity, reaching a HR of 1.42, 95% CI 1.06-1.88 in women who had 5 or more live births (p for trend 0.02). Among parous women, age at first live birth was inversely associated with risk. Women who had their first live birth at age 30 or older were at reduced risk relative to women who had their first live birth below age 23 (HR 0.68, 95% CI 0.50-0.93, p for trend 0.004). These associations did not differ by age at enrollment (40-49 vs. 50-59 years old), but were somewhat strengthened when attention was restricted to never smokers. Ever use of exogenous hormones showed little association with lung cancer risk; however, long-term users of hormone replacement therapy were at slightly increased risk. Our results add to the limited existing evidence that certain reproductive and hormonal factors may be associated with lung cancer risk in women.     

Mammographic density and estrogen receptor status of breast cancer.

BACKGROUND: The density of breast tissue on a mammogram is a strong predictor of breast cancer risk and may reflect cumulative estrogen effect on breast tissue. Endogenous and exogenous estrogen exposure increases the risk of estrogen receptor (ER)-positive breast cancer. We determined if mammographic density is associated more strongly with ER-positive breast cancer than with ER-negative breast cancer.METHODS: We analyzed data from 44,811 participants in the San Francisco Mammography Registry of whom 701 developed invasive breast cancer. Mammographic density was measured using the Breast Imaging Reporting and Data System (BI-RADS) classification system (1 = almost entirely fat, 2 = scattered fibroglandular, 3 = heterogeneously dense, 4 = extremely dense). We tested for associations between mammographic density and ER-positive and ER-negative breast cancer separately. Analyses were adjusted for age, body mass index, postmenopausal hormone use, family history of breast cancer, menopausal status, parity, and race/ethnicity.RESULTS: Mammographic density was strongly associated with both ER-positive and ER-negative breast cancers. Compared with women with BI-RADS 2, women with BI-RADS 1 (lowest density) had a lower risk of ER-positive cancer [adjusted hazard ratio (HR), 0.28; 95% confidence interval (95% CI), 0.16-0.50] and ER-negative cancer (adjusted HR, 0.17; 95% CI, 0.04-0.70). Women with BI-RADS 4 (highest density) had an increased risk of ER-positive breast cancer (adjusted HR, 2.21; 95% CI, 1.64-3.04) and an increased risk of ER-negative breast cancer (adjusted HR, 2.21; 95% CI, 1.16-4.18).CONCLUSION: Surprisingly, women with high mammographic density have an increased risk of both ER-positive and ER-negative breast cancers. The association between mammographic density and breast cancer may be due to factors besides estrogen exposure.     

Italian mediterranean index and risk of colorectal cancer in the Italian section of the EPIC cohort

Colorectal cancer is among the commonest cancers worldwide. Dietary factors have been linked to colorectal cancer risk, however, few studies have evaluated the relationship between a priori dietary patterns and colorectal cancer risk. We evaluated the effect of adherence to a Mediterranean dietary pattern, as measured by the Italian Mediterranean Index, on the risk of colorectal cancer in the 45,275 participants of the Italian section of the EPIC study who completed a dietary questionnaire. Hazard ratios (HRs) with 95% confidence intervals (CIs) for colorectal cancer in relation to categories of Italian Mediterranean Index score were estimated by multivariate Cox models adjusted for known risk factors, on the whole cohort, on men and women and according to cancer subsite. During a mean follow‐up of 11.28 years, 435 colorectal cancer cases were identified. The Italian Mediterranean Index was inversely associated with colorectal cancer risk (HR: 0.50; 95% CI: 0.35–0.71 for the highest category compared to the lowest, P‐trend: 0.043). Results did not differ by sex. Highest Italian Mediterranean Index score was also significantly associated with reduced risks of any colon cancer (HR: 0.54, 95% CI: 0.36–0.81), distal colon cancer (HR: 0.44, 95% CI: 0.26–0.75) and rectal cancer (HR: 0.41, 95% CI: 0.20–0.81), but not of proximal colon cancer. These findings suggest that adherence to a Mediterranean diet (as measured by the Italian Mediterranean Index) protects against colorectal cancer in general but not against cancer developing in the proximal colon.     

Volume-outcome relation in palliative systemic treatment of metastatic oesophagogastric cancer

IntroductionPalliative systemic therapy has been shown to improve survival in metastatic oesophagogastric cancer. Administration of palliative systemic therapy in metastatic oesophagogastric cancer varies between hospitals. We aimed to explore the association between the annual hospital volume of oesophagogastric cancer patients and survival.MethodsPatients diagnosed in the Netherlands between 2005 and 2013 with metastatic oesophagogastric cancer were identified in the Netherlands Cancer Registry. Patients were attributed according to three definitions of high volume: (1) high-volume incidence centre, (2) high-volume treatment centre and (3) high-volume surgical centre. Independent predictors for administration of palliative chemotherapy were evaluated by means of multivariable logistic regression analysis, and multivariable Cox proportional hazard regression analysis was performed to assess the impact of high-volume centres on survival.ResultsOur data set comprised 4078 patients with metastatic oesophageal cancer, and 5425 patients with metastatic gastric cancer, with a median overall survival of 20 weeks (95% confidence interval [CI] 19–21 weeks) and 16 weeks (95% CI 15–17 weeks), respectively. Patients with oesophageal cancer treated in a high-volume surgical centre (adjusted hazard ratio [HR] 0.80, 95% CI 0.70–0.91) and a high-volume treatment centre (adjusted HR 0.88, 95% CI 0.78–0.99) exhibited a decreased risk of death. For gastric cancer, patients treated in a high-volume surgical centre (adjusted HR 0.83, 95% CI 0.74–0.92) had a superior outcome.ConclusionImproved survival in patients undergoing palliative systemic therapy for oesophagogastric cancer was associated with treatment in high-volume treatment and surgical centres. Further research should be implemented to explore which specific factors of high-volume centres are associated with improved outcomes.     

Hair dye and chemical straightener use and breast cancer risk in a large US population of black and white women

Many hair products contain endocrine-disrupting compounds and carcinogens potentially relevant to breast cancer. Products used predominately by black women may contain more hormonally-active compounds. In a national prospective cohort study, we examined the association between hair dye and chemical relaxer/straightener use and breast cancer risk by ethnicity. Sister Study participants (n = 46,709), women ages 35–74, were enrolled between 2003 and 2009, and had a sister with breast cancer but were breast cancer-free themselves. Enrollment questionnaires included past 12-month hair product use. Cox proportional hazards models estimated adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between hair products and breast cancer; effect measure modification by ethnicity was evaluated. During follow-up (mean = 8.3 years), 2,794 breast cancers were identified. Fifty-five percent of participants reported using permanent dye at enrollment. Permanent dye use was associated with 45% higher breast cancer risk in black women (HR = 1.45, 95% CI: 1.10–1.90), and 7% higher risk in white women (HR = 1.07, 95% CI: 0.99–1.16; heterogeneity p = 0.04). Among all participants, personal straightener use was associated with breast cancer risk (HR = 1.18, 95% CI 0.99–1.41); with higher risk associated with increased frequency (p for trend = 0.02). Nonprofessional application of semipermanent dye (HR = 1.28, 95% CI 1.05–1.56) and straighteners (HR = 1.27, 95% CI 0.99–1.62) to others was associated with breast cancer risk. We observed a higher breast cancer risk associated with any straightener use and personal use of permanent dye, especially among black women. These results suggest that chemicals in hair products may play a role in breast carcinogenesis.