Exposure to oral bisphosphonates and risk of cancer

Recently, oral bisphosphonate use has increased markedly in the United States and elsewhere. Little is known about cancer risks associated with these drugs. A few studies have observed associations between bisphosphonates and the risk of breast, colorectal and esophageal cancer. However, the risk of all cancer and the risk of other cancers have not been investigated. In our study, we examined the risk of all cancer and site specific cancers in individuals taking bisphosphonates. Data were extracted from the UK General Practice Research Database to compare site-specific cancer incidence in a cohort of oral bisphosphonate users and a control cohort. Hazard ratios (HRs) were calculated using Cox regression modeling. The bisphosphonate and control cohort contained 41,826 participants (mean age 70, 81% female). Overall, the bisphosphonate cohort compared with the control cohort had a reduced risk of all cancer after any bisphosphonate usage [HR=0.87, 95% confidence interval (CI) 0.82, 0.92]. In the bisphosphonate cohort, compared with the control cohort, there was no evidence of a difference in the risk of lung (HR=1.03, 95% CI 0.88, 1.20) or prostate cancer (HR=0.86, 95% CI 0.67, 1.09) but breast (HR=0.71, 95% CI 0.62, 0.81) and colorectal cancer (HR=0.74, 95% CI, 0.60-0.91) were both reduced. Our findings indicate that bisphosphonates do not appear to increase cancer risk. Although reductions in breast and colorectal cancer incidence were observed in bisphosphonate users it is unclear, particularly for breast cancer, to what extent confounding by low bone density may explain the association.     

Metformin and other anti-diabetic medication use and breast cancer incidence in the Nurses' Health Studies

We aimed to examine the association between the use of metformin and other anti-diabetic medications and breast cancer incidence within two large prospective cohort studies. We followed 185,181 women who participated in the Nurses' Health Study (NHS; 1994–2016) and the NHSII (1995–2017), with baseline corresponding to the date metformin was approved for type 2 diabetes (T2D) treatment in the US Information on T2D diagnosis, anti-diabetes medications, and other covariates was self-reported at baseline and repeatedly assessed by follow-up questionnaires every 2 years. Breast cancer cases were self-reported and confirmed by medical record review. Hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between medication use and breast cancer were estimated using Cox proportional hazards regression models, adjusting for breast cancer risk factors. During 3,324,881 person-years of follow-up, we ascertained 9,192 incident invasive breast cancer cases, of which 451 were among women with T2D. Compared with women without T2D (n = 169,263), neither metformin use (HR = 0.97; 95% CI = 0.81–1.15) nor other anti-diabetic medications use (HR = 1.11; 95% CI = 0.90–1.36) associated with significantly lower breast cancer incidence. Among women with T2D (n = 15,918), compared with metformin never users, metformin ever use was not significantly inversely associated with breast cancer (HR = 0.92; 95% CI = 0.74–1.15). Although we observed that past use of metformin was inversely associated with breast cancer in the T2D population (HR = 0.67; 95% CI = 0.48–0.94), current use (HR = 1.01; 95% CI = 0.80–1.27) and longer duration of metformin use were not associated with breast cancer (each 2-year interval: HR = 1.01; 95% CI = 0.95–1.07). Overall, metformin use was not associated with the risk of developing breast cancer among the overall cohort population or among women with T2D.     

Hypertension,use of antihypertensive medications,and risk of epithelial ovarian cancer

Few studies have examined the associations of hypertension and antihypertensive medications with ovarian cancer. In particular, beta‐blockers, one of the most commonly prescribed medications to treat hypertension, may reduce ovarian cancer risk by inhibiting beta‐adrenergic signaling. We prospectively followed 90,384 women in the Nurses' Health Study (NHS) between 1988–2012 and 113,121 NHSII participants between 1989–2011. Hypertension and use of antihypertensive medications were self‐reported biennially. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). We documented 948 ovarian cancer cases during follow‐up. Similar results were observed in the two cohorts. While hypertension was not associated with ovarian cancer risk (Pooled HR = 1.01; 95% CI = 0.88, 1.16), current use of any antihypertensive medication was associated with slightly increased risk compared to never users (Pooled HR = 1.18; 95% CI: 1.02, 1.37). This increased risk was primarily due to use of thiazide diuretics (Pooled HR = 1.37; 95% CI: 1.13, 1.68). No associations were observed for beta‐blockers or angiotensin‐converting‐enzyme inhibitors. Calcium channel blockers (CCBs) were associated with suggestively reduced risk (NHS HR = 0.73; 95% CI: 0.53, 1.01), after adjusting for all antihypertensive medications. Associations were similar among hypertensive women and stronger for longer use of thiazide diuretics and CCBs. In conclusion, our results provided no evidence that beta‐blockers were associated with reduced ovarian cancer risk. In contrast, we observed an increased risk for use of thiazide diuretics that should be confirmed in other studies.     

Menopausal hormone therapy and risk of ovarian cancer in the European prospective investigation into cancer and nutrition

The association between menopausal hormone therapy (HT) and risk of ovarian cancer was assessed among 126,920 post-menopausal women recruited into the European Prospective Investigation into Cancer and Nutrition. After an average of 9-year follow-up, 424 incident ovarian cancers were diagnosed. Cox models adjusted for body mass index, smoking status, unilateral ovariectomy, simple hysterectomy, age at menarche, number of full-term pregnancies, and duration of oral contraceptives were used. Compared with baseline never use, current use of any HT was positively associated with risk (HR [hazard ratio], 1.29; 95% CI [confidence interval], 1.01-1.65), while former use was not (HR, 0.96; 95% CI, 0.70-1.30). Current estrogen-only HT was associated with a 63% higher risk (HR, 1.63; 95% CI, 1.08-2.47), while current estrogen plus progestin was associated with a smaller and non-significant higher risk (HR, 1.20; 95% CI, 0.89-1.62). Use of tibolone was associated with a twofold greater risk (HR, 2.19; 95% CI, 1.06-4.50), but was based on small numbers. In conclusion, women who currently use HT have a moderate increased risk of ovarian cancer, and which may be stronger for estrogen-only than estrogen plus progestin preparations.     

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.     

Influence of education level on breast cancer risk and survival in Sweden between 1990 and 2004

On account of limited recent data regarding the role of education in breast cancer risk and prognosis, we conducted this study to assess the association between education level and in situ and invasive breast cancer risk and invasive breast cancer survival, using the 2006 update of the Swedish Family-Cancer Database. Cox's proportional hazards models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) adjusted for age, time-period, parity, age at first birth, county of residence, and family history of breast cancer. Compared to women completing less than 9 years of education, university graduates were more likely to be diagnosed with in situ (HR = 1.44, 95% CI: 1.28-1.63) and invasive (HR = 1.28, 95% CI: 1.20-1.36) breast cancer, and the lack of homogeneity between these two HRs was statistically significant, p = 0.007. Further stratification revealed that the lack of homogeneity was greatest for breast cancers diagnosed before age 50. Compared to women completing less than 9 years of education, university graduates were associated with the highest survival following a breast cancer diagnosis (lowest fatality hazard ratio), HR = 0.68, 95% CI: 0.61-0.75. Further research is warranted to elucidate possible behaviors or characteristics associated with education that could explain the differences in incidence and survival, such as compliance with cancer screening.     

Postmenopausal hormone therapy and breast cancer risk: the Multiethnic Cohort

Epidemiological studies indicate that menopausal estrogen-progestin therapy (EPT) use is associated with an increase in breast cancer risk. Further data are needed on whether this association varies by specific prognostic factors and ethnicity. We conducted a cohort study among 55,371 African-American, Native Hawaiian, Japanese-American, Latina and White postmenopausal women aged 45-75 years old in the Multiethnic Cohort Study (MEC). A total of 1,615 incident invasive breast cancer cases were identified over an average of 7.3 years. Adjusted relative risks (RRs) were computed for the various forms of hormone therapy (HT). Assuming current users continued HT use to the end of follow-up, current EPT use was associated with a 29% increased risk of breast cancer per 5 years of use (95% confidence interval (CI) = 23-35%), and current estrogen therapy (ET) use with a 10% increase in risk per 5 years of use (95% CI = 5-16%). These figures increased to only a very small extent when we adjusted for the estimated 3% of such women who stop HT use per year of follow-up. EPT and ET use were associated with greater risk among leaner women, but the increase in risk with EPT use was still very evident in women with BMI > or =30 kg/m(2). Current EPT use was associated with increased risk for ER+/PR+, ER+/PR- and ER-/PR- tumors. There was little difference in risk by stage of disease or histologic subtype. The increase with EPT use was clearly seen in all 5 ethnic groups; and the increase with ET in 4 of the 5 groups.     

Hormone replacement therapy containing progestins and given continuously increases breast carcinoma risk in Sweden

BACKGROUND: The authors previously reported an increased risk of breast carcinoma with longer duration of hormone replacement therapy (HRT) use. It is unclear if different types of HRT confer different risks. METHODS: In this study, a population-based cohort of 29,508 women were interviewed during 1990-1992 to determine whether there are any differences in breast carcinoma risk according to different types and duration of HRT use. RESULTS: At the end of the follow-up period in December 2001, the cohort constituted 298,649 person-years. Slightly more breast carcinoma cases were seen (n = 556) than expected (n = 508.37; standardized morbidity ratio =1.09, 95% confidence interval [CI] = 1.00-1.19). Approximately 3663 women had ever used HRT. In Cox regression models, time to breast carcinoma in relation to duration and type of HRT use was analyzed, adjusting for age at menarche, age at first full-term pregnancy, parity, age at menopause, family history of breast carcinoma, and age at interview. In women with a natural menopause, a significantly higher risk was observed for longer duration of combined continuous HRT use compared with never users (hazard ratio [HR] = 4.60, 95% CI = 2.39-8.84). Nonsignificant elevated risks also were observed for longer combined sequential (HR = 2.23, 95% CI = 0.90-5.56), gestagen only (HR = 3.74,9 5% CI = 0.94-14.97), and estriol use (HR = 1.89, 95% CI = 0.81-4.39). No increased risk was seen in women after 5 years of nonuse. When studying women who ever used only one type of HRT, even more elevated HRs for gestagen-containing preparations were seen. The highest risks were associated with the combined continuous and gestagen-only therapy in women with >/= 48 months of use. Use of estradiol without progestins did not increase breast carcinoma risk significantly. The authors estimated the cumulative risk of breast carcinoma in a 50-year-old woman with gestagen-containing therapies for >/= 48 months, with a follow-up of 10 years, to be 7% (95% CI = 5.4-11.4%) compared with 2% (95% CI = 1.6%-2.9%) for never-users of HRT. CONCLUSIONS: Longer use of HRT containing progestins significantly elevates breast carcinoma risk whereas estradiol use does not. Continued use of progestins rendered the highest risks. The yearly risk of breast carcinoma for long-term users of progestins is of the magnitude of 50% the risk of a BRCA1 mutation carrier.     

Mortality following development of breast cancer while using oestrogen or oestrogen plus progestin: a computer record-linkage study

The literature on the relationship between breast cancer mortality and postmenopausal oestrogen and combined oestrogen/progestin therapy is seemingly contradictory. This study explored survival after exposure to oestrogen or oestrogen plus progestin at or in the year prior to breast cancer diagnosis. Information on patients first diagnosed with invasive breast cancer between 1993 and 1998 was linked with outpatient pharmacy data from 1992 to 2000. Patients were classified according to use of oestrogen alone or oestrogen plus progestin at or in the year prior to diagnosis. Compared to nonusers, and adjusting for age at diagnosis, race/ethnicity, tumour size and grade, oestrogen receptor status, surgery status, and chemotherapy and hormone therapy for breast cancer treatment, oestrogen plus progestin users had lower all-cause mortality (stage I hazard ratio (HR) = 0.69, 95% confidence interval (CI)= 0.48-0.99; stage II HR = 0.53, 95% CI = 0.39-0.72) and breast cancer mortality (stage I HR = 0.52, 95% CI = 0.26-1.04; stage II HR = 0.69, 95% CI = 0.48-0.98). Oestrogen users experienced little or no survival benefit for all-cause mortality (stage I HR = 1.04, 95% CI = 0.77-1.42; stage II HR = 0.86, 95% CI = 0.65-1.14) or breast cancer mortality (stage I HR = 1.23, 95% CI 0.72-2.10; stage II HR = 1.01, 95% CI 0.72-1.41). Our findings suggest, relative to nonusers, a lower risk of death from all causes and from breast cancer in patients who were diagnosed with breast cancer while exposed to oestrogen plus progestin, but not in patients exposed to oestrogen only.     

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.     

Diet and risk for breast cancer recurrence and survival

Dietary factors may influence the risk for breast cancer and also the prognosis following diagnosis and treatment. The aim of this study was to assess whether self-reported prediagnosis diet or other patient factors associated with breast cancer incidence were predictive of recurrence and survival. Patients (n=149) diagnosed with primary breast cancer between 1989 and 1991 were followed for five or more years. Total energy (hazard ratio (HR)=1.58, 95%, confidence interval (CI)= 1.05, 2.38) as well as total (HR = 1.46, 95% CI = 1.05, 2.01), saturated (HR = 1.79,95% CI = 1.05, 3.04), and monounsaturated (HR = 1.65, 95% CI = 1.09,2.49) fat intakes were associated with increased risk, and energy-adjusted bread and cereal consumption (HR = 0.55, 95% CI = 0.33, 0.93) with decreased risk of recurrence. Both total energy (HR = 1.58, 95% CI = 1.03, 2.43) and polyunsaturated fat (HR = 1.84, 95% CI = 1.09, 3.13) intakes were associated with an increased risk of death. All associations between dietary fat and recurrence and survival attenuated following energy adjustment. Oral contraceptive use (HR = 1.28, 95% CI = 1.03, 1.60), lymph node positive status (HR = 2.36, 95% CI = 1.01, 5.49), and tumor stage (HR = 2.22, 95% CI = 1.02, 4.81) were associated with increased risk of recurrence. Tumor stage (HR = 4.96, 95% CI = 1.86, 13.23), lymph node positive status (HR = 3.31, 95% CI = 1.38, 7.95, and estrogen receptor negative status (HR = 2.46, 95% CI = 1.02, 5.94) were associated with increased risk, and arm muscle circumference (HR = 0.27, 95% CI = 0.09, 0.86) and mammographic utilization (HR = 0.77, 95% CI = 0.61, 0.98) with decreased risk of death. Higher levels of energy, fat intakes, and selected patient characteristics (particularly disease stage and anthropometric indicators of adiposity) appear to increase risk of recurrence and/or shortened survival following the diagnosis of breast cancer.     

Hormone replacement therapy and incidence of hormone-dependent cancers in the Norwegian Women and Cancer study

Increasing use of HRT over the last 2 decades could have contributed to the increasing incidence of cancer in women. Our aim was to investigate the relation between use of HRT and risk of hormone-dependent cancers in a Norwegian cohort of women. The Norwegian Women and Cancer (NOWAC) study is a representative, national, population-based cohort study. This report includes 35,456 postmenopausal women aged 45-64 years who answered a postal questionnaire in 1996-1998 providing information on reproduction, lifestyle and use of HRT. The women were followed up for cancer incidence. The main analyses were restricted to 31,451 postmenopausal women with complete information. Ever use of HRT was reported by 43.5% and current use, by 35% of the women. Current users had an increased risk of breast cancer (adjusted RR=2.1, 95% CI 1.5-2.5). The risk increased with increasing duration of use (ptrend < 0.0001). Using a regimen of continuous estrogen-progestagen implied an increased risk. Adjusted RRs associated with <5 and > or =5 years' duration of use were 2.6 (95% CI 1.9-3.7) and 3.2 (95% CI 2.2-4.6), respectively. The population-attributable risk of breast cancer due to current use of HRT was 27%. We found no significant increase in risk of ovarian cancer. Neither did we find users of estrogen-progestagen preparations to have any increase in risk of endometrial cancer. Our results suggest that HRT could be considered a major determinant for the increasing incidence of breast cancer in Norway.     

Role of mammography screening as a predictor of survival in postmenopausal breast cancer patients

We examined the effect of population-based screening programme on tumour characteristics by comparing carcinomas diagnosed during the prescreening (N=341) and screening (N=552) periods. We identified screen detected (N=224), interval (N=99) and clinical cancer (N=229) cases. Median tumour size and proportion of axillary lymph node negative cases were 1.5 cm and 65% in the screen detected group, 2.0 cm and 44% in cases found outside the screening, and 3.2 cm and 41% in the cases from the prescreening period. Survival of the breast cancer patients was 66% (95% CI, 60-71%) in the prescreening era group and 73% (95% CI, 66-78%) in the screening era group after 10 years of follow-up. In the screening era group the survival of the screen detected cases was 86% (95% CI, 80-90%) and that of the clinical cancer cases 73% (95% CI, 66-78%) after 10 years. In multivariate analysis the risk of breast cancer death was not significantly different between the prescreening and screening periods (HR 0.82; 95% CI 0.59-1.12, P=0.21). Detection by screening was not an independent prognostic factor in multivariate analysis (HR 0.75; CI 95% 0.50-1.12; P=0.17).     

Confounded association between proton pump inhibitor use and risk of biliary tract cancer: Result from three cohorts

Recent epidemiological studies suggested that proton pump inhibitor (PPI) use was associated with an increased risk of biliary tract cancer (BTC), however, confounders were not adequately controlled. Our study aimed to evaluate PPI use and subsequent risk of BTC and its subtypes in three well-established cohorts. We conducted a pooled analysis of the subjects free of cancers in UK Biobank (n = 463 643), Nurses' Health Study (NHS, n = 80 235) and NHS II (n = 95 869). Propensity score weighted Cox models were used to estimate marginal HRs of PPIs use on BTC risk, accounting for potential confounders. We documented 284 BTC cases in UK Biobank (median follow-up: 7.6 years), and 91 cases in NHS and NHS II cohorts (median follow-up: 15.8 years). In UK biobank, PPI users had a 96% higher risk of BTC compared to nonusers in crude model (HR 1.96, 95% CI 1.44-2.66), but the effect was attenuated to null after adjusting for potential confounders (HR 0.95, 95% CI 0.60-1.49). PPI use was not associated with risk of BTC in the pooled analysis of three cohorts (HR 0.93, 95% CI 0.60-1.43). We also observed no associations between PPI use with risk of intrahepatic (HR 1.00, 95% CI 0.49-2.04), extrahepatic bile duct (HR 1.09, 95% CI 0.52-2.27) and gallbladder cancers (HR 0.66, 95% CI 0.26-1.66) in UK Biobank. In summary, regular use of PPIs was not associated with the risk of BTC and its subtypes.     

Contraceptive methods and ovarian cancer risk among Chinese women: A report from the Shanghai Women's Health Study

Oral contraceptive use is associated with reduced ovarian cancer risk; however, associations with other contraceptive methods, such as intrauterine device (IUD) and tubal ligation, are less clear. Women in China differ from western women in regard to mechanisms and duration of use of contraception. This study was undertaken to evaluate associations between contraceptive methods and ovarian cancer risk using data from the prospective Shanghai Women's Health Study. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression. A total of 174 epithelial ovarian cancer cases were found to occur among 70,259 women who were followed‐up for a total of 888,258 person‐years. The majority of women had ever used any contraception (77.0%), including IUD (55.6%), oral contraceptive (20.4%), tubal ligation (14.7%) or contraceptive shots (2.6%). Ever use of any contraception was associated with a nonsignificant reduction in ovarian cancer risk (HR: 0.86, 95% CI: 0.60–1.24). Longer duration of IUD use was associated with lower ovarian cancer risk (p‐value for trend = 0.04). Compared with never users, women with durations of IUD use longer than the median (20 years) were 38% less likely to develop ovarian cancer (HR: 0.62, 95% CI: 0.40–0.97). Based on the high prevalence and long duration of IUD use among Chinese women, we estimate a preventive fraction of 9.3%, corresponding to approximately 16 ovarian cancer cases. High prevalence of long‐term IUD use may, therefore, contribute to the low incidence of ovarian cancer observed in China.     

Progestagens use before menopause and breast cancer risk according to histology and hormone receptors

In a previous study, we found a positive association between premenopausal use of progestagens and breast cancer risk. We conducted the present study to assess the risk of breast cancers defined by their histology and hormone receptors status. We evaluated the association between progestagen-only intake (except for mini pills) before menopause and after the age of 40 years and invasive breast cancer risk in 67,057 women participating in the French E3N cohort study. Histologically confirmed invasive breast cancers (2,264) were identified through biennial self-administered questionnaires completed from 1992 to 2002. Risk estimates were calculated using the Cox proportional hazard model. We found an increased risk of lobular carcinoma associated with premenopausal use of progestagens among both current and past users [hazard ratio (HR), 1.51; 95% confidence interval (95% CI), 1.02-2.24 and HR, 1.38; 95% CI, 1.08-1.75, respectively]. Among current users, the use of progestagens for 4.5 years or more was associated with an increased risk of estrogen receptor-positive/progesterone receptor-positive carcinomas (HR, 1.68; 95% CI, 1.05-2.68), whereas current use of progestagens for <4.5 years was associated with an increase in the estrogen receptor-positive/progesterone receptor-negative carcinoma risk (HR, 1.61; 95% CI, 1.05-2.46). The premenopausal use of progestagens after the age of 40 years may be preferentially associated with the risk of lobular breast cancer and differentially affect the risk of breast cancer according to the hormone receptor status.     

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.     

Postmenopausal breast cancer risk and interactions between body mass index,menopausal hormone therapy use,and vitamin D supplementation: Evidence from the E3N cohort

Experimental studies suggest protective effects of vitamin D on breast carcinogenesis, but epidemiological evidence is not conclusive. Body mass index (BMI) has been shown to modulate the effect of supplementation on the vitamin D status, but its potential influence on the relationship with breast cancer risk has been little studied. We investigated a potential interaction between BMI and vitamin D supplementation on breast cancer risk while considering an already reported interaction between vitamin D supplementation and menopausal hormone therapy (MHT) use. Vitamin D supplementation was prospectively investigated in 57,403 postmenopausal women from the French E3N cohort including 2,482 incident breast cancer cases diagnosed between 1995 and 2008. Multivariable hazard ratios (HR) for primary invasive breast cancer and 95% confidence intervals (CI) were estimated using Cox models. Among MHT ever users, vitamin D supplementation was associated with decreased breast cancer risk, similarly across BMI strata (P_homogeneity = 0.83). Among MHT never users, ever vitamin D supplementation was associated with increased postmenopausal breast cancer risk in women with baseline BMI <25 kg/m² (HR = 1.51, 95% CI: 1.13, 2.02), but not in women with higher BMI (0.98, 95% CI: 0.62, 1.56), P_homogeneity = 0.12. In conclusion, our findings suggest that vitamin D supplementation may reduce the excess breast cancer risk in MHT users, but draw attention on a potential risk in postmenopausal women not exposed to high exogenous or endogenous hormones, i.e. non‐overweight MHT‐non users, especially in the present context of increasing vitamin D supplement use and decreasing MHT use.