Oral contraceptives and cancers of the breast and of the female genital tract. Interim results from a case-control study

We analysed data from a case-control investigation conducted in Milan, Northern Italy, to evaluate the relation between the use of combination oral contraceptives and the risk of cancers of the breast, ovary, endometrium and cervix uteri. For the present analysis, 776 cases of histologically confirmed breast cancer, 406 of epithelial ovarian cancer and 170 of endometrial cancer aged under 60 were compared with a group of 1,282 subjects below age 60 admitted for a spectrum of acute conditions apparently unrelated to oral contraceptive use or to any of the known or potential risk factors for the diseases under study. Likewise, 225 cases of invasive cervical cancer were compared with 225 age-matched inpatient controls, and 202 cases of cervical intra-epithelial neoplasia with 202 outpatient controls identified in the same screening clinics. The age-adjusted relative risk estimates for ever vs. never use of combination oral contraceptives were 1.04 (95% confidence interval (CI) 0.73-1.37) for breast cancer, 0.68 (95% CI = 0.48-0.97) for epithelial ovarian cancer, 0.50 (95% CI = 0.23-1.12) for endometrial cancer, 1.49 (95% CI = 0.88-2.55) for cervical cancer and 0.77 (95% CI = 0.50-1.18) for cervical intra-epithelial neoplasia. The risk of ovarian cancer decreased and that of invasive cervical cancer increased with longer duration of use. Neither duration of oral contraceptive use nor time since first or last use significantly altered a user's risk of other neoplasms considered. Likewise, analysis of sub-groups of age, parity or other potentially important covariates did not show any important interaction, and allowance for them by means of logistic regression did not materially modify any of the results. These data confirm that combination oral contraceptives confer some protection against ovarian and endometrial cancers but may increase the risk of invasive cervical cancer if used for several years, and indicate that the past or current pattern of oral contraceptive use in Italy is unlikely materially to affect the risk of breast cancer.     

Coffee consumption and the risk of endometrial cancer: Evidence from a case-control study of female hormone-related cancers in Japan

Coffee has become a popular beverage worldwide. Caffeine, a major ingredient of coffee, has been proposed to have a favorable affect on the modulation of circulating estrogen levels and therefore may be of importance in developments on hormone-related cancers. However, epidemiological evidence is limited and inconsistent. We examined the relationship between intake of coffee and hormone-related cancer risk among Japanese women using data from the hospital-based epidemiological research program at Aichi Cancer Center (HERPACC). In total, 2122 breast, 229 endometrial and 166 ovarian cancer cases were included, and 12 425 women, confirmed as free of cancer, were recruited as the control group. Odds ratios (OR) and 95% confidence intervals (95% CI) were determined by multiple logistic regression analysis. A statistically significant inverse association between risk of endometrial cancer and coffee consumption was noted in Japanese women, with no clear association evident for breast and ovarian cancer risk. Compared to non-drinker, the OR of daily drinking of 1-2 cups and 3 or more cups per day for endometrial cancer were 0.64 (95% CI: 0.43-0.94) and 0.41 (95% CI: 0.19-0.87), respectively, and the linear trend was also statistically significant (P < 0.01). However, there was no statistically significant association between caffeine intake and endometrial cancer. In summary, the results of the present study suggest that coffee consumption reduces the risk of endometrial cancer in Japanese subjects. Given the scarcity of studies of coffee intake and endometrial cancer and other hormone-dependent cancer risk, additional investigations are warranted.     

Family history of hormonal cancers and colorectal cancer risk: A case‐control study conducted in Ontario

Aggregation of cancers among families with highly penetrant genetic mutations such as hereditary nonpolyposis colorectal cancer is well‐described. However, there is a paucity of data regarding familial aggregation of hormonal cancers (cancers of the breast, endometrial, ovarian and prostate) and colorectal cancer (CRC) in the general population. We investigated the association between having a first‐degree family history of breast, endometrial, ovarian, or prostate cancer and CRC risk. Population‐based CRC cases and controls were recruited by the Ontario Familial Colorectal Cancer Registry (OFCCR). Logistic regression was conducted to obtain odds ratio (OR) estimates and 95% confidence intervals (95% CIs). First‐degree family history of breast cancer was associated with a modest, borderline statistically significant increased CRC risk (age‐, sex‐adjusted OR = 1.2, 95% CI = 1.0, 1.5). The magnitude of CRC risk was greatest if more than one first‐degree kin had breast cancer (age‐, sex‐adjusted OR = 1.7, 95% CI = 1.0, 2.0), as well as if the kin was diagnosed at >50 years of age (age‐, sex‐adjusted OR = 1.4, 95% CI = 1.1, 1.8). Family history of ovarian cancer was associated with reduced CRC risk (multivariate‐adjusted OR = 0.6, 95% CI = 0.3, 1.0). Although statistically significant increases in CRC risk were observed in the age‐, sex‐adjusted OR estimates for family history of endometrial and prostate cancers, the associations were no longer significant after multivariate‐adjustment. In conclusion, individuals with a first‐degree kin with breast cancer may have a modest increased risk for CRC compared to individuals without. © 2009 UICC     

Cancer incidence among Finnish women with surgical treatment for cervical intraepithelial neoplasia, 1987–2006

A cohort of 26,876 women with surgical treatment for cervical intraepithelial neoplasia (CIN) during 1986–2004 was identified from the national Hospital Discharge Register. This cohort was followed up until December 31, 2006 (mean 8.4 years) through the Finnish Cancer Registry for cancer incidence during 1987–2006. There were 572 cases of cancer which is slightly more than would be expected on the basis of the national average cancer incidence in Finland. The standardized incidence ratio (SIR) was 1.14 and 95% confidence interval (CI) was 1.05–1.24. There was a statistically significant excess of cancers of the vulva (SIR: 6.15, 95% CI: 3.18–10.7), vagina (SIR: 9.08, 95% CI: 2.95–21.2), cervical cancer (SIR: 1.69, 95% CI: 1.07–2.53) and precancerous high‐grade lesion of the uterine cervix (SIR: 1.29, 95% CI: 1.10–1.50). The SIR for smoking‐related cancers combined, excluding cervical cancer, was 1.45 (95% CI: 1.12–1.86). The differences in cancer risk between treatment modalities were minor. Delivery after the CIN surgery did not decrease the overall cancer risk. In conclusion, women previously treated for CIN have an increased long‐term risk of cancers related to human papillomavirus (HPV) and smoking.     

Cigarette smoking increases risk for breast cancer in high-risk breast cancer families.

Most epidemiological studies of cigarette smoking and breast cancer have failed to demonstrate a strong association. Only one study has been performed on women at high genetic risk, and smoking was reported to be a protective factor. To further explore this observation, we examined the association of cigarette smoking with the risk of breast cancer in a historical cohort study of high-risk breast cancer families. A total of 426 families ascertained through a consecutive series of breast cancer patients (probands) between 1944 and 1952 were followed through 1996. Occurrence of breast cancer and detailed smoking histories for sisters, daughters, granddaughters, nieces, and marry-ins were obtained through telephone interviews between 1991 and 1996. Cox proportional hazards regression, accounting for age, birth cohort, and other risk factors, was used to calculate relative risks and 95% confidence intervals (CIs) of breast cancer. All of the models were constructed within strata defined by relationship to the index case (proband), with nonsmokers designated as the referent group. Of the 426 families in the cohort, 132 had at least three incident breast and/or ovarian cancers in the biological relatives at the end of the follow-up period. Among sisters and daughters in these 132 high-risk families, those who ever smoked were at 2.4-fold increased risk of breast cancer (95% CI, 1.2-5.1) relative to never-smokers. No association between breast cancer and smoking was observed among nieces and granddaughters of probands or among marry-ins. When the analysis was restricted to 35 families at highest genetic risk (each containing five breast and/or ovarian cancers), smoking became an even stronger risk factor. Among sisters and daughters, ever-smokers were at 5.8-fold greater risk than nonsmokers (95% CI, 1.4-23.9). Among nieces and granddaughters, the risk of breast cancer associated with smoking was increased 60% (95% CI, 0.8-3.2). These results suggest that smoking may increase risk for breast cancer in families with multiple cases of breast or ovarian cancer, especially those with the strongest apparent familial predisposition.     

Postmenopausal cancer risk after self-reported endometriosis diagnosis in the Iowa Women's Health Study

BACKGROUND: Endometriosis, the presence of endometrial tissue outside the uterus, has an estimated prevalence between 4% and 10%. A recent study reported that women with a hospital discharge diagnosis of endometriosis were at increased risk of cancer at any site, breast cancer, ovarian cancer, and hematopoietic malignancies, especially non-Hodgkin lymphoma (NHL). METHODS: The authors examined whether self-reported diagnosis of endometriosis was associated with increased risk of various cancers in the Iowa Women's Health Study. Incident cancer cases were identified from 1986 through 1998. Cox proportional hazards regression models were used to calculate relative risks and 95% confidence intervals for the particular cancers of interest. RESULTS: Of 37,434 participants in this analysis, 3.8% reported a history of endometriosis at baseline in 1986. After 13 years of follow-up, 1795 breast, 188 ovarian, and 243 NHL cases were detected in the cohort. Endometriosis was not associated with risk of all cancers combined (age-adjusted relative risk [RR], 0.9; 95% confidence interval [CI], 0.7-1.2), breast carcinoma (RR, 1.0; 95% CI, 0.8-1.3), or ovarian carcinoma (RR, 0.8; 95% CI, 0.2-2.4). However, endometriosis was significantly associated with risk of NHL (age-adjusted RR, 1.8; 95% CI, 1.0-3.0), especially diffuse NHL (RR, 3.2; 95% CI, 1.8-5.6). Multivariate adjustment had minimal effect on the point estimates of risk (NHL RR, 1.7; 95% CI, 0.97-2.7; diffuse NHL RR, 3.3; 95% CI, 1.9-5.9). Endometriosis was not associated with elevated risk of lung, urinary tract, endometrial, melanoma, or colorectal carcinomas (RRs, 1.2, 0.8, 1.2, 0.7, and 0.7, respectively). CONCLUSIONS: These results corroborate a previously reported association between endometriosis and increased risk of NHL but not cancer at other sites.     

Smoking and the risk of endometrial cancer: results from the Nurses' Health Study

An inverse association between smoking and endometrial cancer has generally been observed, primarily among current smokers. To assess this association, we analyzed data from the prospective Nurses' Health Study. From 1976 to 2000, 702 cases of invasive endometrial cancer were identified during 1.8 million person-years of follow-up. Smoking status was assessed in 1976 and updated every 2 years. Cox proportional hazards models were used to calculate multivariate relative risks (RRs), controlling for endometrial cancer risk factors. Compared to never smokers, the multivariate RR of endometrial cancer was significantly lower among both current smokers (RR = 0.63; 95% CI = 0.50-0.79) and past smokers (RR = 0.73; 95% CI = 0.62-0.87). When additionally adjusting for body mass index (BMI), the RR for current smokers was attenuated (RR = 0.72; 95% CI = 0.57-0.90), but the RR for past smokers did not change. Risk was lower among women who smoked 35 or more cigarettes a day (RR = 0.60; 95% CI = 0.39-0.91) and among those who smoked for 40 or more years (RR = 0.63; 95% CI = 0.45-0.87). Tests for trend, which excluded never smokers, were not statistically significant for any of the smoking variables analyzed. These data indicate that both current and past smoking are associated with a lower risk of endometrial cancer. The findings provide insight into disease etiology and suggest that the influence of smoking on endometrial cancer risk occurs even in early adulthood, is long-lasting, and may not be attributed solely to short-term hormonal modulation.     

A prospective study of smoking and risk of breast cancer in young adult women.

OBJECTIVES: To investigate the association between smoking and invasive breast cancers characterized by their estrogen receptor status in a large prospective study of mainly premenopausal women. METHODS: 112,844 women aged 25-42 years in 1989 were followed 10 years; questionnaire information on medical illnesses and risk factors was collected biennially and information on diet was collected in 1991 and 1995. During this period of follow-up (1,077,536 person-years), 1009 incident breast cancer cases were documented. RESULTS: In the multivariate-adjusted models, smoking status was not significantly related to overall breast cancer risk: compared with never smokers, the relative risks (RRs) were 1.18 [95% confidence interval (CI) 1.02-1.36] for past smokers and 1.12 (95% CI 0.92-1.37) for current smokers. Increasing duration of smoking before the first pregnancy was associated with a greater risk of breast cancer, although little increase was seen in the highest category: compared with never smokers, RRs were 1.42 (95% CI 1.10-1.83) for 15-19 years of smoking and 1.10 (95% CI 0.80-1.52) for >/=20 years of smoking (P for trend = 0.01). Smoking was related most strongly to the risk of estrogen receptor-positive breast cancers. For women who had smoked for >/=20 years, the RR of estrogen receptor-positive cancer was 1.37 (95% CI 1.07-1.74) and the RR of estrogen receptor-negative cancer was 1.04 (95% CI 0.71-1.53). For smoking before age 15, the RRs were 1.49 (95% CI 1.03-2.17) for estrogen receptor-positive cancer and 1.19 (95% CI 0.69-2.08) for estrogen receptor-negative cancer. CONCLUSIONS: Our results suggest that longer duration of smoking may be related to the risk of estrogen receptor-positive breast cancer but possibly less so for estrogen receptor-negative breast cancer.     

Milk, Dairy Products and Cancer Risk (Italy)

Background Inconclusive information is available on the potential role of milk and dairy products on the risk of cancer at several sites. Methods We analyzed data from a large and integrated network of hospital-based case–control studies in Italy on cancers of the oral cavity and pharynx (598 cases, 1491 controls), oesophagus (304 cases, 743 controls), colorectum (1953 cases, 4154 controls), larynx (460 cases, 1088 controls), breast (2569 cases, 2588 controls), ovary (1031 cases, 2411 controls) and prostate (1294 cases, 1451 controls). Results Multivariate odds ratio (OR) for the highest consumption level of any type of milk was 0.94 (95% confidence interval, CI: 0.61–1.33) for cancers of the oral cavity and pharynx, 1.20 (95% CI: 0.76–1.90) for oesophageal, 0.77 (95% CI: 0.62–0.96) for colon, 0.80 (95% CI: 0.60–1.05) for rectal, 0.83 (95% CI: 0.56–1.21) for laryngeal, 0.91 (95% CI: 0.76–1.10) for breast, 0.89 (95% CI: 0.68–1.15) for ovarian and 1.08 (95% CI: 0.84–1.37) for prostate cancer. A significant trend in risk was found for colon cancer only. Inverse associations were observed between consumption of skim milk and cancers of colon (OR=0.84; 95% CI: 0.73–0.97), rectum (OR=0.76; 95% CI: 0.64–0.91), breast (OR=0.87; 95% CI: 0.77–0.98) and ovary (OR=0.77; 95% CI: 0.66–0.91). Conversely, whole milk consumption was directly associated with cancer of the rectum (OR=1.22; 95% CI: 1.03–1.44) and ovary (OR=1.25; 95% CI: 1.07–1.46). High consumption of cheese was inversely related to colon cancer risk (OR=0.80; 95% CI: 0.67–0.95). Conclusions There was a modest direct association between milk and dairy products and prostate cancer, and a moderate inverse one for colorectal cancer. However, our findings indicate that milk and dairy products are not strong risk indicators for any of the cancers considered.     

Family history of cancer and risk of breast cancer

The relationship between breast cancer risk and family history of cancer in first-degree relatives was investigated using data from a multicentric case-control study conducted in Italy between June 1991 and April 1994 on 2,569 women aged less than 75 years, with histologically confirmed incident breast cancer, and 2,588 control women admitted to hospital for acute, non-neoplastic, non-gynaecological conditions. Relative to women with no history, those with a family history of breast cancer had an odds ratio (OR) of 2.4 [95% confidence interval (CI) 1.9–3.0], and those with family history of intestinal cancer had an OR of 1.3 (95% CI 1.0–1.7). No significant relations emerged between breast cancer risk and family history of prostate (OR 1.1), ovarian (OR 1.3), cervical or endometrial (OR 1.2) or other cancers, except gallbladder (OR 8.6). The OR for family history of any type of cancer except breast cancer was 1.1. For family history of breast cancer the ORs were similar across strata of age of the proband, being 2.4 below age 45, 2.2 at age 45–59 and 2.7 above age 60, and whether the relative affected was the mother, sister(s) or both, while the risk appeared higher if the age at onset of breast cancer in the relative was lower than 40 years (OR 3.5), rather than higher (OR 2.2). Thus, our results, based on the investigation of all neoplasms in first-degree relatives, confirm that breast cancer risk is increased in women with a family history of breast cancer, while there was no material association with family history of cancer in general, excluding breast cancer. Int. J. Cancer 72:735–738, 1997. © 1997 Wiley-Liss, Inc.     

Tamoxifen and toremifene treatment of breast cancer and risk of subsequent endometrial cancer: a population-based case-control study

A population-based case-control study was performed to evaluate the risk of endometrial cancer related to tamoxifen or toremifene treatment. All patients with breast cancer diagnosis since 1980 in Finland who subsequently developed an endometrial cancer by the end of 1995 and 3 matched controls were identified among the 38,000 breast cancer patients of the Finnish Cancer Registry database. Detailed information on treatment of breast cancer and potential confounders was collected from hospital records. The OR for tamoxifen treatment (59 cases), adjusted for significant cofactors (increased risk associated with obesity, low parity and PR positivity) was 2.9 (95% CI 1.8-4.7). The OR for toremifene (3 cases) was 0.9 (95% CI 0.3-3.9). The OR related to adjuvant tamoxifen treatment reached its maximum 2-5 years after the beginning of treatment (OR 5.1, 95% CI 2.1-13), while the OR for tamoxifen used for palliative treatment of advanced breast cancer was especially high after a lag of over 5 years (OR 9.5, 95% CI 2.5-36). The risk increase due to tamoxifen was slightly higher if the age at initiation was below 55, and risk was more pronounced among patients with well-differentiated endometrial cancer than patients with cancers of clinical grades 2 or 3. According to our results, treatment with tamoxifen increases the risk of endometrial cancer. Due to the rare use of toremifene up to the mid-1990s, the risk assessment concerning it was inconclusive.     

Reduced risk of breast, endometrial and ovarian cancer in women with celiac disease

Women with celiac disease (CD) may be at decreased risk of female hormone-related cancers given the observed reduction in breast cancer seen in some cohorts. Using biopsy data from all 28 pathology departments in Sweden, we identified 17,852 women with CD who were diagnosed between 1969 and 2007. We used Cox regression model to estimate their risk of breast, endometrial and ovarian cancer and then compared them with 88,400 age- and sex-matched controls. The results indicate that individuals with CD were at a lower risk for all three outcomes: breast cancer (hazard ratio, HR = 0.85; 95% CI = 0.72-1.01), endometrial cancer (HR = 0.60; 95% CI =0.41-0.86) and ovarian cancer (HR = 0.89; 95% CI =0.59-1.34). This inverse relationship was strengthened when we excluded the first year of follow-up beyond CD diagnosis (breast: HR = 0.82; 95% CI =0.68-0.99; endometrial: HR = 0.58; 0.39-0.87; ovarian cancer: HR = 0.72; 0.45-1.15). In conclusion, CD seems to be inversely related not only to breast cancer but also to endometrial and ovarian cancer. Potential explanations include shared risk factors and early menopause.     

Twinning and the Incidence of Breast and Gynecological Cancers (United States)

Increasing epidemiological and experimental evidence indicates that the carcinogenic pathway in the breast and female reproductive organs is driven, at least in part, by factors associated with reproduction. We conducted a retrospective cohort study, comparing the risk of ovarian, breast, endometrial, and cervical cancers among women who had records of at least one twin pregnancy, compared with women who had given birth to only single children. Subjects were selected from the Utah Population Database, which consists of multiple linked datasets including genealogy, births and deaths and cancer registries. We used Poisson regression to calculate relative risks, adjusted for the number of pregnancies and the age of the mother at the birth of first and last children, with singleton mothers as the reference group in each case. The risks of breast and ovarian cancers did not differ between mothers of twins and mothers of single children. The risk of endometrial cancer was slightly lower in mothers of twins than in mothers of singleton children (RR = 0.90, 95% CI 0.67-1.21). Conversely the risk of cervical cancer was higher among twin mothers (RR = 1.78, 95% CI 0.88-3.52). This latter finding supports previous data suggesting that reproductive hormones act as cofactors in the etiology of cervical cancer.     

Digoxin use and the risk of cancers of the corpus uteri, ovary and cervix

Digoxin is a phyto-estrogen capable of inducing hormonal effects. Use has been associated with increased risk of breast cancer, an estrogen-sensitive malignancy. The incidence of corpus uteri (uterus) cancer is also strongly increased with exposure to estrogens. Therefore, we evaluated whether digoxin use might also increase its incidence. In all women in Denmark, we identified digoxin users from 1995 through 2008 using a nationwide pharmacy registry system. Cancer occurrence was obtained from Danish Cancer Registry. Relative risk was determined using incidence risk ratios (RR) and 95% confidence intervals (CIs) relative to non-users after adjustment for age- and calendar-time. For ovarian and cervical cancers, RRs in users and non-users were similarly evaluated, these cancers representing gynecological cancers with weak or no associations to estrogen exposure. Of 2.1 million women, 104,648 (4.9%) had digoxin exposure and 137,493 6.5% had exposure to angina drugs but not digoxin during the study period. For uterus cancer, the RR was increased in current digoxin users (1.48, 95% CI: 1.32-1.65; N = 350). Incidence was marginally increased in former users. For ovary and cervix cancers, RRs in current digoxin users were 1.06 (95% CI: 0.92-1.22; N = 207) and 1.00 (95% CI: 0.79-1.25; N = 81), respectively. We examined risks in women using angina drugs but not digoxin to determine whether being under cardiac care affected risk. Among women using angina drugs only, RRs for uterus, ovary or cervix cancers were not statistically significant. We conclude that women currently using digoxin, a phyto-estrogen, have an increased risk of developing uterus cancers.     

Prospective Study of Antibody to Human Papilloma Virus type 16 and Risk of Cervical, Endometrial, and Ovarian Cancers (United States)

Objective: Human papilloma virus (HPV) is frequently detectable in cancers of the cervix, vagina, and vulva, but its role in endometrial and ovarian cancers is less certain. This analysis aimed to examine the association of presence of HPV type 16 (HPV-16) antibodies with subsequent risk of cervical, endometrial, and ovarian cancers. Methods: In a prospective study enrolling over 15,000 pregnant women, pre-cancer sera from women who developed cervical (n = 83), endometrial (n = 34), and ovarian (n = 35) cancers were compared with sera from 172 control women frequency-matched by age group and race. Results: HPV-16 seropositivity (OR = 2.0, 95% CI 1.0–3.4) was associated with cervical cancer, with the association more prominent for cancers occurring within 10 years of serum sampling (OR = 2.3, 95% CI 1.0–5.3) than cancers occurring later (OR = 1.6, 95% CI 0.75–3.6). Overall, the associations between HPV-16 seropositivity and endometrial (OR = 1.6, 95% CI 0.64–3.8) and ovarian cancers (OR = 1.1, 95% CI 0.43–2.8) were not significant, although the odds ratios for those cancers occurring within 20 years after serum sampling were similar to that for cervical cancer (OR = 2.2 for both). Conclusions: Our results confirm that HPV-16 infection precedes the development of cervical cancer. Predictability of HPV-16 seropositivity for risk of other female cancers warrants further investigation.     

Work stress and the risk of cancer: A meta-analysis of observational studies

Epidemiological studies have explored the relationship between work stress and the risk of cancer, but it remains unclear on whether work stress could increase the risk of cancer, or by other factors such as smoking and physical activity. Our study aimed to investigate the association between work stress and the risk of cancer and in relation to major potential confounding and modifying factors. We systematically searched three electronic databases, hand-searched references and citations of retrieved articles, and consulted experts to identify studies on assessing the association between work stress and the risk of cancer. The relative risks (RRs) of cancer associated with work stress were estimated using a random-effects model, and stratified by exposure measurement, study design, gender, study location, cancer site, smoking, drinking, body mass index, and physical activity. A total of 281,290 participants were included in this analysis. The significant association between work stress and the risk of colorectal (RR = 1.36; 95%CI: 1.16–1.59), lung (RR = 1.24; 95%CI: 1.02–1.49), and esophagus (RR = 2.12; 95%CI: 1.30–3.47) cancers were found. A statistically significant effect of work stress on colorectal cancer risk was observed in North America (RR = 1.51, 95% CI: 1.23–1.86, but not significant in Europe (RR = 1.16, 95% CI: 0.90–1.48). By contrast, a significant association between work stress and esophagus cancer was found in Europe, but not in North America. In addition, we did not observe any association between work stress and the risk of prostate, breast, or ovarian cancers. Findings of our study show that work stress is an important risk factor for colorectal, lung, and esophagus cancers. General public should be aware of the increased risk of cancer in employers with work stress. More efforts should be focused on understanding and studying the potential mechanisms which would help to identify employees at higher risk of these cancers.     

A prospective cohort study of cancer incidence following the diagnosis of Parkinson's disease.

BACKGROUND: Prior studies suggest a decreased risk of cancer among patients with Parkinson's disease (PD). METHODS: Matched cohort analysis among the 22,071 participants in the Physician's Health Study. A total of 487 incident cases of PD without preceding cancer were identified by self-report. Each PD case was matched by age to a reference participant who was alive and cancer free at the time of PD diagnosis. Both cohorts were followed for incident cancer. We used proportional hazards models to calculate adjusted relative risks (RR) for cancer. RESULTS: A total of 121 cancers were confirmed during a median follow-up of 5.2 years (PD) and 5.9 years (reference). Those with PD developed less cancer (11.0% versus 14.0%), with an adjusted RR of 0.85 [95% confidence interval (95% CI), 0.59-1.22]. Reduced risk was present for smoking-related cancers such as lung (RR, 0.32), colorectal (RR, 0.54), and bladder (RR, 0.68), as well as for most non-smoking-related cancers such as prostate cancer (RR, 0.74). In contrast, PD patients were at significantly increased risk (RR, 6.15; 95% CI, 1.77-21.37) for melanoma. PD patients who smoked were at reduced risk for smoking-related cancer (RR, 0.33; 95% CI, 0.12-0.92), whereas nonsmokers with PD were at increased risk (RR, 1.80; 95% CI, 0.60-5.39). This interaction was statistically significant (P(interaction) = 0.02). CONCLUSIONS: Our results suggest a decreased incidence of most cancers in patients with PD. PD patients had a significantly increased risk of malignant melanoma, a finding consistent with prior studies. We confirmed an interaction between smoking and the relationship of PD to smoking-related cancer that may fit the pattern of a gene-environment interaction.     

Smoking and the risk of breast cancer among carriers of BRCA mutations

The effect of cigarette smoking on the risk of breast cancer is controversial, although most studies show little or no effect. It has been suggested that smoking may reduce the risk of developing hereditary breast cancer. We completed a case-control study on 1,097 women with breast cancer who were BRCA1 or BRCA2 mutation carriers and 1,097 age-matched controls with a mutation in the same gene but without breast cancer. There were no statistically significant differences between the cases and controls in terms of the number of current and ex-smokers (41.2% and 40.4%, respectively) or the age at smoking commencement (18.2 years and 18.5 years, respectively). There were no statistically significant differences between cases and controls regarding beginning smoking within 5 years of menarche (OR = 1.03; 95% CI 0.83 to l.28) or before the first pregnancy (OR = 1.09; 95% CI = 0.90 to 1.33). In conclusion, contrary to our previous report, smoking does not appear to be a risk factor for breast cancer among carriers of BRCA mutations.     

Active and passive smoking and the risk of breast cancer in women aged 36-45 years: a population based case-control study in the UK

Active smoking has little or no effect on breast cancer risk but some investigators have suggested that passive smoking and its interaction with active smoking may be associated with an increased risk. In a population based case-control study of breast cancer in women aged 36-45 years at diagnosis, information on active smoking, passive smoking in the home, and other factors, was collected at interview from 639 cases and 640 controls. Women were categorised jointly by their active and passive smoking exposure. Among never smoking controls, women who also reported no passive smoking exposure were significantly more likely to be nulliparous and to be recent users of oral contraceptives. Among those never exposed to passive smoking, there was no significant association between active smoking and breast cancer, relative risk (RR) of 1.12 (95% confidence interval (CI) 0.72-1.73) for past smokers and RR of 1.19 (95% CI 0.72-1.95) for current smokers, nor was there an association with age started, duration or intensity of active smoking. Compared with women who were never active nor passive smokers, there was no significant association between passive smoking in the home and breast cancer risk in never smokers, RR of 0.89 (95% CI 0.64-1.25), in past smokers, RR of 1.09 (95% CI 0.75-1.56), or in current smokers, RR of 0.93 (95% CI 0.67-1.30). There was no trend with increasing duration of passive smoking and there was no heterogeneity among any of the subgroups examined. In this study, there was no evidence of an association between either active smoking or passive smoking in the home and risk of breast cancer.     

Aspirin and cancer risk: a quantitative review to 2011

BackgroundAspirin has been associated to a reduced risk of colorectal and possibly of a few other common cancers.MethodsTo provide an up-to-date quantification of this association, we conducted a meta-analysis of all observational studies on aspirin and 12 selected cancer sites published up to September 2011.ResultsRegular aspirin is associated with a statistically significant reduced risk of colorectal cancer [summary relative risk (RR) from random effects models = 0.73, 95% confidence interval (CI) 0.67–0.79], and of other digestive tract cancers (RR = 0.61, 95% CI = 0.50–0.76, for squamous cell esophageal cancer; RR = 0.64, 95% CI = 0.52–0.78, for esophageal and gastric cardia adenocarcinoma; and RR = 0.67, 95% CI = 0.54–0.83, for gastric cancer), with somewhat stronger reductions in risk in case–control than in cohort studies. Modest inverse associations were also observed for breast (RR = 0.90, 95% CI = 0.85–0.95) and prostate cancer (RR = 0.90, 95% CI = 0.85–0.96), while lung cancer was significantly reduced in case–control studies (0.73, 95% CI = 0.55–0.98) but not in cohort ones (RR = 0.98, 95% CI = 0.92–1.05). No meaningful overall associations were observed for cancers of the pancreas, endometrium, ovary, bladder, and kidney.ConclusionsObservational studies indicate a beneficial role of aspirin on colorectal and other digestive tract cancers; modest risk reductions were also observed for breast and prostate cancer. Results are, however, heterogeneous across studies and dose–risk and duration–risk relationships are still unclear.