Reproductive and hormonal factors and the risk of lung cancer: The EAGLE study

Evidence about the role for reproductive and hormonal factors in the etiology of lung cancer in women is conflicting. To clarify this question, we examined 407 female cases and 499 female controls from the Environment And Genetics in Lung cancer Etiology population‐based case–control study. Subjects were interviewed in person using a computer‐assisted personal interview to assess demographics, education, smoking history, medical history, occupational history, reproductive and hormonal factors. Associations of interest were investigated using logistic regression models, adjusted for catchment area and age (matching variables), cigarette smoking (status, pack‐years and time since quitting). Additional confounding variables were investigated but did not substantially affect the results. We observed a reduced risk of lung cancer among women with later age at first live birth [≥31 years: odds ratio (OR) = 0.57, 95% confidence interval (CI) = 0.31–1.06, p‐trend = 0.05], later age at menopause (≥51 years: OR = 0.49, 95%CI = 0.31–0.79, p‐trend = 0.003) and longer reproductive periods (≥41 years: OR = 0.44, 95%CI = 0.25–0.79, p‐trend = 0.01). A reduced risk was also observed for hormone replacement therapy (OR = 0.63, 95%CI = 0.42–0.95, p = 0.03) and oral contraceptive use (OR = 0.67, 95%CI = 0.45–1.00, p = 0.05) but no trend with duration of use was detected. Menopausal status (both natural and induced) was associated with an augmented risk. No additional associations were identified for other reproductive variables. This study suggests that women who continue to produce estrogens have a lower lung cancer risk. Large studies with great number of never smoking women, biomarkers of estrogen and molecular classification of lung cancer are needed for a more comprehensive view of the association between reproductive factors and lung cancer risk.     

Physical activity and postmenopausal endometrial cancer risk (Sweden)

Objectives:To examine the hypothesis that sedentary women have an increased risk of endometrial cancer compared to physically active women. Methods:This is a population-based case–control study in the entire Swedish female population aged 50–74 years in 1994–1995. We obtained self-reported information on leisure-time physical activity during childhood, at ages 18–30, and recently from 709 incident case women with endometrial cancer and 3368 population controls. Occupational physical activity was estimated through record linkage to the Swedish census data from 1960, 1970, 1980, and 1990. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for different activity levels by multivariate logistic regression, taking into account potential confounders. Results:Comparing lowest to highest (reference) levels of physical exercise, we observed statistically significant associations with risk of endometrial cancer for leisure-time activity at age 18–30 years (multivariate OR = 1.4; 95% CI = 1.0–1.8; p for trend 0.01) and in recent years (multivariate OR=1.3; 95% CI = 1.0–1.7; p for trend 0.01). We found similar associations comparing lowest to highest (reference) levels of occupational activity assessed at the censuses in 1980 (multivariate OR = 1.4; 95% CI = 1.0–1.9; p for trend 0.03) and 1990 (multivariate OR = 1.3; 95% CI = 0.9–1.9, p for trend 0.05), but a less consistent association with censuses in 1960 and 1970. The increased risk associated with low level of occupational physical activity was confined to women who were not obese and to women who were smokers. Conclusion:Our data, in conjunction with past epidemiological studies, indicate that both occupational and leisure-time physical activity may reduce the risk for postmenopausal endometrial cancer.     

Dietary carotenoids and the risk of invasive breast cancer

Certain classes of vitamins and nutrients found in fruits and vegetables have been of particular interest in relation to cancer prevention, owing to their potential anticarcinogenic properties. We examined the association between certain fruits, vegetables, carotenoids, and vitamin A and breast cancer risk in a large population‐based case‐control study of women residing in the states of Massachusetts, New Hampshire and Wisconsin. The study was comprised of 5,707 women with incident invasive breast cancer (2,363 premenopausal women and 3,516 postmenopausal women) and 6,389 population controls (2,594 premenopausal women and 3,516 postmenopausal women). In an interview, women were asked about their intake of carotenoid rich fruits and vegetables 5 years prior to a referent date. An inverse association observed among premenopausal women was for high levels of vitamin A (OR: 0.82, 95% CI: 0.68–0.98, p for trend = 0.01), β‐carotene (OR: 0.81, 95% CI 0.68–0.98, p for trend = 0.009), α‐carotene (OR: 0.82, 95% CI: 0.68–0.98, p for trend = 0.07) and lutein/zeaxanthin (OR: 0.83, 95% CI 0.68–0.99, p for trend = 0.02). An inverse association was not observed among postmenopausal women. Among premenopausal women who reported ever smoking, these results were stronger than among never smokers, although tests for interaction were not statistically significant. Results from this study are comparable to previous prospective studies, and suggest that a high consumption of carotenoids may reduce the risk of premenopausal but not postmenopausal breast cancer, particularly among smokers. © 2009 UICC     

Factors influencing ovulation and the risk of ovarian cancer in BRCA1 and BRCA2 mutation carriers

The role of the lifetime number of ovulatory cycles has not been evaluated in the context of BRCA‐associated ovarian cancer. Thus, we conducted a matched case–control study to evaluate the relationship between the cumulative number of ovulatory cycles (and contributing components) and risk of developing ovarian cancer in BRCA mutation carriers (1,329 cases and 5,267 controls). Information regarding reproductive and hormonal factors was collected from a routinely administered questionnaire. Conditional logistic regression was used to evaluate all associations. We observed a 45% reduction in the risk of developing ovarian cancer among women in the lowest vs. highest quartile of ovulatory cycles (OR = 0.55; 95% CI 0.41–0.75, p = 0.0001). Breastfeeding for more than 12 months was associated with a 38% (95% CI 0.48–0.79) and 50% (95% CI 0.29–0.84) reduction in risk among BRCA1 and BRCA2 mutation carriers, respectively. For oral contraceptive use, maximum benefit was seen with five or more years of use among BRCA1 mutation carriers (OR = 0.50; 95% CI 0.40–0.63) and three or more years for BRCA2 mutation carriers (OR = 0.42; 95% CI 0.22–0.83). Increasing parity was associated with a significant inverse trend among BRCA1 (OR = 0.87; 95% CI 0.79–0.96; p‐trend = 0.005) but not BRCA2 mutation carriers (OR 0.98; 95% CI 0.81–1.19; p‐trend = 0.85). A later age at menopause was associated with an increased risk in women with a BRCA1 mutation (OR trend = 1.18; 95% CI 1.03–1.35; p = 0.02). These findings support an important role of breastfeeding and oral contraceptive use for the primary prevention of ovarian cancer among women carrying BRCA mutations.     

Exogenous hormones and colorectal cancer risk in Canada: associations stratified by clinically defined familial risk of cancer

Objective This work assessed associations between colorectal cancer risk and postmenopausal/contraceptive hormones; subgroup analyses included women with a clinically defined family history of cancer. Methods A population based case–control study of incident colorectal cancer was conducted among women aged 20–74 years in Ontario and Newfoundland & Labrador, Canada. Incident cases (n = 1,404) were selected from provincial cancer registries and controls (n = 1,203) were identified through property records, and other means, between January 1997 and April 2006. Family history of cancer, exogenous hormone-use, and other risk factors were collected via self-administered questionnaires. Multivariate unconditional logistic regression analyses were used to estimate odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Results Decreased risks of colorectal cancer were observed with ever-users of: hormonal contraceptives (OR: 0.77; CI: 0.65–0.91), estrogen-only postmenopausal hormones (OR: 0.60; CI: 0.47–0.75), and estrogen–progestin postmenopausal hormones (OR: 0.70; CI: 0.52–0.95). Risk estimates were similar between women with and without a strong familial history of cancer. Age at initiation of hormonal contraceptives was associated with colorectal cancer risk; women who initiated use at younger ages (age <22 years: OR: 0.60; CI: 0.47–0.77) experienced a greater reduced risk of disease than women who initiated use at later ages (age 30+: OR: 0.92; CI: 0.68–1.24; p _trend: 0.0026). Conclusions These results indicate that exogenous hormone-use is linked with reduced risk of colorectal cancer among women with a strong familial risk of cancer, consistent with observations on population samples of sporadic colorectal cancer cases. A potential age-effect for use of hormonal contraceptives warrants further attention.     

Cancer patients' desire for psychological support: prevalence and implications for screening patients' psychological needs

Objectives: To investigate cancer patients' desire for psychological support and to identify patients' sociodemographic, disease‐related and psychological factors associated with this desire. Methods: The study is part of a multicenter, cross‐sectional study assessing cancer patients' needs and desire for psychological support. Patients completed the Hospital Anxiety and Depression Scale, the Ways of Coping Checklist, the Cancer Rehabilitation Evaluation System and reported their desire for psychological support. Results: Among the 381 included patients, women (26%) desired psychological support significantly more often than men (11%) (p<0.001). Patients' desire for psychological support was associated with being younger (OR=0.94; p<0.001 for women and OR=0.93; p=0.007 for men) and having a support‐seeking coping (OR=1.10; p=0.010 for women and OR=1.36; p=0.003 for men). Other contextual factors such as difficulties encountered and treatment modalities were diversely associated with women and men's desire for psychological support. Neither women's, nor men's psychological distress was associated with their desire for psychological support. Conclusions: One female cancer patient out of four and one male cancer patient out of ten desire psychological support. Results emphasize the need to screen not only for cancer patients' distress but also for their desire for psychological support. This will allow implementing psychological interventions according to patients' needs and desire. Copyright © 2009 John Wiley & Sons, Ltd.     

Serum carotenoid,tocopherol and retinol concentrations and breast cancer risk in the E3N‐EPIC study

Evidence of a protective effect of fruit and vegetable intake on breast cancer risk is inconsistent. Epidemiologic cohort studies based on blood carotenoid intakes as biomarkers of consumption of fruits and vegetable in individuals are still scare and findings are discrepant. The study population included women in the E3N Study, the large French component of the European Prospective Investigation into Cancer and Nutrition (EPIC). During an average of 7 years follow‐up, 366 cases of incident invasive breast cancer (84 premenopausal women and 282 postmenopausal women) among 19,934 women who completed a dietary questionnaire and had available blood samples at baseline (1995–1998) were included in the study. Controls were randomly matched on age, menopausal status at blood collection, fasting status at blood collection, date and collection center. Serum carotenoids, tocopherols and retinol concentrations were assessed by high pressure liquid chromatography. Odds ratios for breast cancer risk adjusted for established breast cancer risk factors were calculated by quintile of serum micronutrient concentrations. No significant associations between breast cancer risk and serum carotenoids (highest versus lowest quintile, odds ratio (OR) = 0.74, 95% confidence interval (CI) = 0.47–1.16, p for trend 0.38), tocopherols (OR = 0.68, 95% CI = 0.41–1.10, p for trend 0.26) and retinol (OR = 0.85, 95% CI = 0.53–1.35, p for trend 0.34) were found. Our findings did not support the hypothesis that lipophilic antioxidant micronutrients found in fruits and vegetables protect against breast cancer, at least in postmenopausal women.     

Lung cancer risk by geologic coal deposits: A case–control study of female never-smokers from Xuanwei and Fuyuan,China

Coal types vary around the world because of geochemical differences in their source deposits; however, the influence of coal emissions from different deposits on human health remains unexplored. To address this issue, we conducted the first study of the relationship between coal use from various deposits and lung cancer risk in Xuanwei and Fuyuan, counties in China where lung cancer rates are among the highest in the world among female never-smokers due to use of bituminous (“smoky”) coal for heating and cooking. We conducted a population-based case–control study of 1031 lung cancer cases and 493 controls among never-smoking women in Xuanwei and Fuyuan. Logistic regression models were used to estimate associations between coal use from various deposits across the lifecourse and lung cancer risk. There was substantial heterogeneity in risks by coal deposit (p = 7.8E-05). Compared to non-smoky coal users, risks by smoky coal deposit ranged from OR = 7.49 (95% CI: 3.43–16.38) to OR = 33.40 (95% CI: 13.07–85.34). Further, women born into homes that used smoky coal and subsequently changed to non-smoky coal had a higher risk (OR = 10.83 (95% CI: 4.61–25.46)) than women born into homes that used non-smoky coal and changed to smoky coal (OR = 4.74 (95% CI: 2.03–11.04, p_difference = 0.04)). Our study demonstrates that various sources of coal have considerably different impact on lung cancer in this population and suggests that early-life exposure to carcinogenic emissions may exert substantial influence on health risks later in life. These factors should be considered when evaluating the health risks posed by exposure to coal combustion emissions.     

Family history and risk of breast cancer in hispanic and non-hispanic women: the New Mexico Women's Health Study

Objectives: Many epidemiologic studies have demonstrated that an increased risk of breast cancer is associated with positive family history of this disease. Little information had been available on the relationship of breast cancer risk with family history in Hispanic women. To investigate the association of family history of breast cancer on the risk of breast cancer, we examined the data from the New Mexico Women's Health Study (NMWHS), a statewide case–control study. Methods: In this study 712 women (332 Hispanics and 380 non-Hispanic whites) with breast cancer and 844 controls (388 Hispanics and 456 non-Hispanic whites) were included. Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI), adjusted for sociodemographic, medical, and reproductive factors. Results: We found an increased risk in women with a history of breast cancer in one or more first-degree or second-degree relatives (OR = 1.5, 95% CI 1.2–1.9), first-degree relatives (OR = 1.3, 95% CI 1.0–1.8) and second-degree relatives (OR = 1.6, 95% CI 1.2–2.2). Hispanic women had higher risk estimates for a positive family history (OR = 1.7, 95% CI 1.1–2.5) than non-Hispanic white women (OR = 1.4, 95% CI 1.0–2.0); however, the differences were not statistically significant. In both ethnic groups a higher risk was observed in premenopausal women compared with postmenopausal women and women diagnosed with breast cancer before age 50years compared with older women. Conclusions: The results indicate that Hispanic women with a family history of breast cancer are at increased risk of breast cancer.     

Associations of dietary folate,Vitamins B6 and B12 and methionine intake with risk of breast cancer among African American and European American women

African American (AA) women are more likely than European American (EA) women to be diagnosed with breast cancer at younger ages and to develop poor prognosis tumors. However, these racial differences are largely unexplained. Folate and other methyl‐group nutrients may be related to breast carcinogenesis, but few studies have examined these associations in AA populations. We examined the associations of dietary intake of these nutrients with breast cancer risk overall, by menopausal and estrogen receptor (ER) status among 1,582 AA (749 cases) and 1,434 EA (744 cases) women using data from a case–control study, the Women's Circle of Health Study. Unconditional multivariable logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) for the association of each nutrient and breast cancer risk. In AA women, inverse associations were observed for natural food folate intake among premenopausal women (fourth vs. first quartile: OR = 0.57, 95% CI, 0.33–1.00; p for trend = 0.06) and for ER‐positive tumors (fourth vs. first quartile: OR = 0.58, 95% CI, 0.36–0.93; p for trend = 0.03), whereas in EA women, a positive association was observed for intake of synthetic folate (fourth vs. first quartile: OR = 1.53, 95% CI, 1.06–2.21; p for trend = 0.03). Our findings suggest that natural food folate intake is inversely associated with breast cancer risk and that this association may vary by race, menopausal status or ER status. The finding of an increased risk observed among EA women with the highest intake of synthetic folate from fortified foods warrants further investigation.     

Obesity,weight gain,and ovarian cancer risk in African American women

Although there is growing evidence that higher adiposity increases ovarian cancer risk, little is known about its impact in African American (AA) women, the racial/ethnic group with the highest prevalence of obesity. We evaluated the impact of body mass index (BMI) 1 year before diagnosis and weight gain since age 18 years on ovarian cancer risk in a population‐based case‐control study in AA women in 11 geographical areas in the US. Cases (n = 492) and age and site matched controls (n = 696) were identified through rapid case ascertainment and random‐digit‐dialing, respectively. Information was collected on demographic and lifestyle factors, including self‐reported height, weight at age 18 and weight 1 year before diagnosis/interview. Multivariable logistic regression was used to compute odds ratios (OR) and 95% confidence intervals (CI), adjusting for potential covariates. Obese women had elevated ovarian cancer risk, particularly for BMI ≥ 40 kg/m² compared to BMI <25 (OR = 1.72, 95% CI: 1.12‐2.66; p for trend: 0.03). There was also a strong association with weight gain since age 18 (OR: 1.52; 95% CI: 1.07–2.16; p for trend: 0.02) comparing the highest to lowest quartile. In stratified analyses by menopausal status, the association with BMI and weight gain was limited to postmenopausal women, with a 15% (95% CI: 1.05–1.23) increase in risk per 5 kg/m² of BMI and 6% (95% CI: 1.01–1.10) increase in risk per 5 kg of weight gain. Excluding hormone therapy users essentially did not change results. Obesity and excessive adult weight gain may increase ovarian cancer risk in post‐menopausal AA women.     

Patient-mediated factors predicting early- and late-stage presentation of breast cancer in Egypt

Objective: Breast cancer fatality rates are high in low‐ and middle‐income countries because of the late stage at diagnosis. We investigated patient‐mediated determinants for late‐stage presentation of breast cancer in Egypt. Methods: A case–case comparison was performed for 343 women with breast cancer, comparing those who had been initially diagnosed at Stage I or II with those diagnosed at Stage III or IV. Patients were recruited from the National Cancer Institute of Cairo University and Tanta Cancer Center in the Nile delta. Patients were either newly diagnosed or diagnosed within the year preceding the study. Interviews elicited information on disease history and diagnosis, beliefs and attitudes toward screening practices, distance to treatment facility, education, income, and reproductive history. Results: Forty‐six per cent of the patients had presented at late stage. Women seen in Cairo were more likely to present at late stages than patients in Tanta (OR=5.05; 95% CI=1.30, 19.70). Women without any pain were more likely to present at later stage (OR=2.68; 95% CI=1.18, 6.08). Knowledge of breast self‐examination increased the likelihood of women to present in early stages significantly (OR=0.24; 95% CI=0.06, 0.94). Conclusions: Despite increasing numbers of cancer centers in Egypt during the past 20 years, additional regional facilities are needed for cancer management. In addition, increasing awareness about breast cancer will have significant long‐term impact on breast cancer prevention. Copyright © 2010 John Wiley & Sons, Ltd.     

Serum organochlorines and breast cancer: a case–control study among African-American women

This population-based case–control study of African-American women (355 breast cancer case patients, 327 controls) examined the association between breast cancer and circulating levels of PCBs and dichlorodiphenyldichloroethene (DDE), a metabolite of DDT. Case patients were diagnosed with invasive breast carcinoma and interviewed between June 1995 and July 1998, and control subjects were identified by random digit dialing methods. Serum levels of DDE and total PCBs were adjusted for total lipid content. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable unconditional logistic regression methods. Effect modification by tumor receptor status and cancer treatment was investigated. Breast cancer risk was not associated with increasing quintiles of lipid-adjusted PCBs or DDE (highest versus lowest quintile adjusted for age, body mass index (BMI) and breastfeeding for DDE: OR = 1.02, 95% CI = (0.61, 1.72), p-trend = 0.74; for PCBs: OR = 1.01, 95% CI = (0.63, 1.63), p-trend = 0.56). Risk did not differ by strata of BMI, breastfeeding, parity, menopausal status or tumor receptor status. This study, the largest study of African-American women to date, does not support a role of DDE and total PCBs in breast cancer risk at the levels measured.     

Vitamin D receptor rs2228570 polymorphism and invasive ovarian carcinoma risk: Pooled analysis in five studies within the Ovarian Cancer Association Consortium

The association of invasive ovarian carcinoma risk with the functional polymorphism rs2228570 (aka rs10735810; FokI polymorphism) in the vitamin D receptor (VDR) gene was examined in 1820 white non‐Hispanic cases and 3479 controls in a pooled analysis of five population‐based case–control studies within the Ovarian Cancer Association Consortium. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Carriers of the rare T allele were at increased risk of ovarian carcinoma compared to women with the CC genotype in all studies combined; each copy of the T allele was associated with a modest 9% increased risk (OR = 1.09; 95% CI: 1.01–1.19; p = 0.04). No significant heterogeneity among studies was observed (p = 0.37) and, after excluding the dataset from the Hawaii study, the risk association for rs2228570 among replication studies was unchanged (OR = 1.09; 95% CI: 1.00–1.19; p = 0.06). A stronger association of rs2228570 with risk was observed among younger women (aged < 50 years versus 50 years or older) (p = 0.04). In all studies combined, the increased risk per copy of the T allele among younger women was 24% (OR = 1.24; 95% CI: 1.04–1.47; p = 0.02). This association remained statistically significant after excluding the Hawaii data (OR = 1.20; 95% CI: 1.01–1.43; p = 0.04). No heterogeneity of the association was observed by stage (p = 0.46), tumor histology (p = 0.98), or time between diagnosis and interview (p = 0.94). This pooled analysis provides further evidence that the VDR rs2228570 polymorphism might influence ovarian cancer susceptibility.     

Sarcopenia Is Associated with Quality of Life and Depression in Patients with Advanced Cancer

Background

Patients with advanced cancer often experience muscle wasting (sarcopenia), yet little is known about the characteristics associated with sarcopenia and the relationship between sarcopenia and patients’ quality of life (QOL) and mood.

Materials and Methods

As part of a randomized trial, we assessed baseline QOL (Functional Assessment of Cancer Therapy‐General [FACT‐G]) and mood (Hospital Anxiety and Depression Scale [HADS]) in patients within 8 weeks of diagnosis of incurable lung or gastrointestinal cancer, and prior to randomization. Using computed tomography scans collected as part of routine clinical care, we assessed sarcopenia at the level of the third lumbar vertebra with validated sex‐specific cutoffs. We used logistic regression to explore characteristics associated with presence of sarcopenia. To examine associations between sarcopenia, QOL and mood, we used linear regression, adjusted for patients’ age, sex, marital status, education, and cancer type.

Results

Of 237 participants (mean age = 64.41 ± 10.93 years), the majority were male (54.0%) and married (70.5%) and had lung cancer (56.5%). Over half had sarcopenia (55.3%). Older age (odds ratio [OR] = 1.05, p = .002) and education beyond high school (OR = 1.95, p = .047) were associated with greater likelihood of having sarcopenia, while female sex (OR = 0.25, p < .001) and higher body mass index (OR = 0.79, p < .001) correlated with lower likelihood of sarcopenia. Sarcopenia was associated with worse QOL (FACT‐G: B = ?4.26, p = .048) and greater depression symptoms (HADS‐depression: B = ?1.56, p = .005).

Conclusion

Sarcopenia was highly prevalent among patients with newly diagnosed, incurable cancer. The associations of sarcopenia with worse QOL and depression symptoms highlight the need to address the issue of sarcopenia early in the course of illness.

Implications for Practice

This study found that sarcopenia, assessed using computed tomography scans acquired as part of routine clinical care, is highly prevalent in patients with newly diagnosed, incurable cancer. Notably, patients with sarcopenia reported worse quality of life and greater depression symptoms than those without sarcopenia. These findings highlight the importance of addressing muscle loss early in the course of illness among patients with incurable cancer. In the future, investigators should expand upon these findings to develop strategies for assessing and treating sarcopenia while striving to enhance the quality of life and mood outcomes of patients with advanced cancer.     

A deletion in CHEK2 of 5,395 bp predisposes to breast cancer in Poland

Abstract To investigate the contribution of a founder deletion in the CHEK2 gene to the burden of breast cancer in Poland we studied 4,454 women with breast cancer and 5,496 population controls. Cases and controls were genotyped for the presence of a 5,395 bp founder deletion that removes exons 9 and 10 of the CHEK2 gene. This deletion has recently been described in a Czech and Slovak population. The cases and controls had previously been tested for two protein-truncating (IVS2 + 1G > A and 1100delC) and one missense CHEK2 mutation (I157T) which are characteristic for the population. The exons 9 and 10 deletion was present in 0.4% of the controls, in 1.0% (19 of 1,978) of unselected breast cancer cases (OR=2.2; 95% CI: 1.2–4.0; p = 0.01) and in 0.9% (28 of 3,228) of the early-onset cases (OR=2.0; 95% CI: 1.3–1.8; p = 0.02). One of the three truncating CHEK2 mutations (del5395; 1100delC or IVS2 + 1G > A) was seen in 101 of 4,454 (2.3%) cases and in 58 of 5,496 controls (1.1%) (OR=2.2; 95% CI: 1.6–3.0 p < 0.0001). A 5,395 bp founder deletion contributes to the burden of breast cancer in Poland. The deletion was present in 0.9% of the women with breast cancer diagnosed under the age of 51 and in 0.9% of women with breast cancer over the age of 50. This is one of the most common protein-truncating CHEK2 variants in Poland. Overall, 2% of all breast cancers in Poland can be attributed to one of three protein-truncating mutatiosns in CHEK2.     

Effects of mammographic density and benign breast disease on breast cancer risk (United States)

Background: Having either a history of benign breast disease, particularly atypical hyperplasia or extensive mammographic breast density, is associated with increased breast cancer risk. Previous studies have described an association between benign breast disease histology and breast density. However, whether these features measure the same risk, or are independent risk factors, has not been addressed. Methods: This case–control study, nested within the prospective follow-up of the Breast Cancer Detection Demonstration Project, evaluated both benign histologic and mammographic density information from 347 women who later developed breast cancer and 410 age- and race-matched controls without breast cancer. Multivariate logistic regression analyses provided maximum-likelihood estimates of the odds ratios (OR) and 95% confidence intervals (CI) to evaluate the relative risk of breast cancer associated with each exposure. Results: Adjusting for mammographic density, the OR for atypical hyperplasia was 2.1 (95% CI: 1.3–3.6), and adjusting for benign breast histology, the OR for 75% density was 3.8 (95% CI: 2.0–7.2). Women with nonproliferative benign breast disease and 75% density had an OR of 5.8 (95% CI: 1.8–18.6), and women with <50% density and atypical hyperplasia had an OR of 4.1 (95% CI: 2.1–8.0). Conclusions: In this study, both benign breast disease histology and the percentage of the breast area with mammographic density were associated with breast cancer risk. However, women with both proliferative benign breast disease and 75% density were not at as high a risk of breast cancer due to the combination of effects (p = 0.002) as women with only one of these factors.     

Circulating endogenous sex steroids and risk of differentiated thyroid carcinoma in men and women

Thyroid cancer (TC) is substantially more common in women than in men, pointing to a possible role of sex steroid hormones. We investigated the association between circulating sex steroid hormones, sex hormone binding globulin (SHBG) and the risk of differentiated TC in men and women within the European Prospective Investigation into Cancer and nutrition (EPIC) cohort. During follow-up, we identified 333 first primary incident cases of differentiated TC (152 in pre/peri-menopausal women, 111 in post-menopausal women, and 70 in men) and 706 cancer-free controls. Women taking exogenous hormones at blood donation were excluded. Plasma concentrations of testosterone, androstenedione, dehydroepiandrosterone, estradiol, estrone and progesterone (in pre-menopausal women only) were performed using liquid chromatography/mass spectrometry method. SHBG concentrations were measured by immunoassay. Odds ratios (ORs) were estimated using conditional logistic regression models adjusted for possible confounders. No significant associations were observed in men and postmenopausal women, while a borderline significant increase in differentiated TC risk was observed with increasing testosterone (adjusted OR T3 vs T1: 1.68, 95% CI: 0.96–2.92, p_trend = .06) and androstenedione concentrations in pre/perimenopausal women (adjusted OR T3 vs T1: 1.78, 95% CI: 0.96–3.30, p_trend = .06, respectively). A borderline decrease in risk was observed for the highest progesterone/estradiol ratio (adjusted OR T3 vs T1: 0.54, 95% CI: 0.28–1.05, p_trend = .07). Overall, our results do not support a major role of circulating sex steroids in the etiology of differentiated TC in post-menopausal women and men but may suggest an involvement of altered sex steroid production in pre-menopausal women.     

Genetic polymorphism in CYP17 and breast cancer risk in Japanese women

A case–control study was conducted to investigate the association of two genetic polymorphisms (1931T/C and 1951G/A) in the promoter region of the CYP17 gene with breast cancer risk in Japanese women. No significant association was observed between CYP17 polymorphism^1951G/A and breast cancer risk (odds ratio (OR)=1.71, 95% confidence interval (CI): 0.28–1.84). In contrast, a significant increase in breast cancer risk (OR=1.82, 95% CI: 1.07–3.12) was observed in CYP17^1931C/C homozygotes compared with CYP17^1931T/C heterozygotes and CYP17^1931T/T homozygotes when women aged 55 years were considered, but such a significant increase was not observed when women aged 54 years were considered (OR=0.96, 95% CI: 0.56–1.63). These results suggest that CYP17 polymorphism^1931T/C would be useful in the selection of Japanese women at a high risk for developing breast cancer at the age of 55 years.     

Polymorphisms of matrix metalloproteinases 1, 2, 3 and 9 and susceptibility to lung,breast and colorectal cancer in over 30,000 subjects

A variety of susceptibility genes have been associated with cancer but definitive conclusions have been difficult to draw partly hampered by the small number of subjects in each study. We undertook a comprehensive genetic meta‐analysis of all matrix metalloproteinase (MMP) genes investigated using an allelic‐association case–control model in the 3 major cancers of lung, breast and colorectal cancer. Electronic databases were searched until and including July 2008 for any MMP genetic association study in lung, breast and colorectal cancer. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models. Twenty‐five studies addressing 5 polymorphisms in 4 genes were analyzed among 30,651 individuals (15,328 cases and 15,253 controls). The MMP‐1 nt‐1607 polymorphism was significantly associated with colorectal cancer in both the dominant (OR, 1.66; 95% CI, 1.14–2.42; p = 0.008) and recessive (OR, 1.59; 95% CI, 1.15–2.20; p = 0.005) models. MMP‐2^1306C→T (OR, 0.53; 95% CI, 0.40–0.72; p < 0.0001) and 735^C→T (OR, 0.65; 95% CI, 0.53–0.79; p < 0.0001) were significantly associated with protection against lung cancer. No association was found with the MMP 1, 2, 3 or 9 polymorphisms with breast cancer, MMP‐1, 3 or 9 with lung cancer or MMP‐2, 3 or 9 with colorectal cancer. There may be a genetic influence in the development of colorectal and lung cancer. Subjects with the MMP‐1 nt‐1607 polymorphism have an increased association with colorectal cancer. Those homozygous for either the MMP‐2/1306T or 735T allele may be at reduced risk of lung cancer, although the evidence base is small. © 2009 UICC