Dietary glycemic index, glycemic load and ovarian cancer risk: a case-control study in Italy.

BACKGROUND: Dietary carbohydrates vary in their ability to raise blood glucose and insulin levels, which, in turn, influence levels of sex hormones and insulin-like growth factors. We analyzed the effect of type and amount of carbohydrates on ovarian cancer risk, using the glycemic index (GI) and the glycemic load (GL) measurement in a large case-control study conducted in Italy. MATERIALS AND METHODS: Cases included 1031 women with incident, histologically confirmed epithelial ovarian cancer, from four Italian regions. Controls included 2411 women admitted to the same hospital networks for acute, non-neoplastic conditions. Average daily GI and GL were calculated from a validated food frequency questionnaire. Odds ratios (OR) and the corresponding 95% confidence intervals (CI) were computed using multiple logistic regression. RESULTS: Ovarian cancer was directly associated with dietary GI (OR for highest versus lowest quartile = 1.7, 95% CI 1.3-2.1) and GL (OR = 1.7, 95% CI 1.3-2.1). The associations were observed in pre- and postmenopausal women, and they remained consistent across strata of major covariates identified. CONCLUSIONS: This study supports the hypothesis of a direct association between GI and GL and ovarian cancer risk and, consequently, of a possible role of hyperinsulinemia/insulin resistance in ovarian cancer development.     

Association of NAT2 and smoking in relation to breast cancer incidence in a population-based case-control study (United States)

Objective: To evaluate the potential interaction between N-acetyltransferase 2 (NAT2) and smoking in breast cancer incidence. Methods: The data are derived from a population-based case–control study of women aged 20–69 years who were residents of Massachusetts or Wisconsin during 1997–1998. Incident cases of invasive breast cancer were identified through state tumor registries and age-similar controls were selected at random from population lists. Telephone interviews were conducted to obtain information on known and suspected risk factors including smoking history. Women provided oral mucosal DNA through the mail for genetic studies. Results: A total of 791 cases and 797 controls were included in the analysis. Overall, smoking was modestly associated with breast cancer risk (multivariate odds ratio (OR) for ever smoking: 1.37; 95% confidence interval (CI): 1.12–1.69), and there was a trend in risk for greater pack-years of smoking among postmenopausal women (p for trend = 0.02). Overall, NAT2 was not related to invasive breast cancer (multivariate OR: 1.11; 95% CI: 0.90–1.36). Associations of smoking with breast cancer tended to be somewhat stronger among the women with the slow acetylator genotype for NAT2: when compared to those who never smoked and were rapid acetylators, the OR for ever smoking was 1.50 (95% CI: 1.11–2.02) in slow acetylators, and OR: 1.24 (95% CI: 0.91–1.70) in rapid acetylators. However, tests for multiplicative interaction were not significant in case–control comparisons, or in case-only analyses. Conclusion: Results of the study are compatible with the majority of previous studies that indicate little or no association of NAT2, smoking, or their interaction with the occurrence of breast cancer.     

Physical activity and premenopausal breast cancer: an examination of recall and selection bias

Background  Compared with cohort studies, case–control investigations have tended to report clearer protective associations for the relationship between physical activity and premenopausal breast cancer risk. Methods  We conducted a case–control study within the Nurses’ Health Study II cohort to examine whether recall or selection bias could explain the stronger protective associations. Self-reported total recreational physical activity during adulthood and over a woman’s lifetime (ages 12 years to current) were assessed in 1997 before diagnosis and, again, from one to seven years after breast cancer diagnosis among the same women. Results  Eighty-seven percent of cases (417 of 479) and 82% of controls (390 of 474) responded. Selection bias was observed for activity during adulthood but not for activity over a woman’s lifetime. Recall bias was not observed in the direction we expected: the odds ratios (ORs) for breast cancer comparing the highest versus lowest quintile of prospectively reported total activity were not significantly different than the corresponding estimates from retrospective reports (e.g., lifetime activity: prospective OR = 0.58, 95% CI: 0.37, 0.93 versus retrospective OR = 0.80; 95% CI: 0.50,1.29). Conclusion  Recall or selection bias may not have been accounted for protective associations among case–control investigations examining lifetime recreational physical activity and breast cancer. Selection bias related to recreational physical activity during adulthood and random error in the measurement of physical activity remain concerns.     

Manganese superoxide dismutase Ala-9Val polymorphism, environmental modifiers, and risk of breast cancer in a German population

Objective A functional polymorphism at codon 16 (Alanine-to-Valine) of manganese superoxide dismutase (MnSOD) has been hypothesized to increase the risk of breast cancer and to modify the effects of oxidative stress. However, study findings have been inconsistent and sample sizes often small. Methods We used a large population-based age-matched case–control study in German Caucasian women up to age 50 to assess breast cancer risk associated with this polymorphism and to investigate interaction with other known risk factors related to oxidative stress, including alcohol intake, cigarette smoking, and diet. Data on a total of 614 cases and 1,080 controls were evaluated using multivariate conditional logistic models. Results No main effect between genotype and breast cancer was observed. However, risk was significantly increased for Ala carriers who consumed ≥19 g of alcohol per day, compared to women homozygous for the Val allele who did not drink (OR 2.1, 95% CI 1.1–3.9; p = 0.13 for interaction). No significant effect modification was observed for smoking or diet. Conclusions The MnSOD Ala-9Val polymorphism may contribute to an increase in breast cancer risk in the context of high alcohol consumption, however the polymorphism is not an overall risk factor for breast cancer in this primarily premenopausal population. This work was supported by the Medical Faculty of the University of Ulm (P.589 and P.685) and the Deutsche Krebshilfe e.V. (Project number 70492)     

Promoter polymorphisms in matrix metalloproteinases and their inhibitors: few associations with breast cancer susceptibility and progression

The importance of matrix metalloproteinases and their inhibitors in tumor progression is well documented. We wanted to investigate if single nucleotide polymorphisms (SNPs) in the promoter regions of these genes are associated with susceptibility to or progression of breast cancer. In this, so far largest case–control study, we genotyped eight SNPs in the MMP1, MMP2, MMP3, MMP9, MMP13, RECK and TIMP3 genes in a well-characterized breast cancer series of 959 cases and 952 controls from Sweden. Even though we did not correct for multiple comparisons, only a few associations were noted. We observed a moderately increased risk for the TT homozygotes of the MMP9−1562 C/T SNP (OR 1.88, 95% CI 0.97–3.63) and for the C allele carriers of the TIMP3−1296 T/C SNP (OR 1.25, 95% CI 1.05–1.50). In the survival analysis, only the TC heterozygotes of the RECK−420 T/C SNP showed a better survival compared to the TT homozygotes (P = 0.02 in all cases and P = 0.03 in lymph node negative cases). None of the other SNPs conferred an increased breast cancer risk, nor did they correlate with survival. A combination of the −585 TT homozygosity in the RECK gene and the −1296 TT homozygosity in the TIMP3 gene correlated with estrogen and progesterone receptor status (OR 1.81, 95% CI 1.03–3.21 and OR 2.10, 95% CI 1.18–3.86, respectively), and a combination of the −1306 TT homozygosity in the MMP2 gene and the −1562 CC homozygosity in the MMP9 gene with progesterone receptor status (OR 2.34, 95% CI 1.08–5.08). Although our study suggests some correlations between the studied SNPs and the progression of breast cancer, the rarity of the risk genotypes limits their usefulness in the clinic. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Association between alcohol consumption and postmenopausal breast cancer: results of a case-control study in Montreal,Quebec, Canada

OBJECTIVES: To determine the association between postmenopausal breast cancer and prior consumption of alcoholic beverages.METHODS: This case–control study, conducted in all Montreal hospitals between 1996 and 1997, included 556 postmenopausal women (age 50–75 years) who had a new histologically confirmed diagnosis of primary, malignant breast cancer. Control subjects (577) were selected from other histologically confirmed sites of cancer. A detailed history of alcohol consumption and other risk factors was obtained by interview. Indices reflecting alcohol consumption were developed and unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).RESULTS: Current regular drinkers of any type of alcohol were at an increased risk of breast cancer (OR = 1.5; 95% CI 1.0–2.2). For all beverages considered, current regular drinkers showed higher risks than ever regular drinkers. The risk of breast cancer was highest among women who reported exclusive drinking of wine on a weekly or daily basis (e.g. current regular drinking: OR = 2.3; 95% CI 1.2–4.3). Women who started to drink wine on or before the age of 40 were at a 2.5 times increased risk (95% CI 1.4–4.4).CONCLUSIONS: Our findings provide further support for a positive association between the risk of postmenopausal breast cancer and alcohol consumption.     

Effectiveness of service screening: a case-control study to assess breast cancer mortality reduction

The aim of this study was the evaluation of the impact of service screening programmes on breast cancer mortality in five regions of Italy. We conducted a matched case-control study with four controls for each case. Cases were defined as breast cancer deaths occurred not later than 31 December 2002. Controls were sampled from the local municipality list and matched by date of birth. Screening histories were assessed by the local, computerised, screening database and subjects were classified as either invited or not-yet-invited and as either screened or unscreened. There were a total of 1750 breast cancer deaths within the 50 to 74-year-old breast cancer cases and a total of 7000 controls. The logistic conditional estimate of the cumulative odds ratios comparing invited with not-yet-invited women was 0.75 (95% CI: 0.62-0.92). Restricting the analyses to invited women, the odds ratio of screened to never-respondent women corrected for self-selection bias was 0.55 (95% CI: 0.36-0.85). The introduction of breast cancer screening programmes in Italy is associated with a reduction in breast cancer mortality attributable to the additional impact of service screening over and above the background access to mammography.     

The Long Island Breast Cancer Study Project: description of a multi-institutional collaboration to identify environmental risk factors for breast cancer

The Long Island Breast Cancer Study Project is a federally mandated, population-based case-control study to determine whether breast cancer risk among women in the counties of Nassau and Suffolk, NY, is associated with selected environmental exposures, assessed by blood samples, self-reports, and environmental home samples. This report describes the collaborative project's background, rationale, methods, participation rates, and distributions of known risk factors for breast cancer by case-control status, by blood donation, and by availability of environmental home samples. Interview response rates among eligible cases and controls were 82.1% (n = 1,508) and 62.8% (n = 1,556), respectively. Among case and control respondents who completed the interviewer-administered questionnaire, 98.2 and 97.6% self-completed the food frequency questionnaire; 73.0 and 73.3% donated a blood sample; and 93.0 and 83.3% donated a urine sample. Among a random sample of case and control respondents who are long-term residents, samples of dust (83.6 and 83.0%); soil (93.5 and 89.7%); and water (94.3 and 93.9%) were collected. Established risk factors for breast cancer that were found to increase risk among Long Island women include lower parity, late age at first birth, little or no breast feeding, and family history of breast cancer. Factors that were found to be associated with a decreased likelihood that a respondent would donate blood include increasing age and past smoking; factors associated with an increased probability include white or other race, alcohol use, ever breastfed, ever use of hormone replacement therapy, ever use of oral contraceptives, and ever had a mammogram. Long-term residents (defined as 15+ years in the interview home) with environmental home samples did not differ from other long-term residents, although there were a number of differences in risk factor distributions between long-term residents and other participants, as anticipated.