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Mary Beth Terry

Publications and source records attributed to Mary Beth Terry.

At least 19 recordsLinked to original sources
PubMed2026

Risks of non-breast, non-ovarian cancers for BRCA1 and BRCA2 pathogenic variant carriers: a prospective cohort study.

BACKGROUND: The non-breast non-ovarian cancers associated with BRCA1 and BRCA2 pathogenic variants (PVs) are controversial. We aimed to examine this using a prospective cohort design. METHODS: This study included 1260 BRCA1 and 1058 BRCA2 PV carriers (91% were females) from two consortia: the Breast Cancer Family Registry (BCFR) and the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer Follow-Up Study (kConFab-FUS). The carriers were free of cancer other than breast or ovarian cancer at baseline and had a median baseline age of 45.5 years. For 16 types of non-breast, non-ovarian cancers, standardized incidence ratios (SIRs) relative to population incidence, the probabilities of relative risk effect size > 2 (i.e., moderate risk) and cumulative risks to age 80 years were estimated. RESULTS: During a median follow-up time of 11.4 years, 161 non-breast, non-ovarian cancers were observed. For BRCA1 PV carriers, little evidence of increased risk was observed. The prostate, pancreatic, and all non-pancreatic cancer SIRs were 1.7 (95% CI 0.7-4.2), 1.1 (95% CI 0.3-4.6) and 0.85 (95% CI 0.68-1.06), respectively; the probabilities of relative risk > 2 were 0 and 67% for prostate and pancreatic cancers, respectively. For BRCA2 PV carriers, increased risks of pancreatic (SIR = 6.6, 95% CI 3.8-11.6), prostate (SIR = 3.6, 95% CI 1.9-6.8) and stomach (SIR = 3.1, 95% CI 1.01-9.8) cancer were observed, with a cumulative risk to age 80 years of 8.3, 82.0, and 1.6%, respectively. For all the other non-breast, non-ovarian cancers combined, the SIR was 0.85 (95% CI 0.66-1.10). CONCLUSIONS: Apart from pancreatic, prostate, and possibly stomach cancers for BRCA2 PV carriers, and possibly pancreatic cancer for BRCA1 PV carriers, there is no evidence that BRCA1 and BRCA2 PV carriers have substantially increased risks of other non-breast, non-ovarian cancers. Our prospective risk estimates are informative for cancer risk assessment for people with BRCA1 and BRCA2 PVs.

Humans↗
PubMed2025

Modeling Early-Onset Cancer Kinetics Reveals Changes in Underlying Risk and the Impact of Population Screening.

UNLABELLED: Recent studies have reported increases in early-onset cancer cases (diagnosed less than 50 years of age) and raised questions about whether the increase is related to earlier diagnosis from nonspecific medical tests as reflected by decreasing tumor-size-at-diagnosis (apparent effects) or actual increases in underlying cancer risk (true effects), or both. The classic Multistage Clonal Expansion (MSCE) model assumes cancer detection at the first malignant cell's emergence, although later modifications have included lag-times or stochasticity in detection to represent the delay in tumor detection. In this study, we introduced an approach to explicitly incorporate tumor-size-at-diagnosis in the MSCE framework accounting for improvements in cancer detection over time to distinguish between apparent and true increases in early-onset cancer incidence. The model was structurally identifiable and provided better parameter estimation than the classic model. The model was applied to colorectal, breast, and thyroid cancers to examine changes in cancer risk while accounting for detection improvements over time in three representative birth cohorts (1950-1954, 1965-1969, and 1980-1984). The analyses suggested accelerated carcinogenic events and shorter mean sojourn times (the average time from the first malignant cell emergence to cancer detection) in more recent cohorts. Furthermore, using this model to examine the screening impact on the incidence of breast and colorectal cancers, for which both have established screening protocols, provided results that align with well-documented differences in screening effects between these cancers. These findings underscore the importance of incorporating tumor-size-at-diagnosis in cancer modeling and support true increases in early-onset cancer risk in recent years for breast, colorectal, and thyroid cancers. SIGNIFICANCE: A model of early-onset cancer trends that distinguishes true risk from detection effects accurately captures cancer kinetics, trends in cancer progression, and the impact of screening, which could inform cancer prevention strategies. This article is part of a special series: Driving Cancer Discoveries with Computational Research, Data Science, and Machine Learning/AI .

Humans↗
PubMed2007

Genetic polymorphisms in folate metabolism and the risk of stomach cancer.

Folate deficiency has been implicated in the etiology of stomach cancer through abnormal DNA methylation and disrupted DNA synthesis and repair. Enzyme-coding genes involved in folate metabolism are often polymorphic. In a population-based study of 305 cases and 427 controls in Warsaw, Poland, we evaluated the risk of stomach cancer in relation to polymorphisms in folate-metabolizing genes, including MTHFR (Ex5+79C>T and Ex8-62A>C), MTR (Ex26-20A>G), and MTRR (Ex2-64A>G, Ex5+123C>T, Ex15+572C>T, Ex15-405A>T, Ex9-85C>T, Ex15-526G>A, and Ex14+14C>T). Polymorphisms in the MTHFR gene were not associated with stomach cancer risk. No notable effect was found for polymorphisms in MTR or MTRR either, although MTR Ex26-20 A>G and MTRR Ex5+123C>T polymorphisms were associated with a borderline increased risk of stomach cancer (MTR Ex26-20A>G, AG/GG versus AA: odds ratio, 1.35; 95% confidence interval, 0.96-1.90; MTRR Ex5+123C>T, CT/TT versus CC: odds ratio, 1.30; 95% confidence interval, 0.93-1.82). We did not find significant interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary folate and alcohol consumption. Our study did not identify strong genetic determinants in the folate metabolism pathway for stomach cancer risk.

Adult↗
PubMed2006

Reproductive factors and breast cancer risk among older women.

Reproductive factors have been shown to affect pre- and postmenopausal breast cancer risk differently, but whether there are additional age-specific differences among menopausal women as they age has not been clarified. We analyzed data from a large population-based case-control study that included 1,508 breast cancer cases and 1,556 controls, aged 20-98 years, who completed an in-home interviewer-administered questionnaire. The following subgroups were created to examine if the associations between reproductive factors and breast cancer risk varied by age- and menopausal-status: premenopausal (n=968), postmenopausal <65 years (n=1,045), postmenopausal >or=65 years (n=958). Among postmenopausal women >or=65 years, ever having breastfed decreased risk (odds ratio (OR)=0.67, 95% confidence interval (CI)=0.48, 0.92), and a strong dose-response relationship was observed for longer durations of breastfeeding (P trend=0.02), with the most pronounced protective effect observed for >or=14 months of breastfeeding (OR=0.40, 95% CI=0.21,0.76). Late age at first birth (AFB) and older age at last birth (ALB) were associated with non-statistically significant increases in breast cancer risk in this older group, while late age at menarche and surgical menopause decreased risk. ORs for multiparity were close to the null. Among premenopausal women and postmenopausal women <65 years, multiparity significantly decreased risk, and older AFB nonsignificantly increased risk. Our findings suggest that the well-known protective effect of multiparity attenuates with older age. Moreover, breastfeeding, one of the few potentially modifiable risk factors for breast cancer, was an important factor in decreasing risk among older parous postmenopausal women.

Adult↗
PubMed2006

IGHMBP2 Thr671Ala polymorphism might be a modifier for the effects of cigarette smoking and PAH-DNA adducts to breast cancer risk.

Laboratory and bioinformatics studies have suggested that immunoglobulin mu-binding protein 2 (IGHMBP2) is involved in DNA repair, replication and recombination. Using 1067 cases and 1110 controls from a population-based case-control study, we sought to clarify the potential role of the IGHMBP2 Thr671Ala polymorphism (A to G substitution) alone and as a modifier of the effects for cigarette smoking and PAH-DNA adducts on breast cancer risk. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, there was no significant association between the IGHMBP2 variant-G allele and breast cancer risk (OR = 1.1, 95% CI = 0.9-1.3). Increased risk was found among women who had detectable PAH-DNA adducts and carried at least one variant-G allele (OR = 1.4, 95% CI = 1.0-1.8, p for trend = 0.01) compared to women carrying the wild-type AA genotype and with non-detectable adducts. Smokers carrying the IGHMBP2 variant-G allele had no significant increased breast cancer risk compared with non-smoking women with the AA genotype. Heavy smokers (>31 pack years) had a statistically significant association with breast cancer risk (OR=2.0, 95% CI=1.2-3.3) relative to nonsmokers with the AA genotype though the magnitude of association was not different than heavy smokers (> 31 pack years) with the AA genotype (OR=1.6, 95% CI=0.9-2.6). Overall our study observes only modestly higher effect estimates for PAH-DNA adduct exposure and cigarette smoking among those with the high-risk genotype, but these differences are not statistically significant. Additional studies focused on the biological function of the variant-G allele and interactions with other genetic polymorphisms are necessary to confirm our findings.

Aged↗
PubMed2006

Effects of glutathione S-transferase A1 (GSTA1) genotype and potential modifiers on breast cancer risk.

Glutathione S-transferases (GSTs) are phase II enzymes that are involved in the detoxification of a wide range of carcinogens. The novel GSTA1*A and GSTA1*B genetic polymorphism results in differential expression, with lower transcriptional activation of GSTA1*B (variant) than that of GSTA1*A (common) allele. Considering that cruciferous vegetables induce GSTs, which metabolize tobacco smoke carcinogens, we hypothesized that the variant GSTA1*B genotype may predispose women to breast cancer, particularly among low cruciferous vegetable consumers and among smokers. Thus, we evaluated potential relationships between GSTA1 polymorphisms and breast cancer risk, in relation to vegetable consumption and smoking status in the Long Island Breast Cancer Study Project (1996-1997), a population-based case-control study. Genotyping (1036 cases and 1089 controls) was performed, and putative breast cancer risk factors and usual dietary intakes were assessed. Having GSTA1*A/*B or *B/*B genotypes was not associated with increased breast cancer risk, compared to having the common *A/*A genotype. However, among women in the lowest two tertiles of cruciferous vegetable consumption, *B/*B genotypes were associated with increased risk (OR (95% CI)=1.73 (1.10-2.72) for 0-1 servings/week), compared to women with *A/*A genotypes. Among women with *B/*B genotypes, a significant inverse trend between cruciferous vegetable consumption and breast cancer risk was observed (P for trend=0.05), and higher consumption (4+ servings/week) ameliorated the increased risk associated with the genotype. Current smokers with *B/*B genotypes had a 1.89-fold increase in risk (OR (95% CI)=1.89 (1.09-3.25)), compared with never smokers with *A/*A genotypes. These data indicate that GSTA1 genotypes related to reduced GSTA1 expression are associated with increased breast cancer primarily among women with lower consumption of cruciferous vegetables and among current smokers.

Alleles↗
PubMed2006

Catechol-O-methyltransferase haplotypes and breast cancer among women on Long Island, New York.

The gene encoding catechol-O-methyltransferase (COMT), critical to the inactivation of reactive catechol estrogens, has several single nucleotide polymorphisms (SNPs) that influence enzyme activity. A 3-SNP haplotype (IVS1+255 C>T; Ex4-12 G>A; 3'UTR-521 A>G), which has been shown to reduce COMT expression in the human brain, has been identified. To evaluate the influence of genetic variation of COMT on breast cancer risk, these 3-SNPs were genotyped in 1052 cases and 1098 controls. We estimated the associations between breast cancer and individual SNPs, as well as, multilocus haplotypes. We also examined surrogates of hormone exposure as potential modifiers of the putatively functional Ex4-12 SNP-breast cancer association. Odds ratios (OR) and 95% confidence intervals (CI) were based on age-adjusted unconditional logistic regression models. We found no association between the individual SNPs alone and breast cancer. When examining the association between breast cancer and the 3-SNP haplotypes, we observed a 19% increase in risk associated with each copy of the TGG haplotype (OR=1.19, 95% CI 0.96-1.49), relative to the common TAA haplotype, which was statistically significant when assuming a dominant model (OR=1.32, 95% CI 1.05-1.67, p-value=0.02). In this report of COMT haplotypes and breast cancer, we found some evidence that additional genetic variability beyond the Ex4-12 G>A SNP contributes to risk of breast cancer among a small subgroup of women; however, these results need to be replicated in additional studies.

Adult↗
PubMed2006

Influence of nativity status on breast cancer risk among US black women.

Black women are at increased risk for breast cancer mortality. The black category is assumed to be homogeneous, an assumption that may be misleading. This study aims to examine the relationship between nativity and breast cancer risk factors among women identified as black. A sample of 236 black women over 18 years of age in Brooklyn, New York, was recruited. Data were collected on race/ethnicity, breast cancer risk factors, and other sociodemographic, behavioral, and early life experience factors. Logistic regression analyses were used to estimate prevalence ratios for association between nativity and breast cancer risk factors. US-born blacks were more likely to be unemployed, smoke, not breastfeed, and breastfeed for a shorter duration than foreign-born blacks (all p< or =0.01). Foreign-born blacks were more likely to have parents who achieved at least a high school education (p<0.05). After adjustment for smoking, employment, and parental education, US-born blacks were twice as likely to never breastfeed (PR 2.2, 95% CI: 1.1, 4.46) compared to foreign-born blacks. Among women who breastfed, US-born blacks were also less likely to breastfeed for 6-11 months or more than 12 months, but these associations were not statistically significant. Because lactation reduces breast cancer risk and is a leading modifiable risk factor, understanding its variation within black women will help physicians and public health practitioners to target patient counseling and education of breast cancer risk.

Adult↗
PubMed2006

Relationship between urinary 15-F2t-isoprostane and 8-oxodeoxyguanosine levels and breast cancer risk.

To evaluate the role of oxidative stress in breast cancer, we measured urinary levels of 15-F(2t)-isoprostane (15-F(2t)-IsoP) and 8-oxodeoxyguanosine (8-oxodG) in 400 cases and 401 controls, participants of the Long Island Breast Cancer Study Project. We also analyzed the effect of different factors that are associated with oxidative stress and might influence 15-F(2t)-IsoP and 8-oxodG levels. We observed a statistically significant trend in breast cancer risk with increasing quartiles of 15-F(2t)-IsoP levels [odds ratio (OR), 1.25; 95% confidence interval (95% CI), 0.81-1.94; OR, 1.53; 95% CI, 0.99-2.35; OR, 1.88; 95% CI, 1.23-2.88, for the 2nd, 3rd, and 4th quartile relative to the lowest quartile, respectively; P(trend) = 0.002]. Although it is possible that increased levels may reflect the stress associated with recent treatment, the positive association was also observed when the analyses were restricted to case women for whom chemotherapy and radiation therapy had not yet been initiated at the time of the urine collection. The association with the highest quartile compared with lowest quartile of 15-F(2t)-IsoP was similar across strata of age, physical activity, fruit and vegetable intake, alcohol intake, cigarette smoking, body mass index, and menopausal status. We did not observe any association of breast cancer risk with 8-oxodG levels, but when cases with radiation treatment were removed from the analysis, a significant inverse trend (P = 0.04) was observed. Among controls, levels of 15-F(2t)-IsoP were higher among current cigarette smokers but did not differ by the amount of physical activity, fruit and vegetable intake, alcohol intake, body mass index, and menopausal status. Among controls, levels of 8-oxodG were higher among postmenopausal women and current and former cigarette smokers but did not differ by the other factors. In summary, our results suggest that urinary markers of lipid peroxidation and oxidative DNA damage may be associated with breast cancer risk.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2006

OGG1 polymorphisms and breast cancer risk.

The role of oxidative stress in breast cancer risk is still unclear. OGG1 encodes an 8-oxoguanine DNA glycosylase/AP lyase that catalyzes the removal of 8-oxodeoxyguanosine from DNA. 8-Oxodeoxyguanosine, the most abundant lesion generated by oxidative stress, is highly mutagenic. Environmental sources of oxidative stress, such as alcohol consumption, cigarette smoking, high body mass index (BMI), and low fruits and vegetables intake, may modify the association of genetic polymorphisms with breast cancer risk. We investigated the association between three genetic polymorphisms in OGG1 (Ser(326)Cys, 7143A/G, and 11657A/G) and breast cancer risk among 1,058 cases and 1,102 controls participating in the Long Island Breast Cancer Study Project. No associations were observed between individual OGG1 polymorphisms, haplotypes, or diplotypes and breast cancer. The association between having at least one variant allele and breast cancer risk was stronger among moderate alcohol drinkers for Ser(326)Cys [odds ratio (OR), 1.82; 95% confidence interval (95% CI), 1.06-3.10] relative to nondrinkers with the wild-type genotype and among those with higher BMI for 7143A/G (OR, 1.47; 95% CI, 1.10-1.96) and for 11657A/G (OR, 1.41; 95% CI, 1.05-1.88), relative to women with BMI < 25 kg/m(2) and the wild-type genotype. However, the patterns were not seen for all three single nucleotide polymorphisms (SNP) nor were there any clear allele dose associations; only one interaction was statistically significant, assuming a multiplicative model (11657A/G, P(interaction) = 0.04). In summary, although we found some differences between the three OGG1 SNPs and breast cancer risk among moderate alcohol drinkers and women with higher BMI, replication of these results is needed to rule out spurious findings. In addition, data on functionality of these polymorphisms are crucial to understand if these modest differences are important.

Alcohol Drinking↗
PubMed2006

Polymorphisms in nucleotide excision repair genes and DNA repair capacity phenotype in sisters discordant for breast cancer.

Interindividual differences in DNA repair capacity (DRC) may play a critical role in breast cancer risk. Previously, we determined that DRC measured via removal of in vitro-induced benzo[a]pyrene diolepoxide-DNA adducts in lymphoblastoid cell lines was lower in cases compared with controls among sisters discordant for breast cancer from the Metropolitan New York Registry of Breast Cancer Families. We have now determined genotypes for seven single nucleotide polymorphisms in five nucleotide excision repair genes, including Xeroderma pigmentosum complementation group A (XPA +62T>C), group C (XPC Lys939Gln and Ala499Val), group D (XPD Asp312Asn and Lys751Gln), and group G (XPG His1104Asp) and ERCC1 (8092 C>A) in a total of 160 sister pairs for whom DRC phenotype data were available. Overall, there were no statistically significant differences in average DRC for most of the genotypes. A final multivariate conditional logistic model, including three single nucleotide polymorphisms (XPA +62T>C, XPC Ala499Val, and XPG His1104Asp) and smoking status, only modestly predicted DRC after adjusting for case-control status and age of blood donation. The overall predictive accuracy was 61% in the model with a sensitivity of 78% and specificity of 39%. These findings suggest that those polymorphisms we have investigated to date in nucleotide excision repair pathway genes explain only a small amount of the variability in DRC.

Adult↗
PubMed2006

Genetic polymorphisms in the cyclooxygenase-2 gene, use of nonsteroidal anti-inflammatory drugs, and breast cancer risk.

INTRODUCTION: The association between use of nonsteroidal anti-inflammatory drugs (NSAIDs) and breast cancer risk remains unclear. Inconsistencies in previously reported findings may be partly due to differences in expression of cyclooxygenase (COX)-2. We hypothesized that genetic polymorphisms (COX-2 .926, COX-2 .5209, and COX-2 .8473) may reduce overall breast cancer risk or risk for subtypes of breast cancer by modulating the inflammatory response and may interact with aspirin or any NSAID use. METHODS: We conducted a population-based, case-control study in which we genotyped 1,067 breast cancer cases and 1,110 control individuals included in the Long Island Breast Cancer Study Project. RESULTS: No major effects of the three COX-2 variant alleles on breast cancer risk were found. A total of eight distinct haplotypes and 18 diplotypes were observed in the population. Overall, no significant associations between COX-2 haplotypes/diplotypes and breast cancer risk were observed. Among women who used aspirin or any NSAID there was little evidence for an interaction with the at-risk COX-2 genotypes, with one exception. Among women with hormone receptor positive breast cancer, the reduced risk for any NSAID use was only evident among those who had at least one variant C allele of COX-2 .8473 (odds ratio = 0.7, 95% confidence interval = 0.5 to 1.0; P for the interaction = 0.02). There was no corresponding interaction for aspirin use, possibly because of limited power. CONCLUSION: These data provide modest evidence that the C allele of COX-2 .8473 may interact with NSAIDs to reduce risk for hormone receptor positive breast cancer.

Alleles↗
PubMed2005

ADH3 genotype, alcohol intake and breast cancer risk.

Moderate alcohol consumption of approximately 1-2 drinks per day has been associated with a 30-50% increase in breast cancer risk. Individuals differ in their ability to metabolize alcohol through genetic differences in alcohol dehydrogenase (ADH), the enzyme that catalyzes the oxidation of approximately 80% of ethanol to acetaldehyde, a known carcinogen. Individuals differ in their ADH genotype, and one locus in particular (ADH3) is polymorphic in Caucasian populations. Using data from the Long Island Breast Cancer Study Project, we examined whether fast metabolizers of alcohol, as measured by the ADH3(1-1) genotype, have a higher risk of breast cancer from alcohol intake compared with those individuals who are slow metabolizers, but consume similar amounts of alcohol. We combined genotyping information with questionnaire data on 1047 breast cancer cases and 1101 controls and used unconditional logistic regression methods to estimate multivariate-adjusted odds ratios (ORs) and 95% confidence intervals (CIs) between alcohol intake and breast cancer risk. Among individuals homozygous for the fast metabolizing allele (ADH(3)1-1), a lifetime alcohol consumption of 15-30 g/day (approximately 1-2 drinks per day) increased breast cancer risk by 2-fold (OR=2.0, 95% CI=1.1-3.5). In contrast, the increase in risk from a lifetime alcohol consumption of 15-30 g/day was less pronounced in the intermediate and slow metabolizing groups, respectively: ADH3(1-2) (OR=1.5, 95% CI 0.9-2.4) and ADH(3)2-2 (OR=1.3, 95% CI 0.5-3.5). Fast metabolizers who drank 15-30 g/day of alcohol had 2.3 times (95% CI 1.3-4.0) greater risk of breast cancer than non-drinkers who were intermediate or slow metabolizers. This association for fast metabolizers who drank 15-30 g/day was particularly pronounced among premenopausal women (premenopausal women OR=2.9, 95 % CI=1.2-7.1; postmenopausal women OR=1.8, 95% CI=0.9-3.8). These population-based data support the hypothesis that fast metabolizers of alcohol have a higher risk of breast cancer risk, from alcohol intake than slow metabolizers.

Adult↗
PubMed2005

IGF1 CA repeat polymorphisms, lifestyle factors and breast cancer risk in the Long Island Breast Cancer Study Project.

Insulin-like growth factor I (IGF-I) is an important regulator of growth and differentiation and is a potent mitogen for human breast cancer cells. Recent investigations suggest an association between cytosine-adenine dinucleotide (CA)n repeat polymorphisms of the IGF1 gene and IGF-I levels and further evidence indicates that genotype may influence breast cancer risk. We assessed the relation between IGF1 (CA)n repeats and breast cancer, and evaluated modification of genotype effects according to traditional breast cancer risk factors in 1028 breast cancer cases and 1086 controls. An increased risk of breast cancer was seen for genotypes that included alleles with fewer than (CA)19 repeats when compared to (CA)19 repeat carriers, an association that was particularly strong among premenopausal women [odds ratio (OR)=3.31; 95% confidence interval (CI)=1.47, 7.48]. No significant association was observed between an IGF1 genotype with no (CA)19 repeat compared to (CA)19 repeat genotypes in either pre- or postmenopausal women overall. However, when traditional breast cancer risk factors were considered, premenopausal women with genotypes that lacked a (CA)19 repeat had a nearly 60% increased risk of breast cancer among those who had ever used hormonal birth control, while never users had a significantly reduced risk (Pinteraction=0.01). Among postmenopausal women, those with genotypes lacking a (CA)19 repeat allele had significantly increased breast cancer risk among subjects with a lower than median body mass index (BMI) (OR=1.77 95% CI=1.09, 2.87), while no association for IGF1 genotype was seen among women with a higher than median BMI (Pinteraction=0.04). Our results demonstrate a role for alleles with fewer than (CA)19 repeats as a risk factor for breast cancer and also suggest that several traditional breast cancer risk factors modify the association of the IGF1 (CA)19 repeat genotype.

Adult↗
PubMed2005

HIN-1, an inhibitor of cell growth, invasion, and AKT activation.

The HIN-1 gene encoding a small, secreted protein is silenced due to methylation in a substantial fraction of breast, prostate, lung, and pancreatic carcinomas, suggesting a potential tumor suppressor function. The receptor of HIN-1 is unknown, but ligand-binding studies indicate the presence of high-affinity cell surface HIN-1 binding on epithelial cells. Here, we report that HIN-1 is a potent inhibitor of anchorage-dependent and anchorage-independent cell growth, cell migration, and invasion. Expression of HIN-1 in synchronized cells inhibits cell cycle reentry and the phosphorylation of the retinoblastoma protein (Rb), whereas in exponentially growing cells, HIN-1 induces apoptosis without apparent cell cycle arrest and effect on Rb phosphorylation. Investigation of multiple signaling pathways revealed that mitogen-induced phosphorylation and activation of AKT are inhibited in HIN-1-expressing cells. In addition, expression of constitutively activate AKT abrogates HIN-1-mediated growth arrest. Taken together, these studies provide further evidence that HIN-1 possesses tumor suppressor functions, and that these activities may be mediated through the AKT signaling pathway.

Apoptosis↗
PubMed2005

Lifetime alcohol intake and breast cancer risk.

PURPOSE: Moderate alcohol intake of one to two drinks per day has been consistently associated with a 30-50% increase in breast cancer. Despite the consistency in the overall association, several important questions remain, including whether the association between alcohol intake and breast cancer risk is affected by the timing of alcohol exposure, modified by other risk factors such as body mass index (BMI), menopausal status, and hormone replacement therapy (HRT), or more pronounced among hormone receptor positive tumors or invasive rather than in situ disease. METHODS: To address these questions, we conducted a large population-based study (1508 cases and 1556 controls) that collected detailed information on alcohol and other exposures throughout the lifecourse. RESULTS: Consumption of 15-30 grams/day (approximately one to two drinks) throughout life was associated with a modest 33% increase in risk (odds ratio [OR] = 1.33, 95% confidence interval (CI) = 1.01-1.74), but heavier consumption (> or = 30 grams per day) was not. Risk did not vary with alcohol type (beer, wine, or hard liquor) or by patterns of use, such as recent use, intake prior to age 20 years, or whether use began at an early age. The association with lifetime intake was limited to women with a BMI < 25 (OR = 2.13, 95% CI = 1.29-3.54). Alcohol consumption of approximately one drink per day was associated with estrogen receptor positive tumors among women with a BMI < 25, but not among women BMI > or = 25. Also, the elevated OR was observed only among women diagnosed with invasive (OR = 1.56, 95% CI = 1.11-2.18), but not in situ breast tumors. CONCLUSIONS: These data give added support that moderate alcohol consumption over the life course increases breast cancer risk, particularly among women with low BMI and those diagnosed with estrogen receptor positive tumors or with invasive rather than in situ disease. Risk is confined to moderate intake and does not vary with the timing of use, with heavier doses, or with the type of alcohol consumed.

Adolescent↗