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Biomedical subjects

Steven A Narod

Publications and source records attributed to Steven A Narod.

At least 37 records · Page 2Linked to original sources
PubMed2006

Spontaneous and therapeutic abortions and the risk of breast cancer among BRCA mutation carriers.

INTRODUCTION: BRCA1 and BRCA2 mutation carriers are at increased risk for developing both breast and ovarian cancer. It has been suggested that carriers of BRCA1/2 mutations may also be at increased risk of having recurrent (three or more) miscarriages. Several reproductive factors have been shown to influence the risk of breast cancer in mutation carriers, but the effects of spontaneous and therapeutic abortions on the risk of hereditary breast cancer risk have not been well studied to date. METHODS: In a matched case-control study, the frequencies of spontaneous abortions were compared among 1,878 BRCA1 mutation carriers, 950 BRCA2 mutation carriers and 657 related non-carrier controls. The rates of spontaneous and therapeutic abortions were compared for carriers with and without breast cancer. RESULTS: There was no difference in the rate of spontaneous abortions between carriers of BRCA1 or BRCA2 mutations and non-carriers. The number of spontaneous abortions was not associated with breast cancer risk among BRCA1 or BRCA2 mutation carriers. However, BRCA2 carriers who had two or more therapeutic abortions faced a 64% decrease in the risk of breast cancer (odds ratio = 0.36; 95% confidence interval 0.16-0.83; p = 0.02). CONCLUSION: Carrying a BRCA1 or BRCA2 mutation is not a risk factor for spontaneous abortions and spontaneous abortions do not appear to influence the risk of breast cancer in carriers of BRCA1 or BRCA2 mutations. However, having two or more therapeutic abortions may be associated with a lowered risk of breast cancer among BRCA2 carriers.

Abortion, Spontaneous↗
PubMed2006

Coffee consumption and breast cancer risk among BRCA1 and BRCA2 mutation carriers.

Although there are several plausible biologic mechanisms whereby coffee consumption might influence the risk of breast cancer, epidemiologic evidence is limited. We assessed the association between coffee consumption and breast cancer risk among high-risk women who carry BRCA mutations. We performed a matched case-control analysis on 1,690 women with a BRCA1 or BRCA2 mutation from 40 centers in 4 countries. Average lifetime coffee consumption was estimated via a self-administered questionnaire. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using conditional logistic regression. After adjustment for potential confounders, the ORs for breast cancer in BRCA carriers who habitually drank 0, 1-3, 4-5 and 6 or more cups of coffee were 1.00, 0.90 (95% CI 0.72-1.12), 0.75 (95% CI 0.47-1.19) and 0.31 (95% CI 0.13-0.71; p-trend = 0.02). The effect was limited to the consumption of caffeinated coffee. These results suggest that among women with BRCA gene mutation, coffee consumption is unlikely to be harmful and that high levels of consumption may in fact be related to reduced breast cancer risk.

Adult↗
PubMed2006

Influence of selected lifestyle factors on breast and ovarian cancer risk in BRCA1 mutation carriers from Poland.

It has been estimated that the lifetime risk of breast cancer among women who inherit a BRCA1 or BRCA2 mutation is as high as 80%, and the risk estimates for ovarian cancer range from 15 to 40%. Several environmental and lifestyle factors are believed to contribute to the development of breast cancer in the general population and it is of interest to establish if these factors operate among mutation carriers as well. To evaluate the effects of age of menarche, parity, breast-feeding, oophorectomy and oral contraceptive use, as well as smoking and coffee consumption, on the risks of breast and ovarian cancer, we conducted a matched case-control study of Polish women with BRCA1 mutations. There were 348 breast cancer patients, 150 ovarian cancer patients and similar numbers of age-matched controls. BRCA1 carriers with late age of menarche, lower parity and long-term breast-feeding were less likely to develop breast cancer. Oral contraceptives protected against ovarian cancer.

Adolescent↗
PubMed2006

Method of cooking and risk of breast cancer in the Philippines.

OBJECTIVE: Among Asian countries, the highest age-standardized rates of breast cancer have been reported for the Philippines. The influence of diet and lifestyle factors as possible contributors to these high rates has not been well-studied. We conducted a case-control study in Manila to examine the association between methods of cooking and the risk of breast cancer. METHODS: Eligible subjects were women undergoing evaluation at the Philippine General Hospital (PGH), Manila for a breast problem. All of the women completed a risk factor questionnaire prior to the determination of their case (n = 240) or control (n = 240) status. Information regarding current, as well as usual method of cooking in the household at 12 years of age was obtained. RESULTS: Boiling food in coconut milk was associated with a significantly increased risk of breast cancer (odds ratio (OR) = 2.2; 95% confidence interval (CI) 1.3-3.8). There were positive associations between boiling food in coconut milk and the risk of breast cancer currently (OR = 1.9; 95% CI 1.0-3.3), and at 12 years of age (OR = 2.9; 95% CI 1.6-5.5). A positive association between frying food and breast cancer risk was restricted to women whose household fried food at 12 years of age (OR = 1.89; 95% CI 1.1-3.4). CONCLUSIONS: The results of this study suggest that various cooking methods during adolescence and possibly in adulthood may be associated with an increased risk of breast cancer. These findings require confirmation.

Adult↗
PubMed2006

BRCA1 and BRCA2 mutations in breast and ovarian cancer syndrome: reflection on the Creighton University historical series of high risk families.

Over the last four decades, Henry Lynch has collected pedigrees and samples from high risk breast and/or ovarian cancer families, generating a unique resource for the study of breast cancer susceptibility. These families have made a major contribution to increasing our knowledge in the cancer genetic susceptibility field, allowing the discovery of a genetic association between breast and ovarian cancer predisposition, contributing to the mapping of the BRCA1 and BRCA2 genes, advancing the idea of the existence of other breast cancer susceptibility genes, allowing the evaluation of BRCA-associated cancer risks and psychosocial aspects of BRCA testing and so on. Ten years after the cloning of BRCA1 and BRCA2, we report the current status of these families and compare the observed BRCA1/2 mutation detection rate with the estimations obtained by linkage analysis of the Breast Cancer Linkage Consortium families.

BRCA1 Protein↗
PubMed2006

Patient responses to the disclosure of BRCA mutation tests in hereditary breast-ovarian cancer families.

Limited attention has been given to the impact of BRCA mutation disclosure on participants' psychological reaction and cancer control compliance. We asked women (290 mutation-positive, 370 mutation-negative) from 84 hereditary breast-ovarian cancer (HBOC) families with known deleterious BRCA mutations to participate in an evaluation regarding cancer prevention recommendations before and after BRCA mutation disclosure. Both men and women (n = 780) were invited to complete a questionnaire to evaluate their psychological response to BRCA mutation disclosure. Before BRCA testing, 23.0% (152 of 660) of these women underwent prophylactic bilateral mastectomy, oophorectomy, or both; of these, 53% (80 of 152) were subsequently found to be mutation negative. After mutation disclosure, 52.9% (110 of 208) of mutation carriers and 0% (0 of 203) of noncarriers underwent prophylactic surgeries. These changes were statistically significant compared with before disclosure (P < 0.0001). The rate of transvaginal ovarian ultrasound screening was significantly increased in mutation carriers (P < 0.015) and marginally decreased in noncarriers (P = 0.063) post disclosure. Psychologically, compared with noncarriers without cancer, a significantly higher percentage of carriers, regardless of their cancer status, felt guilt about passing a mutation to their children, worried about developing additional cancer or their children developing cancer, and were concerned about health insurance discrimination. Despite these psychological consequences, carriers and noncarriers reported a positive attitude toward genetic testing.

Breast Neoplasms↗
PubMed2006

Making sense of prostate specific antigen: improving its predictive value in patients undergoing prostate biopsy.

PURPOSE: The clinical usefulness of PSA for prostate cancer screening is unclear, although the test remains in common use. New methods to interpret PSA are needed. MATERIALS AND METHODS: We examined a cohort of 2,637 men who underwent prostate biopsies for abnormal DRE or PSA between 1999 and 2004. Using risk factors for prostate cancer, including patient age, ethnicity, family history of prostate cancer, previous negative biopsy, voiding symptoms and prostate volume, we developed risk groups for prostate cancer using recursive partitioning modeling independent of PSA or DRE. We then compared prostate cancer probabilities by PSA ranges by risk group. RESULTS: Of the 2,637 men 1,282 (48.6%) had prostate cancer. Age, ethnicity, family history, previous negative biopsy and prostate volume were predictive for cancer. We constructed 6 risk groups by combining these factors and created tables to assign patients to these groups. Independent of PSA and DRE the probability of cancer ranged from 15% in patients in group 1 to 78% in patients in group 6 (p <0.0001). By adding PSA and DRE to each risk group prostate cancer probabilities were refined from 0% to 100%. Patients in the higher risk groups also had higher grade cancer (p <0.0001). CONCLUSIONS: We generated 6 risk groups based on simple risk factors for prostate cancer. When used in the right context and patient, PSA is highly accurate for predicting prostate cancer and permitting rational decision making in patients with abnormal PSA.

Adult↗
PubMed2006

A novel serum marker, total prostate secretory protein of 94 amino acids, improves prostate cancer detection and helps identify high grade cancers at diagnosis.

PURPOSE: New biomarkers for prostate cancer are needed. We determined whether a novel serum marker, total PSP94 can be used to accomplish these goals. MATERIALS AND METHODS: We conducted a case-control study of 1,212 men with no previous history of prostate cancer and who underwent a prostate biopsy from 1998 to 2000 because of an increased PSA or an abnormal DRE. Serum PSP94 levels were assessed using a sandwich enzyme-linked immunosorbent assay technique. Cases were patients with prostate cancer, and controls were patients who had no evidence of cancer. Multivariate logistic regression analysis was used to determine whether or not PSP94 levels improved the predictive value for prostate cancer. RESULTS: Of the 1,212 men 596 (49.2%) had cancer detected. The median PSP94 level was significantly lower among cases (2.60 ng/ml) than among controls (3.40 ng/ml, p <0.0001). The adjusted odds ratios for the presence of prostate cancer for patients with the lowest quartile of PSP94, compared to patients in the highest quartile was 2.70 (95% CI 1.8 - 4.0, p <0.0001). Among a subgroup of 649 men in whom PSA had a low predictive value (PSA less than 20 ng/ml, normal DRE and less than 70 years), 260 (40.1%) were found to have cancer. In this subgroup total PSP94 levels helped discriminate between patients with high grade disease (Gleason score 8 or more, median 1.90 ng/ml), moderate grade disease (Gleason score 7, median 2.34 ng/ml) and low grade disease (Gleason score 6 or less, median 2.60 ng/ml, p = 0.007). PSA and the FTPSA were not able to distinguish between patients with different grades in this group. CONCLUSIONS: Patients with low total PSP94 levels had a high probability for having prostate cancer detected at biopsy. The total PSP94 level was able to help identify patients with high grade disease among a subset of patients in whom PSA and FTPSA are least informative.

Adult↗
PubMed2006

Screening mammography and risk of breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study.

BACKGROUND: Screening mammography is associated with a small dose of radiation to the breast, and women with increased genetic risk might be particularly sensitive to the DNA-damaging effects of ionising radiation. We aimed to assess whether exposure to ionising radiation through mammography screening was associated with risk of breast cancer in BRCA1 or BRCA2 mutation carriers. METHODS: We identified 1600 cases of breast cancer and 1600 controls without breast cancer who were matched for BRCA mutation, date of birth (within 1 year), and country of residence from an international registry of BRCA1 and BRCA2 mutation carriers. We used a questionnaire to inquire about whether participants had ever had screening mammography, and, if so, the age at which they first had the procedure. RESULTS: We found no association between ever having screening mammography and risk of breast cancer (odds ratio [OR] 1.03 [95% CI 0.85-1.25], adjusted for parity, oral-contraceptive use, ethnic origin, and bilateral oophorectomy). The association was much the same for BRCA1 mutation carriers and BRCA2 mutation carriers (1.04 [0.84-1.29] vs 1.06 [0.67-1.66], respectively, adjusted for parity, oral-contraceptive use, ethnic origin, and bilateral oophorectomy). INTERPRETATION: These findings do not lend support to the idea that exposure to ionising radiation through routine screening mammography contributes substantially to the burden of breast cancer in BRCA1 and BRCA2 mutation carriers. Prospective studies are needed to confirm the results of this initial report, and, where possible, these studies should assess a more appropriate endpoint of total exposure.

Adult↗
PubMed2006

A fluorescent multiplex-DGGE screening test for mutations in the BRCA1 gene.

Screening for mutations in the BRCA1 gene is challenging because of the wide spectrum of mutations found in this large gene. As the extensive exon 11 is commonly screened by the protein truncation test (PTT), here a fluorescent multiplex denaturing gradient gel electrophoresis (FMD) mutation screening technique was developed to test the remaining numerous small exons and splice sites of the gene. The method is based upon the use of an efficient multiplex polymerase chain reaction (PCR) amplification of the target regions, followed by denaturing gradient gel electrophoresis (DGGE) separation of the amplicon mixture, and the immediate achievement of results by wet gel scanning. The technique was applied to screen 16 samples with different BRCA1 sequence variants distributed over 12 exons. All variants were detected. In addition, 188 DNA samples from ovarian cancer patients were screened, identifying 22 new sequence variants (11.7% of the samples) and 243 common polymorphisms in the BRCA1 locus. Variants included 16 single nucleotide substitutions, 3 deletions of 2 nucleotides, 1 deletion of 4 nucleotides, and 2 insertions of 1 nucleotide. The FMD test provides an accurate, fast, nonradioactive and cost-efficient way to scan the BRCA1 gene with high sensitivity and an ease of result interpretation. This technique may prove to be a useful research tool for the detection of mutations and polymorphisms in the BRCA1 gene and for large-scale epidemiologic studies.

BRCA1 Protein↗
PubMed2006

Endometrial cancer risk is associated with variants of the mismatch repair genes MLH1 and MSH2.

Women with germ-line mutations in the mismatch repair genes (responsible for hereditary nonpolyposis colorectal cancer) face an increased risk of colonic and endometrial cancer. However, these germ-line mutations are rare and are responsible for fewer than 1% of endometrial cancers. Therefore, we examined whether or not common variants of the hereditary nonpolyposis colorectal cancer-associated genes might also be associated with an increased risk of endometrial cancer. Three single-nucleotide polymorphisms were selected in the MLH1 and MSH2 mismatch repair genes. All the various 672 women with endometrial cancer and 880 controls were genotyped. Each of these three single-nucleotide polymorphisms was associated with an increased risk of endometrial cancer. Carriers of the MLH1 nt-93 A allele were at a 1.5-fold increased risk of developing endometrial cancer compared with controls [95% confidence interval (95% CI), 1.2-2.0; P = 0.001]. The risk was higher for homozygote carriers [odds ratio (OR), 1.9; 95% CI, 1.2-3.2; P = 0.009]. For carriers of the MSH2 rs2303428 C allele, the OR was 1.4 (95% CI, 1.0-1.9; P = 0.05), and for carriers of the MSH2 rs2059520 G allele, the OR was 1.3 (95% CI, 1.0-1.7; P = 0.03). More than 9% of endometrial cancer cases carried a variant allele in both MLH1 and MSH2. For these women, the risk of endometrial cancer was particularly high (OR, 2.1; 95% CI, 1.2-3.6; P = 0.005). For patients younger than 50 years at diagnosis who carried both variants, the risk was even higher (OR, 3.4; 95% CI, 1.7-6.6; P = 0.0005). In summary, two common variant alleles of the MLH1 and MSH2 genes make a substantial contribution to endometrial cancer incidence in Ontario.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Nomogram prediction for prostate cancer and aggressive prostate cancer at time of biopsy: utilizing all risk factors and tumor markers for prostate cancer.

BACKGROUND: There is a large amount of confusion in interpreting prostate specific antigen (PSA) values for prostate cancer. More precise risk assessments for prostate cancer detection are needed for men faced with an abnormal PSA. METHODS: We studied a sample of 2,637 men who underwent a prostate biopsy for an abnormal digital rectal exam (DRE) or PSA. Using factors including age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA, we constructed nomograms to predict the probability of prostate cancer at biopsy. RESULTS: Of the 2,637 men, 1,282 men (48.6%) had prostate cancer detected. Age, ethnicity, family history of prostate cancer, a previous negative biopsy, prostate volume, DRE and PSA were all significant predictors of prostate cancer. Nomograms were constructed based on these factors to predict the risk of prostate cancer and of aggressive prostate cancer (defined as a Gleason Score 7 or more). The positive predictive value varied from 5% to 95% based on the nomograms. The nomograms were validated using bootstrapping methods and the expected and observed proportions were found to be highly concordant. CONCLUSIONS: For men with an abnormal PSA or DRE, the risk for prostate cancer can be accurately estimated using a nomogram based on age, ethnicity, family history of prostate cancer, previous negative biopsy, presence of voiding symptoms, prostate volume, DRE and PSA. This tool will aid physicians and patients in determining the need for prostate biopsy.

Adult↗
PubMed2005

Effect of pregnancy as a risk factor for breast cancer in BRCA1/BRCA2 mutation carriers.

Early age at first birth and multiparity have been associated with a decrease in the risk of breast cancer in women in the general population. We examined whether this relationship is also present in women at high risk of breast cancer due to the presence of a mutation in either of the 2 breast cancer susceptibility genes, BRCA1 or BRCA2. We performed a matched case-control study of 1,260 pairs of women with known BRCA1 or BRCA2 mutations, recruited from North America, Europe and Israel. Women who had been diagnosed with breast cancer were matched with unaffected control subjects for year of birth, country of residence, and mutation (BRCA1 or BRCA2). Study subjects completed a questionnaire detailing their reproductive histories. Odds ratios (ORs) and 95% confidence intervals (CIs) were derived by conditional logistic regression. Among BRCA1 carriers, parity per se was not associated with the risk of breast cancer (OR for parous vs. nulliparous = 0.94; 95% CI = 0.75-1.19; p = 0.62). However, women with a BRCA1 mutation and 4 or more children had a 38% decrease in breast cancer risk compared to nulliparous women (OR = 0.62; 95% CI = 0.41-0.94). In contrast, among BRCA2 carriers, increasing parity was associated with an increased risk of breast cancer; women with 2 or more children were at approximately 1.5 times the risk of breast cancer as nulliparous women (OR = 1.53; 95% CI = 1.01-2.32; p = 0.05). Among women with BRCA2 mutations and who were younger than age 50, the (adjusted) risk of breast cancer increased by 17% with each additional birth (OR = 1.17; 95% CI = 1.01-1.36; p = 0.03). There was no significant increase in the risk of breast cancer among BRCA2 carriers older than 50 (OR for each additional birth = 0.97; 95% CI = 0.58-1.53; p = 0.92). In the 2-year period following a birth, the risk of breast cancer in a BRCA2 carrier was increased by 70% compared to nulliparous controls (OR = 1.70; 95% CI = 0.97-3.0). There was a much smaller increase in breast cancer risk among BRCA2 carriers whose last birth was 5 or more years in the past (OR = 1.24; 95% CI = 0.79-1.95). A modest reduction in risk of breast cancer was observed among BRCA1 carriers with 4 or more births. Among BRCA2 carriers, increasing parity was associated with a significant increase in the risk of breast cancer before age 50 and this increase was greatest in the 2-year period following a pregnancy.

Adolescent↗
PubMed2005

The use of genetic markers to determine risk for prostate cancer at prostate biopsy.

PURPOSE: We examined a panel of 13 polymorphisms in 13 different genes to determine whether specific genotypes can help predict prostate cancer at the time of biopsy among men prescreened with prostate-specific antigen and digital rectal exam. EXPERIMENTAL DESIGN: We examined 2,088 consecutive men who were referred for prostate biopsy from 1997 to 2003. Thirteen genes were examined, including TNF308, GSTT1, KLK2, endostatin, MCRA, MCRV, tyrosinase, MSR1, CHK2, RNasel, HOGG1-326, HOGG1-11657, and HRAS1. Odds ratio for detection of prostate cancer were adjusted for age, race, prostate-specific antigen, digital rectal exam, family history of prostate cancer, and urinary symptoms. RESULTS: Of the 2,088 men, 996 (47.7%) had cancer detected. Four genes (TNF308, GSTT1, KLK2, and HOGG1-326) were significantly associated with prostate cancer. The adjusted odds ratios (OR) for prostate cancer for patients with the AA genotype of the TNF308 gene was 1.92 [95% confidence interval (95% CI), 1.0-1.5, P = 0.05], compared with those with the GG genotype, and for patients with the TT genotype of the KLK2 gene, the OR was 1.5 (95% confidence interval, 1.0-2.2, P = 0.04), compared with the CC genotype. The OR for patients with a homozygous deletion of the GSTT1 gene was 0.81 (95% CI, 0.6-1.0, P = 0.06) compared with those with the deletion, and the OR for patients with the GG genotype of the HOGG1-326 gene was 0.68 (95% CI, 0.5-1.0, P = 0.05) compared with the CC genotype. Patients who had all four alleles that were positively associated with prostate cancer had an OR of 9.33 (95% CI, 2.4-35.8, P = 0.0005) for prostate cancer compared with patients with alleles that were negatively associated with prostate cancer. CONCLUSIONS: Of the 13 polymorphisms, two were found to be positively associated with prostate cancer (TNF308 and KLK2) and two were negatively associated with prostate cancer (GSTT1 and HOGG1-326). Future studies are required to confirm these results.

Adenocarcinoma↗
PubMed2005

A novel RING-type ubiquitin ligase breast cancer-associated gene 2 correlates with outcome in invasive breast cancer.

The RING finger family of proteins possess ubiquitin ligase activity and play pivotal roles in protein degradation and receptor-mediated endocytosis. In this study, we examined whether the breast cancer-associated gene 2 (BCA2), a novel RING domain protein, has E3 ubiquitin ligase activity and investigated its expression status in breast tumors. The full-length BCA2 gene was cloned from the human breast cancer cell line MDA-MB-468. It encodes an open reading frame of 304 amino acids and contains a RING-H2 domain. BCA2 maps to chromosome 1q21.1, a region known to harbor cytogenetic aberrations in breast cancers. We found that the BCA2 protein has an intrinsic autoubiquitination activity, the hallmark of E3 ligases, whereas mutant RING protein is not autoubiquitinated. This indicates that the BCA2 ubiquitin ligase activity is dependent on the RING-H2 domain. Using tissue microarrays and immunohistochemistry, we found strong to intermediate BCA2 staining in 56% of 945 invasive breast cancers cases, which was significantly correlated with positive estrogen receptor status [odds ratio (OR), 1.51; P = 0.004], negative lymph node status (OR, 0.73; P = 0.02), and an increase in disease-free survival for regional recurrence (OR, 0.45; P = 0.03). Overexpression of BCA2 increased proliferation and small interfering RNA inhibited growth of T47D human breast cancer cells and NIH3T3 mouse cells. The autoubiquitination activity of BCA2 indicates that it is a novel RING-type E3 ligase. Its association with clinical measures and its effects on cell growth indicate that BCA2 may be important for the ubiquitin modification of proteins crucial to breast carcinogenesis and growth.

Adult↗
PubMed2005

A common missense variant in BRCA2 predisposes to early onset breast cancer.

INTRODUCTION: Mutations in the BRCA2 gene are one of the two major causes of hereditary breast cancer. Protein-truncating mutations of BRCA2 are usually deleterious and increase the risk of breast cancer up to 80% over a lifetime. A few missense mutations in BRCA2 are believed to have a similarly high penetrance, apart from more common neutral polymorphisms. It is often difficult to classify a particular sequence variant as a mutation or a polymorphism. For a deleterious variant, one would expect a greater allele frequency in breast cancer cases than in ethnic-matched controls. In contrast, neutral polymorphic variants should be equally frequent in the two groups. METHODS: We genotyped 3,241 cases of breast cancer diagnosed at under 51 years of age, unselected for family history, from 18 hospitals throughout Poland and 2,791 ethnic-matched controls for a single BRCA2 C5972T variant. RESULTS: The variant was present in approximately 6% of the Polish population. In the study, 13 women (11 cases and two controls (OR = 4.7; p = 0.02)) were homozygous for the variant allele. The overall odds ratio for breast cancer in women with a single copy of the BRCA2 C5972T variant was 1.1 (p = 0.7); however, the effect was significant for patients diagnosed at or before age 40 (OR = 1.4; p = 0.04). We reviewed the association between the BRCA2 variant in different histologic subgroups and found the effect most pronounced in women who had ductal carcinoma in situ (DCIS) with micro-invasion (OR = 2.8; p < 0.0001). CONCLUSION: The BRCA2 C5972T allele is a common variant in Poland that increases the risk of DCIS with micro-invasion. The homozygous state is rare but increases the risk of breast cancer five-fold.

Adult↗
PubMed2005

The joint effect of smoking and AIB1 on breast cancer risk in BRCA1 mutation carriers.

Women with BRCA1 mutations are at an elevated risk for breast cancer. AIB1 (NCOA3/SRC3) genotype and smoking may alter this risk. We examined the differences in breast cancer risk by AIB1 polyglutamine repeat polymorphism and pre-diagnosis smoking habits for BRCA1 mutation carriers to determine if there was an interaction between smoking and AIB1 genotype. Multivariate Cox proportional hazards regression was used with 316 female BRCA1 mutation carriers to model breast cancer risk. Ever having smoked was associated with a decreased breast cancer risk [Hazard Ratio (HR) = 0.63, 95% CI, 0.47-0.87]. A dose-response relationship between number of pack-years smoked and breast cancer risk was also found for women who smoked <20 pack years of cigarettes (HR = 0.72, 95% CI, 0.52-1.00) and for women who smoked >/=20 pack years (HR = 0.41, 95% CI, 0.23-0.71; P for trend = 0.0007). Women with a 28 repeat allele for AIB1 had a significantly reduced risk of breast cancer (HR = 0.72, 95% CI, 0.51-1.00). Women who smoked >/=20 pack-years with a 28 repeat allele had an even greater reduced risk of breast cancer (HR = 0.19, 95% CI, 0.07-0.54) compared to women who were never smokers with no 28 allele. Since AIB1 appears to modulate the effect of endogenous hormones via the estrogen receptor, and smoking affects circulating hormone levels, these results support evidence that steroid hormones play an important role in breast carcinogenesis in BRCA1 mutation carriers, and suggest mechanisms for developing novel cancer prevention strategies for BRCA1 mutation carriers.

Acetyltransferases↗