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Nancy D Perrier

Publications and source records attributed to Nancy D Perrier.

At least 37 records · Page 2Linked to original sources
PubMed2005

Glucose transporters in the thyroid.

Glucose transport, mediated by proteins expressed from the glucose transporter genes, plays an essential role in cellular metabolism. Increased uptake of glucose compared to cells in normal tissue is a defining characteristic of malignant cells. This has been the basis for positron emission tomography imaging of thyroid tumor metastases using fluorodeoxyglucose uptake. Despite this key difference between tumor and normal cells, the mechanism which mediates increased glucose uptake is poorly understood. Several research studies have assessed the expression of different glucose transporter (GLUT) proteins and expression of the genes which code for them in thyroid tissues. While no consensus exists on the specifics of which GLUT genes or proteins are expressed, a picture has emerged that a single specific transporter, GLUT1, is expressed at higher levels in thyroid carcinomas compared to a variety of normal and nonmalignant forms of thyroid disease. Greater levels of GLUT1 expression may be associated with poorer prognosis. Experiments in established thyroid carcinoma cells lines may provide useful insights into glucose transport in the thyroid. Thyroid cells show increased glucose uptake in response to thyroid-stimulating hormone (TSH), but expression of GLUT genes does not appear to be significantly affected by TSH suggesting TSH affects glucose uptake by affecting GLUT localization/ translocation rather than through increased GLUT gene expression. Improving technologies are providing a stronger foundation for detailed analyses of glucose transporters in thyroid to better elucidate the mechanisms by which these genes and proteins are regulated in normal and pathogenic tissue.

Glucose Transport Proteins, Facilitative↗
PubMed2005

The scintigraphic appearance of subcapsular parathyroid adenomas.

PURPOSE: Approximately 5 to 10% of parathyroid adenomas are located within the thin, fibrous capsule of the thyroid gland. These subcapsular adenomas can complicate minimally invasive parathyroidectomy. The small incision used in this procedure limits the view of the surgical bed. Palpation is less sensitive when the adenoma is covered by the thyroid capsule. If a subcapsular parathyroid adenoma can be identified on preoperative parathyroid scintigraphy, nuclear medicine physicians can recommend exploration of the thyroid capsule early, leading to an easier, more efficient operation. The objective of this observational study was to identify the scintigraphic appearance of subcapsular parathyroid adenomas. MATERIALS AND METHODS: A total of 109 patients with primary hyperparathyroidism underwent preoperative dual-phase Tc-99m sestamibi parathyroid scintigraphy at our tertiary care center from October 2002 to March 2004. Tc-99m pertechnetate was used as a supplemental technique when deemed necessary for optimal interpretation. Retrospective chart review identified 16 surgically proved subcapsular parathyroid adenomas. Parathyroid scintigraphy was reviewed. RESULTS: Subcapsular parathyroid adenomas tend to conform to the expected shape of the thyroid gland. In this small series, subcapsular parathyroid adenomas followed 1 of 3 patterns on lateral images: (1) focal convex distortion of the posterior wall of the thyroid, (2) polar lentiform configuration, and (3) compression of the posterior thyroid parenchyma. CONCLUSION: Subcapsular parathyroid adenomas often have a distinct appearance on scintigraphy. Preoperative identification of this type of parathyroid adenoma can direct a subcapsular surgical approach, optimizing the efficiency of the minimally invasive parathyroidectomy.

Adenoma↗
PubMed2005

Adrenocortical carcinoma arising from a long-standing adrenal mass.

Adrenocortical carcinoma is a rare tumor with a dismal prognosis. In stark contrast, benign incidental adrenal lesions are detected commonly on routine abdominal imaging. We report a case of a 74-year-old man with a history of germ cell testicular carcinoma who presented with a 4.8-cm left adrenal lesion. The lesion remained stable for 8 years, at which time the patient became symptomatic from an excess of cortisol hormone. Biopsy findings confirmed adrenocortical carcinoma. We describe the presentation, clinical findings, diagnostic work-up, and follow-up of this patient and review the literature.

Adrenal Cortex Neoplasms↗
PubMed2005

Surgical management of thyroid carcinoma.

Thyroid carcinoma has a unique biologic behavior characterized by early spread to regional lymph nodes and occasional extrathyroidal soft tissue extension but a low incidence of distant metastasis and infrequent disease-related death. Therefore, controversy exists over the proper extent of thyroidectomy and regional lymph node dissection in patients with differentiated thyroid carcinoma (DTC) and medullary thyroid carcinoma (MTC). The modest disease-specific mortality makes it unlikely that the extent of surgery will ever be the subject of a prospective randomized trial. Although more extensive cervical surgery may have only a limited effect on the duration of survival in patients with DTC, it may significantly improve quality of life by minimizing cervical recurrence. The high rates of cervical recurrence in patients with DTC and MTC have alerted physicians to the importance of fine-needle aspiration biopsy and ultrasonography for the diagnosis, preoperative staging, and follow-up of thyroid cancer. In patients with MTC, death caused by disease is uncommon in the absence of radiographically evident distant metastasis at the time of thyroidectomy. Cervical recurrence is even more common with MTC, and the need for compartment-oriented lymphadenectomy is accepted as standard surgical treatment to minimize disease recurrence. Postoperatively, calcitonin (CT) levels can be used to guide clinical management, but basal CT levels should not be used to direct the timing of prophylactic thyroidectomy in affected high-risk patients with familial MTC.

Biopsy, Fine-Needle↗
PubMed2004

Medicine's greatest gifts to surgery.

Dr. Robert Graves and Dr. Henry Plummer are immortalized by the thyroid diseases bearing their names. Dr. Graves' clinical lectures and Dr. Plummer's "goiter lunches" were considered medical masterpieces; they introduced novel concepts in physical diagnosis that helped surgeons determine when to operate on patients with thyrotoxicosis. Dr. Plummer's observations with perioperative iodine administration helped lower the mortality associated with thyroidectomy--at that time a treacherous operation--to make it one of the safest operations in history. Their fascinating discoveries laid foundations for thyroid surgery today. They truly are among medicine's greatest gifts to surgery.

General Surgery↗
PubMed2004

Complication of thyroidectomy in patients with radiation-induced thyroid neoplasms.

HYPOTHESIS: The complication rate for thyroidectomy is the same in patients with and without a history of radiation exposure. DESIGN: Retrospective medical record review of 171 consecutive patients who had a previous history of radiation treatment and had undergone a thyroid operation from 1961 to 1999. SETTING: University of California, San Francisco, Medical Center and affiliated hospitals. PATIENTS: We selected 107 patients with a history of radiation exposure who had undergone thyroid operations (81 total thyroidectomies) and 107 control patients who underwent comparable operations but had no history of radiation exposure. RESULTS: Among patients with a history of radiation exposure (mean age, 47.2 years), there was 1 recurrent nerve injury, 1 external nerve injury, 20 patients with transient hypocalcemia, and 1 patient with a hematoma. Among patients without a history of radiation exposure (mean age, 47.5 years), there were 2 recurrent nerve injuries, 18 patients with transient hypocalcemia, and 1 patient with a hematoma. All cases of hypocalcemia and recurrent nerve injury in both groups were transient. One patient had a permanent superior laryngeal nerve injury. In patients who underwent operations since January 1, 1990, duration of hospitalization was 1.2 days in patients with a history of radiation exposure (65 patients) and 1.1 days in patients without (101 patients). CONCLUSIONS: Our data document that the risk of transient and permanent complications after total thyroidectomy is similar in patients with and without a history of radiation exposure. The relatively low long-term complication rate supports prophylactic total thyroidectomy for patients with thyroid nodules and a history of radiation exposure.

Female↗
PubMed2004

Advantages and disadvantages of surgical therapy and optimal extent of thyroidectomy for the treatment of hyperthyroidism.

Surgery is excellent therapy for hyperthyroidism, with no mortality,and few complications or recurrences. It achieves euthyroidism rapidly and consistently, avoids long-term risks of radioactive iodine and antithyroid medications, provides tissue for histology,renders childbearing immediately possible, and allows absolute titration of thyroid hormone. Advancements such as preoperative preparation and intraoperative parathyroid hormone monitoring have decreased risks greatly and improved outcomes. Hartley-Dunhill procedure is the treatment of choice. Patients should be rendered euthyroid before operation to decrease thyroid vascularity, to improve surgical planes, and to prevent life threatening thyroid storm. Patients must be monitored carefully for hypocalcemia, a potentially serious complication. Patients will require lifelong thyroid hormone replacement. Radioactive iodine ablation should be considered for disease recurrence after surgery.

Humans↗
PubMed2004

Differential expression of glucose transporters in normal and pathologic thyroid tissue.

Malignant cells demonstrate increased glucose uptake and utilization. Immunohistochemical studies have suggested that enhanced glucose uptake in cancer cells may be caused by the overexpression of glucose transporters (GLUTs), in most cases GLUT1 and/or GLUT3. The aim of this study was to examine in detail the expression pattern and levels of GLUT genes in normal and pathologic thyroid tissues and to evaluate the clinical significance of GLUT mRNA levels. One hundred fifty-two surgically resected thyroid tissue samples from 103 patients were evaluated. Samples included: normal thyroid tissue (n = 58), benign thyroid disease (n = 61), and thyroid carcinoma (n = 33). Expression of the GLUT1, GLUT2, GLUT3, GLUT4, and GLUT10 genes were examined by reverse transcription-polymerase chain reaction (RT-PCR) and mRNA levels were quantitated by real-time RT-PCR. All thyroid parenchymal cells expressed GLUT1, GLUT3, GLUT4, and GLUT10. GLUT1 showed increased expression in carcinoma cases (p < 0.0001) and also in comparison with paired normal tissue samples from the same patient (p < 0.0001). Other GLUTs were statistically unchanged in pathologic tissues. These results are consistent with the theory that GLUT1 is upregulated during carcinogenesis and may play a major role in enhanced glucose uptake in thyroid cancer cells.

Adolescent↗
PubMed2004

Intraoperative imprint cytologic evaluation of sentinel lymph nodes for lobular carcinoma of the breast.

BACKGROUND: The evaluation of sentinel lymph nodes (SLNs) from a woman with lobular cancer of the breast is frequently challenging. Intraoperative imprint cytology (IIC) is equivalent to frozen sectioning for rapid SLN evaluation and is advantageous because it is rapid, reliable, cost-effective, and conserves tissue. Metastatic lobular carcinoma is difficult to identify in SLN because of its low-grade cytomorphology, its tendency to infiltrate lymph nodes in a single cell pattern, and because individual cells can resemble lymphocytes. We are unaware of any large published studies, using any technique, to evaluate SLN for lobular carcinoma. METHODS: A retrospective review of the intraoperative imprint cytology results of 678 SLN mapping procedures for breast carcinoma was performed. From this cohort, we studied SLN from cases of lobular carcinoma. These SLN were evaluated intraoperatively by either bisecting or slicing the SLN into 4-mm sections. Imprints were made of each cut surface and stained with hematoxylin and eosin and/or Diff-Quik. Permanent sections were evaluated with up to 4 hematoxylin and eosin-stained levels and cytokeratin immunohistochemistry. IIC results were compared with final histologic results. RESULTS: Sixty-one cases of pure invasive lobular carcinoma were identified. Sensitivity was 52%, specificity was 100%, accuracy was 82%, negative predictive value was 78%. No statistically significant differences in sensitivity, specificity or accuracy were identified for the intraoperative detection of lobular carcinoma versus ductal carcinoma. The sensitivity for detecting macrometastases (more than 2 mm) was better than for detecting micrometastases, 73 versus 25%, respectively (P = 0.059). CONCLUSIONS: The sensitivity and specificity of IIC are similar to that of intraoperative frozen section evaluation. Therefore, IIC is a viable alternative to frozen sectioning when intraoperative evaluation is required. If SLN micrometastasis is used to determine the need for further lymphadenectomy, more sensitive intraoperative methods will be needed to avoid a second operation.

Adult↗
PubMed2004

Latency period of thyroid neoplasia after radiation exposure.

OBJECTIVE: To determine the temporal sequence for developing benign and malignant thyroid neoplasms after radiation. SUMMARY BACKGROUND DATA: Therapeutic radiation is associated with thyroid neoplasms in humans and animals. Some question whether thyroid cancers develop de novo or from benign thyroid neoplasms. Little information, however, is available concerning the time to development of benign and malignant thyroid neoplasms after radiation exposure. METHODS: We retrospectively analyzed the records of 171 consecutive patients who had a history of exposure to radiation and were treated surgically at University of California, San Francisco-affiliated hospitals for thyroid neoplasms between 1960 and 1999. RESULTS: There were 66 men and 105 women aged 9 to 80 years (mean, 47.0 years). One hundred patients had benign and 71 had malignant tumors (58 papillary cancers, 10 follicular cancers, 1 Hurthle cell cancer, 1 medullary cancer, and 1 carcinosarcoma). The mean latency period for benign tumors was longer than that for malignant lesions (mean, 34.1 and 28.4 years, P = 0.018; median, 38.0 years and 30.0 years, P = 0.001). Follicular carcinomas developed sooner (mean, 20.5 years; median, 20 years) than did follicular adenomas (mean, 35.3 years; median, 36.5 years; P = 0.003, P = 0.0009). Patients with papillary thyroid cancers presenting as occult papillary cancers (<1 cm) and as a dominant nodule had similar latency periods (mean, 34.0 and 28.0 years P = 0.29; median, 37.5 and 30.5 years, P = 0.09), respectively. CONCLUSION: Although there could be selection bias regarding referral of patients, our data document that malignant thyroid tumors after radiation exposure, including follicular carcinomas, present earlier than do benign thyroid tumors. Occult and manifest papillary thyroid cancers present at about the same time interval after radiation exposure. Our findings question whether benign thyroid neoplasms progress to malignant thyroid neoplasms and that most occult thyroid cancers do not progress to malignant thyroid cancers in radiation-exposed patients.

Age Factors↗
PubMed2004

Is there a racial difference in presentation of primary hyperparathyroidism?

Nearly 50,000 new cases of primary hyperparathyroidism (PHPT) are diagnosed annually in the United States. Most information about the disease focuses on the white population. We evaluated African American (AA) and white patients at our tertiary care university medical center to determine whether there was a racial difference in presentation of PHPT. A retrospective chart review of patients treated surgically for PHPT between 1997 and 2002 was performed. Demographic data, laboratory values, objective symptoms, surgical procedure, and histologic findings were recorded. The AA participants were matched to whites by age and gender. The effect of race was adjusted for the matching variables by including them in regression models. ANOVA chi2 tests were performed on the race effects. Thirty-six (14.4%) of the 286 patients treated for PHPT at Wake Forest University Baptist Medical Center during this 5-year period were AA. There was no difference in serum calcium or presence of objective symptoms, but PTH levels were significantly higher for blacks (207.5 vs 143.5 pg/mL; P = 0.02). In our study, AA patients had significantly higher parathyroid hormone levels at time of surgical intervention but did not present with a difference in symptoms or more advanced disease. Further research is recommended to characterize ethnic differences in patients with PHPT.

Adult↗
PubMed2003

Differing histologic findings after bilateral and focused parathyroidectomy.

BACKGROUND: Minimally invasive parathyroid surgery with intraoperative parathyroid hormone testing has been reported to be as successful as a bilateral operation. This study aimed to determine whether the histologic findings and outcomes differ in patients with primary sporadic hyperparathyroidism treated by a focal or a bilateral parathyroid exploration with intraoperative parathyroid hormone testing. To make the two groups comparable all patients had a solitary parathyroid adenoma identified preoperatively. STUDY DESIGN: Eighty unselected patients with primary hyperparathyroidism and a single abnormal parathyroid gland identified preoperatively by sestamibi scanning or ultrasonography were included in this study. All patients had intraoperative parathyroid hormone testing. RESULTS: Forty-five patients had standard bilateral neck explorations and 35 patients had focal neck explorations. In the bilateral neck exploration group a single adenoma was found in 38 patients (84%), a double adenoma in 3 patients (7%), hyperplasia in 3 patients (7%), and carcinoma in 1 patient (2%). In contrast, a single adenoma was identified in all patients in the focal neck exploration group. Sestamibi scanning and intraoperative parathyroid hormone assay were accurate in 87% and 84%, respectively, in the bilateral neck exploration group and in 96.9% and 94.3%, respectively, in the focal neck exploration group. All patients were normocalcemic (mean followup 17 months). CONCLUSIONS: Patients with primary hyperparathyroidism having a bilateral exploration had about a 15% higher rate of multiple parathyroid tumors than did patient having a focal approach. Despite this observation all patients were normocalcemic postoperatively. This suggests that either some histologically abnormal parathyroid glands do not function or there will be recurrences in patients treated by a focused approach. Longterm followup will be necessary to determine whether patients treated by focal neck exploration will develop recurrent primary hyperparathyroidism.

Adenoma↗
PubMed2003

Enhanced scintigraphic protocol required for optimal preoperative localization before targeted minimally invasive parathyroidectomy.

At our tertiary care institution, a targeted minimally invasive parathyroidectomy (MIP) is the preferred surgical procedure for primary hyperparathyroidism. Similar to unilateral neck exploration (UNE), preoperative scintigraphic localization of the adenoma in relation to the midline is required. However, in contrast to the abbreviated standard incision for UNE, 2 distinct incision sites, 1 medial and 1 lateral, are available on each side with MIP. The incision site is ultimately chosen based on scintigraphic determination of the adenoma's vascular origin to facilitate ligation and removal. Unfortunately, the scintigraphic location of a parathyroid adenoma does not necessarily reflect the site of its vascular origin. We reviewed our database to identify factors that accurately predict the site of vascular origin of parathyroid adenomas. A retrospective chart review was performed on 125 patients who underwent Tc-99m sestamibi scintigraphy and parathyroidectomy. Scintigraphic localization, surgical findings, and histopathology were recorded. Preoperative image interpretations that were discordant with operative findings were independently reviewed. Scintigraphy identified the presence of an adenoma in 105 of 118 patients (89%) with primary hyperparathyroidism. In 17 of the 105 cases (16%), the scintigraphic interpretation did not accurately reflect the site of superior or inferior vascular origin seen at surgery. In many discordant cases, anterior images were insufficient for determining the vascular origin. The posterior displacement of an adenoma in relation to the thyroid on early lateral images was often critical in determining the superior or inferior vascular origin. Scintigraphic determination of the superior or inferior vascular origin of a parathyroid adenoma directs incision placement for MIP. Imaging protocols should include early lateral images when localizing parathyroid adenomas before minimally invasive parathyroidectomy.

Adenoma↗
PubMed2003

Experienced scintigraphers contribute to success of minimally invasive parathyroidectomy by skilled endocrine surgeons.

Minimally invasive parathyroidectomy (MIP) has become the preferred surgical treatment for selected patients diagnosed with primary hyperparathyroidism (PHPT) at our tertiary-care center. Preoperative scintigraphy establishes the position of a parathyroid adenoma, dictates the incision site, and can minimize incision size and consequent tissue dissection. We reviewed our database and sought to identify factors that led to discordant preoperative imaging and operative findings and to assess the effect of experience on these findings. A retrospective review was performed on all patients with biochemically proven PHPT who underwent Tc-99m sestamibi scintigraphy and surgical intervention. Patient demographics, date of surgical intervention, scintigraphic localization, surgical findings, pre- and postoperative biochemical markers, histopathology, coexisting thyroid pathology, and 6-month follow up were recorded. Preoperative images that were discordant with operative findings were independently reviewed. Parathyroid scintigraphy was performed on 125 consecutive patients for PHPT between November 1999 and January 2002. Seventy-six patients had MIPs, 35 had standard cervical explorations, 11 had MIPs that were converted to standard cervical explorations, and three had surgery directed to an ectopic location. At 6-month follow-up 98.4 per cent were cured. Preoperative imaging and surgical findings were ipsilateral and concordant in 105 of 118 (89%) patients with parathyroid adenoma. The anatomic origin of an adenoma was predicted in only 83 of 118 (68%) patients. Most of the inaccurate scintigraphy readings occurred during the first 13 of the 26 months that MIPs were performed at our institution. Only two discordant cases occurred during the last 9 months of this period. Biochemical markers, prior neck operation, and concomitant thyroid pathology had no correlation with imaging sensitivity. Scintigraphic interpretation of smaller adenomas was less reliable; discordant cases were more common in small adenomas. Communication between endocrine surgeons and nuclear medicine physicians about the MIP technique and anatomic orientation of adenomas led to better scintigraphic localization as experience increased. Now that MIP by skilled endocrine surgeons is becoming the favored treatment for PHPT experienced nuclear medicine physicians may be the most important factor to achieve maximum success.

Adenoma↗
PubMed2003

Effect of massage technique on sentinel lymph node mapping for cancer of the breast.

Sentinel lymph node (SLN) mapping has substantially changed the nature of surgery for cancer of the breast. Variables such as tracer type, volume, injection site, timing, and surgical experience have all been extensively evaluated. However, little attention has been paid to the technique of massage for SLN procedures. We sought to evaluate the effects of three different massage techniques on mapping success or accuracy of SLN mapping for breast cancer. All lymphatic mapping procedures for breast cancer at our tertiary-care center were performed by three experienced surgeons using both colloid and dye followed by a 5-minute massage. All data pertaining to SLN identification, histopathology, tumor characteristics, and patient demographics were entered into the Breast Care Center database. Consistent and uniquely differing massage techniques classified as resuscitative, buffer, or knead-like were each used by a specific surgeon. The last 25 consecutive cases performed by two surgeons and the last 24 by one surgeon were evaluated. The overall rate of SLN identification was 97 per cent, and the overall accuracy was 98.7 per cent. There was no statistically significant difference in the rate of SLN identification or accuracy between techniques. The proportions of blue-stained SLNs were similar, but the resuscitative technique yielded fewer hot SLNs (Fisher's exact test, P = 0.02). This method also yielded one false negative case. The three different massage techniques yielded a similar number of blue-stained SLNs. The resuscitative technique yielded fewer hot SLNs than the kneading and buffer methods. Our results failed to demonstrate a superior breast massage technique for identifying sentinel nodes. A larger randomized trial is needed to confirm these findings.

Adult↗
PubMed2003

Biopsy needle technique and the accuracy of diagnosis of atypical ductal hyperplasia for mammographic abnormalities.

The evaluation of mammographic abnormalities has become a substantial effort for surgeons and radiologists. The vacuum-assisted core biopsy (VACB) has been touted as a more accurate tool for the evaluation of mammographic lesions. Diagnosis of atypical ductal hyperplasia (ADH) from a percutaneous needle biopsy of the breast is associated with a significant risk of missing a significant breast lesion. We compared 2 methods of sampling with stereotactic-guided breast biopsy, 14-gauge automated gun core biopsy (AGCB) and VACB, on the accuracy of diagnosis of ADH at a single institution. All cases of ADH, without associated malignancy, found via image-guided breast biopsy of nonpalpable lesions between March 1996 and April 2002 were evaluated. VACB biopsy needles were utilized between July 1998 to April 2002 (686 patients) and 14-gauge AGCB from March 1996 to June 1998 (350 patients). The results of these biopsies were reviewed and compared to surgical biopsy and pathological records. ADH alone was found in 53 cases (5.1% of biopsies; mean age 57.9 years). Of these, 39 patients with ADH subsequently underwent wire-localized excisional biopsy. The other 14 patients were observed. VACB biopsy understaged 7 of 29 (24%) patients with ADH (all of which were DCIS), AGCB understaged 4 of 10 cases (40%) with one being invasive. Of the patients in the core biopsy group who were initially followed, 2 developed significant lesions within 3 years of follow-up in the same quadrant of the breast. If these cases are added to the AGCB group, then 50 per cent were understaged and significantly more invasive lesions were understaged than with VACB (17% vs. 0%; P = 0.018). The VACB resulted in less understaging of ADH than AGCB. However, there remains a significant risk of missing DCIS in this setting even with the VACB. Furthermore, the risk of understaging an invasive lesion is significantly lower in this setting with a VACB than an AGCB. Although the risk of understaging ADH is lower with the VACB, we continue to recommend excisional biopsy in a good-risk patient when a diagnosis of ADH is rendered via VACB biopsy.

Adult↗
PubMed2003

DNA-repair genetic polymorphisms and breast cancer risk.

Mammalian cells are constantly exposed to genotoxic agents from both endogenous and exogenous sources. Genetic variability in DNA repair contributes to deficient repair and breast cancer risk. Using samples collected in an ongoing, clinic-based, case-control study (253 cases and 268 controls), we tested whether breast cancer risk is associated with four amino acid substitution variants in three DNA repair genes, including XRCC1 Arg194Trp and XRCC1 Arg399Gln in base excision repair, XRCC3 Thr241Met in homologous recombination repair, and ERCC4/XPF Arg415Gln in nucleotide excision repair. Carriers of at least one variant allele of XRCC1 Arg194Trp [Arg/Trp and Trp/Trp versus Arg/Arg, odds ratio (OR) = 1.60, 95% confidence interval (CI) = 0.89-2.87] or two variant alleles of XRCC3 241Met/Metmay have an increased risk of breast cancer (Met/Met versus Thr/Thr and Thr/Met, OR = 1.54, 95% CI = 0.94-2.52). No association between XRCC1 Arg399Gln Dgenotype and breast cancer risk was observed. The genotype distribution of ERCC4/XPF Arg415Gln differed significantly between cases and controls (P = 0.02), and the ERCC4/XPF 415Gln/Gln genotype was found in only seven cases (3%) but not in controls. In addition, breast cancer risk was significantly associated with an increasing number of combined variant alleles of XRCC1 Arg194Trp, XRCC3 Thr241Met, and ERCC4/XPF Arg415Gln in a four-level model (P(trend) = 0.04): OR = 1.0 for those without a variant allele (referent group); OR = 1.04 (95% CI = 0.67-1.61) for those with one variant allele; OR = 1.38 (95% CI = 0.83-2.29) for those with two variant alleles; and age-adjusted OR = 2.60 (95% CI = 1.03-6.59) for those with three or more variant alleles after adjustment for age, family history, age at menarche, age at first live birth, and body mass index. We provide evidence that variants of XRCC1, XRCC3, and ERCC4/XPF genes, particularly in combination, contribute to breast cancer susceptibility.

Adult↗