Genetic variation in CXCL12 and risk of cervical carcinoma: a population-based case-control study.

CXCL12 provides a chemotactic signal-directing leucocyte migration and regulates metastatic behaviour of tumour cells. We conducted a population-based case-control study to test the hypothesis that common genetic variation in CXCL12 individual single nucleotide polymorphism (SNP) alleles and haplotypes] is associated with the risk of cervical carcinoma. Cases (n = 917) were residents of western Washington State diagnosed with invasive squamous cell cervical carcinoma (SCC), invasive adenocarcinoma or adenosquamous carcinoma, or adenocarcinoma in situ of the cervix. Control participants (n = 849) were identified from the source population by random digit telephone dialling and frequency matched to cases on county and age. Nine CXCL12 tagSNPs chosen from the SeattleSNPs database were genotyped. The minor allele of intronic SNP rs266085 was inversely associated with cervical cancer under a recessive genetic effects model (OR = 0.74, 95% CI: 0.56-0.98). Among the ten common haplotypes inferred from the nine tagSNPs, one haplotype defined by minor alleles at 5'-flanking SNP rs17885289 and rs266085, and common alleles at the other seven SNPs occurred among 7.8% of cases and 10.6% of controls (dominant model OR = 0.72, 95% CI: 0.56-0.93; recessive model OR = 0.35, 95% CI: 0.12-0.97; and log-additive model OR = 0.72, 95% CI: 0.57-0.90). A stepwise procedure identified rs17885289, rs266085 and 3'-untranslated region (UTR) SNP rs266093 as the most parsimonious subset of SNPs necessary to define the haplotype inversely associated with cervical cancer risk in our study. A 3'-UTR SNP, rs1801157, previously found to be related to HIV pathogenesis, was not associated with cervical cancer risk. Further population-based studies are warranted to confirm these associations between genetic variation in CXCL12 and cervical cancer risk.

Differential patterns of allelic loss in estrogen receptor-positive infiltrating lobular and ductal breast cancer.

The two main histological types of infiltrating breast cancer, lobular (ILC) and the more common ductal (IDC) carcinoma are morphologically and clinically distinct. To assess the molecular alterations associated with these breast cancer subtypes, we conducted a whole-genome study of 166 archival estrogen receptor (ER)-positive tumors (89 IDC and 77 ILC) using the Affymetrix GeneChip(R) Mapping 10K Array to identify sites of loss of heterozygosity (LOH) that either distinguished, or were shared by, the two phenotypes. We found single nucleotide polymorphisms (SNPs) of high-frequency LOH (>50%) common to both ILC and IDC tumors predominately in 11q, 16q, and 17p. Overall, IDC had a slightly higher frequency of LOH events across the genome than ILC (fractional allelic loss = 0.186 and 0.156). By comparing the average frequency of LOH by chromosomal arm, we found IDC tumors with significantly (P < 0.05) higher frequency of LOH on 3p, 5q, 8p, 9p, 20p, and 20q than ILC tumors. We identified additional chromosomal arms differentiating the subtypes when tumors were stratified by tumor size, mitotic rate, or DNA content. Of 5,754 informative SNPs (>25% informativity), we identified 78 and 466 individual SNPs with a higher frequency of LOH (P < 0.05) in ILC and IDC tumors, respectively. Hierarchical clustering of these 544 SNPs grouped tumors into four major groups based on their patterns of LOH and retention of heterozygosity. LOH in chromosomal arms 8p and 5q was common in higher grade IDC tumors, whereas ILC and low-grade IDC grouped together by virtue of LOH in 16q.

Clinical characteristics of different histologic types of breast cancer.

Breast cancer is a heterogeneous disease, though little is known about some of its rarer forms, including certain histologic types. Using Surveillance, Epidemiology, and End Results Program data on 135 157 invasive breast cancer cases diagnosed from 1992 to 2001, relationships between nine histologic types of breast cancer and various tumour characteristics were assessed. Among women aged 50-89 years at diagnosis, lobular and ductal/lobular carcinoma cases were more likely to be diagnosed with stage III/IV, > or =5.0 cm, and node-positive tumours compared to ductal carcinoma cases. Mucinous, comedo, tubular, and medullary carcinomas were less likely to present at an advanced stage. Lobular, ductal/lobular, mucinous, tubular, and papillary carcinomas were less likely, and comedo, medullary, and inflammatory carcinomas were more likely to be oestrogen receptor (ER) negative/progesterone receptor (PR) negative and high grade (notably, 68.2% of medullary carcinomas were ER-/PR- vs 19.3% of ductal carcinomas). In general, similar differences were observed among women diagnosed at age 30-49 years. Inflammatory carcinomas are associated with more aggressive tumour phenotypes, and mucinous, tubular, and papillary tumours are associated with less aggressive phenotypes. The histologic types of breast cancer studied here differ greatly in their clinical presentations, and the differences in their hormone receptor profiles and grades point to their likely different aetiologies.

Reproductive factors and subtypes of breast cancer defined by hormone receptor and histology.

Reproductive factors are associated with reduced risk of breast cancer, but less is known about whether there is differential protection against subtypes of breast cancer. Assuming reproductive factors act through hormonal mechanisms they should protect predominantly against cancers expressing oestrogen (ER) and progesterone (PR) receptors. We examined the effect of reproductive factors on subgroups of tumours defined by hormone receptor status as well as histology using data from the NIHCD Women's Contraceptive and Reproductive Experiences (CARE) Study, a multicenter case-control study of breast cancer. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) as measures of relative risk using multivariate unconditional logistic regression methods. Multiparity and early age at first birth were associated with reduced relative risk of ER + PR + tumours (P for trend=0.0001 and 0.01, respectively), but not of ER - PR - tumours (P for trend=0.27 and 0.85), whereas duration of breastfeeding was associated with lower relative risk of both receptor-positive (P for trend=0.0002) and receptor-negative tumours (P=0.0004). Our results were consistent across subgroups of women based on age and ethnicity. We found few significant differences by histologic subtype, although the strongest protective effect of multiparity was seen for mixed ductolobular tumours. Our results indicate that parity and age at first birth are associated with reduced risk of receptor-positive tumours only, while lactation is associated with reduced risk of both receptor-positive and -negative tumours. This suggests that parity and lactation act through different mechanisms. This study also suggests that reproductive factors have similar protective effects on breast tumours of lobular and ductal origin.

Epidemiologic and molecular risk factors for contralateral breast cancer among young women.

Women diagnosed with a first breast cancer before the age of 45 years have a greater than 5.0-fold risk of developing a second primary contralateral breast cancer (CBC) than women in the general population have of developing a first breast cancer. Identifying epidemiologic or molecular factors that influence CBC risk could aid in the development of new strategies for the management of these patients. A total of 1285 participants in two case-control studies conducted in Seattle, Washington, who were 21-44 years of age when diagnosed with a first invasive breast carcinoma from 1983 to 1992, were followed through December 2001. Of them, 77 were diagnosed with CBC and 907 tumour tissues from first cancers were analysed. Women with body mass indices (BMIs) >/=30 kg m(-2) had a 2.6-fold greater risk (95% CI: 1.1-5.9) of CBC compared to women with BMIs

The relationship of placenta previa and history of induced abortion.

OBJECTIVES: We evaluated the risk of placenta previa being associated with a history of induced abortion by different surgical procedures. METHODS: Cases (n=192) were women who had a singleton delivery complicated by placenta previa at a major obstetric care hospital in western Washington state between April 1, 1990 and December 31, 1992. Controls (n=622) were women with singleton deliveries not complicated by placenta previa or abruption. Odds ratios, determined by logistic regression, approximate the relative risks. RESULTS: Vacuum aspiration abortion was not associated with an increased risk of placenta previa (OR 0.9, 95% CI 0.6-1.5). However, the risk of placenta previa increased with the number of sharp curettage abortions (OR 2.9, 95% CI 1.0-8.5 for > or =3). CONCLUSIONS: Risk of placenta previa may be increased in a dose response fashion by multiple sharp curettage abortions. However, vacuum aspiration does not confer an increased risk, and may be a better alternative.

Hormonal content and potency of oral contraceptives and breast cancer risk among young women.

Recent use of oral contraceptive pills is associated with a modest risk of breast cancer among very young women. In this US population-based case-control study, we evaluated whether the excess risk associated with recent oral contraceptive use is ubiquitous for all pill types or attributable to specific oral contraceptive preparations. Hormonal content and potency of combination oral contraceptives used for the longest duration within 5 years of interview for breast cancer cases aged 20-44 years (N=1640) were compared with age-matched community controls (N=1492). Women who recently used oral contraceptives containing more than 35 microg of ethinyl oestradiol per pill were at higher risk of breast cancer than users of lower dose preparations when compared to never users (respective relative risks of 1.99 and 1.27, P(trend)<0.01). This relationship was more marked among women <35 years of age, where risks associated with high- and low-dose ethinyl oestradiol use were 3.62 and 1.91 (P(trend)<0.01), respectively. We also found significant trends of increasing breast cancer risk for pills with higher progestin and oestrogen potencies (P(trend)<0.05), which were most pronounced among women aged <35 years of age (P(trend)<0.01). Risk was similar across recently used progestin types. Our findings suggest that newer low-potency/low oestrogen dose oral contraceptives may impart a lower risk of breast cancer than that associated with earlier high-potency/high-dose preparations.

Serologic evidence of herpes simplex virus 1 infection and oropharyngeal cancer risk.

In vitro and animal models suggest that the herpes simplex virus 1 (HSV1) may contribute to the development of oropharyngeal squamous cell carcinoma (OSCC). To determine whether the risk of OSCC is related to infection with HSV1 in humans, we recruited 260 patients from 18 to 65 years old who were newly diagnosed with OSCC between 1990-1995 while residing in three western Washington State counties. For comparison, we recruited at random 445 controls frequency matched to cases on age and sex. Participants completed in-person interviews and provided serum samples that were tested for antibody response to HSV1. After adjusting for sex, cigarette smoking, alcohol consumption, age, and income, HSV1 antibody positivity was associated with a slightly increased risk of OSCC [adjusted odds ratio (OR), 1.3; 95% confidence interval (CI), 0.9-2.0]. The adjusted association between HSV1 antibody positivity and OSCC risk among those who were current cigarette smokers (OR, 4.2; CI, 2.4-7.1) was stronger than would be predicted based on the additive combination of smoking alone (OR, 2.3; CI, 1.2-4.2) and HSV1 seropositivity alone (OR, 1.0; CI, 0.6-1.7). There was suggestive evidence that the association between HSV1 infection and OSCC was similarly modified by evidence of HPV infection but no evidence of effect modification with alcohol consumption. This population-based study suggests that HSV1 may enhance the development of OSCC in individuals who are already at increased risk of the disease because of cigarette smoking or HPV infection.

Risk factors for sudden infant death syndrome: changes associated with sleep position recommendations.

OBJECTIVE: To quantify the decreased incidence of sudden infant death syndrome (SIDS) and investigate risk profile changes associated with changes in infant sleep position. DESIGN: A population-based case-control study that used birth and death certificates from Washington State. Cases (n = 1515) were all singletons born in Washington between 1985 and 1995 (excluding 1991) who died of SIDS. Control cases (n = 6060) were randomly selected singletons born in the same period who did not die of SIDS. Multivariate logistic regression compared changes in the magnitude of associations between risk factors and SIDS before and after 1991. RESULTS: The incidence of SIDS in Washington declined from 2.6 (1985) to 1.0 (1998) per 1000 births. Over time, the risk of SIDS increased for low birth weight infants (odds ratio [OR] 2.1 rose to 3.6), and infants born to mothers who were smokers (OR 2.7 rose to 3.7), unmarried (OR 1.4 rose to 2.0), black (OR 1.4 rose to 2.5), or received limited prenatal care (OR 1.5 rose to 2.5). CONCLUSION: Five exposures were associated with increased risks of SIDS. These may not require a prone sleep position for their deleterious impact being associated with distinct causal pathways, or possibly indicating subpopulations yet to recognize the importance of the supine sleep position.

Hypertension, heart rate, use of antihypertensives, and incident prostate cancer.

PURPOSE: Recent studies have reported conflicting results on a possible relationship between hypertension, heart rate, and prostate cancer. A model has been developed suggesting that high blood pressure and high heart rate may both be markers for increased central sympathetic nervous activity, which may result in androgen-mediated stimulation of prostate cancer growth. METHODS: In this study we examined the associations between hypertension, heart rate, use of antihypertensive medications, and incident prostate cancer in a cohort of 2442 men. Data from the Cardiovascular Health Study (CHS), an NHLBI-sponsored observational study of adults age 65 or older in four U.S. communities, were analyzed using Cox proportional hazards regression. Seated systolic and diastolic blood pressures were measured using a standardized protocol at the initial clinical examination and annually at follow-up visits. Medications data were transcribed by trained interviewers from prescription medication containers brought into the clinic by participants. RESULTS: A total of 209 cases of incident prostate cancer were identified from either an ICD-9 code of 185 in hospital medical records (n = 130) or by self-report from annual surveillance interviews (n = 79). An average of 5.6 years of follow-up was available for analyses. No associations between blood pressure measures at entry into the study and prostate cancer were found, although these results may have been affected by subsequent treatment of hypertension. An association between resting heart rate (HR) equal to or greater than 80 beats per minute and incident prostate cancer was found compared to men with a rate of less than 60 beats per minute (HR: 1.6, 95% confidence interval [CI]: 1.03-2.5). An inverse association was found between risk of incident prostate cancer and use of any antihypertensive medication (HR: 0.7, 95% CI: 0.5-0.9). A test of heterogeneity found no difference between use of the specific classes of antihypertensive medication and the association with prostate cancer risk. CONCLUSIONS: These data tend to support the hypothesized causal pathway between vascular disease markers and prostate cancer.

Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma.

BACKGROUND: Obesity has been shown to affect breast carcinoma prognosis, with the heaviest women having a higher mortality due to breast carcinoma. Few studies have focused on premenopausal women or the correlation of body mass index (BMI) to tumor characteristics related to prognosis. METHODS: The authors conducted a population-based follow-up study for mortality of 1177 women younger than 45 years of age who had invasive ductal breast carcinoma diagnosed from 1983 through 1992. Histologic slides and/or tumor tissue were collected for pathologic review, immunohistochemistry assays, and bivariate flow cytometric analysis. RESULTS: Women with breast carcinoma who were in the highest quartile of BMI were 2.5 times as likely (95% confidence interval [CI], 1.6-3.9) to die of their disease within 5 years of diagnosis compared with women in the lowest quartile of BMI. The tumors of the women in the highest quartile of BMI were more likely to be estrogen receptor negative (odds ratio [OR], 1.5; 95% CI, 1.0-2.2) and to have a high S-phase fraction (OR, 1.9; 95% CI, 1.2-3.1), high histologic grade (OR, 1.7; 95% CI, 1.0-2.9), high mitotic cell count (OR, 2.0; 95% CI, 1.2-3.1), and large tumor size (2 to < 5 cm: OR, 2.3; 95% CI, 1.5-3.1; or > or = 5 cm: OR, 2.7; 95% CI, 1.5-4.8) compared with the tumors of women whose BMI was in the first quartile. Relative to the large tumors (> or = 2 cm) in women in the lowest BMI quartile, the large tumors in women in the highest BMI quartile were more likely to express markers of high proliferation, indicating they may have grown faster than similar size tumors of the thinnest women. In a multivariate analysis including the tumor characteristics, obesity, as measured by being in the highest quartile of BMI, remained an independent prognostic factor for mortality (hazard ratio, 1.7; 95% CI, 1.0-2.9; P < 0.05. CONCLUSIONS: Our study results indicated that being in the highest quartile of BMI was a strong predictor of mortality in women with breast carcinoma diagnosed at a young age. The tumors of the heavy women were larger and more likely to have markers of high cellular proliferation than those of thinner women.

Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history.

BACKGROUND: An increased incidence of breast carcinoma has been reported among relatives of individuals who are affected with the rare recessive disorder, ataxia-telangiectasia (A-T), and who are heterozygous for mutations in the ataxia-telangiectasia mutated (ATM) gene. However, most studies of breast carcinoma cases from the general population have failed to find a higher incidence of ATM mutations in cases when compared with controls. METHODS: Genomic DNA samples from 258 individuals were screened for mutations of all types in each of the 62 coding exons of the ATM gene; 142 of these were from breast carcinoma cases with a first-degree family history or early age at diagnosis, 35 were from cases selected for the presence of either known disease-related mutations (n = 25) or missense alterations of unknown consequences (n = 10) in BRCA1 or BRCA2, and 81 were from matched controls. RESULTS: A total of 12 individuals with ATM mutations were identified, 11 among 142 breast carcinoma cases (7.7%; 95% CI, 3.9-13.4%) and 1 among 81 controls (1.2%; 95% CI, 0.0-6.7%) (P = 0.06). All mutations detected were of the missense type; none were predicted to truncate the ATM protein. Among cases, mutations were found exclusively in patients with a family history of breast carcinoma (12.1%; 95% CI, 6.2-20.6%) (P = 0.02). Similar frequencies of ATM mutations were found in 35 additional cases selected for the presence of BRCA1 or BRCA2 mutations when compared with cases overall. CONCLUSIONS: ATM mutations, specifically missense mutations, are more common in breast carcinoma cases selected for first-degree family history and early age at diagnosis.

Tamoxifen therapy for primary breast cancer and risk of contralateral breast cancer.

BACKGROUND: Women diagnosed with breast cancer have a twofold to sixfold greater risk of developing contralateral breast cancer than women in the general population have of developing a first breast cancer. Tamoxifen therapy reduces this risk, but it is unclear if this benefit exists for both estrogen receptor (ER)-positive and ER-negative contralateral tumors. METHODS: Using data from a population-based tumor registry that collects information on the ER status of breast tumors, we followed 8981 women residing in western Washington State who were diagnosed with a primary unilateral invasive breast cancer during the period from 1990 through 1998 to identify cases of contralateral breast cancer. We restricted our analyses to women who were at least 50 years old and whose first breast cancer had a localized or regional stage; women who received adjuvant hormonal therapy but not chemotherapy (n = 4654) were classified as tamoxifen users, while those who received neither adjuvant hormonal therapy nor chemotherapy (n = 4327) were classified as nonusers of tamoxifen. By reviewing selected patient abstracts, we estimated that 94% of the subjects were classified correctly with respect to tamoxifen use. The risk of contralateral breast cancer associated with tamoxifen use was estimated with the use of Cox regression. All statistical tests were two-sided. RESULTS: Of the 89 tamoxifen users and 100 nonusers of tamoxifen diagnosed with contralateral breast cancer, 112 had ER-positive tumors, 20 had ER-negative tumors, and 57 had tumors with an ER status that was unknown or had not been determined by an immunohistochemical assay. The risk of developing an ER-positive and an ER-negative contralateral tumor among tamoxifen users was 0.8 (95% confidence interval [CI] = 0.5 to 1.1) and 4.9 (95% CI = 1.4 to 17.4), respectively, times that of nonusers of tamoxifen. This difference in risk by ER status was statistically significant (P<.0001). CONCLUSIONS: Tamoxifen use appears to decrease the risk of ER-positive contralateral breast tumors, but it appears to increase the risk of ER-negative contralateral tumors.

Human papillomavirus infection and survival in oral squamous cell cancer: a population-based study.

OBJECTIVE: To determine whether human papillomavirus (HPV) type 16 affects survival in oral squamous cell carcinoma. STUDY DESIGN: Two hundred fifty-four patients diagnosed with primary oral cancer were studied for survival in relation to tumor HPV type 16 status. Kaplan-Meier analysis and Cox proportional hazard models were used to assess survival and estimate hazard ratios adjusted for potential confounders. RESULTS: HPV type 16 DNA was detected in 15.1% of tumors. HPV 16 positive patients had significantly reduced all-cause mortality (hazard ratio [HR] estimates = 0.34, 95% CI = 0.14, 0.83) and disease-specific mortality (HR = 0.17, 95% CI = 0.04, 0.76) compared with HPV 16 negative patients after adjustment for age, stage, treatment, smoking, alcohol, education, and comorbid disease. CONCLUSIONS: The presence of HPV type 16 DNA is independently associated with a favorable prognosis in patients with oral squamous cell carcinoma. CLINICAL SIGNIFICANCE: Although HPV genotyping is currently not widely available, it may provide important prognostic information.

Hormone replacement therapy after a diagnosis of breast cancer in relation to recurrence and mortality.

BACKGROUND: Hormone replacement therapy (HRT) is typically avoided for women with a history of breast cancer because of concerns that estrogen will stimulate recurrence. In this study, we sought to evaluate the impact of HRT on recurrence and mortality after a diagnosis of breast cancer. METHODS: Data were assembled from 2755 women aged 35-74 years who were diagnosed with incident invasive breast cancer while they were enrolled in a large health maintenance organization from 1977 through 1994. Pharmacy data identified 174 users of HRT after diagnosis. Each HRT user was matched to four randomly selected nonusers of HRT with similar age, disease stage, and year of diagnosis. Women in the analysis were recurrence free at HRT initiation or the equivalent time since diagnosis. Rates of recurrence and death through 1996 were calculated. Adjusted relative risks were estimated by use of the Cox regression model. All statistical tests were two-sided. RESULTS: The rate of breast cancer recurrence was 17 per 1000 person-years in women who used HRT after diagnosis and 30 per 1000 person-years in nonusers (adjusted relative risk for users compared with nonusers = 0.50; 95% confidence interval [CI] = 0.30 to 0.85). Breast cancer mortality rates were five per 1000 person-years in HRT users and 15 per 1000 person-years in nonusers (adjusted relative risk = 0.34; 95% CI = 0.13 to 0.91). Total mortality rates were 16 per 1000 person-years in HRT users and 30 per 1000 person-years in nonusers (adjusted relative risk = 0.48; 95% CI = 0.29 to 0.78). The relatively low rates of recurrence and death were observed in women who used any type of HRT (oral only = 41% of HRT users; vaginal only = 43%; both oral and vaginal = 16%). No trend toward lower relative risks was observed with increased dose. CONCLUSION: We observed lower risks of recurrence and mortality in women who used HRT after breast cancer diagnosis than in women who did not. Although residual confounding may exist, the results suggest that HRT after breast cancer has no adverse impact on recurrence and mortality.

Human papillomavirus and prognosis of invasive cervical cancer: a population-based study.

PURPOSE: To determine the association between human papillomavirus (HPV) type and prognosis of patients with invasive cervical carcinoma. PATIENTS AND METHODS: Patients diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage IB to IV cervical cancer between 1986 and 1997 while residents of three Washington State counties were included (n = 399). HPV typing was performed on paraffin-embedded tumor tissue using polymerase chain reaction methods. Patients were observed for a median of 50.8 months. Total mortality (TM) and cervical cancer-specific mortality (CCSM) were determined. Hazards ratios (HR) adjusted for age, stage, and histologic type were estimated using multivariable models. RESULTS: Eighty-six patients had HPV 18-related tumors and 210 patients had HPV 16-related tumors. Cumulative TM among patients with HPV 18-related tumors and among patients with HPV 16-related tumors were 33.7% and 27.6%, respectively; cumulative CCSM in these two groups were 26.7% and 18.1%, respectively. Compared with patients with HPV 16-related cancers, patients with HPV 18-related cancers were at increased risk for TM (HR(TM), 2.2; 95% confidence interval [CI], 1.3 to 3.6) and CCSM (HR(CCSM), 2.5; 95% CI, 1.4 to 4.4). The HPV18 associations were strongest for patients with FIGO stage IB or IIA disease (HR(TM), 3.1; 95% CI, 2.3 to 4.2; and HR(CCSM), 5.8; 95% CI, 3.9 to 8.7), whereas no associations were observed among patients with FIGO stage IIB to IV disease. Virtually identical associations were found in the subset of patients with squamous cell carcinoma (n = 219). CONCLUSION: HPV 18-related cervical carcinomas, particularly those diagnosed at an early stage, are associated with a poor prognosis. Elucidating the mechanism or mechanisms underlying this association could lead to new treatment approaches for patients with invasive cervical carcinoma.

Human papillomavirus and long-term oral contraceptive use increase the risk of adenocarcinoma in situ of the cervix.

We examined United States Surveillance, Epidemiology, and End Results incidence data and conducted a population-based case-control study to examine the role of human papillomavirus (HPV) and oral contraceptive (OC) use in the etiology of adenocarcinoma in situ of the cervix (ACIS). One hundred and fifty women diagnosed with ACIS and 651 randomly selected control women completed in-person interviews. The presence of HPV DNA in archival ACIS specimens was determined by E6 and L1 consensus PCR. Serum samples from case and control subjects were collected at interview, and antibodies to HPV-16 L1 and HPV-18 L1 were detected by virus-like particle capture assays. The overall prevalence of HPV DNA was 86.6%, with 39.0% positive for HPV-16 DNA, 52.4% positive for HPV-18 DNA, and 13.4% positive for more than one HPV type. The age-adjusted relative risk of ACIS associated with HPV-18 seropositivity was 3.3 (95% confidence interval 2.2-4.9). No increased risk was associated with antibodies to HPV-16 L1. Among women born after 1945, the relative risk increased with duration of OC use, with the highest risk for 12 or more years of use (odds ratio, 5.5; 95% confidence interval, 2.1-14.6) relative to nonusers. The detection of HPV DNA in 86.6% of ACIS and the strong association of ACIS with HPV-18 L1 seropositivity underscore the importance of HPV, particularly HPV-18, in the etiology of ACIS. In addition, long-term OC use may contribute to the pathogenesis of these tumors in some women.

Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites.

Human papillomavirus (HPV) DNA has been detected in the great majority of cancers of the uterine cervix and anus, whereas the association of HPV DNA with cancer at other anogenital sites has produced less consistent results. This study was designed to compare HPV exposure among anogenital cancer cases and matched controls. Cases (1782) of anogenital cancer diagnosed in the Seattle area from 1978 to 1998 were identified and interviewed. Their responses were compared with those of 2383 age- and sex-matched controls. Blood was drawn at interview from both cases and controls and tested for antibodies to HPV-16 and HPV-18. Tissue blocks were tested for HPV DNA for 649 cases. Serum antibodies to HPV-16 were associated with in situ and invasive cancer at all sites among men and women with the exception of in situ penile cancer. Anti-HPV-18 antibodies were associated with cancers at all sites among women. The increased risk of cancer associated with HPV-16 seropositivity ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for adenocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-10.3) for anal cancer in men. Associations between seroprevalence and cancers were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-positive cases. HPV DNA was detected in >80% of cancers from all sites tested. HPV-16 DNA was the type most frequently detected at all sites (range, 40.9-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix but detected much less often (2.6-18.1%) at other sites. These findings support an important role for HPV infection in anogenital cancer at all sites. Differences in the proportion of seropositives among HPV-16 DNA-positive cases by site suggest either that the immune response varies by site or that cancer development may lead to changes in antibody responses in a site-specific fashion.

Recreational physical activity and risk of papillary thyroid cancer (United States).

OBJECTIVE: Exercise has been hypothesized to influence cancer risk through a variety of mechanisms including hormonal, metabolic and immunologic effects, yet its relation with the risk of thyroid cancer has not been examined. We conducted a population-based case-control study in women aged 18-64 in three counties of western Washington State to assess the relation of recreational physical activity with risk of papillary thyroid cancer. METHODS: Of 558 women with thyroid cancer of the follicular epithelium diagnosed during 1988-1994 who were identified as eligible, 468 (83.9%) were interviewed; this analysis was restricted to women with papillary histology (n = 410). Controls (n = 574) were identified by random digit dialing, with a response proportion of 73.6%. Logistic regression was used to calculate odds ratios (OR) and associated confidence intervals (CI) estimating the relative risk of papillary thyroid cancer associated with various aspects of recreational exercise. RESULTS: Risk of thyroid cancer was reduced among women who reported that they engaged in regular recreational exercise during the 2 years before diagnosis relative to women who did not report exercise during that time period (OR = 0.76, 95% CI 0.59-0.98). A similar risk reduction was noted among women who reported having exercised regularly between ages 12 and 21 (OR = 0.83, 95% CI 0.64-1.1). However, no clear associations with aspects of recreational activity, including average hours exercised per week or weekly energy expenditure, were observed. CONCLUSIONS: These results provide some initial support for the hypothesis that physical activity may reduce risk of thyroid cancer.