Medical-eligibility criteria for contraceptive use.

Two supergene families encode proteins with glutathione S-transferase (GST) activity: the family of soluble enzymes comprises at least 16 genes; the separate family of microsomal enzymes comprises at

Glutathione S-Transferase Polymorphisms and Their Biological Consequences

Dietary long-chain n−3 fatty acids for the prevention of cancer: a review of potential mechanisms

BACKGROUND

This annual report to the nation addresses progress in cancer prevention and control in the U.S. with a special section on colorectal cancer. This report is the joint effort of the American Cancer Society, the National Cancer Institute (NCI), the North American Association of Central Cancer Registries (NAACCR), and the Centers for Disease Control and Prevention (CDC), including the National Center for Health Statistics (NCHS).



METHODS

Age-adjusted rates were based on cancer incidence data from the NCI and NAACCR and underlying cause of death as compiled by NCHS. Joinpoint analysis was based on NCI Surveillance, Epidemiology, and End Results (SEER) program incidence rates and NCHS death rates for 1973–1997. The prevalence of screening examinations for colorectal cancer was obtained from the CDC's Behavioral Risk Factor Surveillance System and the NCHS's National Health Interview Survey.



RESULTS

Between 1990–1997, overall cancer incidence and death rates declined. Joinpoint analyses of cancer incidence and death rates confirmed the declines described in earlier reports. The incidence trends for colorectal cancer have shown recent steep declines for whites in contrast to a leveling off of the rates for blacks. State-to-state variations occurred in colorectal cancer screening prevalence as well as incidence and death rates.



CONCLUSIONS

The continuing declines in overall cancer incidence and death rates are encouraging. However, a few of the top ten incidence or mortality cancer sites continued to increase or remained level. For many cancer sites, whites had lower incidence and mortality rates than blacks but higher rates than Hispanics, Asian and Pacific Islanders, and American Indians/Alaska Natives. The variations in colorectal cancer incidence and death rates by race/ethnicity, gender, age, and geographic area may be related to differences in risk factors, demographic characteristics, screening, and medical practice. New efforts currently are underway to increase awareness of screening benefits and treatment for colorectal cancer. Cancer 2000;88:2398–424. © 2000 American Cancer Society.

/pdf/the-annual-report-to-the-nation-on-the-status-of-cancer-1973-52wbzzwe5f.pdf

The annual report to the nation on the status of cancer, 1973–1997, with a special section on colorectal cancer

PTEN, on 10q23.3, encodes a major lipid phosphatase which signals down the phosphoinositol-3-kinase/Akt pathway and effects G1 cell cycle arrest and apoptosis. Germline PTEN mutations have been found to occur in 80% of classic Cowden syndrome (CS), 60% of Bannayan-Riley-Ruvalcaba syndrome (BRRS), up to 20% of Proteus syndrome (PS), and approximately 50% of a Proteus-like syndrome (PSL). CS is a heritable multiple hamartoma syndrome with a high risk of breast, thyroid, and endometrial carcinomas. BRRS is a congenital autosomal dominant disorder characterized by megencephaly, developmental delay, lipomatosis, and speckled penis. PS and PSL had never been associated with risk of malignancy. Finding germline PTEN mutations in patients with BRRS, PS, and PSL suggests equivalent risks of developing malignancy as in CS with implications for medical management. The mutational spectra of CS and BRRS overlap, with many of the mutations occurring in exons 5, 7, and 8. Genotype-phenotype association analyses have revealed that the presence of germline PTEN mutations is associated with breast tumor development, and that mutations occurring within and 5' of the phosphatase motif were associated with multi-organ involvement. Pooled analysis of PTEN mutation series of CS and BRRS occurring in the last five years reveals that 65% of CS-associated mutations occur in the first five exons encoding the phosphatase domain and the promoter region, while 60% of BRRS-associated mutations occur in the 3' four exons encoding mainly the C2 domain. Somatic PTEN mutations occur with a wide distribution of frequencies in sporadic primary tumors, with the highest frequencies in endometrial carcinomas and glioblastoma multiform. Several mechanisms of PTEN inactivation occur in primary malignancies derived from different tissues, but a favored mechanism appears to occur in a tissue-specific manner. Inappropriate subcellular compartmentalization and increased/decreased proteosome degradation may be two novel mechanisms of PTEN inactivation. Further functional work could reveal more effective means of molecular-directed therapy and prevention.

PTEN: One Gene, Many Syndromes

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.

/pdf/a-prospective-study-of-nat2-acetylation-genotype-cigarette-4d2stz9xh3.pdf

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer.

Heterocyclic amines (HAs) are carcinogens produced by high-temperature cooking of meat and animal protein; metabolism of HA is influenced by polymorphisms in the N-acetyltransferase-2 (NAT-2) gene. Data from a variety of sources suggest that HA may play a role in human carcinogenesis. We examined the associations between meat intake and cooking method, acetylator genotype and breast cancer risk in a sub-cohort of 32,826 women in the Nurses' Health Study who gave a blood sample in 1989-1990. Women who were diagnosed with breast cancer (n = 466) after blood draw and prior to June 1, 1994, were matched to 466 controls. Overall, rapid acetylators were not at increased risk of breast cancer compared with slow acetylators (multivariate OR = 1.1, 95% CI 0.8-1.5), and there were no associations between meat intake or cooking method of meat and breast cancer risk. Rapid acetylators with the highest red meat intake (one or more servings per day) were not at increased risk of breast cancer compared with slow acetylators with the lowest red meat intake (OR = 1.1, 95% CI 0.7-1.8). Frequent intake of charred meat among rapid acetylators (one or more times per week) was not associated with increased risk (OR = 1.2, 95% CI 0.6-2.3) compared with slow acetylators who ate charred meat less than once per month. We observed no significant associations for rapid acetylators who frequently consumed beef, pork or lamb cooked with high-temperature cooking methods, such as barbecuing (OR = 0.9, 95% CI 0.4-1.9) or roasting (OR = 0.9, 95% CI 0.5-1.6). Our data suggest that HAs may not be a major cause of breast cancer, although we cannot exclude misclassification of HA intake as the reason for the lack of association. We observed no evidence of differential susceptibility to these exposures by NAT2 genotype.

https://onlinelibrary.wiley.com/doi/pdf/10.1002/%28SICI%291097-0215%2819990105%2980%3A1%3C13%3A%3AAID-IJC3%3E3.0.CO%3B2-W

N‐acetyl transferase 2 genotypes, meat intake and breast cancer risk

Background: Perineal talc use has been associated with an increased risk of ovarian cancer in a number of case-control studies; however, this association remains controversial because of limited supporting biologic evidence and the potential for recall bias or selection bias in case-control studies. In this study, we conducted a prospective analysis of perineal talc use and the risk of ovarian cancer. Methods: The Nurses' Health Study is a prospective study of 121 700 female registered nurses in the United States who were aged 30-55 Sears at enrollment in 1976. Talc use was ascertained in 1982 by use of a self-administered questionnaire: after exclusions, 78 630 women formed the cohort for analysis. Three hundred seven epithelial ovarian cancers subsequently diagnosed in this cohort through June 1, 1996, were confirmed by medical-record review and met inclusion criteria. Proportional hazards models by use of pooled logistic regression were used to derive relative risks (RRs) and 95% confidence intervals (CIs), Results:: In 1982, 40.4% (n = 31 789) of the cohort reported ever using talc, and 14.5% (n = 11 411) reported ever using talc daily. We observed no overall association with ever talc use and epithelial ovarian cancer (multivariate RR = 1.09; 95% CI 0.86-1.37) and no increase in risk of ovarian cancer with increasing frequency of use. There was a modest elevation in risk for ever talc use and invasive serous ovarian cancer (multivariate RR = 1.40; 95% CI = 1.02-1.91), The risk of epithelial ovarian cancer for talc users was not greater among women who had never had a tubal ligation (multivariate RR = 0.97; 95% CI = 0.71-1.32). Conclusion: Our results provide little support for any substantial association between perineal talc use and ovarian cancer risk overall; however, perineal talc use may modestly increase the risk of invasive serous ovarian cancer.

Prospective Study of Talc Use and Ovarian Cancer

Glutathione S-transferase (GST) M1 and T1 genes encode GST enzymes, and are polymorphic in humans. These enzymes catalyze conjugation with glutathione, which is an important step in the detoxification of certain carcinogens. Several case-control studies have found associations of the homozygous null deletions in GSTM1 and GSTT1 with increasing the risk of colorectal and lung cancer. We prospectively examined the associations of the GSTM1 and GSTT1 polymorphisms with colorectal cancer risk in a nested case-control study (212 cases of colorectal cancer and 221 controls) within the Physicians' Health Study. Among controls, the prevalence of the GSTM1 homozygous null genotype was 53% and for GSTT1 homozygous null genotype, 23%. We found no increase in the risk of colorectal cancer for either GSTM1 null [odds ratio (OR) = 1.0; 95% confidence interval (CI), 0.7-1.5] or GSTT1 null (OR = 0.8; 95% CI, 0.5-1.2) genotypes. No differences were seen by site of colon cancer (proximal versus distal) or by age ( 60 years). Current cigarette smokers with GSTM1 null genotype were not at an increased risk of colon cancer (OR = 1.2; 95% CI, 0.3-4.2) compared with current smokers without the null genotype; for the GSTT1 null genotype this OR was 1.1 = 95% CI (0.3-4.7). This lack of association persisted when we examined pack-years of smoking and age at starting smoking. Our results do not support an association of GSTM1 or GSTT1 polymorphisms with colorectal cancer or an interaction with cigarette smoking.

https://cebp.aacrjournals.org/content/cebp/7/11/1001.full.pdf

Glutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk: a prospective study.

BACKGROUND: Identification of risk factors for sexually transmitted diseases (STDs) assists in development of treatment algorithms, which are potentially important components of STD control when microbiologic facilities are limited. METHODS: A cross-sectional study was performed to assess STD and HIV risk factors of 2285 women attending three family planning clinics in Dar-es-Salaam, Tanzania during 1991-92. Women were interviewed and examined for signs of STDs. Specimens were taken for laboratory diagnosis of HIV, other sexually transmitted organisms, and Candida albicans. RESULTS: The prevalence of gonorrhoea was found to be 4.2%, prevalence of trichomoniasis was 14.3%, and positive syphilis serology was found in 2.5% of women. Unmarried women were at increased risk of trichomoniasis (age-adjusted OR = 1.48 95% CI [1.12, 1.95]), gonorrhoea (age-adjusted OR = 1.81 95% CI [1.14, 2.86]) and syphilis (age-adjusted OR 1.5 [0.84, 2.68]). An increasing number of sexual partners in the past five years was associated with an increased risk of all STDs. Current use of the oral contraceptive pill was positively associated with gonorrhoea, multivariate OR = 1.75 95% CI [1.05, 2.93]. The prevalence of candidiasis was 11.5% and was not associated with any of the demographic or behavioural risk factors examined. Clinical diagnostic algorithms for STDs in this study population had relatively low sensitivity and low positive predictive value. CONCLUSION: Being unmarried and having a higher number of sexual partners were consistently associated with each STD, while the associations for other risk factors varied between STDs, emphasising the complexity of STD distribution. Further development of diagnostic algorithms and other methods for screening women for STDs are needed to reduce the impact of STDs and HIV in developing countries.

https://sti.bmj.com/content/sextrans/73/1/39.full.pdf

Dorota M. Gertig

Papers

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer.

N‐acetyl transferase 2 genotypes, meat intake and breast cancer risk

Prospective Study of Talc Use and Ovarian Cancer

Glutathione S-transferase GSTM1 and GSTT1 polymorphisms and colorectal cancer risk: a prospective study.

Risk factors for sexually transmitted diseases among women attending family planning clinics in Dar-es-Salaam, Tanzania.