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Recurrent CDH1 mutations in families with hereditary diffuse gastric cancer are due to both independent mutational events and common ancestry. The presence of a founder mutation from Newfoundland is strongly supported.

A B S T R A C T PurposeAlthough guidelines recommend in-person counseling before BRCA1/BRCA2 gene testing, genetic counseling is increasingly offered by telephone. As genomic testing becomes more common, evaluating alternative delivery approaches becomes increasingly salient. We tested whether telephone delivery of BRCA1/2 genetic counseling was noninferior to in-person delivery. Patients and MethodsParticipants (women age 21 to 85 years who did not have newly diagnosed or metastatic cancer and lived within a study site catchment area) were randomly assigned to usual care (UC; n ϭ 334) or telephone counseling (TC; n ϭ 335). UC participants received in-person pre-and post-test counseling; TC participants completed all counseling by telephone. Primary outcomes were knowledge, satisfaction, decision conflict, distress, and quality of life; secondary outcomes were equivalence of BRCA1/2 test uptake and costs of delivering TC versus UC. ResultsTC was noninferior to UC on all primary outcomes. At 2 weeks after pretest counseling, knowledge (d ϭ 0.03; lower bound of 97.5% CI, Ϫ0.61), perceived stress (d ϭ Ϫ0.12; upper bound of 97.5% CI, 0.21), and satisfaction (d ϭ Ϫ0.16; lower bound of 97.5% CI, Ϫ0.70) had group differences and confidence intervals that did not cross their 1-point noninferiority limits. Decision conflict (d ϭ 1.1; upper bound of 97.5% CI, 3.3) and cancer distress (d ϭ Ϫ1.6; upper bound of 97.5% CI, 0.27) did not cross their 4-point noninferiority limit. Results were comparable at 3 months. TC was not equivalent to UC on BRCA1/2 test uptake (UC, 90.1%; TC, 84.2%). TC yielded cost savings of $114 per patient. ConclusionGenetic counseling can be effectively and efficiently delivered via telephone to increase access and decrease costs. J Clin

Updated from their original publication in 2004, these cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of counseling at-risk individuals through genetic cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Familial Cancer Risk Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Essential components include the intake, cancer risk assessment, genetic testing for an inherited cancer syndrome, informed consent, disclosure of genetic test results, and psychosocial assessment. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

PURPOSE To estimate age-specific relative and absolute cancer risks of breast cancer and to estimate risks of ovarian, pancreatic, male breast, prostate, and colorectal cancers associated with germline PALB2 pathogenic variants (PVs) because these risks have not been extensively characterized. METHODS We analyzed data from 524 families with PALB2 PVs from 21 countries. Complex segregation analysis was used to estimate relative risks (RRs; relative to country-specific population incidences) and absolute risks of cancers. The models allowed for residual familial aggregation of breast and ovarian cancer and were adjusted for the family-specific ascertainment schemes. RESULTS We found associations between PALB2 PVs and risk of female breast cancer (RR, 7.18; 95% CI, 5.82 to 8.85; P = 6.5 × 10−76), ovarian cancer (RR, 2.91; 95% CI, 1.40 to 6.04; P = 4.1 × 10−3), pancreatic cancer (RR, 2.37; 95% CI, 1.24 to 4.50; P = 8.7 × 10−3), and male breast cancer (RR, 7.34; 95% CI, 1.28 to 42.18; P = 2.6 × 10−2). There was no evidence for increased risks of prostate or colorectal cancer. The breast cancer RRs declined with age ( P for trend = 2.0 × 10−3). After adjusting for family ascertainment, breast cancer risk estimates on the basis of multiple case families were similar to the estimates from families ascertained through population-based studies ( P for difference = .41). On the basis of the combined data, the estimated risks to age 80 years were 53% (95% CI, 44% to 63%) for female breast cancer, 5% (95% CI, 2% to 10%) for ovarian cancer, 2%-3% (95% CI females, 1% to 4%; 95% CI males, 2% to 5%) for pancreatic cancer, and 1% (95% CI, 0.2% to 5%) for male breast cancer. CONCLUSION These results confirm PALB2 as a major breast cancer susceptibility gene and establish substantial associations between germline PALB2 PVs and ovarian, pancreatic, and male breast cancers. These findings will facilitate incorporation of PALB2 into risk prediction models and optimize the clinical cancer risk management of PALB2 PV carriers.

These cancer genetic counseling recommendations describe the medical, psychosocial, and ethical ramifications of identifying at-risk individuals through cancer risk assessment with or without genetic testing. They were developed by members of the Practice Issues Subcommittee of the National Society of Genetic Counselors Cancer Genetic Counseling Special Interest Group. The information contained in this document is derived from extensive review of the current literature on cancer genetic risk assessment and counseling as well as the personal expertise of genetic counselors specializing in cancer genetics. The recommendations are intended to provide information about the process of genetic counseling and risk assessment for hereditary cancer disorders rather than specific information about individual syndromes. Key components include the intake (medical and family histories), psychosocial assessment (assessment of risk perception), cancer risk assessment (determination and communication of risk), molecular testing for hereditary cancer syndromes (regulations, informed consent, and counseling process), and follow-up considerations. These recommendations should not be construed as dictating an exclusive course of management, nor does use of such recommendations guarantee a particular outcome. These recommendations do not displace a health care provider's professional judgment based on the clinical circumstances of a client.

UGT2B7 catalyses the glucuronidation of a diverse range of drugs, environmental chemicals and endogenous compounds. Hence, coding region polymorphisms of UGT2B7 are potentially of pharmacological, toxicological and physiological significance. Two variant UGT2B7 cDNAs encoding enzymes with either His or Tyr at residue 268 have been isolated. The variants, referred to as UGT2B7*1 and UGT2B7*2, respectively, arise from a C to T transversion at nucleotide 802 of the UGT2B7 coding region. Analysis of genomic DNA from 91 unrelated Caucasians and 84 unrelated Japanese demonstrated the presence of the variant alleles encoding UGT2B7*1 and UGT2B7*2 in both populations. However, while there was an approximately equal distribution of subjects homozygous for each allele in the Caucasian population, subjects homozygous for the UGT2B7*1 allele were over 10-fold more prevalent than UGT2B7*2 homozygotes in Japanese. The frequencies of the UGT2B7*1 and UGT2B7*2 alleles were 0.511 and 0.489, respectively, in Caucasians, and 0.732 and 0.268, respectively, in Japanese. The 95% confidence intervals for the two alleles did not overlap between Caucasians and Japanese. Rates of microsomal androsterone, menthol and morphine (3-position) glucuronidation were determined for genotyped livers from Caucasian donors. Statistically significant inter-genotypic differences were not apparent for any of the three substrates. Although the UGT2B7 polymorphism characterized here is probably not associated with altered enzyme activity, the results highlight the need to consider ethnic variability in assessing the consequences of UGT polymorphisms.

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