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Development of Hereditary Cancer Prevention Measures in Pskov Region

Asoc. Prof. Edvīns Miklaševičs, Riga Stradins University

16 November 2011, St.Petersburg, Russia

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Cancer is the second leading cause of death in Latvia and Russia

Hereditary cancer (HC) accounts for 5-20% of all cancers

The lifetime risk of developing cancer disease for carriers of cancer predisposing mutations is up to 80%, or 10-20 times higher than for the rest of the population

Unlike other forms of cancer, HC is the type of cancer that can and should be prevented

Background on hereditary cancer

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Family A075

III:142

BRCA1(+)

III:2

IV:1 IV:223

BRCA1(+)

II:1 II:2Ov 50d 52

III:3

I:1 I:2

II:3 II:4Ut 52

II:5Br 54 Ov 54,5

d 55

II:6II:7

III:4Ov 46

III:5

IV:3 IV:4

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BRCA1 and BRCA2

Mutations in the BRCA1 and BRCA2 genes predispose carriers to cancer at specific sites (breast, ovary)

Mutations are dominant, inheritance of one mutated allele is sufficient for cancer predisposition

Approx. 70 to 80 per cent of women carrying mutant alleles develop cancer

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4154delAGronwald et al., 2005

5382insC

4153delAGayther et al., 1997

300T>G

5382insC

4153delAGórsky et al., 2000

5382insC

4153delATikhomirova et al., 2005

Gardovskis et al., 2005

300T>G

5382insC

4153delA

Oszurek et al., 2001

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Detection of the BRCA1 mutations 4153delA and 5382insC by PCR

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Melt curve profiles(BRCA2 ex8)

G075

D678

886delGT

wt

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G075

wt

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Why to detect mutation?Prophylactic measures

»regular medical check-ups

»no oral contraception

»breast feeding

»family planning and prophylactic bilateral salpingophorectomy

Strategy of operation and post-op therapy

»extent of operation

»effectivness of pharmaceuticals

Removing of family curse

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Clinical case, BRCA1 c.5266dupC

Patient V., 28 years old

Breast cancer pT1N0M0 in 2008

»Mastectomy (right) in 2008

»Cis-platin and doxorubicin

Risk reducing surgery (left) with reconstruction in 2009/2010

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Clinical case, BRCA1 c.4034delA

Patient S., 42 years old in 2003

Risk reducing adnexectomy in 2003

No oncological disease (2011)

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Two partners – Riga Stradins University (RSU) and Pskov Oncological Dispensary (POD)

Transfer of knowledge and expertise in hereditary cancer treatment

Project duration – 24 months

Project budget – 297,176 EUR

Project in brief

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The overall objective - to improve life quality in project area by developing effective population based hereditary cancer screening and management system model and combating hereditary cancer

Specific objectives:

» to ensure information and experience exchange about HC, its preventative measures and management;

» to raise awareness on HC as manageable and curable disease;

» to identify high HC risk individuals through HC screening pilot project

» to develop HC prevention and management base in Pskov.

Project objectives

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The HC cases remain high not because of lack of scientific knowledge, but rather limited knowledge and experience exchange within the greater community of cancer specialists

Recently new and alternative methods for HC management have been introduced and are efficiently used in Latvia

The project aims at transferring the best practice from Latvian HC specialists to colleauges in Pskov

Situation in hereditary cancer treatment

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Work package 1 deals with project management and financial management

Work package 2 will include publicity and visibility actions:

» Opening and closing conferences in Pskov

» Website development in Pskov

» Information updates on partner websites

» 2,000 doctor brochures and 20,000 patient brochures published and distributed in Pskov region

Work package 1 and Work package 2

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2 experience exchange visits of Russian specialists in Riga, at the Hereditary Cancer Institute of RSU (5 participants)

2 joint seminars together with Latvian partners in Riga (around 15-20 participants)

Methodology for HC treatment in Pskov region developed

Work package 3 - transfer of knowledge on HC management

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Establishment of the HC treatment centre in Pskov:

» Clinical part for providing consultations, preventive measures and treatment

» Molecular laboratory for carrying out diagnostic tests (procurement of necessary equipment)

» Tailor-made training programme for head of POD molecular laboratory in Riga, at the Hereditary Cancer Institute

After the project end the HC centre in Pskov will be open to the HC patients and analyses will be made and consultations provided on a regular basis

Work package 3 - development of HC centre in Pskov

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The pilot project will include hospital screenings and registry screenings of patients in POD

1000 breast and ovarian cancer patients will be given family cancer history survey and taken blood sample

The DNA isolations for HC patients and their relatives from the acquired blood samples and BRCA1 founder mutation investigations will be carried out on 500 samples in LV and RU, thus ensuring that results of the test can be compared

For the 10 individuals with the highest risk full sequencing of the BRCA1/2 and MLH1, MSH2, MSH6 genes will be carried out

Work package 4 - Pilot project for the hereditary cancer screening and management

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HC data base will be established, where during the project all the data from the pilot project will be assembled

A program which can calculate person’s HC risk based on family cancer history surveys and DNA data will be established and made compatible with the existing POD oncology disease patient data base

The system will provide dynamic, medical observation not only for patients with oncology illnesses, but also persons of the risk group

Work package 4 - Pilot project for the hereditary cancer screening and management

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The methodology for carrying out consultations of HC patients will be developed and Latvian experts will visit Pskov to assist Russian colleagues carrying out consultations

The joint consultations will provide Russian specialists with knowledge on how to carry out consultations independently after the project end

Experience from the pilot project will allow to carry out population screening of Pskov region with the aim to discover HC cases and offer treatment possibilities to HC patients and HC high-risk individuals

Work package 4 - Pilot project for the hereditary cancer screening and management

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